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1.
Talanta ; 281: 126885, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39277929

RESUMEN

Mitochondria are crucial powerhouses and central organelles for maintaining normal physiological activities in eukaryotic cells. The use of highly specific optical biosensors to monitor mitochondrial autophagy (mitophagy) is an important way for detecting mitochondrial abnormalities. Herein, we report a pH responsive G-quadruplex (G4) structure folded by the oligonucleotide named P24. P24 is composed of four GGCCTG repeating units, and the high guanine content allows it to form an antiparallel G4 topology at pH 4.5 (lysosomal pH). However, when pH increases to around 7.4 (mitochondrial pH), P24 further transforms into a double-stranded structure. Unlike most oligonucleotides that enter lysosomes, P24 highly targets mitochondria in live cells. These characteristics enable P24 to construct a pH responsive optical biosensor by linking a pair of fluorescence resonance energy transfer (FRET) fluorophores. The P24 based biosensor demonstrates reliable applications in detecting mitophagy in live cells.

2.
J Cell Mol Med ; 28(17): e70090, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39261902

RESUMEN

Mitochondrial dysfunction is a pivotal event contributing to the development of ageing-related kidney disorders. Lon protease 1 (LONP1) has been reported to be responsible for ageing-related renal fibrosis; however, the underlying mechanism(s) of LONP1-driven kidney ageing with respect to mitochondrial disturbances remains to be further explored. The level of LONP1 was tested in the kidneys of aged humans and mice. Renal fibrosis and mitochondrial quality control were confirmed in the kidneys of aged mice. Effects of LONP1 silencing or overexpression on renal fibrosis and mitochondrial quality control were explored. In addition, N6-methyladenosine (m6A) modification and methyltransferase like 3 (METTL3) levels, the relationship between LONP1 and METTL3, and the impacts of METTL3 overexpression on mitochondrial functions were confirmed. Furthermore, the expression of insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) and the regulatory effects of IGF2BP2 on LONP1 were confirmed in vitro. LONP1 expression was reduced in the kidneys of aged humans and mice, accompanied by renal fibrosis and mitochondrial dysregulation. Overexpression of LONP1 alleviated renal fibrosis and maintained mitochondrial homeostasis, while silencing of LONP1 had the opposite effect. Impaired METTL3-m6A signalling contributed at least in part to ageing-induced LONP1 modification, reducing subsequent degradation in an IGF2BP2-dependent manner. Moreover, METTL3 overexpression alleviated proximal tubule cell injury, preserved mitochondrial stability, inhibited LONP1 degradation, and protected mitochondrial functions. LONP1 mediates mitochondrial function in kidney ageing and that targeting LONP1 may be a potential therapeutic strategy for improving ageing-related renal fibrosis.


Asunto(s)
Adenosina , Envejecimiento , Fibrosis , Homeostasis , Enfermedades Renales , Riñón , Metiltransferasas , Mitocondrias , Proteínas Mitocondriales , Proteínas de Unión al ARN , Mitocondrias/metabolismo , Animales , Metiltransferasas/metabolismo , Metiltransferasas/genética , Humanos , Envejecimiento/metabolismo , Ratones , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Riñón/patología , Riñón/metabolismo , Masculino , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Enfermedades Renales/etiología , Enfermedades Renales/genética , Proteasas ATP-Dependientes/metabolismo , Proteasas ATP-Dependientes/genética , Transducción de Señal , Ratones Endogámicos C57BL
3.
Ren Fail ; 46(2): 2384585, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39252179

RESUMEN

OBJECTIVES: Patients with end-stage renal disease (ESRD) on hemodialysis (HD) are at risk for hyperkalemia (HK), associated with cardiac arrhythmia and sudden death. Data on the burden of HK and management techniques among HD patients in China are still scarce. This study assessed the treatment modalities, recurrence, and prevalence of HK in Chinese HD patients. METHODS: In this prospective cohort study conducted from May 2021 to July 2022, patients aged ≥18 years who had ESRD and were on HD were enrolled from 15 centers in China (up to 6 months). RESULTS: Overall, 600 patients were enrolled. At the baseline visit, mean (± standard deviation) urea reduction ratio was 68.0% ± 9.70 and Kt/V was 1.45 ± 0.496. Over 6 months, 453 (75.5%) patients experienced HK, of whom 356 (78.6%) recurred. Within 1, 2, 3, 4, 5, and 6 months, 203 (44.8%), 262 (57.8%), 300 (66.2%), 326 (72.0%), 347 (76.6%), and 356 (78.6%) patients had at least one HK recurrence event, respectively. The proportions of patients with ≥1, 2, 3, 4, 5, or 6 HK recurrence events were 356 (78.6%), 306 (67.5%), 250 (55.2%), 208 (45.9%), 161 (35.5%), and 110 (24.3%), respectively. Among the 453 patients who experienced HK, only 24 (5.3%) were treated with potassium binders: seven (1.5%) with sodium polystyrene sulfonate, 13 (2.9%) with calcium polystyrene sulfonate, and six (1.3%) with sodium zirconium cyclosilicate. CONCLUSION: Since HK is a chronic illness, long-term care is necessary. Patients on HD should have effective potassium management on non-dialysis days, yet our real-world population rarely used potassium binders. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04799067.


Asunto(s)
Hiperpotasemia , Fallo Renal Crónico , Diálisis Renal , Humanos , Hiperpotasemia/etiología , Hiperpotasemia/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Diálisis Renal/efectos adversos , China/epidemiología , Fallo Renal Crónico/terapia , Fallo Renal Crónico/complicaciones , Anciano , Adulto , Poliestirenos/uso terapéutico , Poliestirenos/efectos adversos , Silicatos/uso terapéutico , Recurrencia , Potasio/sangre , Prevalencia , Pueblos del Este de Asia
4.
Int J Mol Med ; 54(5)2024 11.
Artículo en Inglés | MEDLINE | ID: mdl-39219279

RESUMEN

Metastasis is the leading cause of cancer­related death in osteosarcoma (OS). OS stem cells (OSCs) and anoikis resistance are considered to be essential for tumor metastasis formation. However, the underlying mechanisms involved in the maintenance of a stem­cell phenotype and anoikis resistance in OS are mostly unknown. Fos­like antigen 1 (FOSL1) is important in maintaining a stem­like phenotype in various cancers; however, its role in OSCs and anoikis resistance remains unclear. In the present study, the dynamic expression patterns of FOSL1 were investigated during the acquisition of cancer stem­like properties using RNA sequencing, PCR, western blotting and immunofluorescence. Flow cytometry, tumor­sphere formation, clone formation assays, anoikis assays, western blotting and in vivo xenograft and metastasis models were used to further investigate the responses of the stem­cell phenotype and anoikis resistance to FOSL1 overexpression or silencing in OS cell lines. The underlying molecular mechanisms were evaluated, focusing on whether SOX2 is crucially involved in FOSL1­mediated stemness and anoikis in OS. FOSL1 expression was observed to be upregulated in OSCs and promoted tumor­sphere formation, clone formation and tumorigenesis in OS cells. FOSL1 expression correlated positively with the expression of stemness­related factors (SOX2, NANOG, CD117 and Stro1). Moreover, FOSL1 facilitated OS cell anoikis resistance and promoted metastases by regulating the expression of apoptosis related proteins BCL2 and BAX. Mechanistically, FOSL1 upregulated SOX2 expression by interacting with the SOX2 promoter and activating its transcription. The results also showed that SOX2 is critical for FOSL1­mediated stem­like properties and anoikis resistance. The current findings indicated that FOSL1 is an important regulator that promotes a stem cell­like phenotype and anoikis resistance to facilitate tumorigenesis and metastasis in OS by regulating the transcription of SOX2. Thus, FOSL1 might represent an attractive target for therapeutic interventions in OS.


Asunto(s)
Anoicis , Carcinogénesis , Regulación Neoplásica de la Expresión Génica , Células Madre Neoplásicas , Osteosarcoma , Proteínas Proto-Oncogénicas c-fos , Factores de Transcripción SOXB1 , Osteosarcoma/patología , Osteosarcoma/genética , Osteosarcoma/metabolismo , Humanos , Proteínas Proto-Oncogénicas c-fos/metabolismo , Proteínas Proto-Oncogénicas c-fos/genética , Factores de Transcripción SOXB1/metabolismo , Factores de Transcripción SOXB1/genética , Anoicis/genética , Animales , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Línea Celular Tumoral , Ratones , Carcinogénesis/genética , Carcinogénesis/patología , Metástasis de la Neoplasia , Neoplasias Óseas/patología , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Neoplasias Óseas/secundario , Ratones Desnudos , Masculino , Femenino , Ratones Endogámicos BALB C
5.
PeerJ ; 12: e17864, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39221285

RESUMEN

Meiosis is a critical process in sexual reproduction, and errors during this cell division can significantly impact fertility. Successful meiosis relies on the coordinated action of numerous genes involved in DNA replication, strand breaks, and subsequent rejoining. DNA topoisomerase enzymes play a vital role by regulating DNA topology, alleviating tension during replication and transcription. To elucidate the specific function of DNA topoisomerase 1α ( A t T O P 1 α ) in male reproductive development of Arabidopsis thaliana, we investigated meiotic cell division in Arabidopsis flower buds. Combining cytological and biochemical techniques, we aimed to reveal the novel contribution of A t T O P 1 α to meiosis. Our results demonstrate that the absence of A t T O P 1 α leads to aberrant chromatin behavior during meiotic division. Specifically, the top1α1 mutant displayed altered heterochromatin distribution and clustered centromere signals at early meiotic stages. Additionally, this mutant exhibited disruptions in the distribution of 45s rDNA signals and a reduced frequency of chiasma formation during metaphase I, a crucial stage for genetic exchange. Furthermore, the atm-2×top1α1 double mutant displayed even more severe meiotic defects, including incomplete synapsis, DNA fragmentation, and the presence of polyads. These observations collectively suggest that A t T O P 1 α plays a critical role in ensuring accurate meiotic progression, promoting homologous chromosome crossover formation, and potentially functioning in a shared DNA repair pathway with ATAXIA TELANGIECTASIA MUTATED (ATM) in Arabidopsis microspore mother cells.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Segregación Cromosómica , ADN-Topoisomerasas de Tipo I , Meiosis , Arabidopsis/genética , Arabidopsis/enzimología , Meiosis/fisiología , Meiosis/genética , ADN-Topoisomerasas de Tipo I/metabolismo , ADN-Topoisomerasas de Tipo I/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Recombinación Genética , Mutación
6.
Dalton Trans ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39233653

RESUMEN

With an electron-deficient rigid planar structure and excellent π-π stacking ability, hexaazatriphenylene (HAT) and its derivatives are widely used as basic building blocks for constructing covalent organic frameworks (COFs), components of organic light-emitting diodes and solar cells, and electrode materials for lithium-ion batteries (LIBs). Here, a HAT derivative, hexaazatriphenylenehexacarbonitrile, is explored as an anode material for LIBs. The HAT anode exhibited high initial reversible capacities of 672 mA h g-1 at 100 mA g-1 and 550 mA h g-1 at 400 mA g-1 and stable cycling with a capacity of 503 mA h g-1 after 1000 cycles at 400 mA g-1 corresponding to a capacity retention of 91.5%. Furthermore, the lithium storage mechanism and the cause of the first irreversible capacity loss of the HAT anode were investigated by X-ray photoelectron spectroscopy (XPS) analysis and density functional theory (DFT) calculations. We have carried out a series of analyses on the mechanism of initial capacity loss. This study provides new insight on initial capacity loss and provides valuable insights into the molecular design and the electrochemical properties of HAT-based anode materials.

9.
Phytomedicine ; 133: 155906, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39089089

RESUMEN

BACKGROUND: Colorectal cancer (CRC) and its chemoresistance pose significant threats to human health. Gegen Qinlian Decoction (GQD) is frequently employed alongside chemotherapy drugs for the treatment of CRC and various intestinal disorders. Despite its widespread use, there is limited research investigating the mechanisms through which GQD reverses chemoresistance. PURPOSE: This study investigated the mechanism by which GQD reverses oxaliplatin (OXA) resistance in CRC. METHODS: A YTH N6-methyladenosine RNA binding protein 1 (YTHDF1)-knockdown OXA-resistant cell line was constructed by lentivirus to clarify YTHDF1-mediated chemoresistance through the regulation of glutaminase 1 (GLS1). The efficacy of GQD in reversing OXA resistance in CRC in vitro was evaluated by Cell Counting Kit-8, western blotting, quantitative real-time polymerase chain reaction, and glutaminase activity assays. In vivo validation was performed by constructing tumor xenografts in nude mice with OXA-resistant cells. In addition, mouse feces were collected and a 16S rDNA assay was performed to assess the regulation of intestinal flora by GQD. RESULTS: Overexpression of YTHDF1 upregulated GLS1 expression and induced OXA-resistance in CRC. GQD induced apoptosis in LoVo/OXAR, increased OXA accumulation in LoVo/OXAR, inhibited expression of YTHDF1 and GLS1 when administered alone and in combination with OXA, and suppressed GLS1 activity to reverse drug resistance with good synergistic effects. GQD and OXA combination or GLS1 inhibitor alleviated OXA toxicity, reduced the volume of tumor xenografts in nude mice, inhibited YTHDF1 and GLS1 protein expression and GLS1 activity, adjusted the intestinal flora, and significantly reversed the increased Firmicutes/Bacteroidetes ratio. CONCLUSION: GQD has shown superior efficacy in reversing OXA-resistance and increasing sensitivity. These findings indicate that the therapy combined with GQD has potential utility in the treatment of OXA-resistant CRC.


Asunto(s)
Neoplasias Colorrectales , Resistencia a Antineoplásicos , Medicamentos Herbarios Chinos , Glutaminasa , Ratones Desnudos , Oxaliplatino , Proteínas de Unión al ARN , Oxaliplatino/farmacología , Animales , Humanos , Neoplasias Colorrectales/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Glutaminasa/metabolismo , Medicamentos Herbarios Chinos/farmacología , Proteínas de Unión al ARN/metabolismo , Línea Celular Tumoral , Ratones Endogámicos BALB C , Ratones , Ensayos Antitumor por Modelo de Xenoinjerto , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Adenosina/análogos & derivados
10.
Talanta ; 280: 126732, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-39216423

RESUMEN

The selective binding of ligand molecules towards the 5' and 3' ends of G-quadruplex (G4) may differentially affect the physiological function of G4s. However, there is still a lack of sensitive and low-cost approaches to accurately measure the binding preference of ligands on G4s, although multiple ways have been developed to evaluate the interaction between ligands and G4s. Here, we propose a new protocol named G4-AFQ to test the selectivity of ligands towards the two terminal G-tetrads of G4s. In this protocol, the fluorophore AMCA is respectively modified at the 5' or 3' end of G4, and which end of AMCA fluorescence is quenched means that the ligand binds to the G-tetrad at that end. Through G4-AFQ, the affinity constant of ligands towards the binding site can also be obtained. Compared with the commonly used nuclear magnetic resonance (NMR) method, G4-AFQ is more convenient, sensitive, cost-effective, and suitable for the measurement of the vast majority of G4 ligands, with a great potential for widespread application.


Asunto(s)
Colorantes Fluorescentes , G-Cuádruplex , Espectrometría de Fluorescencia , Ligandos , Colorantes Fluorescentes/química , Espectrometría de Fluorescencia/métodos , Fluorescencia , Humanos
11.
Acta Biomater ; 186: 454-469, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39098446

RESUMEN

Diabetic wound treatment continues to be a significant clinical issue due to higher levels of oxidative stress, susceptibility to bacterial infections, and chronic inflammatory responses during healing. We rationally developed and synthesized an ultra-small carbon dots (C-dots) loaded with zinc single-atom nanozyme (Zn/C-dots) with the aim of promoting wounds healing by nanocatalytic treatment, especially targeting its complex pathological microenvironment. Zinc single atoms and C-dots form a dual catalytic system with higher enzymatic activity. Furthermore, the Zn/C-dots nanozyme effectively enters cells, accumulates at mitochondria, and removes excess ROS, protecting cells from oxidative stress damage and limiting the release of pro-inflammatory cytokines, hence reducing inflammation. Zinc can synergistically increase the antibacterial action of C-dots (the effective antibacterial rate of 100 µg/mL Zn/C-dots was above 90 %). Unlike traditional C-dots, Zn/C-dots can cause endothelial cell migration and the formation of new blood vessels. In vitro cytotoxicity, blood compatibility, and in vivo toxicity studies of Zn/C-dots show that they are biocompatible. We subsequently utilized the Zn/C-dots nanozymes to treat diabetic rats' chronic wounds for external use, combining them with ROS-responsive hydrogels to create an antioxidative system (H-Zn/C-dots). The hydrogels anchored the Zn/C-dots nanozymes to the wound, allowing for long-term treatment. The results revealed that H-Zn/C-dots can considerably reduce inflammation, accelerate angiogenesis, collagen deposition, and promote tissue remodeling at the diabetic wound site. After 14 days, the wound area had decreased to approximately 9.19 %, making it a potential treatment. STATEMENT OF SIGNIFICANCE: An ultra-small carbon dot with a zinc single-atom nanozyme was designed and manufactured. Zn/C-dots possess antibacterial, ROS-scavenging, and angiogenesis activities. In vivo, the multifunctional ROS-responsive hydrogel incorporating Zn/C-dots could speed up diabetic wound healing.


Asunto(s)
Carbono , Diabetes Mellitus Experimental , Cicatrización de Heridas , Zinc , Animales , Zinc/química , Zinc/farmacología , Cicatrización de Heridas/efectos de los fármacos , Carbono/química , Carbono/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/patología , Humanos , Catálisis , Masculino , Antibacterianos/farmacología , Antibacterianos/química , Ratas , Ratas Sprague-Dawley , Puntos Cuánticos/química , Puntos Cuánticos/uso terapéutico , Células Endoteliales de la Vena Umbilical Humana , Hidrogeles/química , Hidrogeles/farmacología , Especies Reactivas de Oxígeno/metabolismo
12.
Toxicol Appl Pharmacol ; 491: 117064, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39122118

RESUMEN

Propylthiouracil (PTU) and methimazole (MMI), two classical antithyroid agents possess risk of drug-induced liver injury (DILI) with unknown mechanism of action. This study aimed to examine and compare their hepatic toxicity using a quantitative system toxicology approach. The impact of PTU and MMI on hepatocyte survival, oxidative stress, mitochondrial function and bile acid transporters were assessed in vitro. The physiologically based pharmacokinetic (PBPK) models of PTU and MMI were constructed while their risk of DILI was calculated by DILIsym, a quantitative systems toxicology (QST) model by integrating the results from in vitro toxicological studies and PBPK models. The simulated DILI (ALT >2 × ULN) incidence for PTU (300 mg/d) was 21.2%, which was within the range observed in clinical practice. Moreover, a threshold dose of 200 mg/d was predicted with oxidative stress proposed as an important toxic mechanism. However, DILIsym predicted a 0% incidence of hepatoxicity caused by MMI (30 mg/d), suggesting that the toxicity of MMI was not mediated through mechanism incorporated into DILIsym. In conclusion, DILIsym appears to be a practical tool to unveil hepatoxicity mechanism and predict clinical risk of DILI.


Asunto(s)
Antitiroideos , Enfermedad Hepática Inducida por Sustancias y Drogas , Hepatocitos , Metimazol , Estrés Oxidativo , Propiltiouracilo , Propiltiouracilo/toxicidad , Propiltiouracilo/farmacocinética , Metimazol/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Antitiroideos/toxicidad , Humanos , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Modelos Biológicos , Medición de Riesgo , Animales , Supervivencia Celular/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo
13.
Zhonghua Nan Ke Xue ; 30(7): 616-619, 2024 Jul.
Artículo en Chino | MEDLINE | ID: mdl-39212396

RESUMEN

OBJECTIVE: To explore the effect of dietary modification-assisted multimodal therapy in the prevention and treatment of chronic prostatitis. METHODS: A total of 132 cases of chronic prostatitis treated in the Outpatient Department of our hospital were randomly divided into an observation group (n = 68) and a control group (n = 64), the former following the Mediterranean dietary pattern, the latter adhering to their own dietary habits, and meanwhile both receiving lifestyle guidance, psychological counseling, symptomatic medication and physiotherapy according to their specific symptoms. The patients were followed up for 4 weeks, therapeutic effects were observed and comparisons were made between the two groups in the NIH-CPSI scores before and after treatment. RESULTS: Compared with the baseline, the quality of life (QOL) scores, pain and urination discomfort scores and total NIH-CPSI scores were significantly decreased in both the observation and the control groups after treatment (P < 0.05), even more decreased in the former than in the latter, but with no statistically significant difference between the two (P > 0.05). The rate of therapeutic effectiveness was higher in the observation group than in the control (87.1% vs 79.7%, but showed no statistically significant difference between the two groups (P > 0.05). CONCLUSION: Multimodal therapy is suitable for the management of different clinical manifestations of individual patients, while dietary habits vary from person to person as well as from region to region. Therefore, scientific dietary modification for the prevention and treatment of CP/CPPS needs further exploration.


Asunto(s)
Prostatitis , Calidad de Vida , Humanos , Masculino , Prostatitis/terapia , Terapia Combinada , Enfermedad Crónica , Resultado del Tratamiento , Dieta Mediterránea , Estilo de Vida , Adulto
14.
Schizophr Bull ; 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39212651

RESUMEN

Studies of individuals with chronic, untreated schizophrenia (CUS) can provide important insights into the natural course of schizophrenia and how antipsychotic pharmacotherapy affects neurobiological aspects of illness course and progression. We systematically review 17 studies on the neuroimaging, cognitive, and epidemiological aspects of CUS individuals. These studies were conducted at the Shanghai Mental Health Center, Institute of Mental Health at Peking University, and Huaxi MR Research Center between 2013 and 2021. CUS is associated with cognitive impairment, severe symptoms, and specific demographic characteristics and is different significantly from those observed in antipsychotic-treated individuals. Furthermore, CUS individuals have neurostructural and neurofunctional alterations in frontal and temporal regions, corpus callosum, subcortical, and visual processing areas, as well as default-mode and somatomotor networks. As the disease progresses, significant structural deteriorations occur, such as accelerated cortical thinning in frontal and temporal lobes, greater reduction in fractional anisotropy in the genu of corpus callosum, and decline in nodal metrics of gray mater network in thalamus, correlating with worsening cognitive deficits and clinical outcomes. In addition, striatal hypertrophy also occurs, independent of antipsychotic treatment. Contrasting with the negative neurostructural and neurofunctional effects of short-term antipsychotic treatment, long-term therapy frequently results in significant improvements. It notably enhances white matter integrity and the functions of key subcortical regions such as the amygdala, hippocampus, and striatum, potentially improving cognitive functions. This narrative review highlights the progressive neurobiological sequelae of CUS, the importance of early detection, and long-term treatment of schizophrenia, particularly because treatment may attenuate neurobiological deterioration and improve clinical outcomes.

17.
J Am Chem Soc ; 146(32): 22736-22746, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39078265

RESUMEN

G-quadruplex (G4), an unconventional nucleic acid structure, shows polymorphism in its topological morphology. The parallel G4 topology is the most prevalent form in organisms and plays a regulatory role in many biological processes. Designing fluorescent probes with high specificity for parallel G4s is important but challenging. Herein, a supramolecular assembly of the anionic cyanine dye SCY-5 is reported, which selectively identifies parallel G4 topology. SCY-5 can clearly distinguish parallel G4s from other G4s and non-G4s, even including hybrid-type G4s with parallel characteristics. The high specificity mechanism of SCY-5 involves a delicate balance between electrostatic repulsion and π-π interaction between SCY-5 and G4s. Using SCY-5, cellular RNA extracted from peripheral venous blood was quantitatively detected, and a remarkable increase in RNA G4 content in cancer patients compared to healthy volunteers was confirmed for the first time. This study provides new insights for designing specific probes for parallel G4 topology and opens a new path for clinical cancer diagnosis using RNA G4 as a biomarker.


Asunto(s)
Carbocianinas , Colorantes Fluorescentes , G-Cuádruplex , Neoplasias , Humanos , Carbocianinas/química , Colorantes Fluorescentes/química , Neoplasias/diagnóstico , ARN/química , ARN/análisis
18.
J Fungi (Basel) ; 10(7)2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39057377

RESUMEN

Astragalus membranaceus is a famous traditional medicinal plant. However, drought and cadmium (Cd) pollution are the main abiotic stress factors that affect plant growth and yield and the ability to improve the host's stress resistance through the use of beneficial endophytic fungi. To evaluate the tolerance of dark septate endophytes (DSE) to various abiotic stresses, 10 DSE strains [Microsphaeropsis cytisi (Mc), Alternaria alstroemeriae (Aa), Stagonosporopsis lupini (Sl), Neocamarosporium phragmitis (Np), Paraphoma chlamydocopiosa (Pc), Macrophomina phaseolina (Mp'), Papulaspora equi (Pe), Alternaria tellustris (At), Macrophomina pseudophaseolina (Mp), and Paraphoma radicina (Pr)] were investigated under different drought and Cd stressors in vitro by using solid-plate cultures and liquid-shaker cultures in the current study. The experiments involved using varying concentrations of PEG (0, 9, 18, and 27%) and Cd2+ (0, 25, 50, and 100 mg/L) to simulate different stress conditions on DSE. Additionally, the effect of DSE (Np and At) on the growth of A. membranaceus at different field water capacities (70% and 40%) and at different CdCl2 concentrations (0, 5, 10, and 15 mg Cd/kg) in soil was studied. The results demonstrated that the colony growth rates of Aa, Np, Pc, Mp', and Mp were the first to reach the maximum diameter at a PEG concentration of 18%. Aa, Np, and At remained growth-active at 100 mg Cd/L. In addition, Aa, Np, and At were selected for drought and Cd stress tests. The results of the drought-combined-with-Cd-stress solid culture indicated that the growth rate of Np was significantly superior to that of the other strains. In the liquid culture condition, the biomasses of Np and Aa were the highest, with biomasses of 1.39 g and 1.23 g under the concentration of 18% + 25 mg Cd/L, and At had the highest biomass of 1.71 g at 18% + 50 mg Cd/L concentration, respectively. The CAT and POD activities of Np reached their peak levels at concentrations of 27% + 50 mg Cd/L and 27% + 25 mg Cd/L, respectively. Compared to the control, these levels indicated increases of 416.97% and 573.12%, respectively. Aa, Np, and At positively influenced SOD activity. The glutathione (GSH) contents of Aa, Np, and At were increased under different combined stressors of drought and Cd. The structural-equation-modeling (SEM) analysis revealed that Aa positively influenced biomass and negatively affected Cd content, while Np and At positively influenced Cd content. Under the stress of 40% field-water capacity and the synergistic stress of 40% field-water capacity and 5 mg Cd/kg soil, Np and At significantly increased root weight of A. membranaceus. This study provides guidance for the establishment of agricultural planting systems and has good development and utilization value.

19.
ACS Appl Mater Interfaces ; 16(29): 37757-37769, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39001806

RESUMEN

Superwetting surfaces are often applied in oil/water separation. Hydrogels have been widely prepared as superhydrophilic/underwater superoleophobic materials for oil/water separation since they are naturally hydrophilic. Hydrogels usually need to be combined with porous substrates such as stainless steel mesh (SSM) due to their poor mechanical properties. However, it is usually inevitable that the pores of the substrate are clogged during the actual preparation process, leading to a significant decrease in the flux, which limits its effective application. In this study, acrylic acid (AA), chitosan (CS) and modified silica were utilized to form a layer of dual-network PAA/CS@SiO2 hydrogel by photopolymerization on SSM, followed by a simple and novel ultrasonic-assisted pore-making method to generate numerous pores in situ on the surface of the hydrogel-coated mesh, which led to an increase in water flux from 0 to 70,000 L m-2 h-1 without decreasing the separation efficiency. After 100 separations of a mixture of n-hexane and water, the flux was still higher than 50,000 L m-2 h-1 with a separation efficiency above 99%, which is superior to most of hydrogel-coated meshes reported so far. Moreover, the prepared PAA/CS@SiO2 hydrogel-coated mesh also has good environmental stability, low swelling, and self-cleaning properties. We believe that the strategy of this study will provide a simple new perspective when hydrogels block the substrate pores, resulting in low water flux.

20.
Sci Total Environ ; 946: 174436, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-38964403

RESUMEN

Semi-aerobic aged refuse biofilters (SAARB) are commonly-used biotechnologies for treating landfill leachate. In actual operation, SAARB often faces harsh conditions characterized by high concentrations of chemical oxygen demand (COD) and Cl-, as well as a low carbon-to-nitrogen ratio (C/N), which can disrupt the microbial community within SAARB, leading to operational instability. Maintaining the stable operation of SAARB is crucial for the efficient treatment of landfill leachate. However, the destabilization mechanism of SAARB under harsh conditions remains unclear. To address this, the study simulated the operation of SAARB under three harsh conditions, namely, high COD loading (H-COD), high chloride ion (Cl-) concentration environment (H-Cl-), and low C/N ratio environment (L-C/N). The aim is to reveal the destabilization mechanism of SAARB under harsh conditions by analyzing the fluorescence characteristics of effluent DOM and the microbial community in aged refuse. The results indicate that three harsh conditions have different effects on SAARB. H-COD leads to the accumulation of proteins; H-Cl- impedes the reduction of nitrite nitrogen; L-C/N inhibits the degradation of humic substances. These outcomes are attributed to the specific effects of different factors on the microbial communities in different zones of SAARB. H-COD and L-C/N mainly affect the degradation of organic matter in aerobic zone, while H-Cl- primarily impedes the denitrification process in the anaerobic zone. The abnormal enrichment of Corynebacterium, Castellaniella, and Sporosarcina can indicate the instability of SAARB under three harsh conditions, respectively. To maintain the steady operation of SAARB, targeted acclimation of the microbial community in SAARB should be carried out to cope with potentially harsh operating conditions. Besides, timely mitigation of loads should be implemented when instability characteristics emerge, and carbon sources and electron donors should be provided to restore treatment performance effectively.


Asunto(s)
Contaminantes Químicos del Agua , Contaminantes Químicos del Agua/análisis , Filtración , Eliminación de Residuos Líquidos/métodos , Análisis de la Demanda Biológica de Oxígeno , Nitrógeno , Aerobiosis , Eliminación de Residuos/métodos , Reactores Biológicos , Fluorescencia , Microbiota
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