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1.
Mater Horiz ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38567487

RESUMO

Recently, inverted perovskite solar cells (PeSCs) have witnessed significant advancements; however, their long-term stability remains a challenge because of the oxidation of silver cathodes to form AgI by mobile iodides. To overcome this problem, we propose the integration of an electron-deficient naphthalene diimide-based zwitterion (NDI-ZI) as the cathode interlayer. Compared to the physical ion-blocking layer, it effectively captures ions by forming ionic bonds via electrostatic Coulombic interaction to suppress the migration of iodide and Ag ions. The NDI-ZI interlayer also suppresses the shunt paths and modulates the work function of the Ag electrode by forming interface dipoles, thereby enhancing charge extraction. FA0.85Cs0.15PbI3 based PeSCs incorporating NDI-ZI exhibited a noticeably high power conversion efficiency of up to 23.3% and outstanding stability, maintaining ∼80% of their initial performance over 1500 h at 85 °C and over 500 h under continuous 1-sun illumination. This study highlights the potential of a zwitterionic cathode interlayer in diverse perovskite optoelectronic devices, leading to their improved efficiency and stability.

2.
J Behav Addict ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38598290

RESUMO

Background and aims: Impaired inhibitory control accompanied by enhanced craving is hallmark of addiction. This study investigated the effects of transcranial direct current stimulation (tDCS) on response inhibition and craving in Internet gaming disorder (IGD). We examined the brain changes after tDCS and their correlation with clinical variables. Methods: Twenty-four males with IGD were allocated randomly to an active or sham tDCS group, and data from 22 participants were included for analysis. Participants self-administered bilateral tDCS over the dorsolateral prefrontal cortex (DLPFC) for 10 sessions. Stop-signal tasks were conducted to measure response inhibition and participants were asked about their cravings for Internet gaming at baseline and post-tDCS. Functional magnetic resonance imaging data were collected at pre- and post-tDCS, and group differences in resting-state functional connectivity (rsFC) changes from the bilateral DLPFC and nucleus accumbens were examined. We explored the relationship between changes in the rsFC and behavioral variables in the active tDCS group. Results: A significant group-by-time interaction was observed in response inhibition. After tDCS, only the active group showed a decrease in the stop-signal reaction time (SSRT). Although craving decreased, there were no significant group-by-time interactions or group main effects. The anterior cingulate cortex (ACC) showed group differences in post- versus pre-tDCS rsFC from the right DLPFC. The rsFC between the ACC and left middle frontal gyrus was negatively correlated with the SSRT. Discussion and conclusion: Our study provides preliminary evidence that bilateral tDCS over the DLPFC improves inhibitory control and could serve as a therapeutic approach for IGD.

3.
Nanoscale ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38623652

RESUMO

Quasi-2D perovskites have emerged as highly promising materials for application in perovskite light-emitting diodes (PeLEDs), garnering significant attention due to their outstanding semiconductor properties. These materials boast an inherent multi-quantum well structure that imparts a robust confinement effect, particularly advantageous for blue emission. However, the development of blue emitters utilizing quasi-2D perovskites encounters challenges, notably colour instability, multipeak emission, and suboptimal fluorescence yield. The hole transfer layer (HTL) on which the perovskite layer is deposited in PeLEDs further affects the performance and efficiency. In this review, we delve into the evolution of blue PeLEDs and elucidate the optical properties of quasi-2D perovskites with the primary focus on HTL materials. We explore different HTL materials like PEDOT:PSS, metal oxides, and conjugated polyelectrolytes as well as ionic liquids, and their role in enhancing the colour stability, minimizing interfacial defects and increasing the fluorescence yield. This review endeavours to provide a holistic perspective of the different HTLs and serve as a valuable reference for researchers navigating the realm of HTL engineering towards the realization of high-performance blue quasi-2D PeLEDs.

4.
Exp Mol Med ; 56(3): 686-699, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38480902

RESUMO

Cancer cells often exhibit resistance to apoptotic cell death, but they may be vulnerable to other types of cell death. Elucidating additional mechanisms that govern cancer cell death is crucial for developing new therapies. Our research identified cyclic AMP-responsive element-binding protein 3 (CREB3) as a crucial regulator and initiator of a unique cell death mechanism known as karyoptosis. This process is characterized by nuclear shrinkage, deformation, and the loss of nuclear components following nuclear membrane rupture. We found that the N-terminal domain (aa 1-230) of full-length CREB3 (CREB3-FL), which is anchored to the nuclear inner membrane (INM), interacts with lamins and chromatin DNA. This interaction maintains a balance between the outward force exerted by tightly packed DNA and the inward constraining force, thereby preserving INM integrity. Under endoplasmic reticulum (ER) stress, aberrant cleavage of CREB3-FL at the INM leads to abnormal accumulation of the cleaved form of CREB3 (CREB3-CF). This accumulation disrupts the attachment of CREB3-FL to the INM, resulting in sudden rupture of the nuclear membrane and the onset of karyoptosis. Proteomic studies revealed that CREB3-CF overexpression induces a DNA damage response akin to that caused by UVB irradiation, which is associated with cellular senescence in cancer cells. These findings demonstrated that the dysregulation of CREB3-FL cleavage is a key factor in karyoptotic cell death. Consequently, these findings suggest new therapeutic strategies in cancer treatment that exploit the process of karyoptosis.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Membrana Nuclear , Proteômica , Apoptose , DNA , Membrana Nuclear/metabolismo , Humanos , Linhagem Celular Tumoral , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo
5.
J Biotechnol ; 387: 49-57, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38556215

RESUMO

2'-Fucosyllactose (2'-FL), one of the major human milk oligosaccharides, was produced in several engineered microorganisms. However, the low solubility of α-1,2-fucosyltransferase (α1,2-FucT) often becomes a bottleneck to produce maximum amount of 2'-FL in the microorganisms. To overcome this solubility issue, the following studies were conducted to improve the soluble expression of α1,2-FucT. Initially, hydrophobic amino acids in the hydrophilic region of the 6 α-helices were mutated, adhering to the α-helix rule. Subsequently, gfp11 was fused to the C-terminal of futC gene encoding α1,2-FucT (FutC), enabling selection of high-fluorescence mutants through split-GFP. Each mutant library was screened via fluorescence activated cell sorting (FACS) to separate soluble mutants for high-throughput screening. As a result, L80C single mutant and A121D/P124A/L125R triple mutant were found, and a combined quadruple mutant was created. Furthermore, we combined mutations of conserved sequences (Q150H/C151R/Q239S) of FutC, which showed positive effects in the previous studies from our lab, with the above quadruple mutants (L80C/A121D/P124A/L125R). The resulting strain produced approximately 3.4-fold higher 2'-FL titer than that of the wild-type, suggesting that the conserved sequence mutations are an independent subset of the mutations that further improve the solubility of the target protein acquired by random mutagenesis using split-GFP.

6.
Sci Rep ; 14(1): 3925, 2024 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-38366023

RESUMO

Solute carrier family (SLC) transporters are expressed in the digestive system and play important roles in maintaining physiological functions in the body. In addition, SLC transporters act as oncoproteins or tumor-suppressor proteins during the development, progression, and metastasis of various digestive system cancers. SLC22A18, a member of the SLC22 gene family, is an orphan transporter with an unknown endogenous substrate. Previous study revealed that SLC22A18 is downregulated in colorectal cancer tissues and that it acts as a suppressor in colorectal cancer, although the effects of SLC22A18 variants on colon cancer cell proliferation, migration, and invasion are unknown. Therefore, in this study, we identified SLC22A18 variants found in multiple populations by searching public databases and determined the in vitro effects of these missense variations on transporter expression and cancer progression. Our results indicated that three missense SLC22A18 variants-p.Ala6Thr, p.Arg12Gln, and p.Arg86His-had significantly lower cell expression than the wild type, possibly owing to intracellular degradation. Furthermore, these three variants caused significantly higher proliferation, migration, and invasion of colon cancer cells than the wild type. Our findings suggest that missense variants of SLC22A18 can potentially serve as biomarkers or prognostic tools that enable clinicians to predict colorectal cancer progression.


Assuntos
Neoplasias do Colo , Proteínas de Transporte de Cátions Orgânicos , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , Prognóstico , Proteínas Supressoras de Tumor/genética , Proteínas de Transporte de Cátions Orgânicos/genética
7.
J Orthop Res ; 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316622

RESUMO

Normalized signal intensity (SI) obtained from magnetic resonance imaging (MRI) has been used to track anterior cruciate ligament (ACL) postoperative remodeling. We aimed to assess the effect of MRI sequence (PD: proton density-weighted; T2: T2-weighted; CISS: constructive interference in steady state) on postoperative changes in healing ACLs/grafts. We hypothesized that CISS is better at detecting longitudinal SI and texture changes of the healing ACL/graft compared to the common clinical sequences (PD and T2). MR images of patients who underwent ACL surgery were evaluated and separated into groups based on surgical procedure (Bridge-Enhanced ACL Repair (BEAR; n = 50) versus ACL reconstruction (ACLR; n = 24)). CISS images showed decreasing SI across all timepoints in both the BEAR and ACLR groups (p < 0.01), PD and T2 images showed decreasing SI in the 6-to-12- and 12-to-24-month postoperative timeframes in the BEAR group (p < 0.02), and PD images additionally showed decreasing SI between 6- and 24-months postoperation in the ACLR group (p = 0.02). CISS images showed texture changes in both the BEAR and ACLR groups, showing increases in energy and decreases in entropy in the 6-to-12- and 6-to-24-month postoperative timeframes in the BEAR group (p < $\lt $ 0.04), and increases in energy, decreases in entropy, and increases in homogeneity between 6 and 24 months postoperation in the ACLR group (p < 0.04). PD images showed increases in energy and decreases in entropy between 6- and 24-months postoperation in the ACLR group (p < 0.008). Finally, CISS was estimated to require a smaller sample size than PD and T2 to detect SI differences related to postoperative remodeling.

8.
Korean J Physiol Pharmacol ; 28(2): 113-120, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38414394

RESUMO

Solute carrier 40A1 (SLC40A1) encodes ferroportin, which is the only known transmembrane protein that exports elemental iron from mammalian cells and is essential for iron homeostasis. Mutations in SLC40A1 are associated with iron-overload disorders. In addition to ferroportin diseases, SLC40A1 expression is downregulated in various cancer types. Despite the clinical significance of the SLC40A1 transporter, only a few studies have investigated genetic variants in SLC40A1. The present study was performed to identify genetic variations in the SLC40A1 promoter and functionally characterize each variant using in vitro assays. We investigated four haplotypes and five variants in the SLC40A1 promoter. We observed that haplotype 3 (H3) had significantly lower promoter activity than H1, whereas the activity of H4 was significantly higher than that of H1. Luciferase activity of H2 was comparable to that of H1. In addition, four variants of SLC40A1, c.-1355G>C, c.-662C>T, c.-98G>C, and c.-8C>G, showed significantly increased luciferase activity compared to the wild type (WT), whereas c.-750G>A showed significantly decreased luciferase activity compared to the WT. Three transcription factors, cAMP response element-binding protein-1 (CREB-1), chicken ovalbumin upstream promoter transcription factor 1, and hepatic leukemia factor (HLF), were predicted to bind to the promoter regions of SLC40A1 near c.-662C>T, c.-98G>C, and c.-8C>G, respectively. Among these, CREB-1 and HLF bound more strongly to the variant sequences than to the WT and functioned as activators of SLC40A1 transcription. Collectively, our findings indicate that the two SLC40A1 promoter haplotypes affect SLC40A1 transcription, which is regulated by CREB-1 and HLF.

9.
BMB Rep ; 57(2): 79-85, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38303561

RESUMO

Pre-harvest sprouting is a critical phenomenon involving germination of seeds in the mother plant before harvest under relative humid conditions and reduced dormancy. In this paper, we generated HDR mutant lines with one region SNP (C/T) and an insertion of 6 bp (GGT/GGTGGCGGC) in OsERF1 genes for pre-harvest sprouting (PHS) resistance using CRISPR/Cas9 and a geminiviral replicon system. The incidence of HDR was 2.6% in transformed calli. T1 seeds were harvested from 12 HDR-induced calli and named ERF1-hdr line. Molecular stability, key agronomic properties, physiological properties, and biochemical properties of target genes in the ERF1-hdr line were investigated for three years. The ERF1-hdr line showed significantly enhanced seed dormancy and pre-harvest sprouting resistance. qRT-PCR analysis suggested that enhanced ABA signaling resulted in a stronger phenotype of PHS resistance. These results indicate that efficient HDR can be achieved through SNP/InDel replacement using a single and modular configuration applicable to different rice targets and other crops. This work demonstrates the potential to replace all genes with elite alleles within one generation and greatly expands our ability to improve agriculturally important traits. [BMB Reports 2024; 57(2): 79-85].


Assuntos
Oryza , Oryza/genética , Sistemas CRISPR-Cas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sementes/genética , Sementes/metabolismo , Fenótipo
10.
J Korean Med Sci ; 39(6): e55, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374628

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccination is effective in preventing the disease transmission and progression. However, the relatively mild disease course of the omicron variant and the decrease in antibodies over time after vaccination raise questions about the effectiveness of vaccination, especially in young people. We compared the prevalence of pneumonia and chest X-ray severity score according to vaccination status among patients < 50 years old with COVID-19. METHODS: From January 17 to March 17, 2022, 579 patients with COVID-19, who were < 50 years old and had a known vaccination history in our institution, were all included in this study. All patients underwent initial chest radiography, and follow-up chest radiographs were obtained every two days until discharge. Pneumonia was scored from the radiographs using the Brixia scoring system. The scores of the six lung zones were added for a total score ranging from 0 to 18. Patients were divided into four groups according to 10-year age intervals. Differences between groups were analyzed using the χ² or Fisher's exact tests for categorical variables and the Kruskal-Wallis test or analysis of variance for continuous variables. RESULTS: Among patients aged 12-19 years, the prevalence of pneumonia did not differ depending on vaccination status (non-vaccinated vs. vaccinated, 1/47 [2.1%] vs. 1/18 [5.6%]; P = 0.577). Among patients in their 20s, the prevalence of pneumonia was significantly higher among non-vaccinated patients than among vaccinated patients (8/28, 28.6% vs. 7/138, 5.1%, P < 0.001), similar to patients in their 40s (32/52 [61.5%] vs. 18/138 [13.0%]; P < 0.001). The chest X-ray severity score was also significantly higher in non-vaccinated patients than that in vaccinated patients in their 20s to their 40s (P < 0.001), but not among patients aged 12-19 years (P = 0.678). CONCLUSION: In patients aged 20-49 years, vaccinated patients had a significantly lower prevalence of pneumonia and chest X-ray severity score than non-vaccinated patients.


Assuntos
COVID-19 , Humanos , Adolescente , Pessoa de Meia-Idade , COVID-19/epidemiologia , SARS-CoV-2 , Prevalência , Estudos Retrospectivos , Radiografia , Vacinação
11.
iScience ; 27(2): 108829, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38303690

RESUMO

Circadian clocks, generating daily rhythms in biological processes, maintain homeostasis in physiology, so clock alterations are considered detrimental. Studies in brain pathology support this by reporting abnormal circadian phenotypes in patients, but restoring the abnormalities by light therapy shows no dramatic effects. Recent studies on glial clocks report the complex effects of altered clocks by showing their beneficial effects on brain repairs. However, how neuronal clocks respond to brain pathology is elusive. This study shows that neuronal BMAL1, a core of circadian clocks, reduces its expression levels in neurodegenerative excitotoxicity. In the dentate gyrus of excitotoxic hippocampal lesions, reduced BMAL1 in granule cells precedes apoptosis. This subsequently reduces BMAL1 levels in neighbor neural stem cells and progenitors in the subgranular zone, enhancing proliferation. This shows the various BMAL1 roles depending on cell types, and its alterations can benefit brain repair. Thus, cell-type-specific BMAL1 targeting is necessary to treat brain pathology.

12.
J Med Internet Res ; 26: e52134, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38206673

RESUMO

BACKGROUND: Robust and accurate prediction of severity for patients with COVID-19 is crucial for patient triaging decisions. Many proposed models were prone to either high bias risk or low-to-moderate discrimination. Some also suffered from a lack of clinical interpretability and were developed based on early pandemic period data. Hence, there has been a compelling need for advancements in prediction models for better clinical applicability. OBJECTIVE: The primary objective of this study was to develop and validate a machine learning-based Robust and Interpretable Early Triaging Support (RIETS) system that predicts severity progression (involving any of the following events: intensive care unit admission, in-hospital death, mechanical ventilation required, or extracorporeal membrane oxygenation required) within 15 days upon hospitalization based on routinely available clinical and laboratory biomarkers. METHODS: We included data from 5945 hospitalized patients with COVID-19 from 19 hospitals in South Korea collected between January 2020 and August 2022. For model development and external validation, the whole data set was partitioned into 2 independent cohorts by stratified random cluster sampling according to hospital type (general and tertiary care) and geographical location (metropolitan and nonmetropolitan). Machine learning models were trained and internally validated through a cross-validation technique on the development cohort. They were externally validated using a bootstrapped sampling technique on the external validation cohort. The best-performing model was selected primarily based on the area under the receiver operating characteristic curve (AUROC), and its robustness was evaluated using bias risk assessment. For model interpretability, we used Shapley and patient clustering methods. RESULTS: Our final model, RIETS, was developed based on a deep neural network of 11 clinical and laboratory biomarkers that are readily available within the first day of hospitalization. The features predictive of severity included lactate dehydrogenase, age, absolute lymphocyte count, dyspnea, respiratory rate, diabetes mellitus, c-reactive protein, absolute neutrophil count, platelet count, white blood cell count, and saturation of peripheral oxygen. RIETS demonstrated excellent discrimination (AUROC=0.937; 95% CI 0.935-0.938) with high calibration (integrated calibration index=0.041), satisfied all the criteria of low bias risk in a risk assessment tool, and provided detailed interpretations of model parameters and patient clusters. In addition, RIETS showed potential for transportability across variant periods with its sustainable prediction on Omicron cases (AUROC=0.903, 95% CI 0.897-0.910). CONCLUSIONS: RIETS was developed and validated to assist early triaging by promptly predicting the severity of hospitalized patients with COVID-19. Its high performance with low bias risk ensures considerably reliable prediction. The use of a nationwide multicenter cohort in the model development and validation implicates generalizability. The use of routinely collected features may enable wide adaptability. Interpretations of model parameters and patients can promote clinical applicability. Together, we anticipate that RIETS will facilitate the patient triaging workflow and efficient resource allocation when incorporated into a routine clinical practice.


Assuntos
Algoritmos , COVID-19 , Triagem , Humanos , Biomarcadores , COVID-19/diagnóstico , Mortalidade Hospitalar , Redes Neurais de Computação , Triagem/métodos , República da Coreia
13.
J Proteome Res ; 23(3): 905-915, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38293943

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis due to the absence of diagnostic markers and molecular targets. Here, we took an unconventional approach to identify new molecular targets for pancreatic cancer. We chose uncharacterized protein evidence level 1 without function annotation from extensive proteomic research on pancreatic cancer and focused on proline and serine-rich 2 (PROSER2), which ranked high in the cell membrane and cytoplasm. In our study using cell lines and patient-derived orthotopic xenograft cells, PROSER2 exhibited a higher expression in cells derived from primary tumors than in those from metastatic tissues. PROSER2 was localized in the cell membrane and cytosol by immunocytochemistry. PROSER2 overexpression significantly reduced the metastatic ability of cancer cells, whereas its suppression had the opposite effect. Proteomic analysis revealed that PROSER2 interacts with STK25 and PDCD10, and their binding was confirmed by immunoprecipitation and immunocytochemistry. STK25 knockdown enhanced metastasis by decreasing p-AMPK levels, whereas PROSER2-overexpressing cells increased the level of p-AMPK, indicating that PROSER2 suppresses invasion via the AMPK pathway by interacting with STK25. This is the first demonstration of the novel role of PROSER2 in antagonizing tumor progression via the STK25-AMPK pathway in PDAC. LC-MS/MS data are available at MassIVE (MSV000092953) and ProteomeXchange (PXD045646).


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Humanos , Proteínas Quinases Ativadas por AMP , Cromatografia Líquida , Proteômica , Proliferação de Células , Movimento Celular , Espectrometria de Massas em Tandem , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/genética , Modelos Animais de Doenças , Proteínas Serina-Treonina Quinases , Peptídeos e Proteínas de Sinalização Intracelular
14.
ACS Nano ; 18(4): 2992-3001, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38227810

RESUMO

Phenyl-C61-butyric acid methyl ester (PCBM) can be used as a passivation material in perovskite solar cells (PeSCs) in order to reduce the trap site of the perovskite. Here, we show that a thick PCBM layer can form a smoother surface on the SnO2 substrate, improving the grain size and reducing the microstrain of the perovskite. High-temperature annealing treatment of PCBM layer not only increases its solvent resistance to perovskite precursor or antisolvent, but also enhances its molecular alignment, resulting in improved conductivity as an electron transport layer. High-temperature annealed PCBM (HT-PCBM) effectively minimizes trap-assisted nonradiative recombination by reducing trap density in perovskite and improving the electrical properties at the interface between SnO2 and perovskite layers. This HT-PCBM process significantly enhances the performance of the PeSCs, including the open-circuit voltage (VOC) from 0.39 to 0.77 V, fill factor from 52% to 65%, and power conversion efficiency (PCE) from 6.03% to 15.50%, representing substantial improvements compared to devices without PCBM. This PCE is the highest efficiency among conventional (n-i-p) Sn-Pb PeSCs reported to date. Moreover, passivating the trap sites of SnO2 and separating the interface between the Sn-containing perovskite and the substrate effectively have improved the stability of the Sn-Pb perovskite in the n-i-p structure. The optimized best device with HT-PCBM has maintained an efficiency of over 90% for more than 300 h at 85 °C and 5000 h at room temperature in a glovebox atmosphere.

15.
Small Methods ; 8(2): e2300578, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37649231

RESUMO

Over the past couple of decades, immense research has been carried out to understand the photo-physics of an organic solar cell (OSC) that is important to enhance its efficiency and stability. Since OSCs undergoes complex photophysical phenomenon, studying these factors has led to designing new materials and implementing new strategies to improve efficiency in OSCs. In this regard, the invention of the non-fullerene acceptorshas greatly revolutionized the understanding of the fundamental processes occurring in OSCs. However, such vital fundamental research from device physics perspectives is carried out on glovebox (GB) processed OSCs and there is a scarcity of research on air-processed (AP) OSCs. This review will focus on charge carrier dynamics such as exciton diffusion, exciton dissociation, charge-transfer states, significance of highest occupied molecular orbital-offsets, and hole-transfer efficiencies of GB-OSCs and compare them with the available data from the AP-OSCs. Finally, key requirements for the fabrication of efficient AP-OSCs will be presented from a charge-carrier dynamics perspective. The key aspects from the charge-carrier dynamics view to fabricate efficient OSCs either from GB or air are provided.

16.
Nat Chem Biol ; 20(3): 353-364, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37973890

RESUMO

Proteases function as pivotal molecular switches, initiating numerous biological events. Notably, potyviral protease, derived from plant viruses, has emerged as a trusted proteolytic switch in synthetic biological circuits. To harness their capabilities, we have developed a single-component photocleavable switch, termed LAUNCHER (Light-Assisted UNcaging switCH for Endoproteolytic Release), by employing a circularly permutated tobacco etch virus protease and a blue-light-gated substrate, which are connected by fine-tuned intermodular linkers. As a single-component system, LAUNCHER exhibits a superior signal-to-noise ratio compared with multi-component systems, enabling precise and user-controllable release of payloads. This characteristic renders LAUNCHER highly suitable for diverse cellular applications, including transgene expression, tailored subcellular translocation and optochemogenetics. Additionally, the plug-and-play integration of LAUNCHER into existing synthetic circuits facilitates the enhancement of circuit performance. The demonstrated efficacy of LAUNCHER in improving existing circuitry underscores its significant potential for expanding its utilization in various applications.


Assuntos
Peptídeo Hidrolases , Potyvirus , Proteólise , Razão Sinal-Ruído
17.
ACS Appl Mater Interfaces ; 16(1): 704-711, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38148320

RESUMO

Large areas and simple processing methods are necessary for the commercialization of organic photovoltaics (OPVs). However, the efficiency drop due to the variation in thickness of OPVs limits their large-scale applications. Regioregular polymers with good crystallinity and packing properties that exhibit high charge mobility and extraction ability can help overcome these limitations. In this study, a regioregular polymer named PDBD-2FBT was synthesized. The crystallinity and packing properties of PDBD-2FBT were enhanced by a simple thermal treatment. Using PDBD-2FBT material as a donor and Y6-HU as an acceptor, we fabricated binary blend OPV devices. The devices with optimized active layer thickness achieved a power conversion efficiency (PCE) of 14.14%. A PCE of 13.18% was maintained even in thick-film conditions (400 nm), and thickness tolerance was observed. Based on the thickness tolerance, a 5-line module measuring 36 cm2 was fabricated via the bar-coating method, and a PCE of approximately 10% was achieved.

18.
J Proteome Res ; 23(1): 130-141, 2024 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-38104258

RESUMO

Many attempts have been made to develop new agents that target EGFR mutants or regulate downstream factors in various cancers. Cell-based screening showed that a natural small molecule, Ertredin, inhibited the growth of EGFRvIII mutant cancer cells. Previous studies have shown that Ertredin effectively inhibits anchorage-independent 3D growth of sphere-forming cells transfected with EGFRvIII mutant cDNA. However, the underlying mechanism remains unclear. In this study, we investigated the target protein of Ertredin by combining drug affinity-responsive target stability (DARTS) assays with liquid chromatography-mass spectrometry using label-free Ertredin as a bait and HepG2 cell lysates as a proteome pool. NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12 (NDUFA12) was identified as an Ertredin-binding protein that was responsible for its biological activity. The interaction between NDUFA12 and Ertredin was validated by DARTS and cellular thermal shift assays. In addition, the genetic knockdown of the identified target, NDUFA12, was shown to suppress cell proliferation. NDUFA12 was identified as a biologically relevant target protein of Ertredin that is responsible for its antitumor activity, and these results provide insights into the role of NDUFA12 as a downstream factor in EGFRvIII mutants.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Proteômica/métodos , Proteínas/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , NADPH Desidrogenase
19.
Small ; : e2307441, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38054784

RESUMO

The electrode buffer layer is crucial for high-performance and stable OSCs, optimizing charge transport and energy level alignment at the interface between the polymer active layer and electrode. Recently, SnO2 has emerged as a promising material for the cathode buffer layer due to its desirable properties, such as high electron mobility, transparency, and stability. Typically, SnO2 nanoparticle layers require a postannealing treatment above 150°C in an air environment to remove the surfactant ligands and obtain high-quality thin films. However, this poses challenges for flexible electronics as flexible substrates can't tolerate temperatures exceeding 100°C. This study presents solution-processable and annealing-free SnO2 nanoparticles by employing y-ray irradiation to disrupt the bonding between surfactant ligands and SnO2 nanoparticles. The SnO2 layer treated with y-ray irradiation is used as an electron transport layer in OSCs based on PTB7-Th:IEICO-4F. Compared to the conventional SnO2 nanoparticles that required high-temperature annealing, the y-SnO2 nanoparticle-based devices exhibit an 11% comparable efficiency without postannealing at a high temperature. Additionally, y-ray treatment has been observed to eliminate the light-soaking effect of SnO2 . By eliminating the high-temperature postannealing and light-soaking effect, y-SnO2 nanoparticles offer a promising, cost-effective solution for future flexible solar cells fabricated using roll-to-roll mass processing.

20.
Nat Commun ; 14(1): 8460, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38123571

RESUMO

Three-dimensional (3D) microprinting is considered a next-generation manufacturing process for the production of microscale components; however, the narrow range of suitable materials, which include mainly polymers, is a critical issue that limits the application of this process to functional inorganic materials. Herein, we develop a generalised microscale 3D printing method for the production of purely inorganic nanocrystal-based porous materials. Our process is designed to solidify all-inorganic nanocrystals via immediate dispersibility control and surface linking-induced interconnection in the nonsolvent linker bath and thereby creates multibranched gel networks. The process works with various inorganic materials, including metals, semiconductors, magnets, oxides, and multi-materials, not requiring organic binders or stereolithographic equipment. Filaments with a diameter of sub-10 µm are printed into designed complex 3D microarchitectures, which exhibit full nanocrystal functionality and high specific surface areas as well as hierarchical porous structures. This approach provides the platform technology for designing functional inorganics-based porous materials.

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