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Rechargeable sodium-oxygen (Na-O2) battery is deemed as a promising high-energy storage device due to the abundant sodium resources and high theoretical energy density (1,108 Wh kg-1). A series of quasisolid electrolytes are constantly being designed to restrain the dendrites growth, the volatile and leaking risks of liquid electrolytes due to the open system of Na-O2 batteries. However, the ticklish problem about low operating current density for quasisolid electrolytes still hasn't been conquered. Herein, we report a rechargeable Na-O2 battery with polyvinylidene fluoride-hexafluoropropylene recombination Nafion (PVDF-HFP@Nafion) based quasisolid polymer electrolyte (QPE) and MXene-based Na anode with gradient sodiophilic structure (M-GSS/Na). QPE displays good flame resistance, locking liquid and hydrophobic properties. The introduction of Nafion can lead to a high Na+ migration number (tNa+ = 0.68) by blocking the motion of anion and promote the formation of NaF-rich solid electrolyte interphase, resulting in excellent cycling stability at relatively high current density under quasisolid environment. In the meantime, the M-GSS/Na anode exhibits excellent dendrite inhibition ability and cycling stability. Therefore, with the synergistic effect of QPE and M-GSS/Na, constructed Na-O2 batteries run more stably and exhibit a low potential gap (0.166 V) after an initial 80 cycles at 1,000 mA g-1 and 1,000 mAh g-1. This work provides the reference basis for building quasisolid state Na-O2 batteries with long-term cycling stability.
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The inferior oxidative stability of commercial carbonate electrolytes and overgrowth of the electrode-electrolyte interphase (EEI) have largely hindered the development of high-voltage lithium metal batteries. In this study, these challenges are addressed by designing Li+-solvent chelating solvation structures to inhibit solvent decomposition using cyano-alkyl-phosphate as a demonstration. Theoretical and experimental studies confirm that the -PâO and -C≡N groups within diethyl (2-cyanethyl) phosphonate exhibit a comparable ability to coordinate with Li+, facilitating the formation of seven-membered chelating structures. This unique solvation structure contributes to the formation of anion-derived inorganic-rich EEI with high stability and robustness, hindering the further decomposition of the electrolyte. Additionally, the cyano group has a strong complexation with the transition metal (TM) in the cathode to inhibit TM dissolution, thereby ensuring the structural stability of the cathode particle. Utilizing this special chelating structure, the designed electrolyte demonstrates favorable Li plating/stripping reversibility and promising oxidative stability in high-voltage batteries. Consequently, the LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode exhibits a high capacity retention (90%) after operating 300 cycles. Under harsh testing conditions, the 4.6 V Li||NCM811 pouch cell with a capacity of 1.4 Ah (â¼295 Wh kg-1 based on the total mass of the cell) retains 70% capacity after 80 cycles. This work provides new insights into the correlation between the solvation structure and oxidative stability of electrolytes, contributing significantly to the advancement of high-voltage lithium metal batteries.
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Bladder cancer is a common kind of urinary system cancer, in which bladder urothelial carcinoma (BLCA) comprises approximately 90% of all bladder cancer types. In our previous study, we discovered KLHDC7B in urine exosomal messenger RNA (mRNA) as a prospective molecular marker for bladder cancer detection. To systematically study the role and mechanism of KLHDC7B in BLCA, we focused on the most common type of BLCA in this study. First, we used RNA sequencing to discover that KLHDC7B was considerably increased in BLCA patients' urine exosomes compared to healthy controls. Then, we validated this result in an independent cohort and identified it as an effective tool for diagnosing and distinguishing high-grade and low-grade BLCA. Finally, we studied the role and mechanism of KLHDC7B in BLCA at the cellular level, providing a functional basis for its expression as a novel laboratory diagnostic biomarker for BLCA exosomal mRNA, which has important theoretical and clinical significance.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Apoptosis/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Transicionales/patología , Proliferación Celular/genética , ARN Mensajero/genética , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
BACKGROUND: Inflammation and oxidative stress play an important role in the pathophysiology of inflammatory bowel disease (IBD). This study aimed to explore the effects of copper chaperone Antioxidant-1 (Atox1) on macrophages in a mouse model of intestinal inflammation. METHODS: A mouse model of TNBS-induced colitis was established and verified using the disease activity index. Atox1 conditional knockout mice were applied. The proportion of macrophages in colonic lamina propria mononuclear cells and ROS production were analyzed using flow cytometry. Inflammatory cytokines were measured using ELISA. Expression of macrophage M1/M2 polarization markers, p47phox, NLRP3, and Caspase-1 p20 was measured using quantitative RT-PCR and Western blotting. RESULTS: Atox1 expression was up-regulated in colon tissues of TNBS-induced colitis mice. Macrophages isolated from TNBS-induced colitis mice showed M1 polarization and nuclear translocation of Atox1. Inhibiting copper chaperone activity decreased p47phox, ROS production, and M1 polarization induced by CuCl2 in macrophages. TNBS induced up-regulation of inflammatory cytokines, M1 polarization markers, and p47phox expression in mice, an effect which was preempted by Atox1 knockout. Inflammatory cytokines and expression of M1 polarization markers, p47phox, NLRP3, Caspase-1 p20 were also increased in macrophages isolated from TNBS-induced colitis mice. These changes were alleviated in mice with Atox1 knockout. The effects of Atox1 on macrophage polarization were mediated via the ROS-NLRP3 inflammasome pathway. CONCLUSION: Atox1 plays a pro-inflammatory role, promotes M1 polarization of macrophages, and increases the concentrations of pro-inflammatory cytokines in intestinal tissue by regulating the ROS-NLRP3 inflammasome pathway. Atox1 is a potential therapeutic target in IBD.
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Polaridad Celular , Colitis , Inflamasomas , Inflamación , Macrófagos , Ratones Noqueados , Proteína con Dominio Pirina 3 de la Familia NLR , Especies Reactivas de Oxígeno , Transducción de Señal , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Macrófagos/metabolismo , Inflamasomas/metabolismo , Colitis/patología , Colitis/inducido químicamente , Colitis/metabolismo , Inflamación/patología , Inflamación/metabolismo , Ratones Endogámicos C57BL , Chaperonas Moleculares/metabolismo , Ácido Trinitrobencenosulfónico , Citocinas/metabolismo , Intestinos/patología , Masculino , RatonesRESUMEN
OBJECTIVES: To explore the use of deep learning-constrained compressed sensing (DLCS) in improving image quality and acquisition time for 3D MRI of the brachial plexus. METHODS: Fifty-four participants who underwent contrast-enhanced imaging and forty-one participants who underwent unenhanced imaging were included. Sensitivity encoding with an acceleration of 2 × 2 (SENSE4x), CS with an acceleration of 4 (CS4x), and DLCS with acceleration of 4 (DLCS4x) and 8 (DLCS8x) were used for MRI of the brachial plexus. Apparent signal-to-noise ratios (aSNRs), apparent contrast-to-noise ratios (aCNRs), and qualitative scores on a 4-point scale were evaluated and compared by ANOVA and the Friedman test. Interobserver agreement was evaluated by calculating the intraclass correlation coefficients. RESULTS: DLCS4x achieved higher aSNR and aCNR than SENSE4x, CS4x, and DLCS8x (all p < 0.05). For the root segment of the brachial plexus, no statistically significant differences in the qualitative scores were found among the four sequences. For the trunk segment, DLCS4x had higher scores than SENSE4x (p = 0.04) in the contrast-enhanced group and had higher scores than SENSE4x and DLCS8x in the unenhanced group (all p < 0.05). For the divisions, cords, and branches, DLCS4x had higher scores than SENSE4x, CS4x, and DLCS8x (all p ≤ 0.01). No overt difference was found among SENSE4x, CS4x, and DLCS8x in any segment of the brachial plexus (all p > 0.05). CONCLUSIONS: In three-dimensional MRI for the brachial plexus, DLCS4x can improve image quality compared with SENSE4x and CS4x, and DLCS8x can maintain the image quality compared to SENSE4x and CS4x. CLINICAL RELEVANCE STATEMENT: Deep learning-constrained compressed sensing can improve the image quality or accelerate acquisition of 3D MRI of the brachial plexus, which should be benefit in evaluating the brachial plexus and its branches in clinical practice. KEY POINTS: â¢Deep learning-constrained compressed sensing showed higher aSNR, aCNR, and qualitative scores for the brachial plexus than SENSE and CS at the same acceleration factor with similar scanning time. â¢Deep learning-constrained compressed sensing at acceleration factor of 8 had comparable aSNR, aCNR, and qualitative scores to SENSE4x and CS4x with approximately half the examination time. â¢Deep learning-constrained compressed sensing may be helpful in clinical practice for improving image quality and acquisition time in three-dimensional MRI of the brachial plexus.
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Plexo Braquial , Aprendizaje Profundo , Humanos , Imagenología Tridimensional/métodos , Plexo Braquial/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Relación Señal-RuidoRESUMEN
OBJECTIVES: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Its diagnosis poses significant challenges especially at early stages and in atypical cases. The aim of this study was to develop a machine learning model based on common laboratory tests that can aid SLE diagnosis. METHODS: A standard protocol was developed to collect data of SLE and control immune diseases. A 10-fold cross-validation was performed in the modeling dataset (n=862), and an external dataset (n=198) was used for model validation. Machine learning algorithms were applied to construct a diagnostic model. Performance was evaluated based on area under the curve (AUC) values, F1-score, negative predictive value, positive predictive value, accuracy, sensitivity, and specificity. RESULTS: The optimal model was based on a random forest algorithm with 10 clinical features. Thrombin time, prothrombin activity, and uric acid contributed most to the diagnostic model. The SLE diagnostic model showed sufficient predictive accuracy, with AUC values of 0.8286 in the validation dataset. CONCLUSIONS: Our diagnostic model based on 10 common laboratory tests identified the patients with SLE with high accuracy. An online version of the model can potentially be applied in clinical settings for the differential diagnosis of SLE.
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Sistemas de Información en Laboratorio Clínico , Lupus Eritematoso Sistémico , Humanos , Registros Electrónicos de Salud , Lupus Eritematoso Sistémico/diagnóstico , Algoritmos , Aprendizaje AutomáticoRESUMEN
Sepsis induces profound disruptions in cellular homeostasis, particularly impacting mitochondrial function in cardiovascular and cerebrovascular systems. This study elucidates the regulatory role of the Pyruvate Kinase M2 (PKM2)- Prohibitin 2 (PHB2) axis in mitochondrial quality control during septic challenges and its protective effects against myocardial and cerebral injuries. Employing LPS-induced mouse models, we demonstrate a significant downregulation of PKM2 and PHB2 in both heart and brain tissues post-sepsis, with corresponding impairments in mitochondrial dynamics, including fission, fusion, and mitophagy. Overexpression of PKM2 and PHB2 not only restores mitochondrial function, as evidenced by normalized ATP production and membrane potential but also confers resistance to oxidative stress by mitigating reactive oxygen species generation. These cellular mechanisms translate into substantial in vivo benefits, with transgenic mice overexpressing PKM2 or PHB2 displaying remarkable resistance to sepsis-induced cardiomyocyte and neuronal apoptosis, and organ dysfunction. Our findings highlight the PKM2-PHB2 interaction as a novel therapeutic target for sepsis, providing a foundation for future research into mitochondrial-based interventions to treat this condition. The study's insights into the molecular underpinnings of sepsis-induced organ failure pave the way for potential clinical applications in the management of sepsis and related pathologies.
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Mitocondrias , Sepsis , Animales , Ratones , Apoptosis/genética , Miocitos Cardíacos , Estrés Oxidativo , Sepsis/complicaciones , Sepsis/genéticaRESUMEN
Sinomenium acutum (Thunb.) Rehd. et Wils is widely used in the treatment of rheumatoid arthritis, with its alkaloid compound sinomenine (SIN) being renowned for its significant anti-inflammatory properties. However, despite its widespread application, the in vivo anti-inflammatory mechanisms and metabolic pathways of SIN remain incompletely understood. This study established a rapid and reliable method based on an ultra-high-performance liquid chromatography method coupled with Quadrupole-Exactive Orbitrap mass spectrometry and molecular docking to identify and characterize SIN and 69 metabolites in rat plasma, urine, and feces, revealing primary metabolic pathways of hydroxylation, demethylation, sulfation, and glucuronidation. Molecular docking results revealed that phase I reactions, including dedimethylation, demethylation, dehydrogenation, and dihydroxylation, along with their composite reactions, were pivotal in influencing SIN's in vivo anti-inflammatory activity. M28, M36, and M59 are potentially the most anti-inflammatory active metabolites of SIN in vivo. This comprehensive analysis unveils SIN's metabolic pathways, offering insights into its biological processes and suggesting a novel approach for exploring active drug constituents. These findings pave the way for further understanding SIN's anti-inflammatory mechanisms, contributing significantly to the development of new therapeutic strategies.
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Espectrometría de Masas , Simulación del Acoplamiento Molecular , Morfinanos , Animales , Morfinanos/metabolismo , Morfinanos/química , Cromatografía Líquida de Alta Presión/métodos , Ratas , Masculino , Ratas Sprague-Dawley , Antiinflamatorios/química , Antiinflamatorios/metabolismo , Sinomenium/química , Estructura MolecularRESUMEN
Vehicle detection is a research direction in the field of target detection and is widely used in intelligent transportation, automatic driving, urban planning, and other fields. To balance the high-speed advantage of lightweight networks and the high-precision advantage of multiscale networks, a vehicle detection algorithm based on a lightweight backbone network and a multiscale neck network is proposed. The mobile NetV3 lightweight network based on deep separable convolution is used as the backbone network to improve the speed of vehicle detection. The icbam attention mechanism module is used to strengthen the processing of the vehicle feature information detected by the backbone network to enrich the input information of the neck network. The bifpn and icbam attention mechanism modules are integrated into the neck network to improve the detection accuracy of vehicles of different sizes and categories. A vehicle detection experiment on the Ua-Detrac dataset verifies that the proposed algorithm can effectively balance vehicle detection accuracy and speed. The detection accuracy is 71.19%, the number of parameters is 3.8 MB, and the detection speed is 120.02 fps, which meets the actual requirements of the parameter quantity, detection speed, and accuracy of the vehicle detection algorithm embedded in the mobile device.
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Coherent multiwave mixing is in demand for optical frequency conversion, imaging, quantum information science, etc., but has rarely been demonstrated in solid-state systems. Here, we observed three- and five-wave mixing (5WM) in a c-axis growth zinc oxide microwire on a Au film with picosecond pulses in the near-infrared region. An output 5WM of 4.7 × 10-7 µW, only 2-3 orders smaller than the three-wave mixing, is achieved when the excitation power is as low as 1.5 mW and the peak power density as weak as â¼107 W/cm2. The excitation power dependence of 5WM agrees well with the perturbation limit under the low intensity but exhibits a strong deviation at a high pumping power. This extraordinary behavior is attributed to the cooperative resonant enhancement effect when pumping in the near-infrared range. Our study offers a potential solid-state platform for on-chip multiwave mixing and quantum nonlinear optics, such as generating many-photon entangled states or the construction of photon-photon quantum logic gates.
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Limited exploration in fungal mitochondrial genetics has uncovered diverse inheritance modes. The mitochondrial genomes are inherited uniparentally in the majority of sexual eukaryotes, our discovery of persistent mitochondrial heterogeneity within the natural population of the basidiomycete fungus Thelephora ganbajun represents a significant advance in understanding mitochondrial inheritance and evolution in eukaryotes. Here, we present a comprehensive analysis by sequencing and assembling the complete mitogenomes of 40 samples exhibiting diverse cox1 heterogeneity patterns from various geographical origins. Additionally, we identified heterogeneous variants in the nad5 gene, which, similar to cox1, displayed variability across multiple copies. Notably, our study reveals a distinct prevalence of introns and homing endonucleases in these heterogeneous genes. Furthermore, we detected potential instances of horizontal gene transfer involving homing endonucleases. Population genomic analyses underscore regional variations in mitochondrial genome composition among natural samples exhibiting heterogeneity. Thus, polymorphisms in heterogeneous genes, introns, and homing endonucleases significantly influence mitochondrial structure, structural variation, and evolutionary dynamics in this species. This study contributes valuable insights into mitochondrial genome architecture, population dynamics, and the evolutionary implications of mitochondrial heterogeneity in sexual eukaryotes.
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Evolución Molecular , Genoma Mitocondrial , Filogenia , Intrones/genética , Mitocondrias/genética , Basidiomycota/genética , ADN Mitocondrial/genética , Genómica/métodos , Transferencia de Gen HorizontalRESUMEN
Morphological anisotropic engineering is powerful to synthesize metal-organic frameworks (MOFs) with versatile physicochemical properties for diverse applications ranging from gas storage/separation to electrocatalysis and batteries, etc. Herein, we developed a carbon substrate guided strategy to manipulate the facet-dependent coordination for morphology engineering of Fe-THBQ (tetrahydroxy-1,4-benzoquinone) frameworks, which is built with cubic Fe octamer bridged by two parallel THBQ ligands along three orthogonal axes, extending to a three-dimensional (3D) framework with pcu-e network topology. The electronegative O-containing functional groups on carbon surfaces compete with THBQ linkers to selectively interact with the unsaturated coordinated Fe cations on the {111} facets and inhibit crystal growth along the <111> direction. The morphology of Fe-THBQ evolves from thermodynamically favored truncated cube to cuboctahedron depending on the content of O-containing functional groups on the carbon substrate. The Fe-THBQ with varied morphologies exhibits facet-dependent performances for electrochemical lithium storage. This work will shed light on the morphology modulation of MOFs for promising applications.
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The continuous electrolyte decomposition and uncontrolled dendrite growth caused by the unstable solid electrolyte interphase (SEI) have largely hindered the development of Li metal batteries. Here, we demonstrate that tuning the facet of current collector can regulate the composition of SEI and the subsequent Li deposition behavior using single-crystal Cu foils as an ideal platform. The theoretical and experimental studies reveal that the (100) facet of Cu possesses strong adsorption to anions, guiding more anions to participate preferentially in the inner Helmholtz plane and further promoting the formation of the stable inorganic-rich SEI. Consequently, the single-crystal Cu foils with a single [100] orientation (s-Cu(100)) achieve the dendrite-free Li deposition with enhanced Li plating/stripping reversibility. Moreover, the Li anode deposited on s-Cu(100) can stabilize the operation of an Ah-level pouch cell (350â Wh kg-1) with a low negative/positive capacity ratio (~2) and lean electrolyte (2.4â g Ah-1) for 150â cycles. Impressively, this strategy demonstrates universality in a series of electrolytes employed different anions. This work provides new insights into the correlation between the SEI and current collector, opening a universal avenue towards high-performance Li metal batteries.
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Sodium-ion batteries (SIBs) as a promising technology for large-scale energy storage have received unprecedented attention. However, the cathodes in SIBs generally suffer from detrimental cathode-electrolyte interfacial side reactions and structural degradation during cycling, which leads to severe capacity fade and voltage decay. Here, we have developed an ultra-stable Na0.72Ni0.20Co0.21Mn0.55Mg0.036O2 (NCM-CS-GMg) cathode material in which a Mg-free core is encapsulated by a shell with gradient distribution of Mg using coprecipitation method with Mg-hysteretic cascade feedstock followed by calcination. From the interior to outer surface of the shell, as the content of electrochemically inactive Mg gradually increases, the Na+ deintercalation amount gradually decreases after charged. Benefiting from this surface gradient desodiation, the surface transition metal (TM) ion migration from TM layers to Na layers is effectively inhibited, thus suppressing the layered-to-rock-salt phase transition and the resultant microcracks. Besides, the less formation of high-valence TM ions on the surface contributes to a stable cathode-electrolyte interface. The as-prepared NCM-CS-GMg exhibits remarkable cycling life over 3000â cycles with a negligible voltage drop (0.127â mV per cycle). Our findings highlight an effective way to developing sustainable cathode materials without compromising on the initial specific capacity for SIBs.
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Discrimination and quantification of amino acid (AA) enantiomers are particularly important for diagnosing and treating diseases. Recently, dual-mode probes have gained a lot of research interest because they can catch more detecting information compared with the single-mode probes. Thus, it is of great significance to develop a dual-mode sensor realizing AA enantiomer discrimination conveniently and efficiently. In this work, carbon dot L-TCDs were prepared by N-methyl-1,2-benzenediamine dihydrochloride (OTD) and l-tryptophan. With the assistance of H2O2, L-TCDs show an excellent discrimination performance for enantiomers of glutamine (Gln) and valine (Val) in both fluorescent and colorimetric modes. The fluorescence enantioselectivity of Gln (FD/FL) and Val (FL/FD) is 5.29 and 4.13, respectively, and the colorimetric enantioselectivity of Gln (ID/IL) and Val (IL/ID) is 13.26 and 3.42, individually. The chiral recognition mechanism of L-TCDs was systematically studied. L-TCDs can be etched by H2O2, and the participation of AA enantiomers results in different amounts of the released OTD, which provides fluorescent and colorimetric signals for identifying and quantifying the enantiomers of Gln and Val. This work provides a more convenient and flexible dual-mode sensing strategy for discriminating AA enantiomers, which is expected to be of great value in facile and high-throughput chiral recognition.
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Glutamina , Valina , Colorimetría/métodos , Carbono/química , Peróxido de Hidrógeno , Aminoácidos , ColorantesRESUMEN
As one of the most promising cathode materials in sodium-ion batteries, manganese-based layered oxides have aroused wide attention due to their high specific capacity and plentiful reserves. However, they are plagued by poor air stability rooting in water/Na+ exchange and adverse structural reconstruction, hindering their practical applications. Herein, it is demonstrated that utilizing fluorine to substitute oxygen atoms can narrow the interlayer spacing of novel P'2-Na0.67 MnO1.97 F0.03 (NMOF) cathode material, which resists the attack of water molecules, significantly prolonging exposure time in air. Density functional theory (DFT) calculation results indicate that fluorine substitution alleviates the insertion of water molecules and spontaneous extraction of Na+ effectively. Benefiting from the structural modulation, NMOF can deliver a high specific capacity of 227.1 mAh g-1 at 20 mA g-1 and a promising capacity retention of 84.0% after 100 cycles at 200 mA g-1 . This facile and available strategy provides a feasible way to strengthen the air-stability and expands the scope of practical applications of layered oxide cathodes.
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Hydrogen sulfide (H2 S) has been widely recognized as one of gasotransmitters. Endogenous H2 S plays a crucial role in the progression of cancer. However, the effect of endogenous H2 S on the development of nasopharyngeal carcinoma (NPC) is still unknown. In this study, aminooxyacetic acid (AOAA, an inhibitor of cystathionine-ß-synthase), dl-propargylglycine (PAG, an inhibitor of cystathionine-γ-lyase), and l-aspartic acid (l-Asp, an inhibitor of 3-mercaptopyruvate sulfurtransferase) were adopted to detect the role of endogenous H2 S in NPC growth. The results indicated that the combine (PAG + AOAA + l-Asp) group had higher inhibitory effect on the growth of NPC cells than the PAG, AOAA, and l-Asp groups. There were similar trends in the levels of apoptosis and reactive oxygen species (ROS). In addition, the combine group exhibited lower levels of phospho (p)-extracellular signal-regulated protein kinase but higher expressions of p-p38 and p-c-Jun N-terminal kinase than those in the AOAA, PAG, and l-Asp groups. Furthermore, the combine group exerted more potent inhibitory effect on NPC xenograft tumor growth without obvious toxicity. In summary, suppression of endogenous H2 S generation could dramatically inhibit NPC growth via the ROS/mitogen-activated protein kinase pathway. Endogenous H2 S may be a novel therapeutic target in human NPC cells. Effective inhibitors for H2 S-producing enzymes could be designed and developed for NPC treatment.
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Sulfuro de Hidrógeno , Neoplasias Nasofaríngeas , Humanos , Sulfuro de Hidrógeno/farmacología , Sulfuro de Hidrógeno/metabolismo , Cistationina , Carcinoma Nasofaríngeo , Especies Reactivas de Oxígeno , Sulfuros/farmacología , Neoplasias Nasofaríngeas/tratamiento farmacológicoRESUMEN
Chemical modifications in messenger RNA (mRNA) regulate gene expression and play critical roles in stress responses and diseases. Recently we have shown that N6-methyladenosine (m6A), the most abundant mRNA modification, promotes the repair of UVB-induced DNA damage by regulating global genome nucleotide excision repair (GG-NER). However, the roles of other mRNA modifications in the UVB-induced damage response remain understudied. N4-acetylcytidine (ac4C) is deposited in mRNA by the RNA-binding acetyltransferase NAT10. This NAT10-mediated ac4C in mRNA has been reported to increase both mRNA stability and translation. However, the role of ac4C and NAT10 in the UVB-induced DNA damage response remains poorly understood. Here we show that NAT10 plays a critical role in the repair of UVB-induced DNA damage lesions through regulating the expression of the key GG-NER gene DDB2. We found that knockdown of NAT10 enhanced the repair of UVB-induced DNA damage lesions by promoting the mRNA stability of DDB2. Our findings are in contrast to the previously reported role of NAT10-mediated ac4C deposition in promoting mRNA stability and may represent a novel mechanism for ac4C in the UVB damage response. Furthermore, NAT10 knockdown in skin cancer cells decreased skin cancer cell proliferation in vitro and tumorigenicity in vivo. Chronic UVB irradiation increases NAT10 protein levels in mouse skin. Taken together, our findings demonstrate a novel role for NAT10 in the repair of UVB-induced DNA damage products by decreasing the mRNA stability of DDB2 and suggest that NAT10 is a potential novel target for preventing and treating skin cancer.
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Daño del ADN , Neoplasias Cutáneas , Animales , Ratones , Reparación del ADN , Rayos Ultravioleta/efectos adversos , Neoplasias Cutáneas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
BACKGROUND: MRI-targeted biopsy (MRTB) improves the clinically significant prostate cancer (csPCa) detection rate with fewer biopsy cores in men with suspected PCa. However, whether concurrent systematic biopsy (SB) can be avoided in patients undergoing MRTB remains unclear. PURPOSE: To evaluate the potential value of MRI-based radiomics models in avoiding unnecessary SB in biopsy-naïve patients. STUDY TYPE: Retrospective. POPULATION: A total of 226 patients (mean age 66.6 ± 9.02 years) with suspicion of PCa (PI-RADS score ≥ 3) and received combined cognitive MRTB with SB were retrospectively recruited and randomly divided into training (N = 180) and test (N = 46) cohorts at an 8:2 ratio. FIELD STRENGTH/SEQUENCE: A 3.0 T, biparametric MRI (bpMRI) including T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) map. ASSESSMENT: The whole prostate gland (PG) and the index lesion (IL) were delineated. Three radiomics models of bpMRIPG , bpMRIIL , and bpMRIPG+IL were constructed, respectively, and the performance of each radiomics model was compared with that of PI-RADS assessment. STATISTICAL TESTS: The least absolute shrinkage and selection operator (LASSO) regression method was used to select texture features. The area under the curve (AUC) and decision curve analysis were used to estimate the models. RESULTS: The bpMRIPG+IL radiomics model exhibited good discrimination, calibration, and net benefits, which would reduce the SB biopsy in 71.2% and 71.4% of men with PI-RADS ≥ 5 lesions in the training and test cohorts, respectively. DATA CONCLUSION: A bpMRIPG+IL radiomics model may outperform PI-RADS category in help reducing unnecessary SB in biopsy-naïve patients. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 6.
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Neoplasias de la Próstata , Anciano , Humanos , Masculino , Persona de Mediana Edad , Biopsia , Biopsia Guiada por Imagen/métodos , Imagen por Resonancia Magnética/métodos , Próstata/diagnóstico por imagen , Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Estudios RetrospectivosRESUMEN
A novel time-resolved fluorescence nanoprobe (PBMO, PLNR-BSA-Mn2+-OPD) is fabricated for the label-free determination of acetylcholinesterase (AChE). The ZnGeO:Mn persistent luminescence nanorod (PLNR) and Mn(II) are, respectively, exploited as the signal molecule and quencher to construct the PBMO nanopobe using bovine serum albumin (BSA) as the surface-modified shell and o-phenylenediamine (OPD) as the reducing agent. In the presence of H2O2, the persistent luminescence of PBMO at 530 nm is enhanced remarkably within 30 s due to the oxidation of Mn(II). H2O2 can react with thiocholine (TCh), which is produced through the enzymatic degradation of acetylcholine (ATCh) by AChE. The PBMO nanoprobe is successfully applied to the determination of AChE in the linear range of 0.08-10 U L-1, with a detection limit of 0.03 U L-1 (3σ/s). The practicability of this PBMO nanoprobe is confirmed by accurately monitoring AChE contents in human serum samples, giving rise to satisfactory spiking recoveries of 96.2-103.6%.