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S-adenosylmethionine (SAM) is the methyl-donor substrate for DNA and histone methyltransferases that regulate epigenetic states and subsequent gene expression. This metabolism-epigenome link sensitizes chromatin methylation to altered SAM abundance, yet the mechanisms that allow organisms to adapt and protect epigenetic information during life-experienced fluctuations in SAM availability are unknown. We identified a robust response to SAM depletion that is highlighted by preferential cytoplasmic and nuclear mono-methylation of H3 Lys 9 (H3K9) at the expense of broad losses in histone di- and tri-methylation. Under SAM-depleted conditions, H3K9 mono-methylation preserves heterochromatin stability and supports global epigenetic persistence upon metabolic recovery. This unique chromatin response was robust across the mouse lifespan and correlated with improved metabolic health, supporting a significant role for epigenetic adaptation to SAM depletion in vivo. Together, these studies provide evidence for an adaptive response that enables epigenetic persistence to metabolic stress.
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Metilação de DNA/genética , Heterocromatina/genética , Metaboloma/genética , S-Adenosilmetionina/metabolismo , Animais , Núcleo Celular/genética , Núcleo Celular/metabolismo , Cromatina/genética , Citoplasma/genética , Citoplasma/metabolismo , Epigênese Genética/genética , Regulação da Expressão Gênica/genética , Células HCT116 , Heterocromatina/metabolismo , Histona-Lisina N-Metiltransferase/genética , Histonas/genética , Humanos , Metionina/genética , Camundongos , Processamento de Proteína Pós-Traducional/genética , Proteômica/métodosRESUMO
Chromophobe (Ch) renal cell carcinoma (RCC) arises from the intercalated cell in the distal nephron. There are no proven treatments for metastatic ChRCC. A distinguishing characteristic of ChRCC is strikingly high levels of reduced (GSH) and oxidized (GSSG) glutathione. Here, we demonstrate that ChRCC-derived cells exhibit higher sensitivity to ferroptotic inducers compared with clear-cell RCC. ChRCC-derived cells are critically dependent on cystine via the cystine/glutamate antiporter xCT to maintain high levels of glutathione, making them sensitive to inhibitors of cystine uptake and cyst(e)inase. Gamma-glutamyl transferase 1 (GGT1), a key enzyme in glutathione homeostasis, is markedly suppressed in ChRCC relative to normal kidney. Importantly, GGT1 overexpression inhibits the proliferation of ChRCC cells in vitro and in vivo, suppresses cystine uptake, and decreases levels of GSH and GSSG. Collectively, these data identify ferroptosis as a metabolic vulnerability in ChRCC, providing a potential avenue for targeted therapy for these distinctive tumors.
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Sistema y+ de Transporte de Aminoácidos , Carcinoma de Células Renais , Cistina , Ferroptose , Glutationa , Neoplasias Renais , Sistema y+ de Transporte de Aminoácidos/metabolismo , Transporte Biológico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Cistina/metabolismo , Glutationa/metabolismo , Dissulfeto de Glutationa/deficiência , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Terapia de Alvo Molecular , gama-Glutamiltransferase/metabolismoRESUMO
Low-protein (LP) diets are associated with a decreased risk of diabetes in humans, and promote leanness and glycaemic control in both rodents and humans. While the effects of an LP diet on glycaemic control are mediated by reduced levels of the branched-chain amino acids, we have observed that reducing dietary levels of the other six essential amino acids leads to changes in body composition. Here, we find that dietary histidine plays a key role in the response to an LP diet in male C57BL/6J mice. Specifically reducing dietary levels of histidine by 67% reduces the weight gain of young, lean male mice, reducing both adipose and lean mass without altering glucose metabolism, and rapidly reverses diet-induced obesity and hepatic steatosis in diet-induced obese male mice, increasing insulin sensitivity. This normalization of metabolic health was associated not with caloric restriction or increased activity, but with increased energy expenditure. Surprisingly, the effects of histidine restriction do not require the energy balance hormone Fgf21. Histidine restriction that was started in midlife promoted leanness and glucose tolerance in aged males but not females, but did not affect frailty or lifespan in either sex. Finally, we demonstrate that variation in dietary histidine levels helps to explain body mass index differences in humans. Overall, our findings demonstrate that dietary histidine is a key regulator of weight and body composition in male mice and in humans, and suggest that reducing dietary histidine may be a translatable option for the treatment of obesity. KEY POINTS: Protein restriction (PR) promotes metabolic health in rodents and humans and extends rodent lifespan. Restriction of specific individual essential amino acids can recapitulate the benefits of PR. Reduced histidine promotes leanness and increased energy expenditure in male mice. Reduced histidine does not extend the lifespan of mice when begun in midlife. Dietary levels of histidine are positively associated with body mass index in humans.
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Histidina , Magreza , Masculino , Humanos , Animais , Camundongos , Idoso , Histidina/metabolismo , Camundongos Endogâmicos C57BL , Dieta , Obesidade/metabolismo , Proteínas , Metabolismo EnergéticoRESUMO
Solid-electrolyte interphases (SEIs) in advanced rechargeable batteries ensure reversible electrode reactions at extreme potentials beyond the thermodynamic stability limits of electrolytes by insulating electrons while allowing the transport of working ions. Such selective ion transport occurs naturally in biological cell membranes as a ubiquitous prerequisite of many life processes and a foundation of biodiversity. In addition, cell membranes can selectively open and close the ion channels in response to external stimuli (e.g., electrical, chemical, mechanical, and thermal), giving rise to "gating" mechanisms that help manage intracellular reactions. We wondered whether the chemistry and structure of SEIs can mimic those of cell membranes, such that ion gating can be replicated. That is, can SEIs realize a reversible switching between two electrochemical behaviors, i.e., the ion intercalation chemistry of batteries and the ion adsorption of capacitors? Herein, we report such SEIs that result in thermally activated selective ion transport. The function of open/close gate switches is governed by the chemical and structural dynamics of SEIs under different thermal conditions, with precise behaviors as conducting and insulating interphases that enable battery and capacitive processes within a finite temperature window. Such an ion gating function is synergistically contributed by Arrhenius-activated ion transport and SEI dissolution/regrowth. Following the understanding of this new mechanism, we then develop an electrochemical method to heal the SEI layer in situ. The knowledge acquired in this work reveals the possibility of hitherto unknown biomimetic properties of SEIs, which will guide us to leverage such complexities to design better SEIs for future battery chemistries.
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We report a pulse Fe: ZnSe laser pumped by an optical chopper Q-switched Er: YAG laser. By analyzed the spatial and temporal match of the gain and chopper, the maximum energy of the optical chopper Q-switched Er: YAG laser is 31mJ with the pulse width of 165â ns. By employing this Er: YAG laser as pump laser of Fe: ZnSe crystal, the maximum output energy of Fe: ZnSe laser is 10mJ with the pulse width of 80â ns at room temperature, that is the maximum energy of Fe: ZnSe laser at this Q-switched system to the best of our knowledge. We also study the directly Q-switched Fe: ZnSe laser, and the 2.7mJ mid-infrared laser with the pulse width of 200â ns is obtained at 80â K.
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With the increasing concerns of food safety and public health, tremendous efforts have been concentrated on the development of effective, reliable, nondestructive methods to evaluate the freshness level of different kinds of food. Natural colorants-based intelligent colorimetric indicators which are typically constructed with natural colorants and polymer matrices has been regarded as an innovative approach to notify the customers and retailers of the food quality during the storage and transportation procedure in real-time. This review briefly elucidates the mechanism of natural colorants used for intelligent colorimetric indicators and fabrication methodologies of natural colorants-based food freshness indicators. Subsequently, their multifunctional applications in intelligent food packaging systems like antioxidant packaging, antimicrobial packaging, biodegradable packaging, UV-blocking packaging and inkless packaging are well introduced. This paper also summarizes several optimizing strategies for the practical application of this advanced technology from different perspectives. Strategies like adopting a hydrophobic matrix, constructing double-layer film and encapsulation have been developed to improve the stability of the indicators. Co-pigmentation, metal ion complexation, pigment-mixing and using substrates with high surface area are proved to be effective to enhance the sensitivity of the indicators. Approaches include multi-index evaluation, machine learning and smartphone-assisted evaluation have been proven to improve the accuracy of the intelligent food freshness indicators. Finally, future research opportunities and challenges are proposed. Based on the fundamental understanding of natural colorants-based intelligent colorimetric food freshness indicators, and the latest research and findings from literature, this review article will help to develop better, lower cost and more reliable food freshness evaluation technique for modern food industry.
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Recent work has begun to investigate the role of protein damage in cell death because of ionizing radiation (IR) exposure, but none have been performed on a proteome-wide basis, nor have they utilized MS (MS) to determine chemical identity of the amino acid side chain alteration. Here, we use Escherichia coli to perform the first MS analysis of IR-treated intact cells on a proteome scale. From quintuplicate IR-treated (1000 Gy) and untreated replicates, we successfully quantified 13,262 peptides mapping to 1938 unique proteins. Statistically significant, but low in magnitude (<2-fold), IR-induced changes in peptide abundance were observed in 12% of all peptides detected, although oxidative alterations were rare. Hydroxylation (+15.99 Da) was the most prevalent covalent adduct detected. In parallel with these studies on E. coli, identical experiments with the IR-resistant bacterium, Deinococcus radiodurans, revealed orders of magnitude less effect of IR on the proteome. In E. coli, the most significant target of IR by a wide margin was glyceraldehyde 3'-phosphate dehydrogenase (GAPDH), in which the thiol side chain of the catalytic Cys residue was oxidized to sulfonic acid. The same modification was detected in IR-treated human breast carcinoma cells. Sensitivity of GAPDH to reactive oxygen species (ROS) has been described previously in microbes and here, we present GAPDH as an immediate, primary target of IR-induced oxidation across all domains of life.
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Escherichia coli/metabolismo , Escherichia coli/efeitos da radiação , Proteômica , Radiação Ionizante , Sequência de Aminoácidos , Aminoácidos/metabolismo , Domínio Catalítico , Deinococcus/metabolismo , Deinococcus/efeitos da radiação , Hidroxilação , Peso Molecular , Oxirredução/efeitos da radiação , Peptídeos/química , Peptídeos/metabolismo , Proteólise/efeitos da radiação , Proteoma/metabolismoRESUMO
BACKGROUND: Concurrent chemoradiotherapy is the common first-line treatment for patients with advanced cervical cancer. However, radioresistance remains a major clinical challenge, which results in recurrence and poor survival. Many studies have shown the potential of Delta-like Ligand 4 (DLL4) as a novel prognostic biomarker and therapeutic target in many solid tumors. Previously, we have found that high DLL4 expression in tumor cells may predict the pelvic lymph node metastasis and poor prognosis in patients with cervical cancer. In our present study, we further studied the effects of DLL4 on the biological behavior and radiosensitivity of cervical cancer cells. METHODS: The expression of DLL4 and epithelial-mesenchymal transition (EMT) phenotype markers in cervical cancer cell lines or tissues were detected using Western blotting, and the expression of DLL4 mRNA in cervical cancer cell lines or tissues was detected using Quantitative real-time PCR. The effect of DLL4 on cell proliferation, migration, and radiosensitivity was evaluated using the CCK8 assay, flow cytometry, Transwell assays for cell invasion and migration, and Immunofluorescence staining in vitro. RESULTS: The expression of DLL4 in radiotherapy-resistant SiHa cells was significantly higher than that in radiotherapy-sensitive Me-180 cells. Furthermore, downregulation of DLL4 enhanced the radiosensitivity of SiHa and Caski cells via the inhibition of cell proliferation, promotion of radiation-induced apoptosis, and inhibition of the DNA damage repair. Moreover, downregulation of DLL4 inhibited the EMT and reduced the proliferation, invasion, and migration ability in SiHa and Caski cells. Consistent with the DLL4 expression in the cell lines, the expression of DLL4 in the tissues of the radioresistant group was also higher than that of the radiosensitive group. CONCLUSIONS: Downregulation of DLL4 inhibited the progression and increased the radiosensitivity in cervical cancer cells by reversing EMT. These results indicated the promising prospect of DLL4 against the radioresistance and metastasis of cervical cancer and its potential as a predictive biomarker for radiosensitivity and prognosis in patients with cervical cancer patients receiving concurrent chemoradiotherapy (cCRT).
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We present a pulse linearly polarized diode-pumped cesium-vapor laser (Cs-DPAL) based on an acousto-optical modulator (AOM) for the first time. The continuous wave (CW) performance of the Cs-DPAL was first investigated, and ~1.05 W linearly polarized CW laser was obtained. Next, we applied a rectangular signal to modulate the AOM. The Cs-DPAL realized a pulse laser output with a maximum repetition rate of 1 MHz and minimum pulse duration of 238 ns. To the best of our knowledge, this is the highest repetition rate reported thus far for a diode-pumped alkali-vapor laser (DPAL). The maximum output power of the pulse laser reached ~0.20 W, and the corresponding Mx 2 and My 2 factors were 1.31 and 1.19, respectively. Finally, we realized code modulation of the Cs-DPAL, with a maximum bit rate of 2 Mb/s.
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Obesity and diabetes are major challenges to global health, and there is an urgent need for interventions that promote weight loss. Dietary restriction of methionine promotes leanness and improves metabolic health in mice and humans. However, poor long-term adherence to this diet limits its translational potential. In this study, we develop a short-term methionine deprivation (MD) regimen that preferentially reduces fat mass, restoring normal body weight and glycemic control to diet-induced obese mice of both sexes. The benefits of MD do not accrue from calorie restriction, but instead result from increased energy expenditure. MD promotes increased energy expenditure in a sex-specific manner, inducing the fibroblast growth factor (Fgf)-21-uncoupling protein (Ucp)-1 axis only in males. Methionine is an agonist of the protein kinase mechanistic target of rapamycin complex (mTORC)-1, which has been proposed to play a key role in the metabolic response to amino acid-restricted diets. In our study, we used a mouse model of constitutive hepatic mTORC1 activity and demonstrate that suppression of hepatic mTORC1 signaling is not required for the metabolic effects of MD. Our study sheds new light on the mechanisms by which dietary methionine regulates metabolic health and demonstrates the translational potential of MD for the treatment of obesity and type 2 diabetes.-Yu, D., Yang, S. E., Miller, B. R., Wisinski, J. A., Sherman, D. S., Brinkman, J. A., Tomasiewicz, J. L., Cummings, N. E., Kimple, M. E., Cryns, V. L., Lamming, D. W. Short-term methionine deprivation improves metabolic health via sexually dimorphic, mTORC1-independent mechanisms.
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Metabolismo Energético , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Metionina/deficiência , Obesidade/metabolismo , Caracteres Sexuais , Animais , Restrição Calórica , Feminino , Fatores de Crescimento de Fibroblastos/metabolismo , Masculino , Camundongos , Obesidade/dietoterapia , Obesidade/patologia , Proteína Desacopladora 1/metabolismoRESUMO
KEY POINTS: We recently found that feeding healthy mice a diet with reduced levels of branched-chain amino acids (BCAAs), which are associated with insulin resistance in both humans and rodents, modestly improves glucose tolerance and slows fat mass gain. In the present study, we show that a reduced BCAA diet promotes rapid fat mass loss without calorie restriction in obese mice. Selective reduction of dietary BCAAs also restores glucose tolerance and insulin sensitivity to obese mice, even as they continue to consume a high-fat, high-sugar diet. A low BCAA diet transiently induces FGF21 (fibroblast growth factor 21) and increases energy expenditure. We suggest that dietary protein quality (i.e. the precise macronutrient composition of dietary protein) may impact the effectiveness of weight loss diets. ABSTRACT: Obesity and diabetes are increasing problems around the world, and although even moderate weight loss can improve metabolic health, reduced calorie diets are notoriously difficult to sustain. Branched-chain amino acids (BCAAs; leucine, isoleucine and valine) are elevated in the blood of obese, insulin-resistant humans and rodents. We recently demonstrated that specifically reducing dietary levels of BCAAs has beneficial effects on the metabolic health of young, growing mice, improving glucose tolerance and modestly slowing fat mass gain. In the present study, we examine the hypothesis that reducing dietary BCAAs will promote weight loss, reduce adiposity, and improve blood glucose control in diet-induced obese mice with pre-existing metabolic syndrome. We find that specifically reducing dietary BCAAs rapidly reverses diet-induced obesity and improves glucoregulatory control in diet-induced obese mice. Most dramatically, mice eating an otherwise unhealthy high-calorie, high-sugar Western diet with reduced levels of BCAAs lost weight and fat mass rapidly until regaining a normal weight. Importantly, this normalization of weight was mediated not by caloric restriction or increased activity, but by increased energy expenditure, and was accompanied by a transient induction of the energy balance regulating hormone FGF21 (fibroblast growth factor 21). Consumption of a Western diet reduced in BCAAs was also accompanied by a dramatic improvement in glucose tolerance and insulin resistance. Our results link dietary BCAAs with the regulation of metabolic health and energy balance in obese animals, and suggest that specifically reducing dietary BCAAs may represent a highly translatable option for the treatment of obesity and insulin resistance.
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Aminoácidos de Cadeia Ramificada/administração & dosagem , Aminoácidos de Cadeia Ramificada/metabolismo , Diabetes Mellitus Tipo 2/prevenção & controle , Dieta/efeitos adversos , Obesidade/prevenção & controle , Animais , Glicemia/análise , Restrição Calórica , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Metabolismo Energético , Fatores de Crescimento de Fibroblastos/metabolismo , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/metabolismo , Redução de PesoRESUMO
The cross-section is crucial for quantitative characterization and analysis of the absorption process. A model on the absorption cross-section of the simultaneous two-photon excitation in Rb-vapor four-wave mixing process is established by using the coupled-wave equation. Taken into account of the hyperfine structures for 85Rb and 87Rb, the third-order susceptibility and hyperfine line strength are calculated respectively. Then, the influences of hyperfine transition on cross section are investigated and simulation results agree well with the experiment results. The calculated results suggest that high pumping power intensity is essential in Rb two-photon excitation, while narrow linewidth is the limiting factor of high absorption efficiency by comparing normalized absorption profile between pumping beam and two-photon excitation process. Additionally, two approaches to improving absorption efficiency, linewidth narrowness of the pumping beam and absorption linewidth broadening, are proposed.
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In recent years, ternary transition metal oxides (TTMOs), especially spinel type TTMOs have attracted widespread attention as promising candidates for electrode materials. Among all of the popular TTMOs, MgCo2 O4 is an outstanding one, owing to its superior theoretical capacitance. In this work, MgCo2 O4 nanosheet arrays (NSAs) grown directly on nickel foams were fabricated through a facile hydrothermal process at 120 °C for 4â h. With a series of structural and morphological characterization techniques, it was found that the ethanol played a key role in controlling the composition and morphology during the synthesis process. The MgCo2 O4 NSAs exhibited a superior specific capacitance of 853.06â C g-1 (at 1â mA cm-2 ) and enhanced cycling performance, with 94.65 % of initial capacitance retained after 3000â cycles when used as a binder-free integrated electrode for electrochemical supercapacitors; much higher than other reported data for MgCo2 O4 as well. The excellent electrochemical properties mainly came from the unique morphology of the MgCo2 O4 NSAs. This study will demonstrate the applications of MgCo2 O4 NSAs based large-scale supercapacitors grown on low-cost nickel foams.
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Tissue proteomics is increasingly recognized for its role in biomarker discovery and disease mechanism investigation. However, protein solubility remains a significant challenge in mass spectrometry (MS)-based tissue proteomics. Conventional surfactants such as sodium dodecyl sulfate (SDS), the preferred surfactant for protein solubilization, are not compatible with MS. Herein, we have screened a library of surfactant-like compounds and discovered an MS-compatible degradable surfactant (MaSDeS) for tissue proteomics that solubilizes all categories of proteins with performance comparable to SDS. The use of MaSDeS in the tissue extraction significantly improves the total number of protein identifications from commonly used tissues, including tissue from the heart, liver, and lung. Notably, MaSDeS significantly enriches membrane proteins, which are often under-represented in proteomics studies. The acid degradable nature of MaSDeS makes it amenable for high-throughput MS-based proteomics. In addition, the thermostability of MaSDeS allows for its use in experiments requiring high temperature to facilitate protein extraction and solubilization. Furthermore, we have shown that MaSDeS outperforms the other MS-compatible surfactants in terms of overall protein solubility and the total number of identified proteins in tissue proteomics. Thus, the use of MaSDeS will greatly advance tissue proteomics and realize its potential in basic biomedical and clinical research. MaSDeS could be utilized in a variety of proteomics studies as well as general biochemical and biological experiments that employ surfactants for protein solubilization.
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Espectrometria de Massas/métodos , Proteômica , Tensoativos/química , Animais , SuínosRESUMO
Two novel thermo-responsive polymer brushes were prepared from L-alanine derivatives using the surface-initiated atom transfer radical polymerization (SI-ATRP) technique. The temperature-induced cell capture and release on both polymer brush modified substrates were further explored.
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Acrilamidas/química , Alanina/análogos & derivados , Materiais Biocompatíveis/química , Molhabilidade , Adesão Celular , Linhagem Celular Tumoral , Humanos , Polimerização , TemperaturaRESUMO
Polymer electrolytes have received tremendous interest in the development of solid-state batteries, but often fall short in one or more key properties required for practical applications. Herein, a rigid gel polymer electrolyte prepared by immobilizing a liquid mixture of a lithium salt and poly(ethylene glycol) dimethyl ether with only 8 wt% poly(2,2'-disulfonyl-4,4'-benzidine terephthalamide) (PBDT) is reported. The high charge density and rigid double helical structure of PBDT lead to formation of a nanofibrillar structure that endows this electrolyte with stronger mechanical properties, wider temperature window, and higher battery rate capability compared to all other poly(ethylene oxide) (PEO)-based electrolytes. The ion transport mechanism in this rigid polymer electrolyte is systematically studied using multiple complementary techniques. Li/LiFePO4 cells show excellent capacity retention over long-term cycling, with thermal cycling reversibility between ambient temperature and elevated temperatures, demonstrating compelling potential for solid-state batteries targeting fast charging at high temperatures and slower discharging at ambient temperature.
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Obesity has become a serious global public health risk threatening millions of people. In this study, the astaxanthin-anthocyanin nanoparticles (AXT-ACN NPs) were used to investigate their effects on the lipid accumulation and antioxidative capacity of the high-sugar-diet-induced high-fat Caenorhabditis elegans (C. elegans). It can be found that the lifespan, motility, and reproductive capacity of the high-fat C. elegans were significantly decreased compared to the normal nematodes in the control group. However, treatment of high-fat C. elegans with AXT-ACN NPs resulted in a prolonged lifespan of 35 days, improved motility, and a 22.06% increase in total spawn production of the nematodes. Furthermore, AXT-ACN NPs were found to effectively extend the lifespan of high-fat C. elegans under heat and oxidative stress conditions. Oil-red O staining results also demonstrated that AXT-ACN NPs have a remarkable effect on reducing the fat accumulation in nematodes, compared with pure astaxanthin and anthocyanin nanoparticles. Additionally, AXT-ACN NPs can significantly decrease the accumulation of lipofuscin and the level of reactive oxygen species (ROS). The activities of antioxidant-related enzymes in nematodes were further measured, which revealed that the AXT-ACN NPs could increase the activities of catalase (CAT), superoxidase dismutase (SOD), and glutathione peroxidase (GSH-Px), and decrease the malondialdehyde (MDA) content. The astaxanthin and anthocyanin in AXT-ACN NPs showed sound synergistic antioxidation and lipid-lowering effects, making them potential components in functional foods.
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Understanding Li+ transport in organic-inorganic hybrid electrolytes, where Li+ has to lose its organic solvation shell to enter and transport through the inorganic phase, is crucial to the design of high-performance batteries. As a model system, we investigate a range of Li+-conducting particles suspended in a concentrated electrolyte. We show that large Li1.3Al0.3Ti1.7P3O12 and Li6PS5Cl particles can enhance the overall conductivity of the electrolyte. When studying impedance using a cell with a large cell constant, the Nyquist plot shows two semicircles: a high-frequency semicircle related to ion transport in the bulk of both phases and a medium-frequency semicircle attributed to Li+ transporting through the particle/liquid interfaces. Contrary to the high-frequency resistance, the medium-frequency resistance increases with particle content and shows a higher activation energy. Furthermore, we show that small particles, requiring Li+ to overcome particle/liquid interfaces more frequently, are less effective in facilitating Li+ transport. Overall, this study provides a straightforward approach to study the Li+ transport behavior in hybrid electrolytes.
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The inherent ability of melanoma cells to alter the differentiation-associated transcriptional repertoire to evade treatment and facilitate metastatic spread is well accepted and has been termed phenotypic switching. However, how these facets of cellular behavior are controlled remains largely elusive. Here, we show that cysteine availability, whether from lysosomes (CTNS-dependent) or exogenously derived (SLC7A11-dependent or as N-acetylcysteine), controls melanoma differentiation-associated pathways by acting on the melanocyte master regulator MITF. Functional data indicate that low cysteine availability reduces MITF levels and impairs lysosome functions, which affects tumor ferroptosis sensitivity but improves metastatic spread in vivo. Mechanistically, cysteine-restrictive conditions reduce acetyl-CoA levels to decrease p300-mediated H3K27 acetylation at the melanocyte-restricted MITF promoter, thus forming a cysteine feedforward regulation that controls MITF levels and downstream lysosome functions. These findings collectively suggest that cysteine homeostasis governs melanoma differentiation by maintaining MITF levels and lysosome functions, which protect against ferroptosis and limit metastatic spread.
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Diferenciação Celular , Cisteína , Lisossomos , Melanoma , Fator de Transcrição Associado à Microftalmia , Metástase Neoplásica , Melanoma/patologia , Melanoma/metabolismo , Melanoma/genética , Humanos , Cisteína/metabolismo , Fator de Transcrição Associado à Microftalmia/metabolismo , Fator de Transcrição Associado à Microftalmia/genética , Lisossomos/metabolismo , Linhagem Celular Tumoral , Animais , Camundongos , FerroptoseRESUMO
Aflatoxin B1 is highly mutagenic in humans, and long-term exposure can impair immunity and increase the risk of cancer. It is imperative to develop immunoassays with convenient operation and high sensitivity to detect aflatoxin B1. This study presents a polystyrene microcolumn-mediated magnetic relaxation switching immunosensor based on a tyramine signal amplification strategy for detecting aflatoxin B1. An environmentally friendly hand-held polystyrene microcolumn was designed as an effective immunoreaction carrier, remaining 91% efficiency after 12 repeated uses. And the microcolumn provides a user-friendly procedure for rapid separation and reagent switching within 3 s by simple stirring in solution. The combination of a strong anti-interference magnetic relaxation switching biosensing and an efficient tyramine signal amplification enables the quantitative detection of aflatoxin B1 in the range of 0.01-10 ng/mL, with a limit of detection of 0.006 ng/mL. This method has potential application in the rapid detection of trace food contaminants.