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1.
Biotechnol Bioeng ; 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39252409

RESUMO

The harvesting of microalgae is the main bottleneck of its large-scale biomass production, and seeking an efficient, green, and low-cost microalgae harvesting technology is one of the urgent problems to be solved. Microbubble air flotation has been proven to be an effective measure, but the mechanisms of microbubbles-algal cell attachment are still unclear. In this study, microbubble air flotation was used as a harvesting method for Microcystis cultured in agricultural wastewater. The process mechanism of microbubble air flotation harvesting microalgae in wastewater was fully revealed from three aspects (the design of bubble formation, the adhesion law, and the recovery rate of microalgae under different working conditions). The results show that the length of the release pipe is the main factor affecting the proportion of microbubbles with a particle size of less than 50 µm. In the process of adhesion, when the particle size of microbubbles is 0.6-1.7 times the size of Microcystis, the adhesion efficiency of microbubbles to Microcystis is the highest. Under the conditions of pressure 0.45 MPa, gas-liquid ratio 5%, and release pipe length 100 cm, the harvesting performance of Microcystis was the best. Microbubble air flotation has better harvesting performance (63.5%, collection rate) of Microcystis with higher density. By understanding the mechanism of microbubble flotation, the technical parameters of microbubble flotation for harvesting energy microalgae are optimized to provide support for the development of efficient and low-cost devices and equipment for collecting microalgae.

2.
J Hazard Mater ; 479: 135605, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-39191007

RESUMO

Nitrate pollution poses significant threats to both aquatic ecosystems and human well-being, particularly due to eutrophication and increased risks of methemoglobinemia. Conventional treatment for nitrate-contaminated wastewater face challenges stemming from limited availability of carbon sources and the adverse impacts of toxins on denitrification processes. This study introduces an innovative Intimately Coupled Photocatalysis and Biodegradation (ICPB) system, which utilizes Ag3PO4/Bi4Ti3O12, denitrifying sludge, and polyurethane sponge within an anoxic environment. This system demonstrates remarkable efficacy in simultaneously removing bio-recalcitrant organic compounds (such as sulfamethoxazole) and nitrates, surpassing standalone treatment methods. Optimally, the ICPB achieves complete removal of sulfamethoxazole, along with 87.7 % removal of DOC, and 81.8 % reduction in nitrate levels. Its ability to sustain pollutant removal and biological activity over multiple cycles can be attributed to the special formation of biofilm and mineralization of sulfamethoxazole, minimizing both photocatalytic damage and toxic inhibitory effects on microbes. The dominant microbial genera of ICPB system included Castellaniella, Acidovorax, Raoultella, Giesbergeria, and Alicycliphilus. Additionally, the study sheds light on a potential mechanism for the concurrent treatment of recalcitrant organics and nitrates by the ICPB system, presenting a novel and highly effective approach for addressing biologically resistant wastewater.


Assuntos
Biodegradação Ambiental , Nitratos , Sulfametoxazol , Poluentes Químicos da Água , Nitratos/química , Nitratos/metabolismo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/química , Sulfametoxazol/metabolismo , Sulfametoxazol/química , Catálise , Esgotos , Poliuretanos/química , Fotólise , Bismuto/química , Titânio/química , Bactérias/metabolismo , Eliminação de Resíduos Líquidos/métodos , Elétrons , Águas Residuárias/química , Biofilmes
3.
Environ Res ; 259: 119522, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38960356

RESUMO

Constructed wetlands (CWs) have been widely used to ensure effective domestic wastewater treatment. Microorganisms-derived CWs have received extensive attention as they play a crucial role. However, research on the succession patterns of microbial communities and the influencing mechanisms of internal environmental factors throughout entire CW operations remains limited. In this context, three parallel-operated CWs were established in this study to assess the microbial communities and their influencing environmental factors at different substrate depths throughout the operation process using 16S rRNA gene high-throughput sequencing and metagenomic sequencing. The results showed gradual reproduction and accumulation of the microbial communities throughout the CW operation. Although gradual increases in the richness and diversity of the microbial communities were found, there were decreases in the functional expression of the dominant microbial species. The excessive accumulation of microorganisms will decrease the oxidation-reduction potential (ORP) within CWs and attenuate their influence on effluent. Dissolved oxygen (DO) was the major factor influencing the microbial community succession over the CW operation. The main identified functional bacterial genera responsible for the ammonium oxidation, nitrification, and denitrification processes in the CWs were Nitrosospira, Nitrobacter, Nitrospira, Rhodanobacter, and Nakamurella. The narG gene was identified as a key functional gene linking various components of nitrogen cycling, while pH, electrical conductivity (EC), and ORP were the major environmental factors affecting the metabolism characteristics of nitrogen functional microorganisms. This study provides a theoretical basis for the effective regulation of related microbial communities to achieve long-term, efficient, and stable CW operations.


Assuntos
Microbiota , Áreas Alagadas , RNA Ribossômico 16S/genética , Eliminação de Resíduos Líquidos/métodos , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/metabolismo
4.
Chemosphere ; 362: 142664, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38901704

RESUMO

In this study, a novel carbon fiber brush (CFB) electrode was designed using carbon fiber filaments and conductive metals. It was used as the cathode to construct an efficient coupled electro-Fenton and electrocoagulation (EF-EC) process for tetracycline (TC) treatment. An optimal 97.9% removal rate of 10 mg L-1 TC was achieved within 20 min. The coupled process is less pH-dependent and more effective in treating TC compared to the traditional individual electro-Fenton (EF) or electrocoagulation (EC) process, achieving efficient TC removal under neutral pH conditions. The removal rate of 10 mg L-1 TC consistently remained above 92% at 20 min after ten cycle experiments using the same electrodes in a Fe-CFB system (92.7-97.9%), indicating excellent reusability and stability of the CFB cathode. Mechanism analysis showed both EF and EC processes were involved in the system. Radicals (such as •OH and SO4-•) generated by EF contributed to the degradation of TC, yielding nine intermediates. Coagulants (such as Fe(OH)3) generated by EC contributed to the removal of TC. Toxicity prediction results indicated that over half of the nine intermediates exhibited lower biotoxicity compared to TC. This study provides a feasible alternative cathode for the efficient treatment of TC using EF-EC process.


Assuntos
Ferro , Tetraciclina , Poluentes Químicos da Água , Tetraciclina/química , Tetraciclina/toxicidade , Poluentes Químicos da Água/química , Poluentes Químicos da Água/toxicidade , Ferro/química , Eletrocoagulação/métodos , Peróxido de Hidrogênio/química , Eletrodos , Técnicas Eletroquímicas/métodos , Fibra de Carbono/química , Antibacterianos/química , Antibacterianos/toxicidade , Concentração de Íons de Hidrogênio
5.
Cell Rep Med ; 5(7): 101612, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38878776

RESUMO

High-grade ovarian cancer (HGOC) is a major cause of death in women. Early detection of HGOC usually leads to a cure, yet it remains a clinical challenge with over 90% HGOCs diagnosed at advanced stages. This is mainly because conventional biomarkers are not sensitive enough to detect the microscopic yet metastatic early lesions. In this study, we sequence the blood T cell receptor (TCR) repertoires of 466 patients with ovarian cancer and controls and systematically investigate the immune repertoire signatures in HGOCs. We observe quantifiable changes of selected TCRs in HGOCs that are reproducible in multiple independent cohorts. Importantly, these changes are stronger during stage I. Using pre-diagnostic patient blood samples from the Nurses' Health Study, we confirm that HGOC signals can be detected in the blood TCR repertoire up to 4 years preceding conventional diagnosis. Our findings may provide the basis for future immune-based HGOC early detection criteria.


Assuntos
Neoplasias Ovarianas , Receptores de Antígenos de Linfócitos T , Humanos , Feminino , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/genética , Pessoa de Meia-Idade , Gradação de Tumores , Adulto , Biomarcadores Tumorais/sangue , Idoso , Detecção Precoce de Câncer/métodos
6.
Clin Interv Aging ; 19: 303-311, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38404478

RESUMO

Background: Contrast-associated acute kidney injury (CA-AKI) is a prevalent complication following coronary angiography (CAG). However, there is ongoing controversy surrounding its precise definition. Although previous studies have demonstrated the successful application of appropriate definitions in managing high-risk CA-AKI patients, there remains limited research on the association between different definitions and prognosis specifically in patients with chronic kidney disease (CKD). Methods: A total of 4197 CKD patients undergoing coronary angiography (CAG) were included in this study. Two definitions of contrast-associated acute kidney injury (CA-AKI) were used: CA-AKIA, which was defined as an increase of ≥0.5 mg/dL or >25% in serum creatinine (SCr) from baseline within 72 hours after CAG, and CA-AKIB, which was defined as an increase of ≥0.3 mg/dL or >50% in SCr from baseline within 48 hours after CAG. Cox regression analysis was employed to assess the association between these two definitions and long-term mortality. Additionally, population attributable risks (PARs) were calculated to evaluate the impact of CA-AKI definitions on long-term prognosis. Results: During the median follow-up period of 4.70 (2.50-7.78) years, the overall long-term mortality was 23.6%, and the long-term mortality in patients with CA-AKI according to both CA-AKIA and CA-AKIB criteria were 33.5% and 33.8%, respectively. We found that CA-AKIA (HR: 1.45, 95% CI: 1.23-1.70, p<0.001) and CA-AKIB (HR: 1.44, 95% CI: 1.23-1.69, p<0.001) were associated with long-term mortality. The PARs were the highest for CA-AKIA (5.87%), followed by CA-AKIB (5.70%). Conclusion: Contrast-associated acute kidney injury (CA-AKI) is a frequently observed complication in CKD patients undergoing coronary angiography (CAG), and both definitions of CA-AKI are significantly correlated with a poor long-term prognosis. Consequently, in the clinical management of CKD patients, it is crucial to prioritize CA-AKI, irrespective of the specific CA-AKI definition used.


Assuntos
Injúria Renal Aguda , Insuficiência Renal Crônica , Humanos , Angiografia Coronária/efeitos adversos , Meios de Contraste/efeitos adversos , Fatores de Risco , Insuficiência Renal Crônica/diagnóstico por imagem , Insuficiência Renal Crônica/complicações , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/diagnóstico por imagem , Creatinina
7.
Sci Total Environ ; 918: 170653, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38331294

RESUMO

The capacity of microplastics to harbor and propagate bacteria has been the focus of attention over the last decade. Such microplastic-supported bacterial colonization behavior in the municipal sewer system could be a critical ecological link influencing the biogeochemical activities and risks in receiving waters in urban areas, given the alarming microplastic loads discharged there. This study conducted a large-scale survey covering a wide range of residential and industrial catchments in Shanghai, China. We aimed to assess the microplastic prevalence and bacterial colonization patterns in different sewer habitats and to explore the role of land use, stratified wastewater and sediment, and microplastic attributes in shaping the patterns. We found that the sewer system formed a temporal but pronounced microplastic pool, with land use playing a significant role in the variability of microplastic prevalence. Industrial sewers contained a high abundance of microplastics with large particle sizes, diverse polymer compositions, and shapes. However, while there was a spatial discrepancy between urban and suburban areas in the abundance of microplastics in residential sewers, their predominant polymer and shape types were simple, i.e., polyethylene terephthalate (PET) and fibers. Sewer habitat characteristics, particularly the stratified wastewater and sediment determined microbial colonization patterns. The latter acted as a long-term sink for microplastics and supported the high growth of colonizers. In contrast, the wastewater plastisphere presented novel niches, hosting communities with a marked proportion of unique bacterial genera after colonization. Besides, statistics showed a highly positive and dense co-occurrence network of the plastisphere communities, especially those from the industrial sewer sediment, with enhanced metabolic activity, cellular processes and systems, and increased human pathogenic potential. Findings indicated a coarse and uncertain effect of the selective pressure of microplastic attributes on plastisphere community structure differentiation.


Assuntos
Microplásticos , Poluentes Químicos da Água , Humanos , Plásticos , Águas Residuárias , Prevalência , Poluentes Químicos da Água/análise , China , Ecossistema , Bactérias , Monitoramento Ambiental
8.
Environ Pollut ; 342: 123136, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38092341

RESUMO

Municipal sewer systems have received increasing attention due to the magnitude of the microplastic stock and its potential ecological impacts. However, as a critical aspect of the adverse impacts, little is known about the plastisphere that forms in these engineered environments. Using high-throughput absolute quantification sequencing, we conducted a systemic study combining field survey and laboratory batch test to explain the general plastisphere pattern and the role of environmental and polymeric factors in driving plastisphere succession and assembly there. We demonstrated the capacity of microplastics to support high levels of microbial colonization, increasing by 8.7-56.0 and 1.26-5.62 times at field and laboratory scales, respectively, despite the less diverse communities hosted in the resulting plastisphere. Sediment communities exhibited higher diversity but greater loss of specific operational taxonomic units in their plastisphere than in the wastewater. The former plastisphere had primarily an enhanced methanogenesis-oriented metabolic network linked to hydrolysis fermentation, hydrogen-producing acetogenesis, and denitrification, while the latter had a pronounced niche partitioning and competitive interaction network. Exogenous substrate flux and composition were key in stimulating plastisphere community growth and succession. Furthermore, the high nitrogen baseline facilitated alternative niche formation for plastisphere nitrifiers and denitrifiers, and the plastisphere pathogens associated with denitrification and plastic biodegradation functions increased significantly. The aerobic state also promoted a 1.71 times higher colonizer load and a denser interaction pattern than the anaerobic state. Selective filtering by polymers was evident: polyethylene supported higher plastisphere diversity than polypropylene. This study provides new insights into the mechanisms driving colonizer loads and the adaptive succession and assembly of the plastisphere in such a typically hydrodynamic and highly contaminated environment. The results help to fill the knowledge gap in understanding the potential role of microplastics in shaping the microecology of sewers and increasing health risks and substrate loss during sewer transfer.


Assuntos
Microplásticos , Plásticos , Biodegradação Ambiental , Fermentação , Sequenciamento de Nucleotídeos em Larga Escala
9.
Discov Med ; 35(179): 1134-1146, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38058079

RESUMO

BACKGROUND: Inflammation and oxidative stress (OS) are major causes of aneurysmal subarachnoid hemorrhage (aSAH)-induced early brain injury (EBI). Eriocitrin (EC), a flavonoid compound, has anti-inflammatory and antioxidant actions. However, there is still no relevant studies on the role of EC in SAH. Accordingly, this research aims to clarify the anti-OS and anti-inflammatory efficacy of EC in SAH. METHOD: Rat SAH model was established in vivo and administered with Eriocitrin (25 mg/kg). In vitro, BV2 cells were exposed to oxyhemoglobin (OxyHb) for 24 hours and pretreated with Eriocitrin (1 uM/mL, 2 uM/mL, 4 uM/mL) for 30 minutes. Water maze experiments and neurological function scores were conducted to assess cognitive and motor function. TdT-mediated dUTP Nick-End Labeling (TUNEL) staining was used to detect cortical cell apoptosis. Enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) were used to detect the inflammatory factors and malondialdehyde (MDA), as well as the expression of superoxide dismutase (SOD) and glutathione peroxidase (GSH-px). Western blots were used to semi quantify nuclear factor erythroid-2-related factor 2 (Nrf2), nuclear factor-κB (NF-κB), dual specificity phosphatase 14 (DUSP14) expression. RESULTS: The findings suggest that EC (25 mg/kg) reduced SAH-induced central nervous system (CNS) damage, neuronal apoptosis, inflammatory reactions and OS. Regarding a mechanistic study, EC enhanced Nrf2 and NF-κB by increasing DUSP14 activation, thereby reducing the inflammatory cytokines interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and IL-6. In addition, EC decreased MDA while markedly elevating SOD and enhancing GSH-px. Furthermore, specifically inhibiting DUSP14 expression via using protein-tyrosine-phosphatase (PTP) inhibitor IV, neutralized the protective action of EC and aggravated inflammation and OS. In vitro experiments of OxyHb-induced BV2 cells revealed that EC promoted Nrf2 while markedly suppressing NF-κB by increasing DUSP14 activation, thereby reducing the concentrations of the above inflammatory cytokines. Moreover, EC decreased MDA while evidently increasing SOD and GSH-px. CONCLUSION: In summary, this paper lays a theoretical grounding for EC treatment of SAH-induced inflammatory reactions and OS by regulating DUSP14.


Assuntos
NF-kappa B , Hemorragia Subaracnóidea , Ratos , Animais , NF-kappa B/metabolismo , NF-kappa B/farmacologia , NF-kappa B/uso terapêutico , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/farmacologia , Fator 2 Relacionado a NF-E2/uso terapêutico , Ratos Sprague-Dawley , Estresse Oxidativo , Inflamação/tratamento farmacológico , Inflamação/patologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Citocinas/metabolismo , Superóxido Dismutase/metabolismo , Superóxido Dismutase/farmacologia , Superóxido Dismutase/uso terapêutico
10.
Cell Death Discov ; 9(1): 378, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37845209

RESUMO

Homeobox A5 (HOXA5), a homeodomain transcription factor, is considered a tumor suppressor in cancer progression; however, its function in prostate cancer (PCa) remains unclear. This study focused on the relevance of HOXA5 in PCa progression. We identified the downregulation of HOXA5 in PCa tissues based on the TCGA database and further verified in 30-paired PCa and adjacent normal tissues. Functional studies revealed that HOXA5 upregulation impaired the stem-like characteristics and malignant behaviors of PCa cells in vitro and in vivo. Mechanistically, HOXA5 was found to be regulated by tumor necrosis factor receptor-associated factor 7 (TRAF7), a putative E3-ubiquitin ligase. We observed that TRAF7 was overexpressed in PCa and subsequently enhanced the degradation of HOXA5 protein via its ubiquitin ligase activity, contributing to the acquisition of an aggressive PCa phenotype. For its downstream mechanism, we demonstrated that sprouty RTK signaling antagonist 2 (SPRY2) served as a downstream target of HOXA5. HOXA5 could directly bind to the SPRY2 promoter, thereby regulating the SPRY2-mediated MEK/ERK signaling pathway. Silencing SPRY2 largely compromised the tumor-suppressive effect of HOXA5 in PCa progression and cancer stemness. Our findings highlight the previously-underappreciated signaling axis of TRAF7-HOXA5-SPRY2, which provides a novel prognostic and therapeutic target for PCa treatment.

11.
Cancer Cell ; 41(10): 1788-1802.e10, 2023 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-37816332

RESUMO

Mitochondria (MT) participate in most metabolic activities of mammalian cells. A near-unidirectional mitochondrial transfer from T cells to cancer cells was recently observed to "metabolically empower" cancer cells while "depleting immune cells," providing new insights into tumor-T cell interaction and immune evasion. Here, we leverage single-cell RNA-seq technology and introduce MERCI, a statistical deconvolution method for tracing and quantifying mitochondrial trafficking between cancer and T cells. Through rigorous benchmarking and validation, MERCI accurately predicts the recipient cells and their relative mitochondrial compositions. Application of MERCI to human cancer samples identifies a reproducible MT transfer phenotype, with its signature genes involved in cytoskeleton remodeling, energy production, and TNF-α signaling pathways. Moreover, MT transfer is associated with increased cell cycle activity and poor clinical outcome across different cancer types. In summary, MERCI enables systematic investigation of an understudied aspect of tumor-T cell interactions that may lead to the development of therapeutic opportunities.


Assuntos
DNA Mitocondrial , Neoplasias , Animais , Humanos , DNA Mitocondrial/genética , Linfócitos T/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Mamíferos/genética , Mamíferos/metabolismo
12.
bioRxiv ; 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37905034

RESUMO

High grade serous ovarian cancer (HGOC) is a major cause of death in women. Early detection of HGOC usually leads to a cure, yet it remains a clinical challenge with over 90% HGOCs diagnosed at advanced stages. This is mainly because conventional biomarkers are not sensitive to detect the microscopic yet metastatic early HGOC lesions. In this study, we sequenced the blood T cell receptor (TCR) repertoires of 466 ovarian cancer patients and controls, and systematically investigated the immune repertoire signatures in HGOCs. We observed quantifiable changes of selected TCRs in HGOCs that are reproducible in multiple independent cohorts. Importantly, these changes are stronger during stage I. Using pre-diagnostic patient blood samples from the Nurses' Health Study, we confirmed that HGOC signals can be detected in the blood TCR repertoire up to 4 years proceeding conventional diagnosis. Our findings may provide the basis of an immune-based HGOC early detection criterion.

13.
Huan Jing Ke Xue ; 44(8): 4353-4363, 2023 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-37694630

RESUMO

Dissolved organic matter (DOM) is an essential component of river pollutants. Under the new situation of black water treatment in urban areas of China, in view of the widespread problem of unclear sources of multiple pollutants, further analysis of DOM components in urban rivers from the molecular level is a key link to deeply explore the sources, causes, and mechanism of river pollution so as to achieve efficient management. In this study, the urban rivers in the central city were selected as the research object, and a total of five rivers were selected that were seriously affected by the discharge sewage of four combined and separated sewer systems, respectively. Using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS), this study identified the molecular formulae and analyzed the elemental composition and compound groups of DOM in water and sediment samples at each site in dry and wet weather. The results showed that:①although CHO molecules and lignins were the main compounds in the urban river DOM, the high proportion of lipids, proteins, and heteroatomic compounds (especially CHOS molecules) revealed the anthropogenic pollution in rivers, which also led to the increase in DOC, TN, and NH+4-N. ②Surfactants such as C17H28O3S and C18H30O3S were ubiquitous in all urban rivers, which could be used as markers of domestic wastewater pollution. ③In wet weather, the rainfall inputs, storm runoffs, and hydraulic disturbance jointly led to the increase in the proportion of CHO molecules and lignin compounds; the decrease in proteins and lipids; the rise of DOC, TN, and NH+4-N concentrations in river water; and the decrease in DOC, TN, and NH+4-N concentrations and proteins and lipids in river sediments. ④The abundance of multi-heteroatomic compounds and condensed aromatics in the combined sewer system was higher than that in the separated sewer system, which may have been more severely polluted by domestic wastewater and storm runoff, especially kitchen wastewater. This study provides new insight for clarifying the critical causes of pollution in the new stage and provides an essential basis for further precision prevention and control of water pollution.

14.
Cancer Cell ; 41(8): 1427-1449.e12, 2023 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-37478850

RESUMO

Tumor mutational burden and heterogeneity has been suggested to fuel resistance to many targeted therapies. The cytosine deaminase APOBEC proteins have been implicated in the mutational signatures of more than 70% of human cancers. However, the mechanism underlying how cancer cells hijack the APOBEC mediated mutagenesis machinery to promote tumor heterogeneity, and thereby foster therapy resistance remains unclear. We identify SYNCRIP as an endogenous molecular brake which suppresses APOBEC-driven mutagenesis in prostate cancer (PCa). Overactivated APOBEC3B, in SYNCRIP-deficient PCa cells, is a key mutator, representing the molecular source of driver mutations in some frequently mutated genes in PCa, including FOXA1, EP300. Functional screening identifies eight crucial drivers for androgen receptor (AR)-targeted therapy resistance in PCa that are mutated by APOBEC3B: BRD7, CBX8, EP300, FOXA1, HDAC5, HSF4, STAT3, and AR. These results uncover a cell-intrinsic mechanism that unleashes APOBEC-driven mutagenesis, which plays a significant role in conferring AR-targeted therapy resistance in PCa.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Mutagênese , Mutação , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Receptores Androgênicos/genética , Proteínas Cromossômicas não Histona , Ribonucleoproteínas Nucleares Heterogêneas , Citidina Desaminase , Antígenos de Histocompatibilidade Menor , Complexo Repressor Polycomb 1
15.
Cell Stem Cell ; 30(5): 611-616.e7, 2023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-37146582

RESUMO

Understanding the mechanisms of blastocyst formation and implantation is critical for improving farm animal reproduction but is hampered by a limited supply of embryos. Here, we developed an efficient method to generate bovine blastocyst-like structures (termed blastoids) via assembling bovine trophoblast stem cells and expanded potential stem cells. Bovine blastoids resemble blastocysts in morphology, cell composition, single-cell transcriptomes, in vitro growth, and the ability to elicit maternal recognition of pregnancy following transfer to recipient cows. Bovine blastoids represent an accessible in vitro model for studying embryogenesis and improving reproductive efficiency in livestock species.


Assuntos
Blastocisto , Trofoblastos , Gravidez , Feminino , Bovinos , Animais , Implantação do Embrião , Desenvolvimento Embrionário , Células-Tronco , Técnicas de Cultura de Células
16.
Chem Biol Drug Des ; 101(6): 1348-1355, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36762503

RESUMO

Ginsenoside Rg5 has been implicated in a variety of diseases. However, it is unknown whether Ginsenoside Rg5 can protect against hypoxia-induced neonatal rat cardiomyocytes (NRMs). The purpose of this study was to look into the effect of Ginsenoside Rg5 on hypoxia-induced NRMs apoptosis as well as the underlying molecular mechanism. In this study, following isolation and culture of ventricular myocardial cells from neonatal rats, the appropriate concentration of Rg5 was determined using the MTT assay, the effect of Rg5 on apoptosis was assessed employing TUNEL staining and flow cytometry assays. Levels of apoptosis-related proteins and phosphorylated level of Akt (ser 473 and ser 308) were analyzed using the western blot analysis. Finally, the experimental results shown that Ginsenoside Rg5 significantly inhibited hypoxia-induced NRMs apoptosis, decreased the expression pro-apoptotic protein Bax, increased the expression of anti-apoptotic protein Bcl-2 ratio and the level of cleaved caspase 3. Akt signaling activation was found to be the mechanism of Ginsenoside Rg5s protective effect on hypoxia-induced NRMs apoptosis, as an Akt inhibitor eliminated the anti-apoptotic effects of Ginsenoside Rg5. Various analyses were performed and verified, ginsenoside Rg5 suppressed hypoxia-induced apoptosis in NRMs via activation of the Akt signaling.


Assuntos
Ginsenosídeos , Proteínas Proto-Oncogênicas c-akt , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ginsenosídeos/farmacologia , Miócitos Cardíacos/metabolismo , Apoptose , Hipóxia/metabolismo
17.
Cardiooncology ; 9(1): 6, 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36670511

RESUMO

BACKGROUND: Acute myocardial infarction (AMI) and cancer are diseases with high morbidity and mortality worldwide, bringing a serious economic burden, and they share some risk factors. The purpose of this study was to determine the effect of cancer on the all-cause in-hospital mortality of patients with AMI. METHODS: This multicenter retrospective study analyzed patients with AMI from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and eICU Collaborative Research Database (eICU-CRD) in the United States. Patients were divided into two groups based on whether they had concomitant malignant cancer: cancer and noncancer groups. The outcome was all-cause in-hospital mortality. The association between the two groups and their outcomes were analyzed using Kaplan-Meier and Cox proportional-hazards regression models. Propensity score matching (PSM) and propensity score based inverse probability of treatment weighting (IPTW) were used to further adjust for confounding variables to verify the stability of the results. RESULTS: The study included 3,034 and 5,968 patients with AMI from the MIMIC-IV database and the eICU-CRD, respectively. Kaplan-Meier survival curves indicated that the probability of in-hospital survival was lower in patients with cancer than in those without cancer. After adjusting for potential confounding variables using multivariable Cox proportional hazards regression, the risk of all-cause in-hospital mortality was significantly higher in the cancer than the noncancer group, and the HR (95% CI) values for the cancer group were 1.56(1.22,1.98) and 1.35(1.01,1.79) in the MIMIC-IV database and the eICU-CRD, respectively. The same results were obtained after using PSM and IPTW, which further verified the results. CONCLUSIONS: Among the patients with AMI, the all-cause in-hospital mortality risk of those with cancer was higher than those without cancer. Therefore, when treating such patients, comprehensive considerations should be made from a multidisciplinary perspective involving cardiology and oncology, with the treatment plan adjusted accordingly.

18.
Assessment ; 30(7): 2247-2257, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36633098

RESUMO

Early identification and intervention of cognitive decline could be effective to prevent progression to dementia. We developed a self-delivered cognitive screening tool, Automated Memory and Executive Screening (AMES), to assess cognitive domains including memory, language, and executive function. 189 participants with diagnoses of mild cognitive impairment (MCI, n = 43), subjective cognitive decline (SCD, n = 29), objectively-defined subtle cognitive decline (obj-SCD, n = 18), and normal controls (NC, n = 99) completed the study. AMES had good convergent validity with conventional scales, and was good to discriminate patients with MCI (area under the curve [AUC] = 0.88; sensitivity = 86%; specificity = 80%) and obj-SCD (AUC = 0.78; sensitivity = 89%; specificity = 63%) from NC. These findings support that AMES is an easy to administer and effective instrument to screen for early cognitive impairment in community-based settings.


Assuntos
Disfunção Cognitiva , Humanos , Testes Neuropsicológicos , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Função Executiva , Medição de Risco , Atenção Primária à Saúde
19.
J Hazard Mater ; 443(Pt B): 130295, 2023 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-36335904

RESUMO

Black-odor water is a serious environmental issue in many developing counties. Iron sulfides and chromophoric dissolved organic matter are considered possible blackening substances. However, the specific type of blackening iron sulfides and the contributions of blackening substances are unclear. This study performed a laboratory simulation experiment to identify the blackening iron sulfides and quantify the contribution of blackening substances. The environmental conditions for forming blackening substances and their blackening process were also determined. We demonstrated that the black iron sulfide was mackinawite. Humic acid is another substance that absorbs light. The equivalent contributions of mackinawite and humic acid were 18.94 m-1/mg Fe2+ and 1.11 m-1/mg DOC, respectively. A pH of more than 6 is a precondition for producing mackinawite. The production of black substances is the foundation of the blackening process, but the suspension of black substances is essential in causing water blackening. Fulvic acid stabilizes the suspension by changing the surface charge of blackening substances. Moreover, blackening substances can also be suspended with microbial flocs. Determining blackening substances and their role during the blackening process would allow for developing precise and targeted control technologies, improving urban water over the long term.


Assuntos
Substâncias Húmicas , Água , Substâncias Húmicas/análise , Odorantes/análise , Ferro/análise , Sulfetos/química
20.
Sci Total Environ ; 859(Pt 2): 160148, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36375558

RESUMO

Urban surface runoff (USR) and drainage system overflows during wet weather (WWF) play a key role in shaping water pollution. Particularly, the impact of large amounts of microplastic pollution on urban water bodies is unclear. We conducted an in-field investigation in six central urban drainage systems along Suzhou Creek in the Shanghai megacity of China and identified the impacts of storm factors and land use on the real-time dynamic changes in microplastic abundance and characteristics in USR and WWF. Microplastic abundances ranged from 228.3 ± 105.4-4969.51 ± 348.8, 309.3 ± 144.3-5195.8 ± 425.5, and 130.0 ± 30.0-8500.0 ± 1241.0 particles/L in the traffic and residential catchment USR, and the WWF, respectively. Under similar storm factor conditions, we observed correlations between environmental factors and microplastic abundance, especially the polymer type, verifying the significant role of land use. The microplastic abundance were 90.2 particles/L higher in the traffic catchment USR than in the residential catchment USR. Notably, we found unique microplastic polymers comprising ethylene vinyl acetate copolymer and thermoplastic elastomers in the residential and traffic catchment USR, respectively. However, land use had a minimum impact on the size and shape of microplastics: small-sized and film microplastics dominated in both USR types. We found statistical evidence of the widespread correlations between microplastic abundance and storm factors (accumulated storm depth and WWF flow) in both USR and WWF. The first flush phenomenon of microplastic dynamics was found in both USR and WWF. Microplastic characteristics also changed dynamically with storm time. With heavy storm factors, polypropylene and small-sized (<1 mm) microplastics in USR events increased and then decreased. This was also true for WWF events in granular and polyethylene terephthalate microplastics. Our results can facilitate the targeted mitigation of emerging pollutants to enhance stormwater management strategies and prevent future contamination.


Assuntos
Microplásticos , Poluentes Químicos da Água , Plásticos , Monitoramento Ambiental , Poluentes Químicos da Água/análise , China , Poluição da Água
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