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To better understand the migration behavior of plastic fragments in the environment, development of rapid non-destructive methods for in-situ identification and characterization of plastic fragments is necessary. However, most of the studies had focused only on colored plastic fragments, ignoring colorless plastic fragments and the effects of different environmental media (backgrounds), thus underestimating their abundance. To address this issue, the present study used near-infrared spectroscopy to compare the identification of colored and colorless plastic fragments based on partial least squares-discriminant analysis (PLS-DA), extreme gradient boost, support vector machine and random forest classifier. The effects of polymer color, type, thickness, and background on the plastic fragments classification were evaluated. PLS-DA presented the best and most stable outcome, with higher robustness and lower misclassification rate. All models frequently misinterpreted colorless plastic fragments and its background when the fragment thickness was less than 0.1mm. A two-stage modeling method, which first distinguishes the plastic types and then identifies colorless plastic fragments that had been misclassified as background, was proposed. The method presented an accuracy higher than 99% in different backgrounds. In summary, this study developed a novel method for rapid and synchronous identification of colored and colorless plastic fragments under complex environmental backgrounds.
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Monitoreo del Ambiente , Aprendizaje Automático , Plásticos , Espectroscopía Infrarroja Corta , Espectroscopía Infrarroja Corta/métodos , Monitoreo del Ambiente/métodos , Plásticos/análisis , Análisis de los Mínimos Cuadrados , Análisis Discriminante , ColorRESUMEN
Chemodynamic therapy (CDT), an emerging cancer treatment modality, uses multivalent metal elements to convert endogenous hydrogen peroxide (H2O2) to toxic hydroxyl radicals (â¢OH) via a Fenton or Fenton-like reaction, thus eliciting oxidative damage of cancer cells. However, the antitumor potency of CDT is largely limited by the high glutathione (GSH) concentration and low catalytic efficiency in the tumor sites. The combination of CDT with chemotherapy provides a promising strategy to overcome these limitations. In this work, to enhance antitumor potency by tumor-targeted and GSH depletion-amplified chemodynamic-chemo therapy, the hyaluronic acid (HA)/polydopamine (PDA)-decorated Fe2+-doped ZIF-8 nano-scaled metal-organic frameworks (FZ NMs) were fabricated and utilized to load doxorubicin (DOX), a chemotherapy drug, via hydrophobic, π-π stacking and charge interactions. The attained HA/PDA-covered DOX-carrying FZ NMs (HPDFZ NMs) promoted DOX and Fe2+ release in weakly acidic and GSH-rich milieu and exhibited acidity-activated â¢OH generation. Through efficient CD44-mediated endocytosis, the HPDFZ NMs internalized by CT26 cells not only prominently enhanced â¢OH accumulation by consuming GSH via PDA-mediated Michael addition combined with Fe2+/Fe3+ redox couple to cause mitochondria damage and lipid peroxidation, but also achieved intracellular DOX release, thus eliciting apoptosis and ferroptosis. Importantly, the HPDFZ NMs potently inhibited CT26 tumor growth in vivo at a low DOX dose and had good biosafety, thereby showing promising potential in tumor-specific treatment.
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Accelerating perovskite solid solution discovery and sustainable synthesis is crucial for addressing challenges in wireless communication and biosensors. However, the vast array of chemical compositions and their dependence on factors such as crystal structure, and sintering temperature require time-consuming manual processes. To overcome these constraints, we introduce an automated materials discovery approach encompassing machine learning (ML) assisted material screening, robotic synthesis, and high-throughput characterization. Our proposed platform for rapid sintering and dielectric analysis streamlines the characterization of perovskites and the discovery of disordered materials. The setup has been successfully validated, demonstrating processing materials within minutes, in stark contrast to conventional procedures that can take hours or days. Following setup validation with established samples, we showcase synthesizing single-phase solid solutions within the barium family, such as (BaxSr1-x)CeO3, identified through ML-guided chemistry.
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Visual adaptation is essential for optimizing the image quality and sensitivity of artificial vision systems in real-world lighting conditions. However, additional modules, leading to time delays and potentially increasing power consumption, are needed for traditional artificial vision systems to implement visual adaptation. Here, an ITO/PMMA/SiC-NWs/ITO photoelectric synaptic device is developed for compact artificial vision systems with the visual adaption function. The theoretical calculation and experimental results demonstrated that the heating effect, induced by the increment light intensity, leads to the photoelectric synaptic device enabling the visual adaption function. Additionally, a visual adaptation artificial neuron (VAAN) circuit was implemented by incorporating the photoelectric synaptic device into a LIF neuron circuit. The output frequency of this VAAN circuit initially increases and then decreases with gradual light intensification, reflecting the dynamic process of visual adaptation. Furthermore, a visual adaptation spiking neural network (VASNN) was constructed to evaluate the photoelectric synaptic device based visual system for perception tasks. The results indicate that, in the task of traffic sign detection under extreme weather conditions, an accuracy of 97% was achieved (which is approximately 12% higher than that without a visual adaptation function). Our research provides a biologically plausible hardware solution for visual adaptation in neuromorphic computing.
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Background: Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC. Patients and methods: We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time. Results: We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort. Conclusion: We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.
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Drug resistance presents a significant challenge to achieving positive clinical outcomes in anti-tumor therapy. Prior research has illuminated reasons behind drug resistance, including increased drug efflux, alterations in drug targets, and abnormal activation of oncogenic pathways. However, there's a need for deeper investigation into the impact of drug-resistant cells on parental tumor cells and intricate crosstalk between tumor cells and the malignant tumor microenvironment (TME). Recent studies on extracellular vesicles (EVs) have provided valuable insights. EVs are membrane-bound particles secreted by all cells, mediating cell-to-cell communication. They contain functional cargoes like DNA, RNA, lipids, proteins, and metabolites from mother cells, delivered to other cells. Notably, EVs are increasingly recognized as regulators in the resistance to anti-cancer drugs. This review aims to summarize the mechanisms of EV-mediated anti-tumor drug resistance, covering therapeutic approaches like chemotherapy, targeted therapy, immunotherapy and even radiotherapy. Detecting EV-based biomarkers to predict drug resistance assists in bypassing anti-tumor drug resistance. Additionally, targeted inhibition of EV biogenesis and secretion emerges as a promising approach to counter drug resistance. We highlight the importance of conducting in-depth mechanistic research on EVs, their cargoes, and functional approaches specifically focusing on EV subpopulations. These efforts will significantly advance the development of strategies to overcome drug resistance in anti-tumor therapy.
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Multifactorial diseases demand therapeutics that can modulate multiple targets for enhanced safety and efficacy, yet the clinical approval of multitarget drugs remains rare. The integration of machine learning (ML) and deep learning (DL) in drug discovery has revolutionized virtual screening. This study investigates the synergy between ML/DL methodologies, molecular representations, and data augmentation strategies. Notably, we found that SVM can match or even surpass the performance of state-of-the-art DL methods. However, conventional data augmentation often involves a trade-off between the true positive rate and false positive rate. To address this, we introduce Negative-Augmented PU-bagging (NAPU-bagging) SVM, a novel semi-supervised learning framework. By leveraging ensemble SVM classifiers trained on resampled bags containing positive, negative, and unlabeled data, our approach is capable of managing false positive rates while maintaining high recall rates. We applied this method to the identification of multitarget-directed ligands (MTDLs), where high recall rates are critical for compiling a list of interaction candidate compounds. Case studies demonstrate that NAPU-bagging SVM can identify structurally novel MTDL hits for ALK-EGFR with favorable docking scores and binding modes, as well as pan-agonists for dopamine receptors. The NAPU-bagging SVM methodology should serve as a promising avenue to virtual screening, especially for the discovery of MTDLs.
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Descubrimiento de Drogas , Descubrimiento de Drogas/métodos , Humanos , Simulación del Acoplamiento Molecular , Ligandos , Máquina de Vectores de Soporte , Aprendizaje Profundo , Aprendizaje Automático Supervisado , Aprendizaje AutomáticoRESUMEN
Semiaquilegia danxiashanensis is currently known only from the type locality, Danxia Mountain, characterized by its spectacular red sandstone cliffscape. In this study, we assembled the complete chloroplast genome sequence of S. danxiashanensis and inferred its phylogenetic relationships. Total length of the chloroplast genome was 160,548 bp, with an overall GC content of 39%. The chloroplast genome had typical quadripartite structure and contained one LSC region (89,882 bp) and one SSC region (17,386 bp), which were separated by two IRs regions (26,640 bp, respectively). It comprised 133 genes, including 84 protein coding genes, 41 tRNA genes and eight rRNA genes. The maximum likelihood phylogenetic analysis indicated that S. danxiashanensis was sister to S. adoxoides; meanwhile, Semiaquilegia was closely related to both Urophysa and Aquilegia in Ranunculaceae. This study sheds light on the evolutionary history of Semiaquilegia and provides preliminary data for future comparative analysis of chloroplast genomes.
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Inefficient active site utilization of oxygen evolution reaction (OER) catalysts have limited the energy efficiency of proton exchange membrane (PEM) water electrolysis. Here, an atomic grid structure is demonstrated composed of high-density Ir sites (≈10 atoms per nm2) on reactive MnO2-x support which mediates oxygen coverage-enhanced OER process. Experimental characterizations verify the low-valent Mn species with decreased oxygen coordination in MnO2-x exert a pivotal impact in the enriched oxygen coverage on the surface during OER process, and the distributed Ir atomic grids, where highly electrophilic IrâO(II-δ)- bonds proceed rapidly, render intense nucleophilic attack of oxygen radicals. Thereby, this metal-support cooperation achieves ultra-low overpotentials of 166 mV at 10 mA cm-2 and 283 mV at 500 mA cm-2, together with a striking mass activity which is 380 times higher than commercial IrO2 at 1.53 V. Moreover, its high OER performance also markedly surpasses the commercial Ir black catalyst in PEM electrolyzers with long-term stability.
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BACKGROUND: In patients undergoing total joint arthroplasty (TJA), the administration of dexamethasone may contribute to perioperative blood glucose (BG) disturbances, potentially resulting in complications, even in patients without diabetes. This study aimed to demonstrate the impact of different administration regimens of dexamethasone in postoperative BG levels. METHODS: In this randomized, controlled, double-blind trial, 136 patients without diabetes scheduled for TJA were randomly assigned to three groups: two perioperative saline injections (Group A, placebo); a single preoperative injection of 20 mg dexamethasone and a postoperative saline injection (Group B), and two perioperative injections of 10 mg dexamethasone (Group C). Primary outcomes were the postoperative fasting blood glucose (FBG) levels. Secondary outcome parameters were the postoperative postprandial blood glucose (PBG) levels. Postoperative complications within 90 days were also recorded. Risk factors for FBG ≥ 140 mg/dl and PBG ≥ 180 mg/dl were investigated. RESULTS: Compared to Group A, there were transient increases in FBG and PBG on postoperative days (PODs) 0 and 1 in Groups B and C. Statistical differences in FBG and PBG among the three groups were nearly absent from POD 1 onward. Both dexamethasone regimens did not increase the risk for postoperative FBG ≥ 140 mg/dl or PBG ≥ 180 mg/dl. Elevated preoperative HbA1c levels may increase the risk of postoperative FBG ≥ 140 mg/dl or PBG ≥ 180 mg/dl, respectively. CONCLUSION: Perioperative intravenous high-dose dexamethasone to patients without diabetes has transient effects on increasing BG levels after TJA. However, no differences were found between the split-dose and single high-dose regimens. The elevated preoperative HbA1c, but not the dexamethasone regimens were the risk factor for FBG ≥ 140 mg/dl and PBG ≥ 180 mg/dl. TRIAL REGISTRATION: Chinese Clinical Trail Registry, ChiCTR2300069473. Registered 17 March 2023, https://www.chictr.org.cn/showproj.html?proj=186760 .
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Glucemia , Dexametasona , Humanos , Dexametasona/administración & dosificación , Método Doble Ciego , Masculino , Femenino , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Persona de Mediana Edad , Anciano , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/sangre , Inyecciones Intravenosas , Periodo Posoperatorio , Artroplastia de Reemplazo de Cadera/efectos adversos , Glucocorticoides/administración & dosificación , Artroplastia de Reemplazo/efectos adversos , Administración IntravenosaRESUMEN
The phosphoinositide 3-kinase (PI3K)-Akt axis is one of the most frequently activated pathways and is demonstrated as a therapeutic target in Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutated colorectal cancer (CRC). Targeting the PI3K-Akt pathway has been a challenging undertaking through the decades. Here we unveiled an essential role of E3 ligase SMAD ubiquitylation regulatory factor 1 (Smurf1)-mediated phosphoinositide-dependent protein kinase 1 (PDK1) neddylation in PI3K-Akt signaling and tumorigenesis. Upon growth factor stimulation, Smurf1 immediately triggers PDK1 neddylation and the poly-neural precursor cell expressed developmentally downregulated protein 8 (poly-Nedd8) chains recruit methyltransferase SET domain bifurcated histone lysine methyltransferase 1 (SETDB1). The cytoplasmic complex of PDK1 assembled with Smurf1 and SETDB1 (cCOMPASS) consisting of PDK1, Smurf1 and SETDB1 directs Akt membrane attachment and T308 phosphorylation. Smurf1 deficiency dramatically reduces CRC tumorigenesis in a genetic mouse model. Furthermore, we developed a highly selective Smurf1 degrader, Smurf1-antagonizing repressor of tumor 1, which exhibits efficient PDK1-Akt blockade and potent tumor suppression alone or combined with PDK1 inhibitor in KRAS-mutated CRC. The findings presented here unveil previously unrecognized roles of PDK1 neddylation and offer a potential strategy for targeting the PI3K-Akt pathway and KRAS mutant cancer therapy.
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OBJECTIVE: To compare the effectiveness of intraosseous versus intravenous vascular access in the treatment of adult patients with out-of-hospital cardiac arrest. DESIGN: Cluster randomised controlled trial. SETTING: The VICTOR (Venous Injection Compared To intraOsseous injection during resuscitation of patients with out-of-hospital cardiac arrest) trial involved emergency medical service agencies with all four advanced life support ambulance teams in Taipei City, Taiwan. The enrolment period spanned 6 July 2020 to 30 June 2023 and was temporarily suspended between 20 May 2021 and 31 July 2021 owing to the covid-19 pandemic. PARTICIPANTS: Adult (age 20-80 years) patients with non-traumatic out-of-hospital cardiac arrest. INTERVENTIONS: Biweekly randomised clusters of four participating advanced life support ambulance teams were assigned to insert either intravenous or intraosseous access. MAIN OUTCOME MEASURES: The primary outcome was survival to hospital discharge. Secondary outcomes included return of spontaneous circulation, sustained return of spontaneous circulation (≥2 hours), and survival with favourable neurological outcomes (cerebral performance category score ≤2) at hospital discharge. RESULTS: Among 1771 enrolled patients, 1732 (741 in the intraosseous group and 991 in the intravenous group) were included in the primary analysis (median age 65.0 years; 1234 (71.2%) men). In the intraosseous group, 79 (10.7%) patients were discharged alive, compared with 102 (10.3%) patients in the intravenous group (odds ratio 1.04, 95% confidence interval 0.76 to 1.42; P=0.81). The odds ratio of intraosseous versus intravenous access was 1.23 (0.89 to 1.69; P=0.21) for pre-hospital return of spontaneous circulation, 0.92 (0.75 to 1.13; P=0.44) for sustained return of spontaneous circulation, and 1.17 (0.82 to 1.66; P=0.39) for survival with favourable neurological outcomes. CONCLUSIONS: Among adults with non-traumatic out-of-hospital cardiac arrest, initial attempts to establish vascular access through the intraosseous route did not result in different outcomes compared with intravenous access in terms of the proportion of patients surviving to hospital discharge, pre-hospital return of spontaneous circulation, sustained return of spontaneous circulation, and favourable neurological outcomes. TRIAL REGISTRATION: NCT04135547ClinicalTrials.gov NCT04135547.
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Infusiones Intraóseas , Paro Cardíaco Extrahospitalario , Humanos , Paro Cardíaco Extrahospitalario/terapia , Paro Cardíaco Extrahospitalario/mortalidad , Femenino , Masculino , Infusiones Intraóseas/métodos , Persona de Mediana Edad , Anciano , Adulto , Anciano de 80 o más Años , Taiwán/epidemiología , Servicios Médicos de Urgencia/métodos , Extremidad Superior , COVID-19 , Resultado del Tratamiento , Reanimación Cardiopulmonar/métodos , Adulto Joven , Inyecciones Intravenosas , SARS-CoV-2RESUMEN
Nanozymes, nanostructured materials emulating natural enzyme activities, exhibit potential in catalyzing reactive oxygen species (ROS) production for cancer treatment. By facilitating oxidative reactions, elevating ROS levels, and influencing the tumor microenvironment (TME), nanozymes foster the eradication of cancer cells. Noteworthy are their superior stability, ease of preservation, and cost-effectiveness compared to natural enzymes, rendering them invaluable for medical applications. This comprehensive review intricately explores the interplay between ROS and tumor therapy, with a focused examination of metal-based nanozyme strategies mitigating tumor hypoxia. It provides nuanced insights into diverse catalytic processes, mechanisms, and surface modifications of various metal nanozymes, shedding light on their role in intra-tumoral ROS generation and applications in antioxidant therapy. The review concludes by delineating specific potential prospects and challenges associated with the burgeoning use of metal nanozymes in future tumor therapies.
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Phthalate acid esters (PAEs) are one of the most widely used plasticizers globally, extensively employed in various decoration materials. However, studies on the impact of these materials on indoor environmental PAE pollution and their effects on human health are limited. In this study, forty dust samples were collected from four types of stores specializing in decoration materials (flooring, furniture boards, wall coverings, and household articles). The levels, sources, exposure doses, and potential health risks of PAEs in dust from decoration material stores were assessed. The total concentrations of Σ9PAE (the sum of nine PAEs) in dust from all decoration-material stores ranged from 46,100 ng/g to 695,000 ng/g, with a median concentration of 146,000 ng/g. DMP, DEP, DBP, and DEHP were identified as the predominant components. Among all stores, furniture board stores exhibited the highest Σ9PAE (159,000 ng/g, median value), while flooring stores exhibited the lowest (95,300 ng/g). Principal component analysis (PCA) showed that decoration materials are important sources of PAEs in the indoor environment. The estimated daily intakes of PAEs through non-dietary dust ingestion and dermal-absorption pathways among staff in various decoration-material stores were 60.0 and 0.470 ng/kg-bw/day (flooring stores), 113 and 0.780 ng/kg-bw/day (furniture board stores), 102 and 0.510 ng/kg-bw/day (wall covering stores), and 114 and 0.710 ng/kg-bw/day (household article stores). Particularly, staff in wall-covering and furniture-board stores exhibited relatively higher exposure doses of DEHP. Risk assessment indicated that although certain PAEs posed potential health risks, the exposure levels for staff in decoration material stores were within acceptable limits. However, staff in wall covering stores exhibited relatively higher risks, necessitating targeted risk-management strategies. This study provides new insights into understanding the risk associated with PAEs in indoor environments.
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The integrated stress response (ISR) is activated in response to intrinsic and extrinsic stimuli, playing a role in tumor progression and drug resistance. The regulatory role and mechanism of ISR in liver cancer, however, remain largely unexplored. Here, we demonstrate that OTU domain-containing protein 3 (OTUD3) is a deubiquitylase of eukaryotic initiation factor 2α (eIF2α), antagonizing ISR and suppressing liver cancer. OTUD3 decreases interactions between eIF2α and the kinase EIF2ΑK3 by removing K27-linked polyubiquitylation on eIF2α. OTUD3 deficiency in mice leads to enhanced ISR and accelerated progression of N-nitrosodiethylamine-induced hepatocellular carcinoma. Additionally, decreased OTUD3 expression associated with elevated eIF2α phosphorylation correlates with the progression of human liver cancer. Moreover, ISR activation due to decreased OTUD3 expression renders liver cancer cells resistant to sorafenib, while the combined use of the ISR inhibitor ISRIB significantly improves their sensitivity to sorafenib. Collectively, these findings illuminate the regulatory mechanism of ISR in liver cancer and provide a potential strategy to counteract sorafenib resistance.
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Resistencia a Antineoplásicos , Neoplasias Hepáticas , Sorafenib , Proteasas Ubiquitina-Específicas , Sorafenib/farmacología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Animales , Humanos , Resistencia a Antineoplásicos/efectos de los fármacos , Ratones , Proteasas Ubiquitina-Específicas/metabolismo , Proteasas Ubiquitina-Específicas/genética , Progresión de la Enfermedad , Estrés Fisiológico/efectos de los fármacos , Línea Celular Tumoral , Ubiquitinación/efectos de los fármacos , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Factor 2 Eucariótico de Iniciación/metabolismo , Fosforilación/efectos de los fármacos , Ratones Endogámicos C57BLRESUMEN
Heavy metal poisoning of soil from oil spills causes serious environmental problems worldwide. Various causes and effects of heavy metal pollution in the soil environment are discussed in this article. In addition, this study explores new approaches to cleaning up soil that has been contaminated with heavy metals as a result of oil spills. Furthermore, it provides a thorough analysis of recent developments in remediation methods, such as novel nano-based approaches, chemical amendments, bioremediation, and phytoremediation. The objective of this review is to provide a comprehensive overview of the removal of heavy metals from oil-contaminated soils. This review emphasizes on the integration of various approaches and the development of hybrid approaches that combine various remediation techniques in a synergistic way to improve sustainability and efficacy. The study places a strong emphasis on each remediation strategy that can be applied in the real-world circumstances while critically evaluating its effectiveness, drawbacks, and environmental repercussions. Additionally, it discusses the processes that reduce heavy metal toxicity and improve soil health, taking into account elements like interactions between plants and microbes, bioavailability, and pollutant uptake pathways. Furthermore, the current study suggests that more research and development is needed in this area, particularly to overcome current barriers, improve our understanding of underlying mechanisms, and investigate cutting-edge ideas that have the potential to completely transform the heavy metal clean up industry.
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Biodegradación Ambiental , Metales Pesados , Contaminación por Petróleo , Contaminantes del Suelo , Restauración y Remediación Ambiental/métodos , Suelo/químicaRESUMEN
This study aims to explore the pharmacological substance basis of Qi Ge Decoction (QG) in antihyperlipidemia through a combination of metabolomics and serum pharmacochemistry. We used ultra-performance liquid chromatography quadrupole-time-of-flight/MS (UPLC Q-TOF/MS) to analyze and identify the chemical constituents of QG in vitro and in blood chemical components. The metabolomics technology was used to analyze serum biomarkers of QG in preventing and treating hyperlipidemia. We constructed a mathematical model of the relationship between constituents absorbed into the blood and endogenous biomarkers and explored the potential therapeutic application of QG for the prevention and treatment of hyperlipidemia. Compared with the model group, the levels of total cholesterol and triglyceride in the QG group were significantly decreased (P < 0.01). A total of 12 chemical components absorbed into the blood were identified, and 48 biomarkers of the hyperlipidemia model were obtained from serum metabolomic analysis, of which 15 metabolites were backregulated after QG intervention. Puerarin, hesperetin, puerarin xyloside, calycosin, and monohydroxy-tetramethoxyflavone had a high correlation with the biomarkers regulated by QG. This study elucidated the material basis of QG in the intervention of hyperlipidemia, thereby facilitating future research aimed at further revealing the pharmacodynamic material basis of QG's antihyperlipidemic effects.
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Medicamentos Herbarios Chinos , Hiperlipidemias , Hipolipemiantes , Metabolómica , Metabolómica/métodos , Hipolipemiantes/sangre , Hipolipemiantes/farmacocinética , Hipolipemiantes/química , Cromatografía Líquida de Alta Presión/métodos , Animales , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/sangre , Masculino , Biomarcadores/sangre , Ratas , Metaboloma/efectos de los fármacos , Ratas Sprague-Dawley , Espectrometría de Masas/métodosRESUMEN
Purpose: This study aims to investigate the relationship between Sodium Glucose Co-transporter-2 inhibitors (SGLT2i) treatment and fibrosis in patients with Metabolic dysfunction-associated steatotic liver disease (MASLD) combined with Type 2 Diabetes Mellitus (T2DM) and Major Adverse Cardiovascular and Cerebrovascular Events (MACCEs). Methods: A case-control study was conducted, involving 280 patients with MASLD combined with T2DM treated at the First Affiliated Hospital of Xinjiang Medical University from January 2014 to October 2023. Among these patients, 135 received SGLT2i treatment. The association between the Fibrosis-4 (FIB-4) index and the occurrence of MACCEs, as well as the association between the Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) scores and MACCEs, were evaluated. Results: The FIB-4 index and APRI scores were significantly lower in the SGLT2i treatment group compared to the non-SGLT2i group (1.59 vs 1.25, P<0.001). SGLT2i treatment tended to reduce the occurrence of MACCEs compared to non-SGLT2i treatment (45.5% vs 38.5%, P=0.28). All patients who developed MACCEs in the non-SGLT2i treatment group had higher FIB-4 index (1.83 vs 1.35, P=0.003). Additionally, after SGLT2i treatment for a median duration of 22 months, patients showed significant reductions in blood glucose, APRI, and FIB-4 index. Conclusion: SGLT2i treatment significantly reduces the occurrence of MACCEs and liver fibrosis in patients with MASLD combined with T2DM. The FIB-4 index may serve as a potential surrogate marker for predicting the occurrence of MACCEs.
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Understanding the role of mechanical force on tissue nutrient transport is essential, as sustained force may affect nutrient levels within the disc and initiate disc degeneration. This study aims to evaluate the time-dependent effects of different compressive force amplitudes as well as tensile force on glucose concentration and cell viability within the disc. Based on the mechano-electrochemical mixture theory, a multiphasic finite element model of the lumbar intervertebral disc was developed. The minimum glucose concentration and minimum cell density in both normal and degenerated discs were predicted for different compressive force amplitudes, tensile force, and corresponding creep time. Under high compressive force, the minimum glucose concentration exhibited an increasing and then decreasing trend with creep time in the normal disc, whereas that of the degenerated disc increased, then decreased, and finally increased again. At steady state, a higher compressive force was accompanied by a lower glucose concentration distribution. In the degenerated disc, the minimum cell density was negatively correlated with creep time, with a greater range of affected tissue under a higher compressive force. For tensile force, the minimum glucose concentration of the degenerated disc raised over time. This study highlighted the importance of creep time, force magnitude, and force type in affecting nutrient concentration and cell viability. Sustained weight-bearing activities could deteriorate the nutrient environment of the degenerated disc, while tensile force might have a nonnegligible role in effectively improving nutrient levels within the degenerated disc.
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Supervivencia Celular , Fuerza Compresiva , Análisis de Elementos Finitos , Glucosa , Disco Intervertebral , Resistencia a la Tracción , Glucosa/metabolismo , Disco Intervertebral/metabolismo , Disco Intervertebral/citología , Modelos Biológicos , Fenómenos Biomecánicos , Estrés MecánicoRESUMEN
Hepatocellular carcinoma (HCC) poses a significant challenge with dismal survival rates, necessitating a deeper understanding of its molecular mechanisms and the development of improved therapies. Metabolic reprogramming, particularly heightened glycolysis, plays a crucial role in HCC progression. Glycolysis-associated genes (GAGs) emerge as key players in HCC pathogenesis, influencing the tumor microenvironment and immune responses. This study aims to investigate the intricate interplay between GAGs and the immune landscape within HCC, offering valuable insights into potential prognostic markers and therapeutic targets to enhance treatment strategies and patient outcomes. Through the exploration of GAGs, we have identified two distinct molecular glycolytic subtypes in HCC patients, each exhibiting significant differences in both the immune microenvironment and prognosis. A risk model comprising five key GAGs was formulated and subsequently evaluated for their predictive accuracy. Our findings underscore the diverse tumor microenvironment and immune responses associated with the varying glycolytic subtypes observed in HCC. The identified key GAGs hold promise as prognostic indicators for evaluating HCC risk levels, predicting patient outcomes, and guiding clinical treatment decisions, particularly in the context of anticipating responses to immunotherapy drugs.