RESUMO

Thiols function as antioxidants in food, prolonging shelf life and enhancing flavor. Moreover, thiols are vital biomolecules involved in enzyme activity, cellular signal transduction, and protein folding among critical biological processes. In this paper, the fluorescent probe PYL-NBD was designed and synthesized, which utilized the fluorescent molecule pyrazoline, the lysosome-targeted morpholine moiety, and the sensing moiety NBD. Probe PYL-NBD was tailored for the recognition of biothiols through single-wavelength excitation, yielding distinct fluorescence emission signals: blue for Cys, Hcy, and GSH; green for Cys, Hcy. Probe PYL-NBD exhibited rapid reaction kinetics (<10 min), distinct fluorescence response signals, and low detection limits (15.7 nM for Cys, 14.4 nM for Hcy, and 12.6 nM for GSH). Probe PYL-NBD enabled quantitative determination of Cys content in food samples and L-cysteine capsules. Furthermore, probe PYL-NBD had been successfully applied for confocal imaging with dual-channel detection of biothiols in various biological specimens, including HeLa cells, zebrafish, tumor sections, and Arabidopsis thaliana.

Assuntos

Cisteína , Corantes Fluorescentes , Análise de Alimentos , Glutationa , Lisossomos , Espectrometria de Fluorescência , Peixe-Zebra , Humanos , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Lisossomos/química , Lisossomos/metabolismo , Células HeLa , Cisteína/análise , Animais , Análise de Alimentos/métodos , Glutationa/análise , Espectrometria de Fluorescência/métodos , Homocisteína/análise , Arabidopsis/química , Limite de Detecção , Microscopia Confocal

RESUMO

Mutation of tet methylcytosine dioxygenase 2 (encoded by TET2) drives myeloid malignancy initiation and progression1-3. TET2 deficiency is known to cause a globally opened chromatin state and activation of genes contributing to aberrant haematopoietic stem cell self-renewal4,5. However, the open chromatin observed in TET2-deficient mouse embryonic stem cells, leukaemic cells and haematopoietic stem and progenitor cells5 is inconsistent with the designated role of DNA 5-methylcytosine oxidation of TET2. Here we show that chromatin-associated retrotransposon RNA 5-methylcytosine (m5C) can be recognized by the methyl-CpG-binding-domain protein MBD6, which guides deubiquitination of nearby monoubiquitinated Lys119 of histone H2A (H2AK119ub) to promote an open chromatin state. TET2 oxidizes m5C and antagonizes this MBD6-dependent H2AK119ub deubiquitination. TET2 depletion thereby leads to globally decreased H2AK119ub, more open chromatin and increased transcription in stem cells. TET2-mutant human leukaemia becomes dependent on this gene activation pathway, with MBD6 depletion selectively blocking proliferation of TET2-mutant leukaemic cells and largely reversing the haematopoiesis defects caused by Tet2 loss in mouse models. Together, our findings reveal a chromatin regulation pathway by TET2 through retrotransposon RNA m5C oxidation and identify the downstream MBD6 protein as a feasible target for developing therapies specific against TET2 mutant malignancies.

RESUMO

Utilizing infrared spectroscopy coupled with batch equilibrium methods, the adsorption and desorption characteristics of the novel Insecticide fluchlordiniliprole were assessed in four different soil types. It was found that fluchlordiniliprole's adsorption and desorption in these soils were consistent with the Freundlich isotherm, exhibiting adsorption capacities (KF-ads) ranging from 8.436 to 36.269. Temperature fluctuations, encompassing both high and low extremes, impaired the ability of soil to adsorb fluchlordiniliprole. In addition, adsorption dynamics were modulated by several other factors, including soil pH, ionic strength, amendments (e.g., biochar and humic substances), and the presence of various surfactants and microplastics. Although capable of leaching, fluchlordiniliprole exhibited weak mobility in most soils. Therefore, it appears that fluchlordiniliprole seems to pose a threat to surface soil and aquatic biota, but a minimal threat to groundwater. SYNOPSIS STATEMENT: This research examines the dynamics of fluchlordiniliprole in soil, an will aid in maintaining ecological safety and managing agricultural pesticides. The study's comprehensive analysis of adsorption, desorption, and soil migration patterns significantly contributes to our understanding of pesticide interactions with diverse soil types. The results of this study will enable the development of environmentally responsible agricultural practices.

RESUMO

Background and aims: Electrical stimulation (ES) has been shown to substantially enhance the quality of life by alleviating pain in patients with chronic wounds. This study aimed to observe the effects of low-frequency pulsed wearable ES at the common peroneal nerve on chronic refractory wounds of the lower limb. Methods: Forty-eight participants were randomly divided into control group (n = 24) and treatment group (n = 24) in this study. The control group received standard wound care (SWC) exclusively, whereas the treatment group was administered both SWC and the wearable low-frequency ES targeting the common peroneal nerve. Measurements of wound area, pain intensity, wound status, and quality of life scores were systematically recorded both before and after 4 weeks treatment. Results: After 4 weeks of intervention, the percentage area reduction was significantly higher in the treatment group compared to the control group (Z = -3.9, p < 0.001), and the healing rate of the treatment group was significantly higher than that of the control group (33% vs. 4%). Moreover, the visual Analog Scale for Pain score (ß = -0.65, p = 0.019), the Bates-Jensen Wound Assessment Tool score (p < 0.05), and the questionnaire on quality of life with chronic wounds (Wound-Qol) score (ß = -4.23, p = 0.003) were significantly decreased in the patients in the treatment group compared to the control group. Conclusion: The wearable low-frequency pulsed ES at the common peroneal nerve for the treatment of chronic refractory wounds showed significant improvement and were far superior compared to SWC. Future research should broaden its scope to include a diverse range of wound types and benefit from collaboration across multiple research centers.

RESUMO

H2O2 as a green oxidant plays a crucial role in numerous green chemical reactions. However, how to improve its activation and utilization efficiency as well as regulate the distribution of ROS remains a pressing challenge. In this work, a sulfur quantum dots (SQDs) modified zero-valent iron (SQDs@ZVI) was delicately designed and prepared, whose iron sites can coordinate with strongly electronegative sulfur atoms to construct highly reactive Fe-S dual active sites, for high-efficient selective H2O2 activation and utilization with potent •OH production. Experimental tests, in situ FTIR/Raman spectra and theoretical calculations demonstrated that SQDs modulates the local coordination structure and electronic density of iron centers, thus effectively enhancing its Fenton reactivity and promoting the rate-limiting H2O2 adsorption and subsequent barrierless dissociation of peroxyl bonds into •OH via the formation of bridged S-O-O-Fe complexes. Consequently, substantial generated surface-bound •OH induced by the highly reactive Fe-S dual sites enabled excellent degradation of miscellaneous organic pollutants over a broad pH range (3.0-9.0). The developed device-scale Fenton filter realized durable performance (up to 200 h), verifying the vast potential of SQDs@ZVI with diatomic sites for practical application. This work presents a promising strategy to construct metal-nonmetal diatomic active sites toward boosting selective activation and effective utilization of H2O2, which may inspire the design of efficient heterogeneous Fenton reaction for water decontamination.

RESUMO

The oil sludge produced while extracting large oil and gas fields in the middle and high latitude regions has caused serious pollution to the surrounding soil. The key to solving this problem in the future is to unify the remediation of soil and the treatment of oil sludge. This study uses supercritical carbon dioxide(scCO2) technology to construct a low-carbon method, providing a new approach to achieve this goal. The study determines the optimal extraction conditions for black calcareous soil with 15% oil content to be 55 °C, 25 MPa, and 90 min through single factor and response surface experiments. Experiments on the scCO2 extraction coupled with freeze-thaw cycles show that oil sludge with a water content of 10% can improve the extraction efficiency of scCO2 by about 2.69% after less than five freeze-thaw cycles. The study also compares the extraction efficiency of the four soils, with a difference of 6.03% observed under the same conditions. Additionally, we analyze the impact of the extraction process on changes in the properties of the oil and soil in the oil sludge. Comprehensive tests, including scanning electron microscope (SEM), nutrient detection, X-ray powder diffractometer (XRD), fourier transform infrared spectroscopy (FTIR), and Gas Chromatography (GC), have been conducted. Results show that standalone scCO2 extraction can remove up to 98.2% of petroleum hydrocarbons from the oil sludge, while simultaneously causing small changes to the soil microstructure and the crystal structure of the oil sludge. Furthermore, this process does not lead to a significant depletion of key nutrients or the generation of new pollutants.

RESUMO

Boron dipyrromethenes (BODIPYs) are some of the most popular and indispensable tetracoordinate boron compounds and have found widespread applications owing to their excellent spectroscopic and photophysical properties. BODIPYs possessing boron-stereogenic centres are scarce, and strategies for the synthesis of enantioenriched boron-stereogenic BODIPYs with structural diversity remain underdeveloped. In theory, the BODIPY core skeleton has several sites that could be decorated with different substituents. However, due to the lack of general and efficient asymmetric synthetic methods, this potential diversity of chiral BODIPYs has not been exploited. Here we demonstrate a modular enantioselective assembly of multi-substituted boron-stereogenic BODIPYs in high efficiency with excellent enantioselectivities. Key to the success is the Pd-catalysed desymmetric Suzuki cross-coupling, enabling the precise discrimination of the two α C-Cl bonds of the designed prochiral BODIPY scaffold, giving access to a wide range of highly functionalized boron-stereogenic BODIPYs. Derivatizations, photophysical properties and applications in chiral recognition of the obtained optical BODIPYs are further explored.

RESUMO

Co-infection with diverse bacteria is commonly seen in patients infected with the novel coronavirus, SARS-CoV-2. This type of co-infection significantly impacts the occurrence and development of novel coronavirus infection. Bacterial co-pathogens are typically identified in the respiratory system and blood culture, which complicates the diagnosis, treatment, and prognosis of COVID-19, and even exacerbates the severity of disease symptoms and increases mortality rates. However, the status and impact of bacterial co-infections during the COVID-19 pandemic have not been properly studied. Recently, the amount of literature on the co-infection of SARS-CoV-2 and bacteria has gradually increased, enabling a comprehensive discussion on this type of co-infection. In this study, we focus on bacterial infections in the respiratory system and blood of patients with COVID-19 because these infection types significantly affect the severity and mortality of COVID-19. Furthermore, the progression of COVID-19 has markedly elevated the antimicrobial resistance among specific bacteria, such as Klebsiella pneumoniae, in clinical settings including intensive care units (ICUs). Grasping these resistance patterns is pivotal for the optimal utilization and stewardship of antibiotics, including fluoroquinolones. Our study offers insights into these aspects and serves as a fundamental basis for devising effective therapeutic strategies. We primarily sourced our articles from PubMed, ScienceDirect, Scopus, and Google Scholar. We queried these databases using specific search terms related to COVID-19 and its co-infections with bacteria or fungi, and selectively chose relevant articles for inclusion in our review.

Assuntos

Infecções Bacterianas , COVID-19 , Coinfecção , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/mortalidade , COVID-19/complicações , Coinfecção/epidemiologia , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/mortalidade , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana

RESUMO

As the most abundant glial cells in the central nervous system (CNS), astrocytes dynamically respond to neurotoxic stress, however, the key molecular regulators controlling the inflammatory status of these sentinels during neurotoxic stress are many and complex. Herein, we demonstrate that the m6A epitranscriptomic mRNA modification tightly regulates the pro-inflammatory functions of astrocytes. Specifically, the astrocytic neurotoxic stressor, manganese (Mn), downregulated the m6A reader YTHDF2 in human and mouse astrocyte cultures and in the mouse brain. Functionally, YTHDF2 knockdown augmented, while its overexpression dampened, the neurotoxic stress-induced proinflammatory response, suggesting YTHDF2 serves as a key upstream regulator of inflammatory responses in astrocytes. Mechanistically, YTHDF2 RIP-sequencing identified MAP2K4 (MKK4; SEK1) mRNA as a YTHDF2 target influencing inflammatory signaling. Our target validation revealed that Mn-exposed astrocytes mediate proinflammatory responses by activating the phosphorylation of SEK1, JNK, and cJUN signaling. Collectively, YTHDF2 serves as a key upstream 'molecular switch' controlling SEK1(MAP2K4)-JNK-cJUN proinflammatory signaling in astrocytes.

RESUMO

RNA N6-methyladenosine (m6A) reader YTHDF1 is implicated in cancer etiology and progression. We discovered that radiotherapy (RT) increased YTHDF1 expression in dendritic cells (DCs) of PBMCs from cancer patients, but not in other immune cells tested. Elevated YTHDF1 expression of DCs was associated with poor outcomes in patients receiving RT. We found that loss of Ythdf1 in DCs enhanced the antitumor effects of ionizing radiation (IR) via increasing the cross-priming capacity of DCs across multiple murine cancer models. Mechanistically, IR upregulated YTHDF1 expression in DCs through STING-IFN-I signaling. YTHDF1 in turn triggered STING degradation by increasing lysosomal cathepsins, thereby reducing IFN-I production. We created a YTHDF1 deletion/inhibition prototype DC vaccine, significantly improving the therapeutic effect of RT and radio-immunotherapy in a murine melanoma model. Our findings reveal a new layer of regulation between YTHDF1/m6A and STING in response to IR, which opens new paths for the development of YTHDF1-targeting therapies.

RESUMO

Brown adipose tissue (BAT) regulates systemic metabolism by releasing signaling lipids. N6-methyladenosine (m6A) is the most prevalent and abundant post-transcriptional mRNA modification and has been reported to regulate BAT adipogenesis and energy expenditure. Here, we demonstrate that the absence of m6A methyltransferase-like 14 (METTL14) modifies the BAT secretome to improve systemic insulin sensitivity independent of UCP1. Using lipidomics, we identify prostaglandin E2 (PGE2) and prostaglandin F2a (PGF2a) as BAT-secreted insulin sensitizers. PGE2 and PGF2a inversely correlate with insulin sensitivity in humans and protect mice from high-fat-diet-induced insulin resistance by suppressing specific AKT phosphatases. Mechanistically, METTL14-mediated m6A promotes the decay of PTGES2 and CBR1, the genes encoding PGE2 and PGF2a biosynthesis enzymes, in brown adipocytes via YTHDF2/3. Consistently, BAT-specific knockdown of Ptges2 or Cbr1 reverses the insulin-sensitizing effects in M14KO mice. Overall, these findings reveal a novel biological mechanism through which m6A-dependent regulation of the BAT secretome regulates systemic insulin sensitivity.

Assuntos

Adenosina , Tecido Adiposo Marrom , Resistência à Insulina , Camundongos Endogâmicos C57BL , RNA Mensageiro , Transdução de Sinais , Proteína Desacopladora 1 , Animais , Tecido Adiposo Marrom/metabolismo , Camundongos , Adenosina/análogos & derivados , Adenosina/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Metilação , Proteína Desacopladora 1/metabolismo , Proteína Desacopladora 1/genética , Masculino , Humanos , Prostaglandinas/metabolismo , Metiltransferases/metabolismo , Metiltransferases/genética , Dieta Hiperlipídica , Camundongos Knockout , Dinoprostona/metabolismo

RESUMO

In this study, we prepared a low-cost novel Cu/Cu2O/BC nanocomposite visible-light photocatalyst by the impregnation method using CuSO4·5H2O and rice husk biochar (BC) as raw materials and Na2S2O4 as a single reductant to improve the stability and dispersion of the Cu/Cu2O nanoparticles, in order to solve their aggregation tendency during photocatalysis. The morphology and structure of the Cu/Cu2O/BC were characterized using various analytical and spectroscopic techniques. The photocatalytic effect and cyclic stability of the synthesized photocatalyst on methyl orange (MO) removal were investigated under visible light radiation and various parameter conditions, including the mass ratio of BC to Cu/Cu2O, initial MO concentration, pH, temperature, and catalyst dosage. The results show that the synthesized Cu/Cu2O/BC nanocomposite composed of Cu/Cu2O spherical particles was loaded on the BC carrier, which has better stability and dispersion. The best adsorption-photocatalytic effect of the Cu/Cu2O/BC is exhibited when the mass ratio of BC to Cu/Cu2O is 0.2. A total of 100 mg of Cu/Cu2O/BC can remove 95% of the MO and 88.26% of the COD in the aqueous solution at pH = 6, T = 25 °C, and an initial MO concentration of 100 mg/L. After five cycles of degradation, the MO degradation rate in the sample can still remain at 78.41%. Both the quasi-secondary kinetic model and the Langmuir isothermal adsorption model describe the adsorption process. Additionally, the thermodynamic analysis demonstrates that the photocatalytic process follows the quasi-primary kinetic model and that the removal process is of spontaneous heat absorption. The photocatalyst described in this paper offers a cost-effective, easily prepared, and visible-light-responsive solution for water pollution treatment.

RESUMO

Redox-inactive metal-ion-driven modulation of the oxidation behavior of high-valent metal-oxo complex has garnered significant interest in biological and chemical synthesis; however, their role in permanganate (Mn(VII)) oxidation for the removal of organic pollutants has been largely neglected. Here, we uncover the impact of six metal ions (i.e., Ca2+, Mg2+, Ni2+, Zn2+, Al3+, and Sc3+) presenting in water environments on Mn(VII) activity. These ions uniformly boost the electron and oxygen transfer capabilities of Mn(VII) while impeding proton transfer, as evidenced by electrochemical tests, thioanisole probe analysis, and the kinetic isotope effect. The observed effects are intricately linked to the Lewis acidity of the metal ions. Further mechanistic insights reveal that Mn(VII) can interact with metal ions without direct reduction. Such interactions modify the electronic configuration of Mn(VII) and create an acidic microenvironment, thus increasing its electrophilicity and the energy barrier for the abstraction of proton from organic substrates. More importantly, the efficacy of Mn(VII) in removing phenolic pollutants is regulated by these ions through changing the driving force for proton and electron transfer, i.e., facilitated at pH > 4.5 and inhibited at lower pH. The contribution of active Mn intermediates is also discussed to reveal the oxidative mechanism of the metal ion/Mn(VII) system. These findings not only facilitate the rational design of Mn(VII) oxidation conditions in the presence of metal ions for water decontamination but also offer an alternative paradigm for enhancing electrophilic oxidation.

RESUMO

N6-methyladenosine (m6A) is the most abundant chemical modification in mRNA and plays important roles in human and mouse embryonic stem cell pluripotency, maintenance, and differentiation. We have recently reported that m6A is involved in the postnatal control of ß-cell function in physiological states and in type 1 and 2 diabetes. However, the precise mechanisms by which m6A acts to regulate the development of human and mouse pancreas are unexplored. Here, we show that the m6A landscape is dynamic during human pancreas development, and that METTL14, one of the m6A writer complex proteins, is essential for the early differentiation of both human and mouse pancreatic cells.

RESUMO

Plants employ distinct mechanisms to respond to environmental changes. Modification of mRNA by N 6-methyladenosine (m6A), known to affect the fate of mRNA, may be one such mechanism to reprogram mRNA processing and translatability upon stress. However, it is difficult to distinguish a direct role from a pleiotropic effect for this modification due to its prevalence in RNA. Through characterization of the transient knockdown-mutants of m6A writer components and mutants of specific m6A readers, we demonstrate the essential role that m6A plays in basal resistance and pattern-triggered immunity (PTI). A global m6A profiling of mock and PTI-induced Arabidopsis plants as well as formaldehyde fixation and cross-linking immunoprecipitation-sequencing of the m6A reader, EVOLUTIONARILY CONSERVED C-TERMINAL REGION2 (ECT2) showed that while dynamic changes in m6A modification and binding by ECT2 were detected upon PTI induction, most of the m6A sites and their association with ECT2 remained static. Interestingly, RNA degradation assay identified a dual role of m6A in stabilizing the overall transcriptome while facilitating rapid turnover of immune-induced mRNAs during PTI. Moreover, polysome profiling showed that m6A enhances immune-associated translation by binding to the ECT2/3/4 readers. We propose that m6A plays a positive role in plant immunity by destabilizing defense mRNAs while enhancing their translation efficiency to create a transient surge in the production of defense proteins.

Assuntos

Adenosina , Proteínas de Arabidopsis , Arabidopsis , Regulação da Expressão Gênica de Plantas , Imunidade Vegetal , Biossíntese de Proteínas , Estabilidade de RNA , RNA Mensageiro , Arabidopsis/genética , Arabidopsis/imunologia , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Imunidade Vegetal/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Doenças das Plantas/imunologia , Doenças das Plantas/genética , RNA de Plantas/genética , RNA de Plantas/metabolismo , Reconhecimento da Imunidade Inata

RESUMO

Recent insights have identified adrenergic (ADRN) and mesenchymal (MES) cell lineages as distinct biologic cell types and T-cell inflammation as a prognostic marker in neuroblastoma. We hypothesized that elucidating unique and overlapping aspects of these biologic features could serve as novel biomarkers for informing ongoing efforts to improve therapeutic approaches for children with high-risk neuroblastoma. We identified lineage-specific, single-stranded super-enhancers to define ADRN and MES specific genes. Publicly available RNA-seq of diagnostic tumor biopsies was used in Discovery and Validation cohorts. Each tumor was assigned a relative MES score and T-cell inflammation (TCI) score. Survival was assessed using the Kaplan-Meier method, and differences were assessed by the log-rank test. Inflammation scores were correlated with MES scores and anticorrelated with MYCN-amplification in both cohorts. Among patients with high-risk, ADRN tumors, those with TCI tumors had superior overall survival to those with non-inflamed tumors. A similar, but nonsignificant, trend was observed in the Validation cohort. Conversely, there was no difference according to TCI status in the MES cohort in either the Discover or Validation cohorts. High-inflammation scores were correlated with improved survival in some patients with high-risk, ADRN but not MES neuroblastoma. Our findings bolster support for further developing T-cell-based and immunotherapy-based approaches for children with high-risk neuroblastoma of varying MES and ADRN expression. SIGNIFICANCE: Adrenergic (ADRN) and mesenchymal (MES) lineages are distinct biologic cell types in neuroblastoma. We defined ADRN and MES specific genes and found that high-risk, ADRN tumors harboring elevated T-cell inflammation signatures had superior overall survival. Our findings bolster support for further developing immunotherapy-based approaches for children with high-risk neuroblastoma.

Assuntos

Inflamação , Neuroblastoma , Linfócitos T , Humanos , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Neuroblastoma/imunologia , Neuroblastoma/genética , Inflamação/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Prognóstico , Masculino , Feminino , Pré-Escolar , Biomarcadores Tumorais/genética , Lactente , Criança , Regulação Neoplásica da Expressão Gênica

RESUMO

Animals adapt to environmental challenges with long-term changes at the behavioral, circuit, cellular, and synaptic levels which often require new protein synthesis. The discovery of reversible N6-methyladenosine (m6A) modifications of mRNA has revealed an important layer of post-transcriptional regulation which affects almost every phase of mRNA metabolism and therefore translational control. Many in vitro and in vivo studies have demonstrated the significant role of m6A in cell differentiation and survival, but its role in adult neurons is understudied. We used cell-type specific gene deletion of Mettl14, which encodes one of the subunits of the m6A methyltransferase, and Ythdf1, which encodes one of the cytoplasmic m6A reader proteins, in dopamine D1 receptor expressing or D2 receptor expressing neurons. Mettl14 or Ythdf1 deficiency blunted responses to environmental challenges at the behavioral, cellular, and molecular levels. In three different behavioral paradigms, gene deletion of either Mettl14 or Ythdf1 in D1 neurons impaired D1-dependent learning, whereas gene deletion of either Mettl14 or Ythdf1 in D2 neurons impaired D2-dependent learning. At the cellular level, modulation of D1 and D2 neuron firing in response to changes in environments was blunted in all three behavioral paradigms in mutant mice. Ythdf1 deletion resembled impairment caused by Mettl14 deletion in a cell type-specific manner, suggesting YTHDF1 is the main mediator of the functional consequences of m6A mRNA methylation in the striatum. At the molecular level, while striatal neurons in control mice responded to elevated cAMP by increasing de novo protein synthesis, striatal neurons in Ythdf1 knockout mice didn't. Finally, boosting dopamine release by cocaine drastically increased YTHDF1 binding to many mRNA targets in the striatum, especially those that encode structural proteins, suggesting the initiation of long-term neuronal and/or synaptic structural changes. While the m6A-YTHDF1 pathway has similar functional significance at cellular level, its cell type specific deficiency in D1 and D2 neurons often resulted in contrasting behavioral phenotypes, allowing us to cleanly dissociate the opposing yet cooperative roles of D1 and D2 neurons.

RESUMO

Cancer is generally defined as a disease of aging. With aging, the composition, diversity and functional characteristics of the gut microbiota occur changes, with a decline of beneficial commensal microbes triggered by intrinsic and extrinsic factors (e.g., diet, drugs and chronic health conditions). Nowadays, dysbiosis of the gut microbiota is recognized as a hallmark of cancer. At the same time, aging is accompanied by changes in innate and adaptive immunity, known as immunosenescence, as well as chronic low-grade inflammation, known as inflammaging. The elevated cancer incidence and mortality in the elderly are linked with aging-associated alterations in the gut microbiota that elicit systemic metabolic alterations, leading to immune dysregulation with potentially tumorigenic effects. The gut microbiota and immunosenescence might both affect the response to treatment in cancer patients. In-depth understanding of age-associated alterations in the gut microbiota and immunity will shed light on the risk of cancer development and progression in the elderly. Here, we describe the aging-associated changes of the gut microbiota in cancer, and review the evolving understanding of the gut microbiota-targeted intervention strategies. Furthermore, we summarize the knowledge on the cellular and molecular mechanisms of immunosenescence and its impact on cancer. Finally, we discuss the latest knowledge about the relationships between gut microbiota and immunosenescence, with implications for cancer therapy. Intervention strategies targeting the gut microbiota may attenuate inflammaging and rejuvenate immune function to provide antitumor benefits in elderly patients.

Assuntos

Microbioma Gastrointestinal , Imunossenescência , Neoplasias , Humanos , Microbioma Gastrointestinal/imunologia , Neoplasias/imunologia , Neoplasias/microbiologia , Neoplasias/etiologia , Imunossenescência/imunologia , Animais , Envelhecimento/imunologia , Disbiose/imunologia , Disbiose/microbiologia

RESUMO

As a type of reactive oxygen species, hypochlorous acid (ClO-) plays an important role in sterilization, disinfection and protection in organisms. However, excessive production of ClO- is closely related to various diseases. In this work, we have designed a robust ratiometric fluorescent probe, RDB-ClO, using the excited-state intramolecular proton transfer (ESIPT) strategy. RDB-ClO was achieved by modifying 2-(2-(benzo[d]thiazol-2-yl)-6-(diethylamino)-3-oxo-3H-xanthen-9-yl) benzoic acid (RDB-OH) with a 1-naphthoyl chloride group, specifically for the sensitive detection of ClO-. In the presence of ClO-, RDB-ClO demonstrated relatively good performance, showing swift response time (35 s), low detection limit of 5.1 nM and high selectivity towards ClO-. Notably, the convenience and accessibility detection of ClO- has been implemented using test strip and agarose probe. RDB-ClO effectively tracked both endogenous and exogenous ClO- in HeLa cells, HepG2 cells and zebrafish. Additionally, it is successfully applied to detect changes of exogenous ClO- content in E. coli. and acetaminophen (APAP)-induced liver injury in mice. The development of RDB-ClO represents a promising molecular tool for studying the pathogenesis of DILI and biotransformation of ClO- in bacteria.

Assuntos

Doença Hepática Induzida por Substâncias e Drogas , Corantes Fluorescentes , Ácido Hipocloroso , Peixe-Zebra , Corantes Fluorescentes/química , Animais , Humanos , Células HeLa , Ácido Hipocloroso/análise , Ácido Hipocloroso/metabolismo , Células Hep G2 , Camundongos , Escherichia coli/efeitos dos fármacos , Espectrometria de Fluorescência , Limite de Detecção

RESUMO

The pollutants such as heavy metals, organic matter, and nitrates in soil and water pose challenges to environmental remediation technology. Nano zero valent iron has shown enormous potential in the field of environmental remediation due to its excellent adsorption performance. By using carbon based materials, rock minerals, biomolecules, etc., as supporting materials for nZVI, and through structural and performance modifications, its performance has been successfully optimized, reducing defects such as aggregation and easy oxidation of the material. This article compares and summarizes the modification effects of different loadings on nZVI, and comprehensively reviews the latest progress, preparation methods, and application of nZVI particles in soil and water remediation. Specifically, this article explores in detail the impact and mechanism of nZVI particles in commonly used antibiotics contaminated environments. Firstly, the combination methods of different types of materials with zero valent iron, as well as the synthesis methods and application scenarios of nZVI, were integrated. Secondly, the interaction mechanism between pollutants and nZVI was introduced in detail, including adsorption, redox reactions, and co-precipitation. Subsequently, environmental factors that affect repair efficiency were emphasized, such as pH value, coexisting components, oxygen, contact time, and temperature. Finally, the challenges faced by the application of nZVI in actual polluted soil and water bodies, as well as the prospects for its long-term efficacy and safety evaluation, are proposed to promote further development in the future.