RESUMEN
Quantum many-body systems away from equilibrium host a rich variety of exotic phenomena that are forbidden by equilibrium thermodynamics. A prominent example is that of discrete time crystals1-8, in which time-translational symmetry is spontaneously broken in periodically driven systems. Pioneering experiments have observed signatures of time crystalline phases with trapped ions9,10, solid-state spin systems11-15, ultracold atoms16,17 and superconducting qubits18-20. Here we report the observation of a distinct type of non-equilibrium state of matter, Floquet symmetry-protected topological phases, which are implemented through digital quantum simulation with an array of programmable superconducting qubits. We observe robust long-lived temporal correlations and subharmonic temporal response for the edge spins over up to 40 driving cycles using a circuit of depth exceeding 240 and acting on 26 qubits. We demonstrate that the subharmonic response is independent of the initial state, and experimentally map out a phase boundary between the Floquet symmetry-protected topological and thermal phases. Our results establish a versatile digital simulation approach to exploring exotic non-equilibrium phases of matter with current noisy intermediate-scale quantum processors21.
RESUMEN
Non-aqueous solvents, in particular N,N-dimethylaniline (NMP), are widely applied for electrode fabrication since most sodium layered oxide cathode materials are readily damaged by water molecules. However, the expensive price and poisonousness of NMP unquestionably increase the cost of preparation and post-processing. Therefore, developing an intrinsically stable cathode material that can implement the water-soluble binder to fabricate an electrode is urgent. Herein, a stable nanosheet-like Mn-based cathode material is synthesized as a prototype to verify its practical applicability in sodium-ion batteries (SIBs). The as-prepared material displays excellent electrochemical performance and remarkable water stability, and it still maintains a satisfactory performance of 79.6% capacity retention after 500 cycles even after water treatment. The in situ X-ray diffraction (XRD) demonstrates that the synthesized material shows an absolute solid-solution reaction mechanism and near-zero-strain. Moreover, the electrochemical performance of the electrode fabricated with a water-soluble binder shows excellent long-cycling stability (67.9% capacity retention after 500 cycles). This work may offer new insights into the rational design of marvelous water stability cathode materials for practical SIBs.
RESUMEN
BACKGROUND: Tumor-associated macrophages (TAMs) constitute a substantial part of human hepatocellular carcinoma (HCC). The present study was devised to explore TAM diversity and their roles in HCC progression. METHODS: Through the integration of multiple 10 × single-cell transcriptomic data derived from HCC samples and the use of consensus nonnegative matrix factorization (an unsupervised clustering algorithm), TAM molecular subtypes and expression programs were evaluated in detail. The roles played by these TAM subtypes in HCC were further probed through pseudotime, enrichment, and intercellular communication analyses. Lastly, vitro experiments were performed to validate the relationship between CD63, which is an inflammatory TAM expression program marker, and tumor cell lines. RESULTS: We found that the inflammatory expression program in TAMs had a more obvious interaction with HCC cells, and CD63, as a marker gene of the inflammatory expression program, was associated with poor prognosis of HCC patients. Both bulk RNA-seq and vitro experiments confirmed that higher TAM CD63 expression was associated with the growth of HCC cells as well as their epithelial-mesenchymal transition, metastasis, invasion, and the reprogramming of lipid metabolism. CONCLUSIONS: These analyses revealed that the TAM inflammatory expression program in HCC is closely associated with malignant tumor cells, with the hub gene CD63 thus representing an ideal target for therapeutic intervention in this cancer type.
Asunto(s)
Carcinoma Hepatocelular , Progresión de la Enfermedad , Transición Epitelial-Mesenquimal , Neoplasias Hepáticas , Tetraspanina 30 , Macrófagos Asociados a Tumores , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Transición Epitelial-Mesenquimal/genética , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/patología , Tetraspanina 30/metabolismo , Tetraspanina 30/genética , Metabolismo de los Lípidos/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Pronóstico , Reprogramación Celular/genéticaRESUMEN
Biomacromolecular condensates formed via phase separation establish compartments for the enrichment of specific compositions, which is also used as a biological tool to enhance molecule condensation, thereby increasing the efficiency of biological processes. Proteolysis-targeting chimeras (PROTACs) have been developed as powerful tools for targeted protein degradation in cells, offering a promising approach for therapies for different diseases. Herein, we introduce an intrinsically disordered region in the PROTAC (denoted PSETAC), which led to the formation of droplets of target proteins in the cells and increased degradation efficiency compared with PROTAC without phase separation. Further, using a nucleus targeting intrinsically disordered domain, the PSETAC was able to target and degrade nuclear-located proteins. Finally, we demonstrated intracellular delivery of PSETAC using lipid nanoparticle-encapsulated mRNA (mRNA-LNP) for the degradation of the endogenous target protein. This study established the PSETAC mRNA-LNP method as a potentially translatable, safe therapeutic strategy for the development of clinical applications based on PROTAC.
Asunto(s)
Proteolisis , ARN Mensajero , Proteolisis/efectos de los fármacos , Humanos , ARN Mensajero/genética , Nanopartículas/química , Lípidos/química , Células HeLa , Proteínas Intrínsecamente Desordenadas/química , Proteínas Intrínsecamente Desordenadas/metabolismo , Separación de Fases , LiposomasRESUMEN
BACKGROUND: The first local outbreak of Delta Variant B.1.617.2 COVID-19 of China occurred in Guangzhou city, south China, in May 2021. This study analyzed the transmission chains and local cluster characteristics of this outbreak, intended to provide information support for the development and adjustment of local prevention and control strategies. METHODS: The transmission chains and local cluster characteristics of 161 local cases in the outbreak were described and analyzed. Incubation period, serial interval and generation time were calculated using the exact time of exposure and symptom onset date of the cases. The daily number of reported cases and the estimated generation time were used to estimate the effective reproduction number (Rt). RESULTS: We identified 7 superspreading events who had more than 5 next generation cases and their infected cases infected 70.81%(114/161) of all the cases transmission. Dining and family exposure were the main transmission routes in the outbreak, with 29.19% exposed through dining and 32.30% exposed through family places. Through further analysis of the outbreak, the estimated mean incubation period was 4.22 (95%CI: 3.66-4.94) days, the estimated mean generation time was 2.60 (95%CI: 1.96-3.11) days, and the estimated Rt was 3.29 (95%CI: 2.25-5.07). CONCLUSIONS: Classification and dynamically adjusted prevention and control measures had been carried out according to analysis of transmission chains and epidemical risk levels, including promoting nucleic acid screening at different regions and different risk levels, dividing closed-off area, controlled area according to the risk of infection, raising the requirements of leaving Guangzhou. By the above control measures, Guangzhou effectively control the outbreak within 28 days without implementing a large-scale lockdown policy.
Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , SARS-CoV-2/genética , Control de Enfermedades Transmisibles , Brotes de Enfermedades , China/epidemiologíaRESUMEN
Diabetes mellitus results in numerous complications. Diabetic pulmonary fibrosis (DPF), a late pulmonary complication of diabetes, has not attracted as much attention as diabetic nephropathy and cardiomyopathy. Mangiferin (MF) is a natural small molecular compound that exhibits a variety of pharmacological effects including anti-inflammatory, anti-cancer, anti-diabetes, and anti-fibrosis effects. In this study, we investigated whether long-term diabetes shock induces DPF, and explored whether MF had a protective effect against DPF. We first examined the lung tissues and sections of 20 diabetic patients obtained from discarded lung surgical resection specimens and found that pulmonary fibrosis mainly accumulated around the pulmonary vessels, accompanied by significantly enhanced endothelial-mesenchymal transition (EndMT). We established a mouse model of DPF by STZ injections. Ten days after the final STZ injection, the mice were administered MF (20, 60 mg/kg, i.g.) every 3 days for 4 weeks, and kept feeding until 16 weeks and euthanized. We showed that pulmonary fibrotic lesions were developed in the diabetic mice, which began around the pulmonary vessels, while MF administration did not affect long-term blood glucose levels, but dose-dependently alleviated diabetes-induced pulmonary fibrosis. In human umbilical vein endothelial cells (HUVECs), exposure to high glucose (33.3 mM) induced EndMT, which was dose-dependently inhibited by treatment with MF (10, 50 µM). Furthermore, MF treatment promoted SIRT3 expression in high glucose-exposed HUVECs by directly binding to AMPK to enhance the activity of FoxO3, which finally reversed diabetes-induced EndMT. We conclude that MF attenuates DPF by inhibiting EndMT through the AMPK/FoxO3/SIRT3 axis. MF could be a potential candidate for the early prevention and treatment of DPF.
Asunto(s)
Proteínas Quinasas Activadas por AMP , Diabetes Mellitus Experimental , Proteína Forkhead Box O3 , Ratones Endogámicos C57BL , Fibrosis Pulmonar , Sirtuina 3 , Xantonas , Animales , Xantonas/farmacología , Xantonas/uso terapéutico , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/metabolismo , Sirtuina 3/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Proteína Forkhead Box O3/metabolismo , Masculino , Humanos , Ratones , Proteínas Quinasas Activadas por AMP/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Estreptozocina , Transducción de Señal/efectos de los fármacos , Transición Endotelial-MesenquimatosaRESUMEN
BACKGROUND: Previous research has extensively examined the role of interleukin 6 (IL-6) in sarcopenia. However, the presence of a causal relationship between IL-6, its receptor (IL-6R), and sarcopenia remains unclear. METHOD: In this study, we utilized summary-level data from genome-wide association studies (GWAS) focused on appendicular lean mass (ALM), hand grip strength, and walking pace. Single nucleotide polymorphisms (SNPs) were employed as genetic instruments for IL-6 and IL-6R to estimate the causal effect of sarcopenia traits. We adopted the Mendelian randomization (MR) approach to investigate these associations using the inverse variance weighted (IVW) method as the primary analytical approach. Additionally, we performed sensitivity analyses to validate the reliability of the MR results. RESULT: This study revealed a significant negative association between main IL-6R and eQTL IL-6R on the left grip strength were - 0.013 (SE = 0.004, p < 0.001) and -0.029 (SE = 0.007, p < 0.001), respectively. While for the right grip strength, the estimates were - 0.011 (SE = 0.001, p < 0.001) and - 0.021 (SE = 0.008, p = 0.005). However, no evidence of an association for IL-6R with ALM and walking pace. In addition, IL-6 did not affect sarcopenia traits. CONCLUSION: Our study findings suggest a negative association between IL-6R and hand grip strength. Additionally, targeting IL-6R may hold potential value as a therapeutic approach for the treatment of hand grip-related issues.
Asunto(s)
Fuerza de la Mano , Interleucina-6 , Análisis de la Aleatorización Mendeliana , Receptores de Interleucina-6 , Sarcopenia , Humanos , Estudio de Asociación del Genoma Completo/métodos , Fuerza de la Mano/fisiología , Interleucina-6/genética , Interleucina-6/sangre , Análisis de la Aleatorización Mendeliana/métodos , Polimorfismo de Nucleótido Simple , Receptores de Interleucina-6/genética , Sarcopenia/genéticaRESUMEN
In this paper, the theoretical model of laser cleaning of paint-rust mixed layer on the surface of a Q235 steel plate is established from the perspective of the laser ablation effect and the thermal vibration effect. The study simulates the temperature and stress field variations of the mixed layer under different laser power densities. The experiment recorded ablative fumes and vibrational spattering generated during the cleaning process and measured the micro-morphology and surface roughness of the cleaned specimens. The results show that the cleaning mechanism of the paint-rust mixed layer is dominated by the ablation effect at low laser power densities, while the combined effects of ablation and thermal vibration dominate at high laser power densities. However, excessive laser energy can damage the substrate. At a laser power density of 12.37×106 W/c m 2, the substrate surface is free from contamination residues and exhibits a bright, white, metallic gloss, which can be determined as the cleaning threshold for laser cleaning of paint-rust mixed layers. This study provides a valuable reference for the laser cleaning of mixed pollutants of paint and rust on metal surfaces.
RESUMEN
Improving the shelf lives of fruits is challenging. The biodegradable polysaccharide pullulan exhibits excellent film-forming ability, gas barrier performance, and natural decomposability, making it an optimal material for fruit preservation. To overcome problems of high cost and film porosity of existing packaging technologies, we aimed to develop pullulan-based packaging paper to enhance the shelf lives of fruits. A thin paper coating comprising a mixture of 15 wt.% pullulan solution at various standard viscosities (75.6, 77.8, and 108.5 mPa·s) with tea polyphenols (15:2) and/or vitamin C (150:1) improved the oxygen transmission rate (120-160 cm3 m-2·24 h·0.1 MPa), water vapor transmission rate (<5.44 g·mm-1 m-2·h·kPa), maximum free radical clearance rate (>87%), and antibacterial properties of base packaging paper. Grapes wrapped with these pullulan-based papers exhibited less weight loss (>4.41%) and improved hardness (>16.4%) after 10 days of storage compared to those of control grapes (wrapped in untreated/base paper). Grapes wrapped with pullulan-based paper had >12.6 wt.% total soluble solids, >1.5 mg/g soluble protein, >0.44 wt.% titratable acidity, and ≥4.5 mg 100 g-1 ascorbic acid. Thus, pullulan-based paper may prolong the shelf life of grapes with operational convenience, offering immense value for fruit preservation.
Asunto(s)
Conservación de Alimentos , Frutas , Glucanos , Frutas/microbiología , Preservación Biológica , Ácido Ascórbico/farmacología , Embalaje de AlimentosRESUMEN
High-capacity metal oxides based on non-toxic earth-abundant elements offer unique opportunities as advanced anodes for lithium-ion batteries (LIBs). But they often suffer from large volumetric expansion, particle pulverization, extensive side reactions, and fast degradations during cycling. Here, an easy synthesis method is reported to construct amorphous borate coating network, which stabilizes conversion-type iron oxide anode for the high-energy-density semi-solid-state bipolar LIBs. The nano-borate coated iron oxide anode has high tap density (1.6 g cm-3 ), high capacity (710 mAh g-1 between 0.5 - 3.0 V, vs Li/Li+ ), good rate performance (200 mAh g-1 at 50 C), and excellent cycling stability (≈100% capacity resention over 1,000 cycles at 5 A g-1 ). When paired with high-voltage cathode LiCoO2 , it enables Cu current collector-free pouch-type classic and bipolar full cells with high voltage (7.6 V with two stack layers), achieving high energy density (≈350 Wh kg-1 ), outstanding power density (≈6,700 W kg-1 ), and extended cycle life (75% capacity retention after 2,000 cycles at 2 C), superior to the state-of-the-art high-power LIBs using Li4 Ti5 O12 anode. The design and methodology of the nanoscale polyanion-like coating can be applied to other metal oxides electrode materials, as well as other electrochemical materials and devices.
RESUMEN
BACKGROUND: Sepsis is a syndrome of physiological, pathological and biochemical abnormalities caused by infection. Although the mortality rate is lower than before, many survivors have persistent infection, which means sepsis calls for new treatment. After infection, inflammatory mediators were largely released into the blood, leading to multiple organ dysfunction. Therefore, anti-infection and anti-inflammation are critical issues in sepsis management. RESULTS: Here, we successfully constructed a novel nanometer drug loading system for sepsis management, FZ/MER-AgMOF@Bm. The nanoparticles were modified with LPS-treated bone marrow mesenchymal stem cell (BMSC) membrane, and silver metal organic framework (AgMOF) was used as the nanocore for loading FPS-ZM1 and meropenem which was delivery to the infectious microenvironments (IMEs) to exert dual anti-inflammatory and antibacterial effects. FZ/MER-AgMOF@Bm effectively alleviated excessive inflammatory response and eliminated bacteria. FZ/MER-AgMOF@Bm also played an anti-inflammatory role by promoting the polarization of macrophages to M2. When sepsis induced by cecal ligation and puncture (CLP) challenged mice was treated, FZ/MER-AgMOF@Bm could not only reduce the levels of pro-inflammatory factors and lung injury, but also help to improve hypothermia caused by septic shock and prolong survival time. CONCLUSIONS: Together, the nanoparticles played a role in combined anti-inflammatory and antimicrobial properties, alleviating cytokine storm and protecting vital organ functions, could be a potential new strategy for sepsis management.
Asunto(s)
Nanopartículas , Sepsis , Ratones , Animales , Macrófagos/metabolismo , Antibacterianos/uso terapéutico , Sepsis/tratamiento farmacológico , Membrana Celular/metabolismo , Modelos Animales de EnfermedadRESUMEN
This paper establishes a new theoretical paint removal model of plasma shock based on Fabbro's model and Newton's second law. A two-dimensional axisymmetric finite element model is established to calculate the theoretical model. By comparing the theoretical and experimental results, it is found that the theoretical model can accurately predict the threshold of laser paint removal. It is indicated that plasma shock is an essential mechanism in laser paint removal. The threshold for laser paint removal is approximately 1.73J/c m 2. The experiments show that, with the increase of the laser fluence, the effect of laser paint removal first increases and then decreases. With the increase of the laser fluence, the paint removal effect is improved due to the increase of the paint removal mechanism. The competition between the plastic fracture and pyrolysis leads to a reduction in paint effectiveness. In summary, this study can provide a theoretical reference for studying the paint removal mechanism of plasma shock.
RESUMEN
In this paper, a theoretical model for laser cleaning of aluminium alloy oxide film is presented from the perspective of thermal stress. Additionally, we developed a two-dimensional axisymmetric finite element model for calculation. Thermal stresses result from thermal expansion. Using thermodynamic equations, numerical calculations enable the determination of a theoretical cleaning threshold by comparing the thermal stresses to the adhesion between the oxide film and the substrate. Through theory and experiments, it is known that the greater the laser fluence, the better is the cleaning effect. The findings indicate that cleaning of the oxide film on aluminum alloys can be achieved under appropriate parameters. The cleaning threshold for laser cleaning of the oxide film is determined to be 3629.47J/c m 2 (continuous laser fluence is 3628.73J/c m 2; nanosecond laser fluence is 0.74J/c m 2). The thermal stress model of laser cleaning is highly useful for selecting the appropriate laser flux in practical applications. Both a simulation and experimental results can provide an explanation for the mechanism of interaction between the laser and the aluminum alloy oxide film, demonstrating that thermal stress is one of the cleaning mechanisms during the laser cleaning process of the oxide film.
RESUMEN
Toxoplasma gondii can infect a wide range of warm-blooded animals, causing a global toxoplasmosis zoonotic epidemic. Surface antigen 1 (SAG1) protein is expressed at the proliferative tachyzoite stage, whereas matrix antigen 1 (MAG1) is expressed at the bradyzoite and tachyzoite stages. These two proteins were found to perform protective roles in previous studies; however, their synergetic protective efficacy as a DNA vaccine against toxoplasmosis has not been clarified. In this study, we constructed recombinant pcDNA3.1( +)-TgMAG1 (pMAG1), pcDNA3.1( +)-TgSAG1 (pSAG1), and pcDNA3.1( +)-TgMAG1-TgSAG1 (pMAG1-SAG1) plasmids and administered them intramuscularly to immunize mice. The levels of anti-T. gondii IgG in serum and cytokines, such as Interleukin (IL)-4, IL-10, and Interferon (IFN)-γ, in splenocytes were measured using ELISA and the respective culture supernatants. Lethal doses of T. gondii (type I) RH strain tachyzoites were administered to immunized mice, and mortality was assessed. Conversely, mice infected with low doses of tachyzoites were monitored to determine their survival rates, and parasite burden analyses of the brains and livers were conducted. The bivalent TgMAG1 and TgSAG1 DNA vaccines exhibited excellent protective immunity against toxoplasmosis in mice, with higher serum IgG and splenocyte IFN-γ release levels, longer survival days, and reduced parasite burden in the brain and liver tissues (p < 0.05). These findings provide a new perspective for the development of T. gondii vaccines.
Asunto(s)
Vacunas Antiprotozoos , Toxoplasma , Toxoplasmosis , Vacunas de ADN , Animales , Ratones , Vacunas de ADN/genética , Antígenos de Protozoos , Proteínas Protozoarias/metabolismo , Antígenos de Superficie/metabolismo , Ratones Endogámicos BALB C , Toxoplasmosis/parasitología , Inmunoglobulina G , Anticuerpos AntiprotozoariosRESUMEN
BACKGROUND: Computational text phenotyping is the practice of identifying patients with certain disorders and traits from clinical notes. Rare diseases are challenging to be identified due to few cases available for machine learning and the need for data annotation from domain experts. METHODS: We propose a method using ontologies and weak supervision, with recent pre-trained contextual representations from Bi-directional Transformers (e.g. BERT). The ontology-driven framework includes two steps: (i) Text-to-UMLS, extracting phenotypes by contextually linking mentions to concepts in Unified Medical Language System (UMLS), with a Named Entity Recognition and Linking (NER+L) tool, SemEHR, and weak supervision with customised rules and contextual mention representation; (ii) UMLS-to-ORDO, matching UMLS concepts to rare diseases in Orphanet Rare Disease Ontology (ORDO). The weakly supervised approach is proposed to learn a phenotype confirmation model to improve Text-to-UMLS linking, without annotated data from domain experts. We evaluated the approach on three clinical datasets, MIMIC-III discharge summaries, MIMIC-III radiology reports, and NHS Tayside brain imaging reports from two institutions in the US and the UK, with annotations. RESULTS: The improvements in the precision were pronounced (by over 30% to 50% absolute score for Text-to-UMLS linking), with almost no loss of recall compared to the existing NER+L tool, SemEHR. Results on radiology reports from MIMIC-III and NHS Tayside were consistent with the discharge summaries. The overall pipeline processing clinical notes can extract rare disease cases, mostly uncaptured in structured data (manually assigned ICD codes). CONCLUSION: The study provides empirical evidence for the task by applying a weakly supervised NLP pipeline on clinical notes. The proposed weak supervised deep learning approach requires no human annotation except for validation and testing, by leveraging ontologies, NER+L tools, and contextual representations. The study also demonstrates that Natural Language Processing (NLP) can complement traditional ICD-based approaches to better estimate rare diseases in clinical notes. We discuss the usefulness and limitations of the weak supervision approach and propose directions for future studies.
Asunto(s)
Procesamiento de Lenguaje Natural , Enfermedades Raras , Humanos , Enfermedades Raras/diagnóstico , Aprendizaje Automático , Unified Medical Language System , Clasificación Internacional de EnfermedadesRESUMEN
PURPOSE: This study aims to investigate the safety and efficacy of our novel technique of single-port endoscopy-assisted thyroidectomy via cervical gas-insufflation approach (SPEAT, also called the Huang procedure) in the treatment of papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: We perform a retrospective comparative study from a prospectively maintained database. A cohort of 82 patients with PTC who underwent total thyroidectomy and central neck dissection were included. Of these patients, 48 underwent SPEAT and 34 underwent conventional open thyroidectomy (COT). The differences in surgical outcome and oncological completeness were compared. RESULTS: Compared with the COT group, the SPEAT group had obviously shorter incision (P < 0.001), less postoperative pain (P = 0.036), better cosmetic satisfaction (P = 0.001)and slightly longer operating time (P = 0.041). In intraoperative bleeding, postoperative drainage, postoperative hospital stay, surgical complications, number of dissected or positive lymph nodes per patient, and postoperative non-stimulated or stimulated thyroglobulin levels, there were no significant differences. CONCLUSIONS: SPEAT (the Huang procedure) is a minimally invasive, safe and oncologically complete surgical option for PTC in selected patients.
Asunto(s)
Carcinoma Papilar , Insuflación , Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo/cirugía , Tiroidectomía/métodos , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Estudios Retrospectivos , Carcinoma Papilar/cirugía , Endoscopía/métodos , Disección del Cuello/métodos , Endoscopía GastrointestinalRESUMEN
Single-cell epigenetics is envisioned to decipher manifold epigenetic phenomena and to contribute to our accurate knowledge about basic epigenetic mechanisms. Engineered nanopipette technology has gained momentum in single-cell studies; however, solutions to epigenetic questions remain unachieved. This study addresses the challenge by exploring N6-methyladenine (m6 A)-bearing deoxyribozyme (DNAzyme) confined within a nanopipette for profiling a representative m6 A-modifying enzyme, fat mass and obesity-associated protein (FTO). Electroosmotic intracellular extraction of FTO could remove the m6 A and cause DNAzyme cleavage, leading to the altered ionic current signal. Because the cleavage can release a DNA sequence, we simultaneously program it as an antisense strand against FTO-mRNA, intracellular injection of which has been shown to induce early stage apoptosis. This nanotool thus features the dual functions of studying single-cell epigenetics and programmable gene regulation.
Asunto(s)
ADN Catalítico , ADN Catalítico/metabolismo , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Regulación de la Expresión Génica , Epigénesis Genética , ARN Mensajero/metabolismoRESUMEN
Ion exchange (IX) is a promising technology for selective nitrogen recovery from urine; however, IX requires chemical-intensive regeneration that escalates energy consumption and carbon emissions. To overcome this barrier, we demonstrated and investigated a novel electrified IX stripping process (EXS) enabling electrochemical in situ IX regeneration with simultaneous ammonia stripping. EXS combines a weak acid cation exchange resin (WAC) to concentrate ammonia, a bipolar membrane to produce protons for WAC regeneration, and membrane stripping to recover the eluted ammonium from WAC. We observed over 80% regeneration (elution from resin) and recovery (membrane stripping) efficiencies during multiple adsorption-recovery cycles with synthetic and real urine. Comparing WAC with a strong acid cation exchange resin illustrated the critical role of the proton affinity of resin moieties in regulating resin regenerability and conductivity in EXS, which we distinguished from the rationale for material choice in electrodeionization. Compared to other electrochemical recovery methods using unamended wastewater as an electrolyte, EXS enabled control of electrolyte composition during recovery by separating and equalizing influent ammonium via WAC-mediated removal. This electrolyte engineering facilitated tunable EXS energy efficiency (100-300 MJ/kg N). This study informs the design of electrified, intensified systems that enable decentralized nitrogen recovery from urine.
Asunto(s)
Compuestos de Amonio , Nitrógeno , Intercambio Iónico , Amoníaco , Agua , Resinas de Intercambio de Catión , Aguas ResidualesRESUMEN
Bisphenol A (BPA) is becoming a potential environmental toxicity factor. However, BPA's effect and function mechanism on maize roots remain unknown. Here, we investigated characters of root growth of maize seedlings exposed to BPA for 8 d and without BPA for 3 d, and a series of indicators on reactive oxygen homeostasis and nitrogen assimilation were measured. High-dose BPA(15 and 50 mg·L-1) suppressed the root growth and caused increased contents of O2Ë-, H2O2 and MDA in maize seedling roots. The disturbed ROS homeostasis resulted from the change of antioxidant enzymes, including the increase of APX, GPX, and CAT, and decrease of SOD and POD, and a decrease of antioxidant substance GSH. Meanwhile, High-dose BPA caused a decrease in the soluble protein content, nitrate reductase (NR), glutamate dehydrogenase (GDH), and glutamine oxoglutarate aminotransferase (GOGAT) under the BPA processing phase and recovery period. The low-dose BPAï¼1.5 and 5 mg·L-1ï¼significantly promoted root growth of maize seedlings and maintained the ROS homeostasis through antioxidant enzyme APX and GPX eliminating redundant ROS. Our results showed that BPA could cause a dual effect on the root growth of maize seedlings, that is, promotion of low-dose and inhibition of high-dose, through ROS homeostasis and nitrogen assimilation in Zea mays.
Asunto(s)
Plantones , Zea mays , Antioxidantes , Nitrógeno , Peróxido de Hidrógeno , Especies Reactivas de OxígenoRESUMEN
Thermodynamic uncertainty principles make up one of the few rare anchors in the largely uncharted waters of nonequilibrium systems, the fluctuation theorems being the more familiar. In this work we aim to trace the uncertainties of thermodynamic quantities in nonequilibrium systems to their quantum origins, namely, to the quantum uncertainty principles. Our results enable us to make this categorical statement: For Gaussian systems, thermodynamic functions are functionals of the Robertson-Schrödinger uncertainty function, which is always non-negative for quantum systems, but not necessarily so for classical systems. Here, quantum refers to noncommutativity of the canonical operator pairs. From the nonequilibrium free energy, we succeeded in deriving several inequalities between certain thermodynamic quantities. They assume the same forms as those in conventional thermodynamics, but these are nonequilibrium in nature and they hold for all times and at strong coupling. In addition we show that a fluctuation-dissipation inequality exists at all times in the nonequilibrium dynamics of the system. For nonequilibrium systems which relax to an equilibrium state at late times, this fluctuation-dissipation inequality leads to the Robertson-Schrödinger uncertainty principle with the help of the Cauchy-Schwarz inequality. This work provides the microscopic quantum basis to certain important thermodynamic properties of macroscopic nonequilibrium systems.