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1.
Nano Lett ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38985501

RESUMO

Stationary energy storage infrastructure based on zinc-ion transport and storage chemistry is attracting more attention due to favorable metrics, including cost, safety, and recycling feasibility. However, splitting water and liquid electrolyte fluidity lead to cathode dissolution and Zn corrosion, resulting in rapid attenuation of the capacity and service life. Herein, a new architecture of solid-state electrolytes with high zinc ionic conductivity at room temperature was prepared via solidification of deep eutectic solvents utilizing MXene as nucleation additives. The ionic conductivity of MXene/ZCEs reached 6.69 × 10-4 S cm-1 at room temperature. Dendrite-free Zn plating/stripping with high reversibility can remain for over 2500 h. Subsequently, the fabricated solid-state zinc-ion battery with eliminated HER and suppressed Zn dendrites exhibited excellent cycling performance and could work normally in a range from -10 to 60 °C. This design inspired by eutectic solidification affords new insights into the multivalent solid electrochemistry suffering from slow ion migration.

2.
World J Clin Cases ; 12(20): 4091-4107, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39015934

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) is the primary form of lung cancer, and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this disease. However, the emergence of drug resistance significantly limits the effectiveness of these therapeutic strategies. Consequently, it is imperative to devise methods for accurately detecting and evaluating the efficacy of these treatments. AIM: To identify the metabolic signatures associated with neutrophil extracellular traps (NETs) and chemoimmunotherapy efficacy in NSCLC patients. METHODS: In total, 159 NSCLC patients undergoing first-line chemoimmunotherapy were enrolled. We first investigated the characteristics influencing clinical efficacy. Circulating levels of NETs and cytokines were measured by commercial kits. Liquid chromatography tandem mass spectrometry quantified plasma metabolites, and differential metabolites were identified. Least absolute shrinkage and selection operator, support vector machine-recursive feature elimination, and random forest algorithms were employed. By using plasma metabolic profiles and machine learning algorithms, predictive metabolic signatures were established. RESULTS: First, the levels of circulating interleukin-8, neutrophil-to-lymphocyte ratio, and NETs were closely related to poor efficacy of first-line chemoimmunotherapy. Patients were classed into a low NET group or a high NET group. A total of 54 differential plasma metabolites were identified. These metabolites were primarily involved in arachidonic acid and purine metabolism. Three key metabolites were identified as crucial variables, including 8,9-epoxyeicosatrienoic acid, L-malate, and bis(monoacylglycerol)phosphate (18:1/16:0). Using metabolomic sequencing data and machine learning methods, key metabolic signatures were screened to predict NET level as well as chemoimmunotherapy efficacy. CONCLUSION: The identified metabolic signatures may effectively distinguish NET levels and predict clinical benefit from chemoimmunotherapy in NSCLC patients.

4.
Neural Regen Res ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38845216

RESUMO

ABSTRACT: Poststroke cognitive impairment is a major secondary effect of ischemic stroke in many patients; however, few options are available for the early diagnosis and treatment of this condition. The aims of this study were to (1) determine the specific relationship between hypoxic and α-synuclein during the occur of poststroke cognitive impairment and (2) assess whether the serum phosphorylated α-synuclein level can be used as a biomarker for poststroke cognitive impairment. We found that the phosphorylated α-synuclein level was significantly increased and showed pathological aggregation around the cerebral infarct area in a mouse model of ischemic stroke. In addition, neuronal α-synuclein phosphorylation and aggregation were observed in the brain tissue of mice subjected to chronic hypoxia, suggesting that hypoxia is the underlying cause of α-synuclein-mediated pathology in the brains of mice with ischemic stroke. Serum phosphorylated α-synuclein levels in patients with ischemic stroke were significantly lower than those in healthy subjects, and were positively correlated with cognition levels in patients with ischemic stroke. Furthermore, a decrease in serum high-density lipoprotein levels in stroke patients was significantly correlated with a decrease in phosphorylated α-synuclein levels. Although ischemic stroke mice did not show significant cognitive impairment or disrupted lipid metabolism 14 days after injury, some of them exhibited decreased cognitive function and reduced phosphorylated α-synuclein levels. Taken together, our results suggest that serum phosphorylated α-synuclein is a potential biomarker for poststroke cognitive impairment.

5.
Front Pharmacol ; 15: 1413699, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38915471

RESUMO

The clinical application and biological function of interferon regulatory factor 1 (IRF1) in non-small cell lung cancer (NSCLC) patients undergoing chemoimmunotherapy remain elusive. The aim of this study was to investigate the predictive and prognostic significance of IRF1 in NSCLC patients. We employed the cBioPortal database to predict frequency changes in IRF1 and explore its target genes. Bioinformatic methods were utilized to analyze the relationship between IRF1 and immune regulatory factors. Retrospective analysis of clinical samples was conducted to assess the predictive and prognostic value of IRF1 in chemoimmunotherapy. Additionally, A549 cells with varying IRF1 expression levels were constructed to investigate its effects on NSCLC cells, while animal experiments were performed to study the role of IRF1 in vivo. Our findings revealed that the primary mutation of IRF1 is deep deletion and it exhibits a close association with immune regulatory factors. KRAS and TP53 are among the target genes of IRF1, with interferon and IL-2 being the predominantly affected pathways. Clinically, IRF1 levels significantly correlate with the efficacy of chemoimmunotherapy. Patients with high IRF1 levels exhibited a median progression-free survival (mPFS) of 9.5 months, whereas those with low IRF1 levels had a shorter mPFS of 5.8 months. IRF1 levels positively correlate with PD-L1 distribution and circulating IL-2 levels. IL-2 enhances the biological function of IRF1 and recapitulates its role in vivo in the knockdown group. Therefore, IRF1 may possess predictive and prognostic value for chemoimmunotherapy in NSCLC patients through the regulation of the IL-2 inflammatory pathway.

6.
Nanotechnology ; 35(38)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38906118

RESUMO

Herein, we demonstrate an optimization of dye-sensitized solar cells (DSSCs) through the development of single-layer and double-layer configurations. Focusing on the incorporation of brookite and anatase phases in varying ratios, the study aims to determine the optimal composition for enhanced photovoltaic performance. The active layer, composed of anatase- and brookite-TiO2nanoparticles, is further modified with a scattering layer comprising a mixture of anatase nanoparticles and brookite-TiO2in the form of nanocube or rice-like particles. The synthesis of TiO2nanostructures with various morphologies and phase compositions and their subsequent application in single-layer and double-layer DSSCs are presented. The results highlight the superior light-harvesting capabilities achieved through the strategic incorporation of brookite phase into the anatase phase, emphasizing the importance of optimizing the anatase: brookite ratio. The single-layer DSSCs exhibit a peak efficiency of 8.73%, achieved with a composition of 30 wt.% brookite and 70 wt.% anatase at a thickness of 15µms. In the context of double-layer DSSCs, the combined optimization of the active layer composition, scattering layer morphology, and utilization of anatase nanoparticles leads to a remarkable efficiency of 9.18%. These findings underscore the critical role of composition and morphology in enhancing the performance of DSSCs, showcasing the potential for brookite-based DSSCs in solar energy conversion.

7.
Biochem Genet ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831231

RESUMO

Myocardial ischemic (MI) injury is a common cardiovascular disease, and the potential therapeutic effects of ginsenoside Rb2 (Rb2) have been lately the focus of interest. Therefore, this study aimed to investigate the effects of Rb2 on pyroptosis of cardiomyocytes in MI progression. An in vitro MI model was developed by subjecting rat's cardiomyocytes (H9c2) to hypoxia/reoxygenation (H/R). The cell viability was determined by CCK-8 assay, while cell death was analyzed by propidium iodide staining. Similarly, pyroptosis-related protein levels and acetylation levels of apoptosis-associated speck-like protein containing a CARD (ASC) were detected by western blotting, and the relationship between Sirtuin 1 (SIRT1) and ASC was confirmed by co-immunoprecipitation (Co-IP) assay. Moreover, hematoxylin-eosin (H&E) and triphenyl tetrazolium chloride staining were used to study pathological structure and infarct size. It was found that post-Rb2 treatment significantly increased the cell viability and decreased the cell death and lactic dehydrogenase release, while the increased gasdermin D-N, NOD-like receptor thermal protein domain-associated protein 3, ASC, and cleaved-caspase-1 protein levels were significantly decreased in H/R-stimulated H9c2 cells. Moreover, the acetylation levels of H92c cells were decreased post-Rb2 treatment via increasing SIRT1 levels, while knocking down SIRT1, translated into an increase in ASC acetylation levels, leading to the increase in ASC protein stability and expressions. Additionally, the Rb2 effects on pyroptosis in H/R-stimulated H92c cells were reversed by overexpressing ASC, while reduced myocardial tissue damage was observed in MI rats following in vivo Rb2 treatment. Rb2 treatment inhibited pyroptosis in MI progression by decreasing the ASC levels. Mechanistically, Rb2 treatment increased the SIRT1 levels, further increasing the acetylation levels of ASC and decreasing the protein stability of ASC.

8.
Macromol Rapid Commun ; : e2400275, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830087

RESUMO

The advent of nonfullerene acceptors (NFAs) has greatly improved the photovoltaic performance of organic solar cells (OSCs). However, to compete with other solar cell technologies, there is a pressing need for accelerated research and development of improved NFAs as well as their compatible wide bandgap polymer donors. In this study, a novel electron-withdrawing building block, succinimide-substituted thiophene (TS), is utilized for the first time to synthesize three wide bandgap polymer donors: PBDT-TS-C5, PBDT-TSBT-C12, and PBDTF-TSBT-C16. These polymers exhibit complementary bandgaps for efficient sunlight harvesting and suitable frontier energy levels for exciton dissociation when paired with the extensively studied NFA, Y6. Among these donors, PBDTF-TSBT-C16 demonstrates the highest hole mobility and a relatively low highest occupied molecular orbital (HOMO) energy level, attributed to the incorporation of thiophene spacers and electron-withdrawing fluorine substituents. OSC devices based on the blend of PBDTF-TSBT-C16:Y6 achieve the highest power conversion efficiency of 13.21%, with a short circuit current density (Jsc) of 26.83 mA cm-2, an open circuit voltage (Voc) of 0.80 V, and a fill factor of 0.62. Notably, the Voc × Jsc product reaches 21.46 mW cm-2, demonstrating the potential of TS as an electron acceptor building block for the development of high-performance wide bandgap polymer donors in OSCs.

9.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(2): 296-304, 2024 Feb 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38755726

RESUMO

Traditional antibody drug conjugates (ADC) combine monoclonal antibodies with cytotoxic drugs to accurately strike cancer cells, but there are still many shortcomings in stability, targeting, efficacy, and safety. Novel ADC, such as bi-specific, site-specific, dual-payload, and pro-drug type ADC, can be optimized by simultaneously binding 2 different antigens or epitopes, selecting more stable linkers, coupling with specific amino acid sites of antibodies, carrying different drug payloads, and adopting prodrug strategies, while retaining the characteristics of traditional ADC. Significantly improving the stability, targeting, efficacy and safety of drugs can better meet the needs of clinical treatment. Novel ADC will play a more important role in cancer treatment in the future. Discussing the progress of novel ADC in cancer treatment and analyzing their advantages and challenges can provide theoretical support for the development of anti-cancer strategies and provide directions for drug research and development.


Assuntos
Imunoconjugados , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Imunoconjugados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Pró-Fármacos/uso terapêutico
10.
Sci Total Environ ; 933: 173166, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38735315

RESUMO

Lead (Pb) contamination in wheat grain is of great concern, especially in North China. Atmospheric deposition is a major contributor to Pb accumulation in wheat grain. Screening low Pb accumulating wheat varieties has been an effective method for addressing Pb contamination in wheat grain. However, identifying wheat varieties with low Pb accumulation based on foliar uptake of atmospheric Pb has been neglected. Therefore, two field trials with distinct atmospheric Pb deposition were conducted to screen for stable varieties with low Pb accumulation. It was verified that YB700 and CH58, which have high thousand-grain weights and stable low Pb accumulation in field 1 (0.19 and 0.13 mg kg-1) and field 2 (0.17 and 0.20 mg kg-1), respectively, were recommended for cultivation in atmospheric Pb contaminated farmlands in North China. Furthermore, indoor experiments were conducted to investigate Pb uptake by the roots and leaves of different wheat varieties. Our findings indicate that Pb accumulation in different wheat varieties is primarily influenced by foliar Pb uptake rather than root Pb uptake. Interestingly, there was a positive correlation (p < 0.05) between the Pb concentrations in leaves and the stomatal width and trichome length of the adaxial epidermal surface. Additionally, there is a positive correlation (p < 0.01) between the Pb concentration in the wheat grain and trichome length. In conclusion, the screening of wheat varieties with narrower stomatal widths or shorter trichomes based on foliar uptake pathways is an effective strategy for ensuring food safety in areas contaminated by atmospheric Pb.


Assuntos
Chumbo , Folhas de Planta , Poluentes do Solo , Triticum , Triticum/metabolismo , Chumbo/metabolismo , Folhas de Planta/metabolismo , China , Poluentes do Solo/metabolismo , Poluentes do Solo/análise , Monitoramento Ambiental/métodos , Poluentes Atmosféricos/análise
11.
BMC Psychiatry ; 24(1): 283, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627661

RESUMO

BACKGROUND: Depressive episodes in adolescents are often accompanied by various physical symptoms, but few studies have explored the association between depression and fever, This case study is the first to report the relationship between unexplained recurrent high fever and depression. CASE PRESENTATION: H is a 15 year old adolescent female currently in junior year. 2 + months ago, H gradually felt depressed after a class change. Around the time, the patient suddenly developed chills with no obvious trigger and fever. H was treated with anti-infective and anti-viral treatments all of which did not show significant improvement. No significant abnormality was seen in any of the related examinations. Considering that the patient's anxiety, depression and somatic symptoms were obvious during the course of the disease, she was given venlafaxine hydrochloride extended-release capsule 75 mg/d; tandospirone citrate capsule 10 mg Bid; alprazolam tablets 0.4 mg qn to improve mood and sleep; supplemented with transcranial repetitive magnetic stimulation therapy 2 times/d; visible light therapy 1 time/d and psychological counseling once. Over the 6 days of treatment, the patient's body temperature gradually returned to the normal range and her mood improved significantly. CONCLUSION: Depression should be considered a potential cause of unexplained recurrent fevers in adolescents, even when the temperature is significantly outside the normal range.


Assuntos
Psicoterapia , Humanos , Adolescente , Feminino , Cloridrato de Venlafaxina/uso terapêutico
12.
Small Methods ; : e2301521, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319029

RESUMO

The study has developed two hemi-isoindigo (HID)-based polymers for printed flexible resistor-type nitrogen oxide (NO2 ) sensors: poly[2-ethylhexyl 3-((3'",4'-bis(dodecyloxy)-3,4-dimethoxy-[2,2':5',2'"-terthiophen]-5-yl)methylene)-2-oxoindoline-1-carboxylate] (P1) and poly[2-ethylhexyl 2-oxo-3-((3,3'",4,4'-tetrakis(dodecyloxy)-[2,2':5',2'"-terthiophen]-5-yl)methylene)indoline-1-carboxylate] (P2). These polymers feature thermally removable carbamate side chains on the HID units, providing solubility and creating molecular cavities after thermal annealing. These cavities enhance NO2 diffusion, and the liberated unsubstituted amide ─C(═O)NH─ groups readily form robust double hydrogen bonds (DHB), as demonstrated by computer simulations. Furthermore, both polymers possess elevated highest occupied molecular orbital (HOMO) energy levels of -4.74 and -4.77 eV, making them highly susceptible to p-doping by NO2 . Gas sensors fabricated from P1 and P2 films, anneal under optimized conditions to partially remove carbamate side chains, exhibit remarkable sensitivities of +1400% ppm-1 and +3844% ppm-1 , and low detection limit (LOD) values of 514 ppb and 38.9 ppb toward NO2 , respectively. These sensors also demonstrate excellent selectivity for NO2 over other gases.

13.
Nanomicro Lett ; 16(1): 119, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363512

RESUMO

Due to the constraints imposed by physical effects and performance degradation, silicon-based chip technology is facing certain limitations in sustaining the advancement of Moore's law. Two-dimensional (2D) materials have emerged as highly promising candidates for the post-Moore era, offering significant potential in domains such as integrated circuits and next-generation computing. Here, in this review, the progress of 2D semiconductors in process engineering and various electronic applications are summarized. A careful introduction of material synthesis, transistor engineering focused on device configuration, dielectric engineering, contact engineering, and material integration are given first. Then 2D transistors for certain electronic applications including digital and analog circuits, heterogeneous integration chips, and sensing circuits are discussed. Moreover, several promising applications (artificial intelligence chips and quantum chips) based on specific mechanism devices are introduced. Finally, the challenges for 2D materials encountered in achieving circuit-level or system-level applications are analyzed, and potential development pathways or roadmaps are further speculated and outlooked.

14.
Small ; 20(5): e2305136, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37759415

RESUMO

This work addresses the challenges in developing carbon fiber paper-based supercapacitors (SCs) with high energy density by focusing on the limited capacity of carbon fiber. To overcome this limitation, a sponge-like porous carbon fiber paper enriched with oxygen functional groups (OFGs) is prepared, and Cu(OH)2 nanorods are grown on its surface to construct the SC anode. This design results in a multi-layered carbon fiber paper-based electrode with a specific structure and enhanced capacitance. The Cu(OH)2 @PCFP anode exhibits an areal capacitance of 547.83 mF cm-2 at a current density of 1 mA cm-2 and demonstrates excellent capacitance retention of 99.8% after 10 000 cycles. Theoretical calculations further confirm that the Cu(OH)2 /OFGs-graphite heterostructure exhibits higher conductivity, facilitating faster charge transfer. A solid-state SC is successfully assembled using Ketjen Black@PCFP as the cathode and KOH/PVA as the gel electrolyte. The resulting device exhibits an energy density of 0.21 Wh cm-2 at 1.50 mW cm-2 , surpassing the performance of reported Cu(OH)2 SCs. This approach, combining materials design with an understanding of underlying mechanisms, not only expands the range of electrode materials but also provides valuable insights for the development of high-capacity energy storage devices.

15.
Glob Med Genet ; 10(4): 285-300, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37915460

RESUMO

Background The purpose of our study was to construct a prognostic model based on ferroptosis-related gene signature to improve the prognosis prediction of lung squamous carcinoma (LUSC). Methods The mRNA expression profiles and clinical data of LUSC patients were downloaded. LUSC-related essential differentially expressed genes were integrated for further analysis. Prognostic gene signatures were identified through random forest regression and univariate Cox regression analyses for constructing a prognostic model. Finally, in a preliminary experiment, we used the reverse transcription-quantitative polymerase chain reaction assay to verify the relationship between the expression of three prognostic gene features and ferroptosis. Results Fifty-six ferroptosis-related essential genes were identified by using integrated analysis. Among these, three prognostic gene signatures (HELLS, POLR2H, and POLE2) were identified, which were positively affected by LUSC prognosis but negatively affected by immune cell infiltration. Significant overexpression of immune checkpoint genes occurred in the high-risk group. In preliminary experiments, we confirmed that the occurrence of ferroptosis can reduce three prognostic gene signature expression. Conclusions The three ferroptosis-related genes could predict the LUSC prognostic risk of antitumor immunity.

16.
Mol Cell Biochem ; 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37639200

RESUMO

Dysregulation of long non-coding RNAs (lncRNAs) is associated with the tumorigenesis and ferroptosis of non-small cell lung cancer (NSCLC). BBOX1 antisense RNA 1 (BBOX1-AS1) functions as an oncogenic driver in NSCLC. Here, we aim to investigate the regulation effect and underlying mechanism of BBOX1-AS1 in NSCLC progression and ferroptosis. RNA expression was detected by quantitative real-time PCR (qRT-PCR), and protein expression was measured by immunoblotting. Cell growth was assessed by CCK-8 and colony formation assays. Transwell assay was applied to evaluate cell invasion and migration. RNA pull-down and dual-luciferase reporter assays were applied to verify the relationship between miR-326 and BBOX1-AS1 or prominin 2 (PROM2). The role of BBOX1-AS1 in NSCLC tumorigenicity was also analyzed by xenograft assays. Silencing BBOX1-AS1 or PROM2 impeded NSCLC cell growth, migration, and invasion. Silencing BBOX1-AS1 induced cell apoptosis and ferroptosis. BBOX1-AS1 up-regulated PROM2 expression, and re-expression of PROM2 reversed the effects of BBOX1-AS1 depletion on cell malignant phenotypes and ferroptosis. BBOX1-AS1 post-transcriptionally modulated PROM2 expression by sponging miR-326. MiR-326 was validated as a mediator of BBOX1-AS1 in regulating NSCLC cell malignant phenotypes and ferroptosis. Additionally, BBOX1-AS1 deficiency in vivo resulted in the suppression of xenograft tumor growth. Together, our study defines a novel BBOX1-AS1/miR-326/PROM2 axis in regulating NSCLC malignant progression and ferroptosis, offering new evidence for the oncogenic role of BBOX1-AS1 in NSCLC. These findings may provide a basis for the future usage of targeting BBOX1-AS1 in NSCLC treatment.

17.
J Cereb Blood Flow Metab ; 43(10): 1656-1671, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37395346

RESUMO

Ischemic stroke (IS) induces neurological damage due to cerebrovascular occlusion. Restoring blood perfusion to the ischemic brain area in a timely fashion is the most effective treatment strategy. Hypoxia is an effective way of restoring blood perfusion by improving cerebrovascular microcirculation, while the effect varies greatly depending on hypoxic mode. This study aimed to screen for the optimal hypoxic mode to improve cerebrovascular microcirculation and prevent IS. Here, we found that compared with continuous hypoxia (CH), intermittent hypoxia (IH) significantly improved cerebral blood flow and oxygen saturation in mice without causing neurological impairment. By analyzing cerebrovascular microcirculation from mice, we found that the IH mode (13%, 5*10) with 13% O2, 5 min interval, and 10 cycles per day significantly improved the cerebrovascular microcirculation by promoting angiogenesis without affecting the integrity of the blood-brain barrier. In addition, IH (13%, 5*10) treatment of distal middle cerebral artery occlusion (dMCAO) mice significantly alleviated neurological dysfunction and reduced cerebral infarct volume by improving cerebrovascular microcirculation. CH had none of these positive effects. In summary, our study screened for an appropriate intermittent hypoxic mode that could improve cerebrovascular microcirculation, laying a theoretical foundation for the prevention and treatment of IS in clinical practice.


Assuntos
Hipóxia-Isquemia Encefálica , Hipóxia , Camundongos , Animais , Hipóxia-Isquemia Encefálica/prevenção & controle , Encéfalo/irrigação sanguínea , Barreira Hematoencefálica , Infarto da Artéria Cerebral Média , Circulação Cerebrovascular/fisiologia
18.
Chem Commun (Camb) ; 59(64): 9774-9777, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37486167

RESUMO

S-Nitrosothiols (SNOs) serve as endogenous carriers and donors of NO within living cells, releasing nitrosonium ions (NO+), NO, or other nitroso derivatives. In this study, we present a bioinspired {Co(NO)2}10 complex 1 that achieved S-nitrosation towards Cys residues. The incorporation of a ferrocenyl group in 1 allowed for fine-tuning of the nitrosation reaction, taking advantage of the redox ability of Cys residues. Complex 1 was synthesized and characterized, demonstrating its NO translation reactivity. Furthermore, complex 1 successfully converted Cys into S-nitrosocysteine (Cys-SNO), as confirmed by UV-Vis, IR, and XAS spectroscopy. This study presents a promising approach for S-nitrosation of Cys residues for further exploration in the modification of Cys-containing peptides.


Assuntos
Cisteína , S-Nitrosotióis , Nitrosação , Cisteína/química , S-Nitrosotióis/química , S-Nitrosotióis/metabolismo , Óxido Nítrico/química , Oxirredução
19.
Int J Biol Sci ; 19(11): 3307-3323, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37496996

RESUMO

Androgenetic alopecia (AGA) affects more than half of the adult population worldwide and is primarily caused by the binding of dihydrotestosterone (DHT) to androgen receptors (AR). However, the mechanisms by which AR affects hair follicles remain unclear. In our study, we found that miR-221 significantly suppressed hair growth and the proliferation of dermal papilla cells (DPCs) and dermal sheath cells (DSCs) in AGA patients. Interestingly, miR-221 and AR were mainly co-located in the same part of the hair follicle. Mechanistic analysis revealed that AR directly promoted the transcription of miR-221, which in turn suppressed IGF-1 expression, leading to the inactivation of the MAPK pathway in DPCs and the PI3K/AKT pathway in DSCs. In AGA patients, miR-221 expression was positively correlated with AR expression and negatively correlated with IGF-1 expression. Our findings indicate that miR-221, as a direct target of AR, plays a crucial role in the pathogenesis of AGA, making it a novel biomarker and potential therapeutic target for treating AGA.


Assuntos
MicroRNAs , Receptores Androgênicos , Adulto , Humanos , Alopecia/genética , Alopecia/tratamento farmacológico , Fator de Crescimento Insulin-Like I/genética , MicroRNAs/genética , MicroRNAs/uso terapêutico , Fosfatidilinositol 3-Quinases , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo
20.
Front Immunol ; 14: 1121096, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37081881

RESUMO

Background: Microbial infection is accompanied by remodeling of the host transcriptome. Involvement of A-to-I RNA editing has been reported during viral infection but remains to be elucidated during intracellular bacterial infections. Results: Herein we analyzed A-to-I RNA editing during intracellular bacterial infections based on 18 RNA-Seq datasets of 210 mouse samples involving 7 tissue types and 8 intracellular bacterial pathogens (IBPs), and identified a consensus signature of RNA editing for IBP infections, mainly involving neutrophil-mediated innate immunity and lipid metabolism. Further comparison of host RNA editing patterns revealed remarkable similarities between pneumonia caused by IBPs and single-strand RNA (ssRNA) viruses, such as altered editing enzyme expression, editing site numbers, and levels. In addition, functional enrichment analysis of genes with RNA editing highlighted that the Rab GTPase family played a common and vital role in the host immune response to IBP and ssRNA viral infections, which was indicated by the consistent up-regulated RNA editing of Ras-related protein Rab27a. Nevertheless, dramatic differences between IBP and viral infections were also observed, and clearly distinguished the two types of intracellular infections. Conclusion: Our study showed transcriptome-wide host A-to-I RNA editing alteration during IBP and ssRNA viral infections. By identifying and comparing consensus signatures of host A-to-I RNA editing, our analysis implicates the importance of host A-to-I RNA editing during these infections and provides new insights into the diagnosis and treatment of infectious diseases.


Assuntos
Infecções Bacterianas , Infecções por Vírus de RNA , Vírus de RNA , Viroses , Animais , Camundongos , Edição de RNA , Viroses/genética , RNA , Vírus de RNA/genética , Infecções Bacterianas/genética
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