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1.
Brain Res ; 1838: 148977, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38705556

RESUMO

OBJECTIVE: Previous research has suggested a connection between major depressive disorder (MDD) and certain comorbidities, including gastrointestinal issues, thyroid dysfunctions, and glycolipid metabolism abnormalities. However, the relationships between these factors and asymmetrical alterations in functional connectivity (FC) in adults with MDD remain unclear. METHOD: We conducted a study on a cohort of 42 MDD patients and 42 healthy controls (HCs). Participants underwent comprehensive clinical assessments, including evaluations of blood lipids and thyroid hormone levels, as well as resting-state functional magnetic resonance imaging (Rs-fMRI) scans. Data analysis involved correlation analysis to compute the parameter of asymmetry (PAS) for the entire brain's functional connectome. We then examined the interrelationships between abnormal PAS regions in the brain, thyroid hormone levels, and blood lipid levels. RESULTS: The third-generation ultra-sensitive thyroid stimulating hormone (TSH3UL) level was found to be significantly lower in MDD patients compared to HCs. The PAS score of the left inferior frontal gyrus (IFG) decreased, while the bilateral posterior cingulate cortex (Bi-PCC) PAS increased in MDD patients relative to HCs. Notably, the PAS score of the left IFG negatively correlated with both TSH and total cholesterol (CHOL) levels. However, these correlations lose significance after the Bonferroni correction. CONCLUSION: MDD patients demonstrated abnormal asymmetry in resting-state FC (Rs-FC) within the fronto-limbic system, which may be associated with CHOL and thyroid hormone levels.

2.
J Nucl Med ; 65(Suppl 1): 54S-63S, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38719233

RESUMO

In recent decades, researchers worldwide have directed their efforts toward enhancing the quality of PET imaging. The detection sensitivity and image resolution of conventional PET scanners with a short axial field of view have been constrained, leading to a suboptimal signal-to-noise ratio. The advent of long-axial-field-of-view PET scanners, exemplified by the uEXPLORER system, marked a significant advancement. Total-body PET imaging possesses an extensive scan range of 194 cm and an ultrahigh detection sensitivity, and it has emerged as a promising avenue for improving image quality while reducing the administered radioactivity dose and shortening acquisition times. In this review, we elucidate the application of the uEXPLORER system at the Sun Yat-sen University Cancer Center, including the disease distribution, patient selection workflow, scanning protocol, and several enhanced clinical applications, along with encountered challenges. We anticipate that this review will provide insights into routine clinical practice and ultimately improve patient care.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Imagem Corporal Total , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Imagem Corporal Total/métodos , Neoplasias/diagnóstico por imagem , Centros de Atenção Terciária , Institutos de Câncer , Processamento de Imagem Assistida por Computador/métodos
3.
J Am Chem Soc ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38743019

RESUMO

Selective RNA delivery is required for the broad implementation of RNA clinical applications, including prophylactic and therapeutic vaccinations, immunotherapies for cancer, and genome editing. Current polyanion delivery relies heavily on cationic amines, while cationic guanidinium systems have received limited attention due in part to their strong polyanion association, which impedes intracellular polyanion release. Here, we disclose a general solution to this problem in which cationic guanidinium groups are used to form stable RNA complexes upon formulation but at physiological pH undergo a novel charge-neutralization process, resulting in RNA release. This new delivery system consists of guanidinylated serinol moieties incorporated into a charge-altering releasable transporter (GSer-CARTs). Significantly, systematic variations in structure and formulation resulted in GSer-CARTs that exhibit highly selective mRNA delivery to the lung (∼97%) and spleen (∼98%) without targeting ligands. Illustrative of their breadth and translational potential, GSer-CARTs deliver circRNA, providing the basis for a cancer vaccination strategy, which in a murine model resulted in antigen-specific immune responses and effective suppression of established tumors.

4.
Nat Genet ; 56(5): 925-937, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38658794

RESUMO

CRISPR base editing screens enable analysis of disease-associated variants at scale; however, variable efficiency and precision confounds the assessment of variant-induced phenotypes. Here, we provide an integrated experimental and computational pipeline that improves estimation of variant effects in base editing screens. We use a reporter construct to measure guide RNA (gRNA) editing outcomes alongside their phenotypic consequences and introduce base editor screen analysis with activity normalization (BEAN), a Bayesian network that uses per-guide editing outcomes provided by the reporter and target site chromatin accessibility to estimate variant impacts. BEAN outperforms existing tools in variant effect quantification. We use BEAN to pinpoint common regulatory variants that alter low-density lipoprotein (LDL) uptake, implicating previously unreported genes. Additionally, through saturation base editing of LDLR, we accurately quantify missense variant pathogenicity that is consistent with measurements in UK Biobank patients and identify underlying structural mechanisms. This work provides a widely applicable approach to improve the power of base editing screens for disease-associated variant characterization.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Genótipo , Fenótipo , RNA Guia de Sistemas CRISPR-Cas , Humanos , Edição de Genes/métodos , RNA Guia de Sistemas CRISPR-Cas/genética , Teorema de Bayes , Receptores de LDL/genética , Células HEK293
5.
Signal Transduct Target Ther ; 9(1): 85, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38575611

RESUMO

NEDD8 (Neural precursor cell expressed developmentally downregulated protein 8) is an ubiquitin-like protein that is covalently attached to a lysine residue of a protein substrate through a process known as neddylation, catalyzed by the enzyme cascade, namely NEDD8 activating enzyme (E1), NEDD8 conjugating enzyme (E2), and NEDD8 ligase (E3). The substrates of neddylation are categorized into cullins and non-cullin proteins. Neddylation of cullins activates CRLs (cullin RING ligases), the largest family of E3 ligases, whereas neddylation of non-cullin substrates alters their stability and activity, as well as subcellular localization. Significantly, the neddylation pathway and/or many neddylation substrates are abnormally activated or over-expressed in various human diseases, such as metabolic disorders, liver dysfunction, neurodegenerative disorders, and cancers, among others. Thus, targeting neddylation becomes an attractive strategy for the treatment of these diseases. In this review, we first provide a general introduction on the neddylation cascade, its biochemical process and regulation, and the crystal structures of neddylation enzymes in complex with cullin substrates; then discuss how neddylation governs various key biological processes via the modification of cullins and non-cullin substrates. We further review the literature data on dysregulated neddylation in several human diseases, particularly cancer, followed by an outline of current efforts in the discovery of small molecule inhibitors of neddylation as a promising therapeutic approach. Finally, few perspectives were proposed for extensive future investigations.


Assuntos
Proteínas Culina , Neoplasias , Humanos , Proteínas Culina/metabolismo , Ubiquitinas/genética , Ubiquitina-Proteína Ligases/metabolismo , Processamento de Proteína Pós-Traducional , Neoplasias/tratamento farmacológico , Neoplasias/genética
6.
Front Pharmacol ; 15: 1330376, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601472

RESUMO

Aristolochic acid (AA)-induced acute kidney injury (AKI) presents with progressive decline in renal function and rapid progression to end-stage renal disease. Among the multiple mechanisms identified in AKI, ferroptosis has been shown to be involved in various forms of AKI. But few studies have elucidated the role of ferroptosis in AA-induced AKI. In this study, we investigated the role of ferroptosis in AA-induced acute renal tubular injury in vivo and in vitro. Mice with acute aristolochic acid nephropathy showed increased malondialdehyde levels, aggravated lipid peroxidation, decreased superoxide dismutase activity, and glutathione depletion. The expression of glutathione peroxidase 4 was decreased and the expression of acyl-CoA synthetase long-chain family member 4 was increased. Inhibition of ferroptosis by ferrostatin-1 significantly improved the renal function, reduced histopathological lesions, partially alleviated lipid peroxidation, and restored the antioxidant capacity. In vitro studies also revealed that AA significantly reduced cell viability, induced reactive oxygen species production, increased intracellular iron level and decreased ferroptosis-related protein expression. Inhibition of ferroptosis significantly increased cell viability and attenuated AA-induced renal tubular epithelial cell injury. It is suggested that ferroptosis plays an important role in AA-induced acute tubular injury. And inhibition of ferroptosis may exert renoprotective effects possibly by preventing lipid peroxidation, restoring the antioxidant activity or regulating iron metabolism.

7.
Mater Horiz ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38686502

RESUMO

Efficient uranium extraction from seawater is critical for the development of the nuclear industry. Herein, a polydopamine/salicylaldoxime decorated hierarchical zeolitic imidazolate framework-8 (H-PDA/SA-ZIF-8) is constructed by using a controlled etching process. Benefiting from the combination of PDA/SA and the zeolitic imidazolate framework-8 (ZIF-8), as well as a controlled etching process, the H-PDA/SA-ZIF-8 possesses multiaffinity sites, excellent specific surface area (1234.92 m2 g-1), and a hierarchical pore structure. The H-PDA/SA-ZIF-8 exhibits excellent adsorption capacity (Qm = 869.6 mg g-1), selectivity, and reusability in uranium adsorption. The adsorption process of H-PDA/SA-ZIF-8 fits very well with the Langmuir isotherm model and pseudo-second-order models, and the adsorption process equilibrates within 20 min (C0 = 20 mg L-1). Furthermore, the H-PDA/SA-ZIF-8 shows remarkable antibacterial ability. Impressively, the adsorption capacity of H-PDA/SA-ZIF-8 to uranium in natural seawater reaches 6.9 mg g-1 after circulation for 15 days. Therefore, the H-PDA/SA-ZIF-8 is a promising and fascinating material for uranium extraction from natural seawater.

8.
Perit Dial Int ; 44(3): 194-202, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38449341

RESUMO

BACKGROUND: Fibroblast growth factor 23 (FGF23) is a phosphate-regulating hormone that is secreted in large amounts early in chronic kidney disease. In this cohort, we aimed to investigate the association between serum FGF23 concentration and mortality in patients undergoing peritoneal dialysis (PD). METHODS: Serum FGF23 level was determined by enzyme-linked immunosorbent assay (ELISA) in a large 15-year prospective cohort study of PD patients with stored serum samples at baseline. Kaplan-Meier survival curves and Cox proportional hazards models were performed to characterise the relationship of FGF23 with mortality. RESULTS: A total of 737 incident PD patients were analysed. The baseline median FGF23 concentration was 683.2 (518.5-896.2) pg/mL. Age, serum phosphorus, high-density lipoprotein cholesterol and high-sensitivity C-reactive protein were independently correlated with serum FGF23 concentration. During a median follow-up of 66.7 (41.1-95.4) months, 171 of the 737 participants (23.2%) died, including 84 (49.1%) cardiovascular disease-related and 50 (29.2%) infection-related deaths. Multivariable Cox regression analysis showed that the adjusted hazard ratios of the highest tertile of serum FGF23 compared with those in the lowest tertile were 1.36 (95% confidence interval (CI): 0.89-2.07; p = 0.154), 0.75 (95% CI: 0.40-1.38; p = 0.353) and 2.66 (95% CI: 1.15-6.15; p = 0.022) for all-cause, cardiovascular disease-related and infection-related mortality, respectively. CONCLUSION: High serum FGF23 concentration is associated with a higher risk of infection-related death for incident PD patients.


Assuntos
Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos , Falência Renal Crônica , Diálise Peritoneal , Humanos , Fatores de Crescimento de Fibroblastos/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Falência Renal Crônica/terapia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/sangue , Adulto , Modelos de Riscos Proporcionais , Estudos de Coortes , Estimativa de Kaplan-Meier , Medição de Risco , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/sangue , Ensaio de Imunoadsorção Enzimática
9.
Front Pharmacol ; 15: 1308655, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38449808

RESUMO

Objective: Psoralea corylifolia L. (FP) has received increasing attention due to its potential hepatotoxicity. Methods: In this study, zebrafish were treated with different concentrations of an aqueous extract of FP (AEFP; 40, 50, or 60 µg/mL), and the hepatotoxic effects of tonicity were determined by the mortality rate, liver morphology, fluorescence area and intensity of the liver, biochemical indices, and pathological tissue staining. The mRNA expression of target genes in the bile acid metabolic signaling pathway and lipid metabolic pathway was detected by qPCR, and the mechanism of toxicity was initially investigated. AEFP (50 µg/mL) was administered in combination with FXR or a peroxisome proliferator-activated receptor α (PPARα) agonist/inhibitor to further define the target of toxicity. Results: Experiments on toxic effects showed that, compared with no treatment, AEFP administration resulted in liver atrophy, a smaller fluorescence area in the liver, and a lower fluorescence intensity (p < 0.05); alanine transaminase (ALT), aspartate transaminase (AST), and γ-GT levels were significantly elevated in zebrafish (p < 0.01), and TBA, TBIL, total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were elevated to different degrees (p < 0.05); and increased lipid droplets in the liver appeared as fatty deposits. Molecular biological validation revealed that AEFP inhibited the expression of the FXR gene, causing an increase in the expression of the downstream genes SHP, CYP7A1, CYP8B1, BSEP, MRP2, NTCP, peroxisome proliferator-activated receptor γ (PPARγ), ME-1, SCD-1, lipoprotein lipase (LPL), CPT-1, and CPT-2 and a decrease in the expression of PPARα (p < 0.05). Conclusion: This study demonstrated that tonic acid extracts are hepatotoxic to zebrafish through the inhibition of FXR and PPARα expression, thereby causing bile acid and lipid metabolism disorders.

10.
J Biomol Struct Dyn ; : 1-13, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38497800

RESUMO

The hydrolysis of lignocellulose into fermentable monosaccharides using cellulases represents a critical stage in lignocellulosic bioconversion. However, the inactivation of cellulase in the presence of lignin is attributed to the high cost of biofinery. To address this challenge, a comprehensive investigation into the structure-function relationship underlying lignin-driven cellulase inactivation is essential. In this study, molecular docking and molecular dynamics (MD) simulations were employed to explore the impacts of lignin fragments on the catalytic efficiency of cellulase at the atomic level. The findings revealed that soluble lignin fragments and cellulose could spontaneously form stable complexes with cellulase, indicating a competitive binding scenario. The enzyme's structure remained unchanged upon binding to lignin. Furthermore, specific amino acid residues have been identified as involved in interactions with lignin and cellulose. Hydrophobic interactions were found to dominate the binding of lignin to cellulase. Based on the mechanisms underlying the interactions between lignin fragments and cellulase, decreased hydrophobicity and change in the charge of lignin may mitigate the inhibition of cellulase. Furthermore, site mutations and chemical modification are also feasible to improve the efficiency of cellulase. This study may contribute valuable insights into the design of more lignin-resistant enzymes and the optimization of lignocellulosic pretreatment technologies.Communicated by Ramaswamy H. Sarma.

11.
J Sci Food Agric ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38445560

RESUMO

BACKGROUND: Whole wheat steamed bread has been recommended for its potential nutritional benefits to human health. Given the positive role of both organic acid and alkali in improving dough development and product quality, the present study investigated the effects of neutralization by addition of alkali (Na2CO3) after dough acidification with traditional Jiaozi starter on the properties of whole wheat dough. RESULTS: The population of yeast and lactic acid bacteria and the acidification level of the dough increased significantly after fermentation with Jiaozi. Incorporation of alkali greatly improved the leavening capacity of the remixed dough and the quality of steamed bread. Jiaozi fermentation and alkali addition changed the water distribution patterns (T2) and affected the secondary structures of gluten protein, starch crystallinity and pasting properties. The storage modulus (G') of the dough increased significantly with the alkali addition, which could be attributed to the promoted cross-linking of the gluten structure and the altered hydration state of the macromolecules. CONCLUSION: The results of the present study indicate that a combination of Jiaozi fermentation and alkali addition could improve the technological properties of whole wheat dough and the quality of steamed bread. The results will help us to further explore the potential application of moderate acidification and alkali addition in the production of leavened whole wheat products. © 2024 Society of Chemical Industry.

12.
J Appl Toxicol ; 44(6): 919-932, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38400677

RESUMO

Isobavachalcone (IBC) is a flavonoid component derived from Psoraleae Fructus that can increase skin pigmentation and treat vitiligo. However, IBC has been reported to be hepatotoxic. Current studies on IBC hepatotoxicity are mostly on normal organisms but lack studies on hepatotoxicity in patients. This study established the depigmented zebrafish model by using phenylthiourea (PTU) and investigated the difference in hepatotoxicity between normal and depigmented zebrafish caused by IBC and the underlying mechanism. Morphological, histological, and ultrastructural examination and RT-qPCR verification were used to evaluate the effects of IBC on the livers of zebrafish larvae. IBC significantly decreased liver volume, altered lipid metabolism, and induced pathological and ultrastructural changes in the livers of zebrafish with depigmentation compared with normal zebrafish. The RNA-sequencing and RT-qPCR results showed that the difference in hepatotoxicity between normal and depigmented zebrafish caused by IBC was closely related to the calcium signaling pathway, lipid decomposition and metabolism, and oxidative stress. This work delved into the mechanism of the enhanced IBC-induced hepatotoxicity in depigmented zebrafish and provided a new insight into the hepatotoxicity of IBC.


Assuntos
Sinalização do Cálcio , Chalconas , Doença Hepática Induzida por Substâncias e Drogas , Peixe-Zebra , Animais , Chalconas/toxicidade , Sinalização do Cálcio/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Transtornos do Metabolismo dos Lipídeos/induzido quimicamente , Transtornos do Metabolismo dos Lipídeos/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos
13.
J Hazard Mater ; 467: 133735, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38335620

RESUMO

Cu2+ contamination and food spoilage raise food and drinking water safety issues, posing a serious threat to human health. Besides, Cu2+ and H2S levels indicate excess Cu2+-caused diseases and protein-containing food spoilage. Herein, a coumarin-containing bifunctional paper-based fluorescent platform integrated with a straightforward smartphone color recognition app is developed by an all-in-one strategy. The proposed fluorescent materials can simultaneously detect Cu2+ and H2S for on-demand food and drinking water safety monitoring at home. Specifically, a coumarin-derived fluorescence sensor (referred to as CMIA) with a low detection limit (0.430 µM) and high-selectivity/-sensitivity for Cu2+ is synthesized through a simple one-step route and then loaded onto commercially used cellulose fiber filter paper to engineer a biomass-based fluorescent material (CMIA-FP). The CMIA-FP offers user-friendly, high-precision, fast-responsive, and real-time visual monitoring of Cu2+. Moreover, CMIA forms a chemically stable complex with Cu2+, loaded onto filter paper to prepare another biomass-based fluorescent platform (CMIA-CU-FP) for visual real-time monitoring of H2S. Based on the exquisite composition design, the proposed dual-function paper-based fluorescent materials equipped with a smartphone color recognition program concurrently realize fast, accurate, and easy real-time monitoring of Cu2+ in drinking water and H2S in chicken breast-/shrimp-spoilage, demonstrating an effective detection strategy for the Cu2+ and H2S monitoring and presenting the new type of biomass-based platforms for concentrated reflection of drinking water and food safety.


Assuntos
Água Potável , Humanos , Alimentos Marinhos , Biomassa , Celulose , Corantes , Cumarínicos
14.
Aging (Albany NY) ; 16(3): 2542-2562, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38305811

RESUMO

The H2A.Z variant histone 1 (H2AZ1) is aberrantly expressed in various tumors, correlating with an unfavorable prognosis. However, its role in hepatocellular carcinoma (HCC) remains unclear. We aimed to elucidate the pathways affected by H2AZ1 and identify promising therapeutic targets for HCC. Following bioinformatic analysis of gene expression and clinical data from The Cancer Genome Atlas and Gene Expression Omnibus database, we found 6,344 dysregulated genes related to H2AZ1 overexpression in HCC tissues (P < 0.05). We performed weighted gene co-expression network analysis to identify the gene module most related to H2AZ1. The H2AZ1-based index was further developed using Cox regression analysis, which revealed that the poor prognosis in the high H2AZ1-based index group could be attributed to elevated tumor stemness (P < 0.05). Moreover, the clinical model showed good prognostic potential (AUC > 0.7). We found that H2AZ1 knockdown led to reduced superoxide dismutase (SOD) activity, elevated malondialdehyde (MDA) levels, and increased apoptosis rate in tumor cells (P < 0.001). Thus, we developed an H2AZ1-based index model with the potential to predict the prognosis of patients with HCC. Our findings provide initial evidence that H2AZ1 overexpression plays a pivotal role in HCC initiation and progression.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Cognição , Histonas , Neoplasias Hepáticas/genética , Prognóstico
15.
Heliyon ; 10(3): e25342, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38356520

RESUMO

The construction system's complexity can generate substantial uncertainties during emergencies. Resilience, as a new perspective on emergency response, can significantly mitigate these challenges. This paper introduces an innovative model to assess the resilience of construction emergency response processes utilizing a scaffold collapse scenario as a demonstrative case study. Grounded in resilience engineering, our model integrates the merits of the Functional Resonance Analysis Method (FRAM) with the probabilistic strengths of Bayesian Networks (BNs). The process commences with FRAM, mapping out the emergency response in qualitative terms by identifying functions, variabilities, and couplings. This culminates in a topological network which serves as a foundational structure for the directed Complex Network (CN) and the BN model. Thereafter, the Delphi method and the modified K-shell (MKS) decomposition algorithm guide the computation of prior probabilities for root nodes and the conditional probability table within the BN model. Subsequently, the BN model is subjected to a simulation using the AgenaRisk software, executing both forward and backward propagation as well as sensitivity analyses. Our findings pinpoint "Intersectoral Coordination and Linkage" as the most crucial function, with rapidity being the most sensitive aspect influencing resilience during a scaffold collapse emergency response process.

16.
Nat Commun ; 15(1): 1066, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316825

RESUMO

Presynthesized perovskite quantum dots are very promising for making films with different compositions, as they decouple crystallization and film-formation processes. However, fabricating large-area uniform films using perovskite quantum dots is still very challenging due to the complex fluidic dynamics of the solvents. Here, we report a robust film-formation approach using an environmental-friendly binary-solvent strategy. Nonbenzene solvents, n-octane and n-hexane, are mixed to manipulate the fluidic and evaporation dynamics of the perovskite quantum dot inks, resulting in balanced Marangoni flow, enhanced ink spreadability, and uniform solute-redistribution. We can therefore blade-coat large-area uniform perovskite films with different compositions using the same fabrication parameters. White and red perovskite light-emitting diodes incorporating blade-coated films exhibit a decent external quantum efficiency of 10.6% and 15.3% (0.04 cm2), and show a uniform emission up to 28 cm2. This work represents a significant step toward the application of perovskite light-emitting diodes in flat panel solid-state lighting.

18.
Light Sci Appl ; 13(1): 25, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38253520

RESUMO

Classical and quantum space-to-ground communications necessitate highly sensitive receivers capable of extracting information from modulated photons to extend the communication distance from near-earth orbits to deep space explorations. To achieve gigabit data rates while mitigating strong background noise photons and beam drift in a highly attenuated free-space channel, a comprehensive design of a multi-functional detector is indispensable. In this study, we present an innovative compact multi-pixel superconducting nanowire single-photon detector array that integrates near-unity detection efficiency (91.6%), high photon counting rate (1.61 Gcps), large dynamic range for resolving different photon numbers (1-24), and four-quadrant position sensing function all within one device. Furthermore, we have constructed a communication testbed to validate the advantages offered by such an architecture. Through 8-PPM (pulse position modulation) format communication experiments, we have achieved an impressive maximum data rate of 1.5 Gbps, demonstrating sensitivities surpassing previous benchmarks at respective speeds. By incorporating photon number information into error correction codes, the receiver can tolerate maximum background noise levels equivalent to 0.8 photons/slot at a data rate of 120 Mbps-showcasing a great potential for daylight operation scenarios. Additionally, preliminary beam tracking tests were conducted through open-loop scanning techniques, which revealed clear quantitative dependence indicating sensitivity variations based on beam location. Based on the device characterizations and communication results, we anticipate that this device architecture, along with its corresponding signal processing and coding techniques, will be applicable in future space-to-ground communication tasks.

19.
Cell Mol Life Sci ; 81(1): 56, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38270638

RESUMO

BACKGROUND: Until now, there has been no particularly effective treatment for chronic kidney disease (CKD). Fibrosis is a common pathological change that exist in CKD. METHODS: To better understand the transcriptional dynamics in fibrotic kidney, we make use of single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq) and single-cell RNA sequencing (scRNA-seq) from GEO datasets and perform scRNA-seq of human biopsy to seek possible transcription factors (TFs) regulating target genes in the progress of kidney fibrosis across mouse and human kidneys. RESULTS: Our analysis has displayed chromatin accessibility, gene expression pattern and cell-cell communications at single-cell level in kidneys suffering from unilateral ureteral obstruction (UUO) or chronic interstitial nephritis (CIN). Using multimodal data, there exists epigenetic regulation producing less Sod1 and Sod2 mRNA within the proximal tubule which is hard to withstand oxidative stress during fibrosis. Meanwhile, a transcription factor Nfix promoting the apoptosis-related gene Ifi27 expression found by multimodal data was validated by an in vitro study. And the gene Ifi27 upregulated by in situ AAV injection within the kidney cortex aggravates kidney fibrosis. CONCLUSIONS: In conclusion, as we know oxidation and apoptosis are traumatic factors during fibrosis, thus enhancing antioxidation and inhibiting the Nfix-Ifi27 pathway to inhibit apoptosis could be a potential treatment for kidney fibrosis.


Assuntos
Antioxidantes , Insuficiência Renal Crônica , Humanos , Animais , Camundongos , Epigênese Genética/genética , Multiômica , Rim , Apoptose/genética , Cromatina , Fibrose , Fatores de Transcrição NFI
20.
Nano Lett ; 24(5): 1563-1569, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38262051

RESUMO

Ferromagnetic (FM) states with high Curie temperatures (Tc) and strong spin-orbit coupling (SOC) are indispensable for the long-sought room-temperature quantum anomalous Hall (QAH) effects. Here, we propose a two-dimensional (2D) iron-based monolayer MgFeP that exhibits a notably high FM Tc (about 1525 K) along with exceptional structural stabilities. The unique multiorbital nature in MgFeP, where localized dx2-y2 and dxz/yz orbitals coexist with itinerant dxy and dz2 orbitals, renders the monolayer a Hund's metal and in an orbital-selective Mott phase (OSMP). This OSMP triggers an FM double exchange mechanism, rationalizing the high Tc in the Hund's metal. This material transitions to a QAH insulator upon consideration of the SOC effect. By leveraging orbital selectivity, the QAH band gap can be enlarged by more than two times (to 137 meV). Our findings showcase Hund's metals as a promising material platform for realizing high-performance quantum topological electronic devices.

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