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Herein, we report a novel strategy for the regioselective synthesis of aromatic and heteroaromatic 2,3-dihydrooxazoles from 2-alkynyl-1,3-dithianes and nitrones. This method exploits the 1,3-dithiane umpolung, nucleophilic cycloaddition, and rearrangement processes to achieve the rapid assembly of dihydrooxazole molecules. The regioselective method is extremely mild, achieving complete conversion within one min under air at 25 °C with high efficiency.
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Exosomes, as a class of small extracellular vesicles closely related to the biological behavior of various types of tumors, are currently attracting research attention in cancer diagnosis and treatment. Regarding cancer diagnosis, the stability of their membrane structure and their wide distribution in body fluids render exosomes promising biomarkers. It is expected that exosome-based liquid biopsy will become an important tool for tumor diagnosis in the future. For cancer treatment, exosomes, as the "golden communicators" between cells, can be designed to deliver different drugs, aiming to achieve low-toxicity and low-immunogenicity targeted delivery. Signaling pathways related to exosome contents can also be used for safer and more effective immunotherapy against tumors. Exosomes are derived from a wide range of sources, and exhibit different biological characteristics as well as clinical application advantages in different cancer therapies. In this review, we analyzed the main sources of exosomes that have great potential and broad prospects in cancer diagnosis and therapy. Moreover, we compared their therapeutic advantages, providing new ideas for the clinical application of exosomes.
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Biomarcadores de Tumor , Exosomas , Neoplasias , Humanos , Exosomas/metabolismo , Exosomas/inmunología , Neoplasias/terapia , Neoplasias/inmunología , Animales , Inmunoterapia/métodos , Biopsia Líquida/métodosRESUMEN
The role of the gut microbiota in host physiology has been previously elucidated for some marine organisms, but little information is available on their metabolic activity involved in transformation of environmental pollutants. This study assessed the metabolic profiles of the gut microbial cultures from grouper (Epinephelus coioides), green mussel (Perna viridis) and giant tiger prawn (Penaeus monodon) and investigated their transformation mechanisms to typical plastic additives. Community-level physiological profiling analysis confirmed the utilization profiles of the microbial cultures including carbon sources of carbohydrates, amines, carboxylic acids, phenolic compounds, polymers and amino acids, and the plastic additives of organophosphate flame retardants, tetrabromobisphenol A derivates and bisphenols. Using in vitro incubation, triphenyl phosphate (TPHP) was found to be rapidly metabolized into diphenyl phosphate by the gut microbiota as a representative ester-containing plastic additive, whereas the transformation of BPA (a representative phenol) was relatively slower. Interestingly, all three kinds of microbial cultures efficiently transformed the hepatic metabolite of BPA (BPA-G) back to BPA, thereby increasing its bioavailability in the body. The specific enzyme analysis confirmed the ability of the gut microbiota to perform the metabolic reactions. The results of 16S rRNA sequencing and network analysis revealed that the genera Escherichia-Shigella, Citrobacter, and Anaerospora were functional microbes, and their collaboration with fermentative microbes played pivotal roles in the transformation of the plastic additives. The structure-specific transformations by the gut microbiota and their distinct bioavailability deserve more attention in the future.
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Microplastics (MPs) have accumulated in the oceans, causing adverse effects on marine organisms and the environment. Biodegradable polylactic acid (PLA) is considered as an excellent substitute for traditional petroleum-based plastics, but it is difficult to degrade completely and easily become MPs in the marine environment. To test the ecological risk of bio-based PLA, we exposed thick-shelled mussels (Mytilus coruscus) to bio-based PLA and petroleum-based polystyrene (PS) (at 102, 104, and 106 particles/L) for 14 days. The significant increase in enzyme activities related to oxidative stress and immune response showed that mussels were under physiological stress after MP ingestion. While enzyme activities of nerve conduction and energy metabolism were significantly disturbed after exposure. Meanwhile, normal physiological activities in respiration, ingestion and assimilation were also suppressed in association with enzyme changes. The negative effects of PS and PLA in mussels were not differentiated, and further integration analysis of integrated biomarker response (IBR) and principal component analysis (PCA) also showed that PLA would induce adverse effects in mussels and ecological risks as PS, especially at environmental concentrations. Therefore, it is necessary to pay more attention to the environmental and ecological risk of bio-based MP PLA accumulating in the marine environment.
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Microplásticos , Poliésteres , Poliestirenos , Contaminantes Químicos del Agua , Animales , Poliestirenos/toxicidad , Poliésteres/toxicidad , Contaminantes Químicos del Agua/toxicidad , Microplásticos/toxicidad , Mytilus/efectos de los fármacos , Mytilus/fisiología , Petróleo/toxicidadRESUMEN
Background: Thioredoxin domain-containing protein 12 (TXNDC12) is upregulated in a variety of tumours, including pancreatic cancer (PAAD), and its high expression is closely associated with poor prognosis. However, the regulatory mechanism of TXNDC12 in PAAD has not been reported. The aim of this study is to reveal the precise mechanism of TXNDC12 in regulating PAAD progression. Methods: The expression of TXNDC12 in pan-cancer as well as PAAD was verified by TCGA and GTEx databases, Western blot and RT-qPCR. CCK8 assay, clone formation assay and cell cycle assay were used to observe the effect of TXNDC12 on the proliferation of PAAD cells, the migration and invasion capacities were verified by wound healing assay and Transwell assay. The effect of TXNDC12 on apoptosis of MIA PaCa-2 and PANC-1 cells was detected using Hochest and flow cytometry. Finally, the interaction of TXNDC12 with GGT7 was predicted by STRING database and confirmed by CO-IP assay, the effect of TXNDC12 on ferroptosis through GGT7 was evaluated by GSH assay, MDA assay, ROS assay and Western blot. Results: TXNDC12 is upregulated in PAAD tissues, and patients with high TXNDC12 levels generally have shorter survival times. Knockdown of TXNDC12 significantly inhibited the proliferation, migration and invasion and promoted apoptosis of MIA PaCa-2 and PANC-1 cells. Mechanistically, knockdown of TXNDC12 resulted in a decrease in intracellular GSH content and an increase in GSSG content, as well as elevated levels of pro-ferroptosis factors, such as MDA and ROS. STRING database predicted that TXNDC12 interacts with GGT7, and CO-IP assay was used to validate this result. Finally, the effect of knocking down TXNDC12 on pancreatic cancer cell functions was able to be reversed by overexpression of GGT7. Conclusion: TXNDC12 inhibits ferroptosis in PAAD cells through the GSH/GGT7 axis thereby promoting their development.
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This study provided a systematic investigation of microplastics in Hong Kong's surface marine waters during the pandemic from 2019 to 2021. Microplastics (2.07 ± 4.00 particles/m3) exhibited significant temporal variations with higher abundance in the wet season, without a consistent trend after the mandatory mask-wearing requirement was announced. The impact of pandemic restrictions on microplastic distribution was found to be relatively minor. However, significant correlations between microplastic abundances and rainfall highlighted the substantial contribution of local emissions through surface runoff. Notably, sites in closer proximity to the Pearl River Delta exhibited higher microplastic abundances, indicating their association with emission sources. The influence of rainfall and adverse weather on marine microplastic loads demonstrated different sensitivities among various locations but can generally last for one month. These results revealed the impact of seasonal rainfall on coastal microplastics and emphasized the need for efforts to reduce microplastic discharge from land-based sources.
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Monitoreo del Ambiente , Microplásticos , Lluvia , Ríos , Contaminantes Químicos del Agua , Hong Kong , Contaminantes Químicos del Agua/análisis , Microplásticos/análisis , Ríos/química , Agua de Mar/química , Estaciones del AñoRESUMEN
The discovery of the significant lethal impacts of the tire additive transformation product N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q) on coho salmon has garnered global attention. However, the bioaccumulation and trophic transfer of tire additives and their transformation products (TATPs) within food webs remain obscure. This study first characterized the levels and compositions of 15 TATPs in the Pearl River Estuary, estimated their bioaccumulation and trophic transfer potential in 21 estuarine species, and identified priority contaminants. Our observations indicated that TATPs were prevalent in the estuarine environment. Eight, six, seven, and 10 TATPs were first quantified in the shrimp, sea cucumber, snail, and fish samples, with total mean levels of 45, 56, 64, and 67 ng/g (wet weight), respectively. N,N'-Diphenyl-p-phenylenediamine (DPPD) and N,N'-bis(2-methylphenyl)-1,4-benzenediamine (DTPD) exhibited high bioaccumulation. Significant biodilution was only identified for benzothiazole, while DPPD and DTPD displayed biomagnification trends based on Monte Carlo simulations. The mechanisms of bioaccumulation and trophodynamics of TATPs could be explained by their chemical hydrophobicity, molecular mass, and metabolic rates. Based on a multicriteria scoring technique, DPPD, DTPD, and 6PPD-Q were characterized as priority contaminants. This work emphasizes the importance of biomonitoring, particularly for specific hydrophobic tire additives.
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Cadena Alimentaria , Fenilendiaminas , Contaminantes Químicos del Agua , Animales , Bioacumulación , Monitoreo del Ambiente , Contaminantes Químicos del Agua/análisisRESUMEN
Estuaries serve as crucial filters for land-based pollutants to the open sea, but there is a lack of information on the migration and fate of organophosphate flame retardants (OPFRs) within estuaries. This study focused on the Pearl River Estuary (PRE) by examining the co-occurrence of OPFRs and their metabolites and quantifying their transport fluxes using a mass balance model. The seawater concentrations of OPFRs and their metabolites exhibited significant seasonal variations (p < 0.01), while the sediment concentrations of OPFRs reflected the long-term distributional equilibrium in the PRE. The concentration of Σ9OPFRs in seawater showed a relentless dilution from the entrance to the offshore region in the normal and wet seasons, which was significantly in accordance with the gradients of pH, dissolved oxygen (DO), and salinity (p < 0.05). Furthermore, horizontal migration dominated the transport of OPFRs, and the inventory assessment revealed that both the water column and sediment were important reservoirs in the PRE. According to the estimated fluxes from the mass balance model, riverine input emerged as the principal pathway for OPFR entry into the PRE (1.55 × 105, 6.28 × 104, and 9.00 × 104 kg/yr in the normal, dry and wet seasons, respectively), whereas outflow to the open sea predominantly determined the main fates of the OPFRs. The risk quotient (RQ) results showed that EHDPHP (0.835) in water posed medium ecological risk, while other OPFRs and metabolites presented relatively lower risk (RQ < 0.1). The risk control effects were evaluated through scenario simulations of mathematical fitting between controllable source factors and the RQ of risky OPFR. The risk of EHDPHP in the PRE could be effectively reduced by restricting its concentrations in entrance region (<9.31, 8.67, and 12.7 ng/L in the normal, dry and wet seasons, respectively) of the PRE. This research offers foundational insights into environmental management and pollution control strategies for emerging pollutants in estuaries.
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Contaminantes Ambientales , Retardadores de Llama , Contaminantes Químicos del Agua , Organofosfatos/análisis , Estuarios , Retardadores de Llama/análisis , Ríos , Contaminantes Químicos del Agua/análisis , Agua , ChinaRESUMEN
Necrotizing fasciitis is a rare, severe, rapidly progressing disease with a high mortality rate. We report a case of a 72-year female with erythematous pemphigus who developed erythema, swelling and ulceration on right vulva, groin, and thigh. The early clinical manifestations of the patient were nonspecific and easily misdiagnosed as cellulitis. However, upon the occurrence of ulceration and necrosis, deep fungal infection, pyoderma gangrenosum or lymphoproliferative disorders were considered. The pathology suggested IgG4-related diseases, plasmacytoma et al. But at last, surgical exploration and postoperative pathology confirmed the diagnosis of necrotizing fasciitis. The patient recovered after multiple aggressive surgical debridement procedures and antibiotic therapy and the patient has been followed up for 2 years without recurrence. Clinicians should be vigilant about the possibility of necrotizing fasciitis in patients with erythema, pain, rapid ulceration of skin and soft tissue, particularly in immunocompromised individuals with long-term use of immunosuppressive agents. It is crucial for saving life by early multi-disciplinary consultation, prompt diagnosis, and aggressive treatment.
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Tetrabromobisphenol A (TBBPA) analogues have been investigated for their prevalent occurrence in environments and potential hazardous effects to humans and wildlife; however, there is still limited knowledge regarding their toxicokinetics and trophic transfer in aquatic food chains. Using a developed toxicokinetic model framework, we quantified the bioaccumulation, biotransformation and trophic transfer of tetrabromobisphenol S (TBBPS) and tetrabromobisphenol A di(allyl ether) (TBBPA-DAE) during trophic transfer from brine shrimp (Artemia salina) to zebrafish (Danio rerio). The results showed that the two TBBPA analogues could be readily accumulated by brine shrimp, and the estimated bioconcentration factor (BCF) value of TBBPS (5.68 L kg-1 ww) was higher than that of TBBPA-DAE (1.04 L kg-1 ww). The assimilation efficiency (AE) of TBBPA-DAE in zebrafish fed brine shrimp was calculated to be 16.3%, resulting in a low whole-body biomagnification factor (BMF) in fish (0.684 g g-1 ww). Based on the transformation products screened using ultra-high-performance liquid chromatograph-high resolution mass spectrometry (UPLC-HRMS), oxidative debromination and hydrolysis were identified as the major transformation pathways of TBBPS, while the biotransformation of TBBPA-DAE mainly took place through ether bond breaking and phase-II metabolism. Lower accumulation of TBBPA as a metabolite than its parent chemical was observed in both brine shrimp and zebrafish, with metabolite parent concentration factors (MPCFs) < 1. The investigated BCFs for shrimp of the two TBBPA analogues were only 3.77 × 10-10 - 5.59 × 10-3 times of the theoretical Kshrimp-water based on the polyparameter linear free energy relationships (pp-LFERs) model, and the BMF of TBBPA-DAE for fish was 0.299 times of the predicted Kshrimp-fish. Overall, these results indicated the potential of the trophic transfer in bioaccumulation of specific TBBPA analogues in higher trophic-level aquatic organisms and pointed out biotransformation as an important mechanism in regulating their bioaccumulation processes. ENVIRONMENTAL IMPLICATION: The internal concentration of a pollutant in the body determines its toxicity to organisms, while bioaccumulation and trophic transfer play important roles in elucidating its risks to ecosystems. Tetrabromobisphenol A (TBBPA) analogues have been extensively investigated for their adverse effects on humans and wildlife; however, there is still limited knowledge regarding their toxicokinetics and trophic transfer in aquatic food chains. This study investigated the bioaccumulation, biotransformation and trophic transfer of TBBPS and TBBPA-DAE in a simulated di-trophic food chain. This state-of-art study will provide a reference for further research on this kind of emerging pollutant in aquatic environments.
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Contaminantes Ambientales , Perciformes , Bifenilos Polibrominados , Contaminantes Químicos del Agua , Animales , Humanos , Cadena Alimentaria , Bioacumulación , Ecosistema , Pez Cebra/metabolismo , Biotransformación , Perciformes/metabolismo , Contaminantes Ambientales/análisis , Éteres , Contaminantes Químicos del Agua/análisisRESUMEN
The substantial utilization of antibiotics causes their "pseudo-persistence" in offshore environments. Published studies on antibiotic surveillance in food webs have primarily emphasized on parent forms; however, the compositions and concentrations of conjugated antibiotics in aquatic organisms remain largely unexplored. This study systematically examined the distribution characteristics and trophodynamics of free antibiotics and their conjugated forms in an estuarine food web. Total antibiotic levels differed insignificantly between the surface and bottom waters. The total mean values of free antibiotics in crabs, fish, shrimps, sea cucumbers, and snails varied from 0.77 to 1.4 ng/g (wet weight). The numbers and values of antibiotics rose in these biological samples after enzymatic hydrolysis. Conjugated antibiotics accounted for 23.8-76.9% of the total antibiotics in the biological samples, revealing that conjugated forms play a non-negligible role in aquatic organisms. More number of antibiotics exhibited bioaccumulation capabilities after enzymatic hydrolysis. In the food web, the free forms of anhydroerythromycin and conjugated forms of trimethoprim and ciprofloxacin underwent trophic dilution, whereas the free forms of trimethoprim and conjugated forms of ofloxacin underwent trophic amplification. The present work provides new insights into the bioaccumulation and trophic transfer of free and conjugated antibiotics in food webs.
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Cadena Alimentaria , Contaminantes Químicos del Agua , Animales , Antibacterianos/análisis , Bioacumulación , Multimedia , Contaminantes Químicos del Agua/análisis , Organismos Acuáticos , Peces , Trimetoprim , Monitoreo del Ambiente , ChinaRESUMEN
Herein, we report a C3 and C1 coupling approach between vinyl 1,3-dithiane derivatives and alkynylsilanes for the construction of highly substituted conjugated dienes. Through the regioselective dual 1,3-sulfur migration process, this method enabled the synthesis of a wide range of highly substituted (E)-1,3-dienes stereoselectively in moderate to high yields, which provided one alternative way to synthesize the corresponding conjugated dienones.
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Rho-associated coiled-coil kinases (ROCKs) are key downstream effectors of small GTPases. ROCK plays a central role in diverse cellular events with accumulating evidence supporting the concept that ROCK is important in tumor development and progression. Numerous ROCK inhibitors have been investigated for their therapeutic potential in the treatment of cancers. In this article, we review recent research progress on ROCK inhibitors, especially those with potential for the treatment of cancers, reported in the literature from 2015 to 2021. Most ROCK inhibitors show potent in vitro and in vivo antitumor activities and have potential in the treatment of cancers.
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Neoplasias , Quinasas Asociadas a rho , Humanos , Neoplasias/tratamiento farmacológicoRESUMEN
Colorectal cancer (CRC) is among the most common malignancies worldwide. Although a recent study has shown that E3 ubiquitin ligases play a major role in regulating the occurrence and development of CRC, there are few reports on the role of the E3 ubiquitin ligase HECW2(HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2) in CRC progression and chemoresistance. We found that HECW2 is highly expressed in CRC tissues. HECW2 knockdown inhibits CRC progression and chemoresistance, whereas HECW2 overexpression has the opposite effect. Mechanistically, HECW2 activates the AKT/mTOR signaling pathway by mediating the ubiquitin-proteasome degradation of lamin B1, thereby promoting CRC progression and chemoresistance. Our findings suggest that HECW2 may be a promising novel therapeutic target for CRC treatment.
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OBJECTIVE: The most common site of metastasis in patients with colon cancer is the liver. This study aimed to identify patients with colon cancer at high risk of developing liver metastasis and to explore their prognosis. METHODS: The clinical characteristics, treatment methods and survival outcomes of patients diagnosed with colon cancer from 2010 to 2015 were identified from the Surveillance, Epidemiology and End Results (SEER) database. Patients were divided into two groups according to the presence of liver metastasis, and multivariate logistic and Cox regression models were used to identify risk and prognostic factors. RESULTS: A total of 60,018 patients with colon cancer were selected from the SEER database. The incidence of liver metastasis was 9.2%. African American ethnicity, poor differentiation, higher tumor stage, higher lymph node ratio, and lung metastases were common factors associated with both liver metastasis risk and prognosis. CONCLUSIONS: Metastasectomy might improve survival among patients with colon cancer with resectable liver metastasis lesions and no other organ involvement.
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Neoplasias del Colon , Neoplasias Hepáticas , Humanos , Población Negra/estadística & datos numéricos , Neoplasias del Colon/epidemiología , Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Neoplasias del Colon/terapia , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Pronóstico , Factores de Riesgo , Programa de VERF/estadística & datos numéricos , Estados Unidos/epidemiologíaRESUMEN
The widespread occurrence of tire tread particles (TPs) has aroused increasing concerns over their impacts. However, how they affect the soil fauna remains poorly understood. Here, based on systematically assessing the toxicity of TPs on soil model speciesEnchytraeus crypticusat environmentally relevant concentrations through both soil and food exposure routes, we reported that TPs affected gut microbiota, intestinal histopathology, and metabolites of the worms both through particulate- and leachate-induced effects, while TP leachates exerted stronger effects. The dominant role of TP leachates in TP toxicity was further explained by the findings that worms did not ingest TPs with a particle size of over 150 µm and actively avoided consuming TP particles. Moreover, by comparing the effects of different brands of TPs as well as new and aged TPs, we demonstrated that it was mainly TP leachates that resulted in the ubiquity of the disturbance in the worm's gut microbiota among different brands of TPs. Notably, the large variations in leachate compositions among different brands of TPs provided us a unique opportunity to identify the determinants of TP toxicity. These results provide novel insights into the toxicity of TPs to soil fauna and a reference for toxicity reduction of tires.
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Microbioma Gastrointestinal , Polvo , Tamaño de la Partícula , SueloRESUMEN
Ingestion is a major exposure route for hydrophobic organic pollutants in fish, but the microbial transformation and estrogenic modification of the novel plastic additives by the gut microbiota of fish remain obscure. Using an in vitro approach, we provide evidence that structure-related transformation of various plastic additives by the gastric and intestinal (GI) microbiota from crucian carp, with the degradation ratio of bisphenols and triphenyl phosphate faster than those of brominated compounds. The degradation kinetics for these pollutants could be limited by oxygen and cometabolic substrates (i.e., glucose). The fish GI microbiota could utilize the vast majority of carbon sources in a Biolog EcoPlate, suggesting their high metabolic potential and ability to transform various organic compounds. Unique microorganisms associated with transformation of the plastic additives including genera of Citrobacter, Klebsiella, and some unclassified genera in Enterobacteriaceae were identified by combining high-throughput genetic analyses and metagenomic analyses. Through identification of anaerobic transformation products by high-resolution mass spectrometry, alkyl-cleavage was found the common transformation mechanism, and hydrolysis was the major pathway for ester-containing pollutants. After anaerobic incubation, the estrogenic activities of triphenyl phosphate and bisphenols A, F, and AF declined, whereas that of bisphenol AP increased.
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Carpas , Contaminantes Ambientales , Microbioma Gastrointestinal , Animales , Plásticos , EstronaRESUMEN
Plastic products such as fishing nets and foam buoys have been widely used in aquaculture. To enhance the desirable characteristics of the final equipment, plastic gear for aquaculture is mixed with a wide range of additives. Recent studies have shown that additives could be leached out to the environment with a long-term use of aquaculture plastics, forming aquaculture-derived plastic leachates. It should be emphasized that some leachates such as phthalic acid esters (PAEs) and organophosphate esters (OPEs) are endocrine disruptors, which could increase the exposure risk of aquatic products and subsequently display potential threats to human health via food chain. However, systematic studies on the release, occurrence, bioaccumulation, and toxic effects of aquaculture-derived plastic leachates are missing, overlooking their potential sources and ecotoxicological risks in aquatic environments. We have reviewed and compared the concentrations of major plastic leachates in the water environment and organisms of global aquaculture and non-farmed areas, confirming that aquaculture leachate is an important source of contaminants in the environment. Moreover, the toxic effects of aquaculture-derived plastic additives and the related mechanisms are summarized with fish as a representative, revealing their potential health risk. In addition, we proposed current challenges and future research needs, which provides scientific guidance for the use and management of plastic products in aquaculture industries.
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Plásticos , Contaminantes Químicos del Agua , Animales , Humanos , Plásticos/toxicidad , Contaminantes Químicos del Agua/análisis , Acuicultura , Ecotoxicología , ÉsteresRESUMEN
BACKGROUND: NF-κB activating protein (NKAP) acts as a transcriptional suppressor in the Notch signaling pathway, It plays a role in hematopoiesis maintenance, immune cell development, maturation, and functional competency acquisition. NKAP has been found to act as an oncogene in many tumors, but it has not been reported in PAAD.The purpose of this study was to investigate the effect of NKAP on the growth and metastasis of pancreatic adenocarcinoma(PAAD). METHODS AND RESULTS: In this study, western blot and qRT-PCR showed that highly expressed NKAP was found in PAAD cell lines, and small interfering RNA (siRNA) was employed to reduce the expression of NKAP in PAAD cell lines. The results of CCK-8, clony formation, Transwell and flow cytometry showed that knockdown of NKAP significantly inhibited biological function of PAAD cells, and increased cell apoptosis. Study also observed that knockdown of NKAP inhibited the expression levels of apoptosis proteins and cyclin in PAAD cells. In addition, mTOR's degree of phosphorylation and the expression of its downstream target p70S6K can both be activated by NKAP. This effect was also confirmed in salvage experiments performed with Rapamycin(RaPa), an inhibitor of mTOR. At the end of the experiment, It was investigated how NKAP affected the drug sensitivity of gemcitabine used to treat PAAD. The results showed that knocking down NKAP could increase the drug sensitivity of gemcitabine. CONCLUSIONS: NKAP as an oncogene regulates the development of PAAD cells. The research found that the mTOR signaling pathway is engaged in the oncogenic role of NKAP in PAAD for the first time.
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Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Línea Celular Tumoral , Proliferación Celular , Gemcitabina , FN-kappa B/metabolismo , Neoplasias Pancreáticas/metabolismo , Proteínas Represoras/genética , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/farmacología , Transducción de Señal , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Neoplasias PancreáticasRESUMEN
The distribution and transport of atmospheric microplastics (AMPs) have raised concerns regarding their potential effects on the environment and human health. Although previous studies have reported the presence of AMPs at ground level, there is a lack of comprehensive understanding of their vertical distribution in urban environments. To gain insight into the vertical profile of AMPs, field observations were conducted at four different heights (ground level, 118 m, 168 m and 488 m) of the Canton Tower in Guangzhou, China. Results showed that the profiles of AMPs and other air pollutants had similar layer distribution patterns, although their concentrations differed. The majority of AMPs were composed of polyethylene terephthalate and rayon fibers ranging from 30 to 50 µm. As a result of atmospheric thermodynamics, AMPs generated at ground level were only partially transported upward, leading to a decrease in their abundance with increasing altitude. The study found that the stable atmospheric stability and lower wind speed between 118 m and 168 m resulted in the formation of a fine layer where AMPs tended to accumulate instead of being transported upward. This study for the first time delineated the vertical profile of AMPs within the atmospheric boundary layer, providing valuable data for understanding the environmental fate of AMPs.