RESUMEN
The adsorption of heavy metal on iron (oxyhydr)oxides is one of the most vital geochemical/chemical processes controlling the environmental fate of these contaminants in natural and engineered systems. Traditional experimental methods to investigate this process are often time-consuming and labor-intensive due to the complexity of influencing factors. Herein, a comprehensive database containing the adsorption data of 11 heavy metals on 7 iron (oxyhydr)oxides was constructed, and the machine learning models was successfully developed to predict the adsorption efficiency. The random forest (RF) models achieved high prediction performance (R2 > 0.9, RMSE < 0.1, and MAE < 0.07) and interpretability. Key factors influencing heavy metal adsorption efficiency were identified as mineral surface area, solution pH, metal concentration, and mineral concentration. Additionally, by integrating our previous binding configuration models, we elucidated the simultaneous effects of input features on adsorption efficiency and binding configuration through partial dependence analysis. Higher pH simultaneously enhanced adsorption efficiency and affinity for cations, whereas lower pH benefited that for oxyanions. While higher mineral surface area improved the metal adsorption efficiency, the adsorption affinity could be weakened. This work presents a data-driven approach for investigating metal adsorption behavior and elucidating the influencing mechanisms from macroscopic to microcosmic scale, thereby offering comprehensive guidance for predicting and managing the environmental behavior of heavy metals.
RESUMEN
The economic burden of brucellosis care on patients can lead to significant financial strain, despite partial coverage by medical insurance. However, there is limited research on the out-of-pocket costs faced by brucellosis patients. Therefore, our study aimed to investigate the costs and out-of-pocket expenses of brucellosis care, specifically examining the varying socioeconomic status of patients in Xinjiang, China. We collected cost and demographic data from 563 respondents and their hospital bills and employed latent variable analysis to assess socioeconomic status. The majority of patients belonged to the middle and lower socioeconomic status categories (85.97%), and they were primarily farmers and herders (82.77%). The median direct cost per brucellosis episode was USD 688.65, with out-of-pocket expenses amounting to USD 391.44. These costs exceeded both the 2020 Xinjiang and national per capita health expenditures (USD 233.66 and USD 267.21, respectively). Notably, the overall medical reimbursement rate was 48.60%, and for outpatient costs, it was merely 12.82%. Despite higher out-of-pocket costs among high socioeconomic status patients, the percentage of income spent was higher (37.23%) for patients in the lower socioeconomic status group compared to other groups (16.25% and 12.96%). In conclusion, our findings highlight that brucellosis patients are predominantly from the middle and lower socioeconomic status, with high out-of-pocket expenses placing them under significant financial pressure. Moreover, there is notable inequity in economic consequences across different socioeconomic status groups. These results call for policy interventions aimed at reducing brucellosis-related poverty and promoting equitable access to care.
RESUMEN
Background: Moyamoya disease (MMD) leads to nerve injury. Exosomes are touted as bio-shuttles for the delivery of distinct biomolecules inside the cells. Recently, UCH-L1 was shown to play a vital role in nerve injury. However, it is still unknown whether UCH-L1 can improve the nerve injury of MMD. Materials and Methods: Exosomes were isolated from the serum of patients with MMD and healthy controls. The total RNA was extracted from the exosomes, and the level of GFAP and UCH-L1 between the serum exosomes of the two groups was analyzed by a quantitative reverse transcription-polymerase chain reaction and western blot. Exosome labeling and uptake by SH-SY5Y cells were observed by confocal laser microscopy. Cell counting kit-8 assay and flow cytometry were used to determine the viability and apoptosis of SH-SY5Y cells, respectively. Results: Exosomes were successfully isolated and identified from serum. The expression of GFAP and UCH-L1 was significantly higher in the serum-derived exosomes from MMD patients compared with the healthy controls (P < 0.05). Compared to the blank and control exosome group, serum-derived exosomes from MMD significantly suppress cellular vitality and promote apoptosis of SH-SY5Y cells, while the use of LDN-91946, a specific inhibitor of UCH-L1, could reverse the effects induced by serum-derived exosomes from MMD. Conclusion: UCH-L1 inhibitor could reverse MMD-induced inhibition of SH-SY5Y cell viability and promotion of apoptosis. UCH-L1 may be a therapeutic target for the treatment of nerve damage caused by MMD.
RESUMEN
Organic semiconductor power devices have been attracting increasing attention due to their advantages such as flexibility, low fabrication cost, and sustainability. They have found wide applications in fields such as flexible electronic devices and biomedical devices. However, in the field of power applications, the lack of reliable organic semiconductor power devices is mainly attributed to the limited thermal stability and electrical stability of organic materials. This article provides a detailed review of the development status of organic semiconductor power devices from three aspects: device structure, organic materials, and fabrication methods. It clarifies that the future development goal is to enhance the voltage resistance and thermal stability of organic transistors through higher-performance structure design, higher-mobility materials, and higher-quality fabrication methods. The continuous innovation and development of the structures, materials, and fabrication of these devices will generate more novel devices, offering more possibilities for the application of organic semiconductor power devices. This information is of great reference value and guidance significance for engineers in related fields.
RESUMEN
Introduction: Immune regulatory small molecule JQ1 can block its downstream effector PD-L1 pathway and effectively reverse the PD-L1 upregulation induced by doxorubicin (DOX). So the synergistic administration of chemotherapeutic drug DOX and JQ1 is expected to increase the sensitivity of tumors to immune checkpoint therapy and jointly enhance the body's own immunity, thus effectively killing tumor cells. Therefore, a drug delivery system loaded with DOX and JQ1 was devised in this study. Methods: Polydopamine nanoparticles (PDA NPs) were synthesized through spontaneous polymerization. Under appropriate pH conditions, DOX and JQ1 were loaded onto the surface of PDA NPs, and the release of DOX and JQ1 were measured using UV-Vis or high performance liquid chromatography (HPLC). The mechanism of fabricated nanocomplex in vitro was investigated by cell uptake experiment, cell viability assays, apoptosis assays, and Western blot analysis. Finally, the tumor-bearing mouse model was used to evaluate the tumor-inhibiting efficacy and the biosafety in vivo. Results: JQ1 and DOX were successfully loaded onto PDA NPs. PDA-DOX/JQ1 NPs inhibited the growth of prostate cancer cells, reduced the expression of apoptosis related proteins and induced apoptosis in vitro. The in vivo biodistribution indicated that PDA-DOX/JQ1 NPs could accumulated at the tumor sites through the EPR effect. In tumor-bearing mice, JQ1 delivered with PDA-DOX/JQ1 NPs reduced PD-L1 expression at tumor sites, generating significant tumor suppression. Furthermore, PDA-DOX/JQ1 NPs could reduce the side effects, and produce good synergistic treatment effect in vivo. Conclusion: We have successfully prepared a multifunctional platform for synergistic prostate cancer therapy.
Asunto(s)
Apoptosis , Azepinas , Doxorrubicina , Indoles , Nanopartículas , Polímeros , Neoplasias de la Próstata , Masculino , Animales , Doxorrubicina/química , Doxorrubicina/farmacología , Doxorrubicina/farmacocinética , Doxorrubicina/administración & dosificación , Indoles/química , Indoles/farmacología , Indoles/farmacocinética , Polímeros/química , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Nanopartículas/química , Humanos , Ratones , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Azepinas/química , Azepinas/farmacología , Azepinas/farmacocinética , Sinergismo Farmacológico , Supervivencia Celular/efectos de los fármacos , Distribución Tisular , Ensayos Antitumor por Modelo de Xenoinjerto , Liberación de Fármacos , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Antígeno B7-H1/metabolismo , TriazolesRESUMEN
To meet evolving humidity monitoring needs, the development of flexible, high-performance humidity sensors is crucial. This study introduces an innovative flexible humidity sensor using a single-step laser scribing technique to fabricate a flexible in situ Co3O4 nanoparticle-embedded laser-induced graphene (Co3O4-LIG) composite electrode. Compared to conventional LIG electrodes, the Co3O4-LIG electrode exhibits improved conductivity and hydrophilicity, enhancing charge transfer and water molecule affinity. The unique two-dimensional structure and exceptional water permeability of graphene oxide (GO) combine with the rapid water response and high specific surface area of carboxylated multiwalled carbon nanotubes (MWCNTs), thereby assuming a crucial function in the modification and optimization of the performance of humidity sensors. Through the application of a homogenously blended aqueous solution comprising GO and MWCNTs in precise proportions onto the Co3O4-LIG composite electrode, an excellent humidity-responsive layer is established, culminating in the realization of a cutting-edge GO-MWCNTs@Co3O4-LIG flexible humidity sensor. Noteworthy attributes of this sensor include a heightened sensitivity [959.1% (ΔR/R0)], rapid response and recovery times (within 5 and 26 s, respectively), and a noteworthy linearity (R2 = 0.994) across a relative humidity range of 14 to 95%. The findings presented herein offer valuable insights and a practical blueprint for the design and production of flexible humidity sensors.
RESUMEN
PURPOSE: To investigate the relationship between the abundance of CD4+ and CD8+ T cells in the tumor microenvironment and the prognosis of patients with esophageal squamous cell carcinoma, and to analyze their correlation and explore its clinical value. MATERIALS AND METHODS: In total, we enrolled 120 cases of esophageal squamous cell carcinoma diagnosed. The abundance of CD4+ and CD8+ T lymphocytes in the tissue specimens of esophageal cancer was examined by immunohistochemistry. We measured the correlation between the abundance of CD4+ and CD8+ T lymphocytes and the clinical and pathological characteristics and prognosis of esophageal squamous cell carcinoma. RESULTS: The tissue abundance of CD4+ T lymphocytes was closely related to tumor prognosis (P < 0.05). Similarly, there was a statistically significant relationship between the tissue abundance of CD8+ T lymphocytes and patients' prognosis (P < 0.05), indicating that a high abundance of CD8+ T lymphocytes predicts better prognosis in esophageal squamous cell carcinoma. Surprisingly, we found that a higher CD4+/CD8+ ratio predicted a better prognosis of esophageal squamous cell carcinoma. CONCLUSIONS: The tissue abundance of CD4+ and CD8+ T lymphocytes can serve as an important indicator for predicting the long-term survival of patients with esophageal squamous cell carcinoma. A high CD4+/CD8+ ratio may improve patients' prognosis through several pathways. The association of this ratio with clinical and pathological characteristics may explain the poor efficacy of immunotherapy in patients with esophageal cancer. These findings may help us find new targets for immunotherapy by exploring the immune microenvironment of esophageal squamous cell carcinoma.
RESUMEN
Emitters produce weak emissions when they undergo structural changes such as molecular configuration transformation (MCT) or excited-state intramolecular proton transfer (ESIPT) but give out strong emissions after terminating these distortions. Herein, an organoplatinum complex, Pt-ppy-ABP, carrying a salicylaldehyde-based Schiff base unit is synthesized. It exhibits weak emission in dilute solutions but shows bright emission at the aggregated state or after interacting with F- and Zn2+. This suggests that it has an aggregation-enhanced emission (AEE) property and holds potential in ion detection. Supported by theoretical calculations and femtosecond transient absorption results, this complex suffers excited-state structural changes including MCT from a square-planar configuration to a tetrahedral one, as well as intramolecular rotation of a monodentate ligand and ESIPT, showing weak emission in its solutions. At the aggregated state, it releases strong yellow emissions because of the restraints of MCT and ligand rotation. Upon interacting with F- or Zn2+, it emits bright-red or -green emissions, achieving detection limits of 10-7 M. The sensing mechanism is concluded as deprotonation- and coordination-induced ESIPT terminations, respectively. Given its AEE property and ion-responsive emissions, its application in information encryption is also explored. Finally, these findings should provide valuable clues for the developments of chemosensors with dual-channel recognition abilities.
RESUMEN
Introduction: Alternol is a natural compound isolated from the fermentation of a mutated fungus. We have demonstrated its potent anti-cancer effect via the accumulation of radical oxygen species (ROS) in prostate cancer cells in vitro and in vivo. In this study, we tested its anti-cancer spectrum in multiple platforms. Methods: We first tested its anti-cancer spectrum using the National Cancer Institute-60 (NCI-60) screening, a protein quantitation-based assay. CellTiter-Glo screening was utilized for ovarian cancer cell lines. Cell cycle distribution was analyzed using flow cytometry. Xenograft models in nude mice were used to assess anti-cancer effect. Healthy mice were tested for the acuate systemic toxicity. Results: Our results showed that Alternol exerted a potent anti-cancer effect on 50 (83%) cancer cell lines with a GI50 less than 5 µM and induced a lethal response in 12 (24%) of those 50 responding cell lines at 10 µM concentration. Consistently, Alternol displayed a similar anti-cancer effect on 14 ovarian cancer cell lines in an ATP quantitation-based assay. Most interestingly, Alternol showed an excellent safety profile with a maximum tolerance dose (MTD) at 665 mg/kg bodyweight in mice. Its therapeutic index was calculated as 13.3 based on the effective tumor-suppressing doses from HeLa and PC-3 cell-derived xenograft models. Conclusion: Taken together, Alternol has a broad anti-cancer spectrum with a safe therapeutic index in vivo.
RESUMEN
INTRODUCTION: Diabetic cataract (DC) is a common ocular complication of diabetes. Mitofusin 2 (MFN2), a mitochondrial fusion protein, is involved in the pathogenesis of cataract and diabetic complications. However, its role and molecular mechanisms in DC remain unclear. MATERIALS AND METHODS: DC models in rats were induced by intraperitoneal injection of streptozocin (STZ) for 12 weeks. We measured the body weight of rats, blood glucose concentrations, sorbitol dehydrogenase (SDH) activity and advanced glycation end products (AGE) content in the lenses of rats. MFN2 mRNA and protein expression levels in the lenses were detected by RT-qPCR and western blot assays. In vitro, human lens epithelial (HLE) B3 cells were treated for 48 h with 25 mM glucose (high glucose, HG) to induce cell damage. To determine the role of MFN2 in HG-induced cell damage, HLE-B3 cells were transfected with lentivirus loaded with MFN2 overexpression plasmid or short hairpin RNA (shRNA) to overexpress or knock down MFN2 expression, followed by HG exposure. Cell viability was assessed by CCK-8 assay. Flow cytometry was used to detect cell apoptosis and reactive oxygen species (ROS) level. JC-1 staining showed the changes in mitochondrial membrane potential (Δψm). The mediators related to apoptosis, mitochondrial damage, and autophagy were determined. RESULTS: STZ-administrated rats showed reduced body weight, increased blood glucose levels, elevated SDH activity and AGE content, suggesting successful establishment of the DC rat model. Interestingly, MFN2 expression was significantly downregulated in DC rat lens and HG-induced HLE-B3 cells. Further analysis showed that under HG conditions, MFN2 overexpression enhanced cell viability and inhibited apoptosis accompanied by decreased Bax, cleaved caspase-9 and increased Bcl-2 expression in HLE-B3 cells. MFN2 overexpression also suppressed the mitochondrial damage elicited by HG as manifested by reduced ROS production, recovered Δψm and increased mitochondrial cytochrome c (Cyto c) level. Moreover, MFN2 overexpression increased LC3Bâ ¡/LC3Bâ ratio and Beclin-1 expression, but decreased p62 level, and blocked the phosphorylation of mTOR in HG-treated HLE-B3 cells. In contrast, MFN2 silencing exerted opposite effects. CONCLUSIONS: Presented findings indicate that MFN2 expression may be essential for preventing lens epithelial cell apoptosis during development of diabetic cataract.
Asunto(s)
Apoptosis , Autofagia , Células Epiteliales , GTP Fosfohidrolasas , Glucosa , Cristalino , Mitocondrias , Apoptosis/efectos de los fármacos , Animales , Humanos , Autofagia/efectos de los fármacos , GTP Fosfohidrolasas/metabolismo , GTP Fosfohidrolasas/genética , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Ratas , Cristalino/metabolismo , Cristalino/efectos de los fármacos , Ratas Sprague-Dawley , Masculino , Diabetes Mellitus Experimental/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Línea Celular , Catarata/metabolismo , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Potencial de la Membrana Mitocondrial/efectos de los fármacosRESUMEN
Since the 1980s, there has been increasing concern over heavy metal pollution remediation. However, most research focused on the individual remediation technologies for heavy metal pollutants in either soil or water. Considering the potential migration of these pollutants, it is necessary to explore effective integrated remediation technologies for soil and water heavy metals. This review thoroughly examines non-phytoremediation technologies likes physical, chemical, and microbial remediation, as well as green remediation approaches involving terrestrial and aquatic phytoremediation. Non-phytoremediation technologies suffer from disadvantages like high costs, secondary pollution risks, and susceptibility to environmental factors. Conversely, phytoremediation technologies have gained significant attention due to their sustainable and environmentally friendly nature. Enhancements through chelating agents, biochar, microorganisms, and genetic engineering have demonstrated improved phytoremediation remediation efficiency. However, it is essential to address the environmental and ecological risks that may arise from the prolonged utilization of these materials and technologies. Lastly, this paper presents an overview of integrated remediation approaches for addressing heavy metal contamination in groundwater-soil-surface water systems and discusses the reasons for the research gaps and future directions. This paper offers valuable insights for comprehensive solutions to heavy metal pollution in water and soil, promoting integrated remediation and sustainable development.
Asunto(s)
Biodegradación Ambiental , Metales Pesados , Contaminantes del Suelo , Contaminantes Químicos del Agua , Metales Pesados/análisis , Metales Pesados/metabolismo , Contaminantes del Suelo/metabolismo , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/metabolismo , Restauración y Remediación Ambiental/métodos , Suelo/químicaRESUMEN
Background: Alternol is a small molecular compound isolated from the fermentation of a mutant fungus obtained from Taxus brevifolia bark. Our previous studies showed that Alternol treatment induced reactive oxygen species (ROS)-dependent immunogenic cell death. This study conducted a comprehensive investigation to explore the mechanisms involved in Alternol-induced immunogenic cell death. Methods: Prostate cancer PC-3, C4-2, and 22RV1 were used in this study. Alternol interaction with heat shock proteins (HSP) was determined using CETSA assay. Alternol-regulated ER stress proteins were assessed with Western blot assay. Extracellular adenosine triphosphate (ATP) was measured using ATPlite Luminescence Assay System. Results: Our results showed that Alternol interacted with multiple cellular chaperone proteins and increased their expression levels, including endoplasmic reticulum (ER) chaperone hypoxia up-regulated 1 (HYOU1) and heat shock protein 90 alpha family class B member 1 (HSP90AB1), as well as cytosolic chaperone heat shock protein family A member 8 (HSPA8). These data represented a potential cause of unfolded protein response (UPR) after Alternol treatment. Further investigation revealed that Alternol treatment triggered ROS-dependent (ER) stress responses via R-like ER kinase (PERK), inositol-requiring enzyme 1α (IRE1α). The double-stranded RNA-dependent protein kinase (PKR) but not activating transcription factor 6 (ATF6) cascades, leading to ATF-3/ATF-4 activation, C/EBP-homologous protein (CHOP) overexpression, and X-box binding protein XBP1 splicing induction. In addition, inhibition of these ER stress responses cascades blunted Alternol-induced extracellular adenosine triphosphate (ATP) release, one of the classical hallmarks of immunogenic cell death. Conclusion: Taken together, our data demonstrate that Alternol treatment triggered multiple ER stress cascades, leading to immunogenic cell death.
RESUMEN
Rhei Radix et Rhizoma is common traditional Chinese medicine with multiple original plants. The content and proportion of the active components in Rhei Radix et Rhizoma from different plant species were compared to accurately evaluate the medicine qua-lity and provide a theoretical basis for precise use of this medicine in clinical practice. In this study, fresh Rhei Radix et Rhizoma samples were collected from the four-year-old plants of Rheum palmatum, R. tanguticum, and R. officinale. The relative content of 220 anthraquinones, anthrones, and tannins in the samples were determined by pseudo-targeted metabolomics, and the differential components were screened by multivariate statistical methods. The principal component analysis classified the samples into three clusters according to the original plants. The orthogonal partial least squares-discriminant analysis(OPLS-DA) screened out 117 differential components, including 8 free anthraquinones, 18 anthraquinone glycosides, 80 anthrones, and 11 tannins. Twenty-eight components had the highest content in R. tanguticum, mainly including sennosides, anthraquinone glycosides, and procyanidins. Thirty-five components showed the highest content in R. officinale, mainly including free anthraquinones and catechines. Fifty-four components showed the highest content in R. palmatum, mainly including dianthrones, while the structures of most of them cannot be determined temporarily. The content distribution of differential components in the three original plants indicates that R. tanguticum has the strongest effect of purging, while R. officinale has the strongest effect of clearing heat and purging fire, and both have stronger effects of resolvong stasis and dredging meridians than R. palmatum.
Asunto(s)
Medicamentos Herbarios Chinos , Metabolómica , Rheum , Rizoma , Rheum/química , Rizoma/química , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Antraquinonas/química , Antraquinonas/análisis , Cromatografía Líquida de Alta PresiónRESUMEN
BACKGROUND: Abuse of fentanyl and its analogs is a major contributor to the opioid overdose epidemic in the United States, but detecting and quantifying trace amounts of such drugs remains a challenge without resorting to sophisticated mass spectrometry-based methods. METHODS: A sensitive immunoassay with a sub-picogram limit of detection for fentanyl and a wide range of fentanyl analogs has been developed, using a novel high-affinity antibody fused with NanoLuc, a small-size luciferase that can emit strong and stable luminescence. When used with human urine samples, the assay has a sub-picogram limit of detection for fentanyl, with results fully concordant with LC-MS. RESULTS: When applied to clinical samples, the novel chemiluminescence immunoassay can detect low positive fentanyl missed by routine screening immunoassays, with a limit of detection of 0.8â pg/mL in human urine. When applied to environmental samples, the assay can detect levels as low as 0.25 pg fentanyl per inch2 of environment surface. Assay turnaround time is less than 1â h, with inexpensive equipment and the potential for high-throughput automation or in-field screening. CONCLUSIONS: We have established a novel assay that may have broad applications in clinical, environmental, occupational, and forensic scenarios for detection of trace amounts of fentanyl and its analogs.
Asunto(s)
Fentanilo , Mediciones Luminiscentes , Fentanilo/orina , Fentanilo/análisis , Humanos , Inmunoensayo/métodos , Mediciones Luminiscentes/métodos , Límite de Detección , Detección de Abuso de Sustancias/métodos , Analgésicos Opioides/orina , Analgésicos Opioides/análisisRESUMEN
Flexible electronic products, with their characteristics of flexibility and wearability, have attracted significant attention and have become an important direction in the research and development of the electronics industry. Planar micro-supercapacitors (MSCs) with flexible composite electrodes can provide reliable energy support for these products, propelling their further development. The research employed a quick, effective, and environmentally friendly method of laser scribing to create shape-controllable flexible composite electrodes on composite films of Poly(3,4-ethylenedioxythiophene) and graphene oxide (PEDOT/GO), which were subsequently assembled into MSCs. An analysis of the composite electrode morphology, structure, and elemental distribution was conducted through the utilization of SEM, TEM, and XPS techniques. Following this, a comprehensive evaluation of the electrochemical performance of the flexible MSCs was carried out, which included cyclic voltammetry (CV), galvanostatic charge/discharge (GCD), and assessment of cyclic stability. The analysis of the CV results indicated that the MSCs achieved the areal capacitance of 5.78 mF/cm2 at 5 mV/s. After 5000 cycles at a current density of 0.05 mA/cm2, the capacitance retention rate was 85.4%. The high areal capacitance and strong cycle stability of MSCs highlight the potential of PEDOT/reduced graphene oxide (PEDOT/rGO) electrodes in electrode applications.
RESUMEN
Inhibitors of Apoptosis Proteins (IAP) are inhibitors that can block programmed cell death, are expressed at high levels in various cancers, and are recognized as a therapeutic target for cancer therapy. In the past few years, several small molecule IAP protein inhibitors have been designed to mimic the endogenous IAP antagonist, but no IAP inhibitors have been approved for marketing worldwide. Previously, xevinapant has been awarded a breakthrough therapy designation by the FDA. In addition, a combination of Smac-mimetics and chemotherapeutic compounds has been reported to improve anticancer efficacy. According to the phase II clinical data, xevinapant has the potential to significantly enhance the standard therapy for patients with head and neck cancer, which is expected to be approved as an innovative therapy for cancer patients. Therefore, this paper briefly describes the mechanism of IAPs (AT-406, APG-1387, GDC- 0152, TL32711, and LCL161) as single or in combination for cancer treatment, their application status as well as the synthetic pathway, and explores the research prospects and challenges of IAPs antagonists in the tumor combination therapy, with the hope of providing strong insights into the further development of Smac mimics in tumor therapy.
RESUMEN
BACKGROUND: Research has suggested significant correlations among ageing, immune microenvironment, inflammation and tumours. However, the relationships among ageing, immune microenvironment, cystitis and bladder urothelial carcinoma (BLCA) in the bladder have rarely been reported. METHODS: Bladder single-cell and transcriptomic data from young and old mice were used for immune landscape analysis. Transcriptome, single-cell and The Cancer Genome Atlas Program datasets of BLCA and interstitial cystitis/bladder pain syndrome (IC/BPS) were used to analyse immune cell infiltration and molecular expression. Bladder tissues from mice, IC/BPS and BLCA were collected to validate the results. RESULTS: Eight types of immune cells (macrophages, B-cells, dendritic cells, T-cells, monocytes, natural killer cells, γδ T-cells and ILC2) were identified in the bladder of mice. Aged mice bladder tissues had a significantly higher number of T-cells, γδ T-cells, ILC2 and B-cells than those in the young group (P < 0.05). Three types of T-cells (NK T-cells, γδ T-cells and naïve T-cells) and three types of B-cells (follicular B-cells, plasma and memory B-cells) were identified in aged mice bladder. Chemokine receptor 7 (CCR7) is highly expressed in aged bladder, IC/BPS and BLCA (P < 0.05). CCR7 is likely to be involved in T- and B-cell infiltration in aged bladder, IC/BPS and BLCA. Interestingly, the high CCR7 expression on BLCA cell membranes was a prognostic protective factor. CONCLUSIONS: In this study, we characterised the expression profiles of immune cells in bladder tissues of aged and young mice and demonstrated that CCR7-mediated T- and B-cell filtration contributes to the development of bladder ageing, IC/BPS and BLCA.
RESUMEN
A macrocyclic compound, hemicucurbit[6]uril (HemiQ[6]), is employed as the carbon source to produce a novel sort of carbon quantum dots (CQDs) with blue fluorescence in aqueous solution. The CQDs are fully identified by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), Nuclear Magnetic Resonance (NMR), zeta potential, ultraviolet/visible (UV-vis) and photoluminescence spectroscopy (PL). The nanomaterial is developed for the analysis of Pb2+ in the light of the Resonance Rayleigh scattering (RRS) changes with the increasing Pb2+ concentration. The proposed probe emerges a high selectivity to Pb2+ and excellent sensitivity in the linear concentration range of 0-6 µM with a detection limit low to 0.42 µM, which is superior to the previous values of Pb2+ sensors, as well as the good anti-interference ability is confirmed by the specifical response to Pb2+ in the presence of other metal cations. Therefore, the proposed analysis of Pb2+ is explored for the application in real samples of tap water and lake water, in satisfied results of acceptable recoveries.
RESUMEN
The interaction effects between the main components (proteins (P), carbohydrates (C), and lipids (L)) of protein-rich biomass during microwave-assisted pyrolysis were investigated in depth with an exploration of individual pyrolysis and copyrolysis (PC, PL, and CL) of model compounds. The average heating rate of P was higher than those of C and L, and the interactions in all copyrolysis groups reduced the max instant heating rate. The synergistic extent (S) of PC and PL for bio-oil yield was 16.78 and 18.24%, respectively, indicating that the interactions promoted the production of bio-oil. Besides, all of the copyrolysis groups exhibited a synergistic effect on biochar production (S = 19.43-28.24%), while inhibiting the gas generation, with S ranging from -20.17 to -6.09%. Regarding the gaseous products, apart from H2, P, C, and L primarily generated CO2, CO, and CH4, respectively. Regarding bio-oil composition, the interactions occurring within PC, PL, and CL exhibited a significantly synergistic effect (S = 47.81-412.96%) on the formation of N-heterocyclics/amides, amides/nitriles, and acids/esters, respectively. Finally, the favorable applicability of the proposed interaction effects was verified with microalgae. This study offers valuable insights for understanding the microwave-assisted pyrolysis of protein-rich biomass, laying the groundwork for further research and process optimization.
Asunto(s)
Biomasa , Microondas , Pirólisis , Proteínas/química , Lípidos/química , Carbón Orgánico/química , Carbohidratos/química , BiocombustiblesRESUMEN
Prostate cancer (PCa) is a common health threat to men worldwide, and castration-resistant PCa (CRPC) is the leading cause of PCa-related deaths. Extracellular vesicles (EVs) are lipid bilayer compartments secreted by living cells that are important mediators of intercellular communication. EVs regulate the biological processes of recipient cells by transmitting heterogeneous cargoes, contributing to CRPC occurrence, progression, and drug resistance. These EVs originate not only from malignant cells, but also from various cell types within the tumor microenvironment. EVs are widely dispersed throughout diverse biological fluids and are attractive biomarkers derived from noninvasive liquid biopsy techniques. EV quantities and cargoes have been tested as potential biomarkers for CRPC diagnosis, progression, drug resistance, and prognosis; however, technical barriers to their clinical application continue to exist. Furthermore, exogenous EVs may provide tools for new therapies for CRPC. This review summarizes the current evidence on the role of EVs in CRPC.