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1.
Anal Chem ; 96(26): 10654-10661, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38875020

RESUMO

The trans-cleavage properties of Cas12a make it important for gene editing and disease diagnosis. In this work, the effect of spatial site resistance on the trans-cleavage activity of Cas12a was studied. First, we have explored the cutting effect of Cas12a when different-sized nanoparticles are linked with various spacings of DNA strands using the fluorescence method. The minimum spacing with different-sized nanoparticles that cas12a can cut was determined. We found that when the size of the nanoparticles increases, the minimum spacing that cas12a can cut gradually increases. Subsequently, we verified the conclusion using the surface-enhanced Raman scattering (SERS) method, and at the same time, we designed a SERS biosensor that can achieve ultrasensitive detection of P53 DNA with a linear range of 1 fM-10 nM and a limit of detection of 0.40 fM. Our work develops a deep study of the trans-cleavage activity of Cas12a and gives a guide for DNA design in cas12a-related studies, which can be applied in biomedical analysis and other fields.


Assuntos
Sistemas CRISPR-Cas , DNA , Análise Espectral Raman , Proteína Supressora de Tumor p53 , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , DNA/química , Humanos , Técnicas Biossensoriais/métodos , Nanopartículas Metálicas/química , Endodesoxirribonucleases/metabolismo , Endodesoxirribonucleases/química , Proteínas Associadas a CRISPR/metabolismo , Limite de Detecção , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/química
2.
J Gene Med ; 26(2): e3679, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38404047

RESUMO

BACKGROUND: Junctional adhesion molecule 2 (JAM2) plays a pivotal role in various biological processes, including proliferation, metastasis and angiogenesis, contributing to tumor progression. While previous studies have highlighted the polarizing functions of JAM2 in different cancer types, its specific role in lung adenocarcinoma (LUAD) remains unclear. METHODS: In this study, we harnessed multiple public databases to analyze the expression and prognostic significance of JAM2 in LUAD. Using the Linkedomics database, Matescape database and R package, we explored the associated genes, the potential biological functions and the impact of JAM2 on the tumor microenvironment. Our findings from public databases were further validated using real-time quantitative PCR, western blot and immunohistochemistry. Additionally, in vitro experiments were conducted to assess the influence of JAM2 on LUAD cell proliferation, invasion, migration, apoptosis and epithelial-mesenchymal transition. Furthermore, we established a xenograft model to investigate the in vivo effects of JAM2 on tumorigenesis. RESULTS: Our results revealed a significant downregulation of JAM2 in LUAD, and patients with low JAM2 expression exhibited unfavorable overall survival outcomes. Functional enrichment analysis indicated that JAM2 may be associated with processes such as cell adhesion, extracellular matrix, cell junctions and regulation of proliferation. Notably, increased JAM2 expression correlated with higher tumor microenvironment scores and reduced immune cell abundance. Furthermore, overexpression of JAM2 induced apoptosis, suppressed tumor proliferation and exhibited potential inhibitory effects on tumor invasion and migration through the modulation of epithelial-mesenchymal transition. Additionally, in vivo experiments confirmed that JAM2 overexpression led to a reduction in tumor growth. CONCLUSION: Overall, our study highlights the clinical significance of low JAM2 expression as a predictor of poor prognosis in LUAD patients. Moreover, JAM2 was found to exert inhibitory effects on various aspects of tumor progression. Consequently, JAM2 emerges as a promising prognostic biomarker and a potential therapeutic target for LUAD patients.


Assuntos
Adenocarcinoma de Pulmão , Molécula B de Adesão Juncional , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/genética , Biomarcadores , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Molécula B de Adesão Juncional/genética , Neoplasias Pulmonares/genética , Prognóstico , Microambiente Tumoral/genética
3.
Small ; 20(5): e2303778, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37752783

RESUMO

Cellulose nanocrystal (CNC) is a renewable resource derived from lignocellulosic materials, known for its optical permeability, biocompatibility, and unique self-assembly properties. Recent years have seen great progresses in cellulose nanocrystal-based chiral photonic materials. However, due to its inherent brittleness, cellulose nanocrystal shows limitations in the fields of flexible materials, optical sensors and food freshness testing. In order to solve the above limitations, attempts have been made to improve the flexibility of cellulose nanocrystal materials without destroying their structural color. Despite these progresses, a systematic review on them is lacking. This review aims to fill this gap by providing an overview of the main strategies and the latest research findings on the flexibilization of cellulose nanocrystal-based chiral nematic film materials (FCNM). Specifically, typical substances and methods used for their preparation are summarized. Moreover, different kinds of cellulose nanocrystal-based composites are compared in terms of flexibility. Finally, potential applications and future challenges of flexible cellulose nanocrystal-based chiral nematic materials are discussed, inspiring further research in this field.

4.
Metab Eng ; 85: 84-93, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39047895

RESUMO

Subcellular compartmentalization is a crucial evolution characteristic of eukaryotic cells, providing inherent advantages for the construction of artificial biological systems to efficiently produce natural products. The establishment of an artificial protein transport system represents a pivotal initial step towards developing efficient artificial biological systems. Peroxisome has been demonstrated as a suitable subcellular compartment for the biosynthesis of terpenes in yeast. In this study, an artificial protein transporter ScPEX5* was firstly constructed by fusing the N-terminal sequence of PEX5 from S. cerevisiae and the C-terminal sequence of PEX5. Subsequently, an artificial protein transport system including the artificial signaling peptide YQSYY and its enhancing upstream 9 amino acid (9AA) residues along with ScPEX5* was demonstrated to exhibit orthogonality to the internal transport system of peroxisomes in S. cerevisiae. Furthermore, a library of 9AA residues was constructed and selected using high throughput pigment screening system to obtain an optimized signaling peptide (oPTS1*). Finally, the ScPEX5*-oPTS1* system was employed to construct yeast cell factories capable of producing the sesquiterpene α-humulene, resulting in an impressive α-humulene titer of 17.33 g/L and a productivity of 0.22 g/L/h achieved through fed-batch fermentation in a 5 L bioreactor. This research presents a valuable tool for the construction of artificial peroxisome cell factories and effective strategies for synthesizing other natural products in yeast.


Assuntos
Peroxissomos , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Sesquiterpenos , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Peroxissomos/metabolismo , Peroxissomos/genética , Sesquiterpenos/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Engenharia Metabólica , Receptor 1 de Sinal de Orientação para Peroxissomos/metabolismo , Receptor 1 de Sinal de Orientação para Peroxissomos/genética , Transporte Proteico
5.
Chemistry ; 30(47): e202401762, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-38888454

RESUMO

Force-related discoloration materials are highly valuable because of their characteristics of visualization, easy operation, and environment friendliness. Most force-related discoloration materials focus on polymers and depend on bond scission, which leads to insensitivity and unrecoverable. Small-molecule systems based on well-defined molecular structures and simple composition with high sensitivity would exhibit considerable mechanochromic potential. However, to date, researches about force-related discoloration materials based on small molecule solution remain limited and are rarely reported. In this study, we developed a repeatable and instantaneous discoloration small molecule solution system by simple one-pot synthesis method. It exhibited an instantaneous chromic change from yellowish to dark green under shaking and reverting back to yellow within 1 minute after removal of the shaking. Experimental results confirmed that the discoloration mechanism is attributed to the oscillation accelerating the production of unstable ortho-OH phenoxyl radical. The newly developed shaking-induced discoloration small molecule system (SDSMS) promises in field of mechanical force sensing and optical encryption.

6.
Chemistry ; 30(15): e202303827, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38183168

RESUMO

The stable Pepsin@covalent organic framework (Pepsin@COF) were constructed base on matching COF pore diameter to pepsin dimension. It exhibits excellent chiral recognition capabilities (e. e. % up to 62.63 %) and potential for enantioseparation. Furthermore, a positive correlation between the immobilized enzyme activity and chiral recognition was revealed, offering insights for the design of biocatalytic nanosystems in chiral separation.

7.
Anal Biochem ; 689: 115495, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38431142

RESUMO

RNA modification, N4-acetylcytidine (ac4C), is enzymatically catalyzed by N-acetyltransferase 10 (NAT10) and plays an essential role across tRNA, rRNA, and mRNA. It influences various cellular functions, including mRNA stability and rRNA biosynthesis. Wet-lab detection of ac4C modification sites is highly resource-intensive and costly. Therefore, various machine learning and deep learning techniques have been employed for computational detection of ac4C modification sites. The known ac4C modification sites are limited for training an accurate and stable prediction model. This study introduces GANSamples-ac4C, a novel framework that synergizes transfer learning and generative adversarial network (GAN) to generate synthetic RNA sequences to train a better ac4C modification site prediction model. Comparative analysis reveals that GANSamples-ac4C outperforms existing state-of-the-art methods in identifying ac4C sites. Moreover, our result underscores the potential of synthetic data in mitigating the issue of data scarcity for biological sequence prediction tasks. Another major advantage of GANSamples-ac4C is its interpretable decision logic. Multi-faceted interpretability analyses detect key regions in the ac4C sequences influencing the discriminating decision between positive and negative samples, a pronounced enrichment of G in this region, and ac4C-associated motifs. These findings may offer novel insights for ac4C research. The GANSamples-ac4C framework and its source code are publicly accessible at http://www.healthinformaticslab.org/supp/.


Assuntos
Citidina/análogos & derivados , Aprendizado de Máquina , RNA , Estabilidade de RNA
8.
Ann Hematol ; 103(4): 1241-1254, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38150112

RESUMO

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the West. With CLL's heterogeneity, some people still develop disease refractory and relapse despite advances in treatment. Thus, early diagnosis and treatment of high-risk CLL patients is critical. Fatty acid (FA) metabolism contributes to tumorigenesis, progression, and therapy resistance through enhanced lipid synthesis, storage, and catabolism. In this study, we aimed to construct a prognostic model to improve the risk stratification of CLL and reveal the link between FA metabolism and CLL. The differentially expressed FA metabolism-related genes (FMGs) in CLL were filtered through univariate Cox regression analysis based on public databases. Functional enrichment was examined using prognostic FA metabolism-related gene enrichment analysis. CIBERSORT and single-sample gene set enrichment analysis (ssGSEA) estimated immune infiltration score and immune-related pathways. Pearson's correlation analysis investigated FA metabolism-related genes and drug sensitivity. A novel prognostic model was built using least absolute shrinkage and selection operator (LASSO) Cox algorithms. This validation cohort included 36 CLL patients from our center. We obtained CLL RNA microarray profiles from public databases and identified 15 prognostic-related FMGs. CLL patients were divided into two molecular clusters based on the expression of FMGs. The Kaplan-Meier analysis revealed a significant difference in TFS (P < 0.001) and OS (P < 0.001) between the two clusters. KEGG functional analysis showed that several pathways were enriched, including the chemokine and immune-related signaling pathways. In the training and validation cohorts, patients with higher FA metabolism-related prognostic index (FAPI) levels had worse outcomes. Finally, a novel nomogram prognostic model including CLL international prognostic index (CLL-IPI) was constructed, exhibiting reliable effectiveness and accuracy. In conclusion, we established a reliable predictive signature based on FA metabolism-related genes and constructed a novel nomogram prognostic model, supporting the potential preclinical implications of FA metabolism in CLL research.


Assuntos
Leucemia Linfocítica Crônica de Células B , Leucemia , Humanos , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/terapia , Algoritmos , Carcinogênese , Ácidos Graxos
9.
Nanotechnology ; 35(15)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38176065

RESUMO

Optical nanoantennas possess broad applications in the fields of photodetection, environmental science, biosensing and nonlinear optics, owing to their remarkable ability to enhance and confine the optical field at the nanoscale. In this article, we present a theoretical investigation of surface-enhanced photoluminescence spectroscopy for single molecules confined within novel Au bowtie nanoantenna, covering a wavelength range from the visible to near-infrared spectral regions. We employ the finite element method to quantitatively study the optical enhancement properties of the plasmonic field, quantum yield, Raman scattering and fluorescence. Additionally, we systematically examine the contribution of nonlocal dielectric response in the gap mode to the quantum yield, aiming to gain a better understanding of the fluorescence enhancement mechanism. Our results demonstrate that altering the configuration of the nanoantenna has a significant impact on plasmonic sensitivity. The nonlocal dielectric response plays a crucial role in reducing the quantum yield and corresponding fluorescence intensity when the gap distance is less than 3 nm. However, a substantial excitation field can effectively overcome fluorescence quenching and enhance the fluorescence intensity. By optimizing nanoantenna configuration, the maximum enhancement of surface-enhanced Raman can be turned to 9 and 10 magnitude orders in the visible and near-infrared regions, and 3 and 4 magnitude orders for fluorescence enhancement, respectively. The maximum spatial resolutions of 0.8 nm and 1.5 nm for Raman and fluorescence are also achieved, respectively. Our calculated results not only provide theoretical guidance for the design and application of new nanoantennas, but also contribute to expanding the range of surface-enhanced Raman and fluorescence technology from the visible to the near-infrared region.

10.
Environ Res ; 245: 118056, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38157958

RESUMO

A good old gateway theory that electronic-cigarettes (e-cigarettes) are widely recognized as safer tobacco substitutes. In actuality, demographics also show that vaping cannibalizes smoking, the best explanation of the data is the "common liability". However, the utilization of e-cigarette products remains a controversial topic at present. Currently, there has been a widespread and substantial growth in e-cigarette use worldwide owing to their endless new flavors and customizable characteristics. Furthermore, e-cigarette has grown widespread among smokers as well as non-smokers, including adolescents and young adults. And some studies have shown that e-cigarette users are at greater risk to start using combustible cigarettes while e-cigarettes use was also observed the potential benefits to people who want to quit smoking or not. Although it is true that e-cigarettes generally contain fewer toxic substances than combustible cigarettes, this does not mean that the chemical composition in e-cigarettes aerosols poses absolutely no risks. While concerns about toxic substances in e-cigarettes and their widespread use in the population are reasonable, it is also crucial to consider that e-cigarettes have been associated with the potential for promoting smoking cessation and the clinically relevant improvements in users with smoking-related pathologies. Meanwhile, there is still short of understanding of the health impacts associated with e-cigarette use. Therefore, in this review, we discussed the health impacts of e-cigarette exposure on oral, nasal, pulmonary, cardiovascular systems and brain. We aspire for this review to change people's previous perceptions of e-cigarettes and provide them with a more balanced perspective. Additionally, we suggest appropriate adjustments on regulation and policy for e-cigarette to gain greater public health benefits.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Adolescente , Adulto Jovem , Humanos , Fumar/epidemiologia , Fumar Tabaco , Eletrônica
11.
Neurol Sci ; 45(11): 5457-5464, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38902569

RESUMO

OBJECTIVE: To describe the association between preoperative ictal scalp electroencephalogram (EEG) results and surgical outcomes in patients with focal epilepsies. METHODS: The data of consecutive patients with focal epilepsies who received surgical treatments at our center from January 2012 to December 2021 were retrospectively analyzed. RESULTS: Our data showed that 44.2% (322/729) of patients had ictal EEG recorded on video EEG monitoring during preoperative evaluation, of which 60.6% (195/322) had a concordant ictal EEG results. No significant difference of surgery outcomes between patients with and without ictal EEG was discovered. Among MRI-negative patients, those with concordant ictal EEG had a significantly better outcome than those without ictal EEG (75.7% vs. 43.8%, p = 0.024). Further logistic regression analysis showed that concordant ictal EEG was an independent predictor for a favorable outcome (OR = 4.430, 95%CI 1.175-16.694, p = 0.028). Among MRI-positive patients, those with extra-temporal lesions and discordant ictal EEG results had a worse outcome compared to those without an ictal EEG result (44.7% vs. 68.8%, p = 0.005). Further logistic regression analysis showed that discordant ictal EEG was an independent predictor of worse outcome (OR = 0.387, 95%CI 0.186-0.807, p = 0.011) in these patients. Furthermore, our data indicated that the number of seizures was not associated with the concordance rates of the ictal EEG, nor the surgical outcomes. CONCLUSIONS: The value of ictal scalp EEG for epilepsy surgery varies widely among patients. A concordant ictal EEG predicts a good surgical outcome in MRI-negative patients, whereas a discordant ictal EEG predicts a poor postoperative outcome in lesional extratemporal lobe epilepsy.


Assuntos
Eletroencefalografia , Epilepsias Parciais , Couro Cabeludo , Humanos , Eletroencefalografia/métodos , Epilepsias Parciais/cirurgia , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/diagnóstico , Estudos Retrospectivos , Masculino , Feminino , Adulto , Adolescente , Criança , Adulto Jovem , Resultado do Tratamento , Pré-Escolar , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos
12.
Entropy (Basel) ; 26(3)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38539728

RESUMO

The SAND algorithm is a family of lightweight AND-RX block ciphers released by DCC in 2022. Our research focuses on assessing the security of SAND with a quantum computation model. This paper presents the first quantum implementation of SAND (including two versions of SAND, SAND-64 and SAND-128). Considering the depth-times-width metric, the quantum circuit implementation of the SAND algorithm demonstrates a relatively lower consumption of quantum resources than that of the quantum implementations of existing lightweight algorithms. A generalized Grover-based brute-force attack framework was implemented and employed to perform attacks on two versions of the SAND algorithm. This framework utilized the g-database algorithm, which considered different plaintext-ciphertext pairs in a unified manner, reducing quantum resource consumption. Our findings indicate that the SAND-128 algorithm achieved the NIST security level I, while the SAND-64 algorithm fell short of meeting the requirements of security level I.

13.
J Biol Chem ; 298(5): 101818, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35278432

RESUMO

Gonadal white adipose tissue (gWAT) can regulate gametogenesis via modulation of neuroendocrine signaling. However, the effect of gWAT on the local microenvironment of the gonad was largely unknown. Herein, we ruled out that gWAT had a neuroendocrine effect on gonad function through a unilateral lipectomy strategy, in which cutting off epididymal white adipose tissue could reduce seminiferous tubule thickness and decrease sperm counts only in the adjacent testis and epididymis of the affected gonad. Consistent with the results in males, in females, ovary mass was similarly decreased by lipectomy. We determined that the defects in spermatogenesis were mainly caused by augmented apoptosis and decreased proliferation of germ cells. Transcriptome analysis suggested that lipectomy could disrupt immune privilege and activate immune responses in both the testis and ovary on the side of the lipectomy. In addition, lipidomics analysis in the testis showed that the levels of lipid metabolites such as free carnitine were elevated, whereas the levels of glycerophospholipids such as phosphatidylcholines and phosphatidylethanolamines were decreased, which indicated that the metabolic niche was also altered. Finally, we show that supplementation of phosphatidylcholine and phosphatidylethanolamine could partially rescue the observed phenotype. Collectively, our findings suggest that gWAT is important for gonad function by not only affecting whole-body homeostasis but also via maintaining local metabolic and immune niches.


Assuntos
Tecido Adiposo Branco , Gônadas , Tecido Adiposo/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Epididimo , Feminino , Masculino , Camundongos , Espermatogênese , Testículo/metabolismo
14.
Anal Chem ; 95(38): 14169-14174, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37712649

RESUMO

In this work, a simple and novel method coupling solid phase extraction (SPE) with X-ray fluorescence spectrometry (XRF) is proposed for the simultaneous determination of 15 kinds of trace rare earth elements (REEs) in water samples. A phosphonic acid functionalized metal-organic framework named BPG-MIL-53(Al) was prepared via postsynthetic modification and served as an efficient adsorbent for these REEs. The prepared BPG-MIL-53(Al) could almost completely adsorb REEs in 5 min under neutral conditions. After filtration, REEs-adsorbed BPG-MIL-53(Al) was deposited on a filter membrane to form a thin film, which was directly analyzed by XRF. The XRF intensities of the REEs-retained MOF disc remained almost unchanged after six months. Taking advantage of this strategy, XRF was able to quantitate ng mL-1 levels of REEs in water samples, achieving impressive limits of detection in the range of 0.4-4.7 ng mL-1. The proposed method was applied to the on-site collection and analysis of REEs in real water samples with desirable accuracy and spike recoveries obtained.

15.
Mol Reprod Dev ; 90(10-11): 774-781, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37733694

RESUMO

Male fertility declines with age. The mevalonate pathway, through which cholesterol and nonsteroidal isoprenoids are synthesized, plays key role in metabolic processes and is an essential pathway for cholesterol production and protein prenylation. Male reproductive aging is accompanied by dramatic changes in the metabolic microenvironment of the testis. Since the mevalonate pathway has an important role in spermatogenesis, we attempted to explore the association between male reproductive aging and the mevalonate pathway to explain the mechanism of male reproductive aging. Alterations in the mevalonate pathway may affect male reproductive aging by decreasing cholesterol synthesis and altering testis protein prenylation. Decreased cholesterol levels affect cholesterol modification, testosterone production, and remodeling of germ cell membranes. Aging-related metabolic disorders also affect the metabolic coupling between somatic cells and spermatogenic cells, leading to male fertility decline. Therefore, we hypothesized that alterations in the mevalonate pathway represent one of the metabolic causes of reproductive aging.


Assuntos
Colesterol , Ácido Mevalônico , Masculino , Humanos , Ácido Mevalônico/metabolismo , Colesterol/metabolismo , Reprodução , Testículo/metabolismo
16.
Cell Mol Neurobiol ; 43(3): 1199-1218, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35748966

RESUMO

Directed migration of neural stem cells (NSCs) is critical for embryonic neurogenesis and the healing of neurological injuries. The long noncoding RNA (lncRNA) Pnky has been reported to regulate neuronal differentiation of NSCs by interacting with PTBP1. However, its regulatory effect on NSC migration remains to be determined. Herein, we identified that Pnky is also a key regulator of NSC migration in mice, as underscored by the finding that Pnky silencing suppressed but Pnky overexpression promoted the in vitro migration of both C17.2 and NE4C murine NSCs. Additionally, in vivo cell tracking demonstrated that Pnky depletion attenuated but Pnky overexpression facilitated the migration of NE4C cells in the spinal canal after transplantation via injection into the spinal canal. Mechanistically, Pnky regulated the expression of a core set of critical regulators that direct NSC migration, including MMP2, MMP9, Connexin43, Paxillin, AKT, ERK, and P38MAPK. Using catRAPID, a web server for large-scale prediction of protein-RNA interactions, the splicing factors U2AF1 and U2AF1L4, as well as the mRNA export adaptors SARNP, Aly/Ref, and THOC7, were predicted to interact strongly with Pnky. Further investigations using colocalization and RNA immunoprecipitation (RIP) assays confirmed the direct binding of Pnky to U2AF1, SARNP, Aly/Ref, and THOC7. Transcriptomic profiling revealed that as many as 5319 differential splicing events of 3848 genes, which were highly enriched in focal adhesion, PI3K-Akt and MAPK signaling pathways, were affected by Pnky depletion. The predominant subtype of differential splicing by Pnky depletion is intron retention, followed by alternative 5' and 3' splice sites and mutually exclusive exons. Moreover, Pnky knockdown substantially blocked but Pnky overexpression facilitated the export of MMP2, Paxillin, AKT, p38MAPK, and other mRNAs to the cytosol. Collectively, our data showed that through interacting with U2AF1, SARNP, Aly/Ref, and THOC7, Pnky couples and modulates the splicing and export of target mRNAs, which consequently controlling NSC migration. These findings provide a possible theoretical basis of NSC migration regulation.


Assuntos
Células-Tronco Neurais , RNA Longo não Codificante , Animais , Camundongos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Paxilina/metabolismo , Metaloproteinase 2 da Matriz , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fator de Processamento U2AF/metabolismo , Células-Tronco Neurais/metabolismo , Fatores de Transcrição/genética , Proteínas de Ligação a RNA/metabolismo , Neurogênese , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
17.
Biomacromolecules ; 24(11): 4605-4621, 2023 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-37917193

RESUMO

With the emergence of challenges in the environmental degradation and resource scarcity fields, the research of biobased self-healing polyurethane (BSPU) has become a prevailing trend in the technology of the polyurethane industry and a promising direction for developing biomass resources. Here, the production of BSPU from lignocellulose, vegetable oil, chitosan, collagen, and coumarin is classified, and the principles of designing polyurethane based on compelling examples using the latest methods and current research are summarized. Moreover, the impact of biomass materials on self-healing and mechanical properties, as well as the tailored performance method, are presented in detail. Finally, the applications of BSPU in biomedicine, sensors, coatings, etc. are also summarized, and the possible challenges and development prospects are explored to helpfully make progress in the development of BSPU. These findings demonstrate valuable references and practical significance for future BSPU research.


Assuntos
Quitosana , Poliuretanos , Biomassa
18.
J Org Chem ; 88(4): 2393-2403, 2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36715636

RESUMO

A novel and convenient K2S2O8-mediated diiodo cyclization of 1,6-enynes for the facile synthesis of functionalized γ-lactam derivatives has been developed. This reaction features mild and transition-metal-free conditions, which offer a green and efficient entry to synthetically important γ-lactam scaffolds. Mechanistic studies suggest that iodide radicals initiate the cascade cyclic transformation.

19.
Nutr Metab Cardiovasc Dis ; 33(12): 2344-2354, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37596135

RESUMO

BACKGROUND AND AIMS: In order to find the exact strategies in the prevention of cardiovascular diseases (CVD), it is necessary to assess their risk factors systematically. Here, we used the Global Burden of Disease (GBD) to review the long-term trends and epidemiological characteristics among Chinese. METHODS AND RESULTS: We comprehensively analyzed the burden of CVD for the Chinese population using GBD 2019, including prevalence, incidence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs). Then, we analyzed trends over time, and predicted mortality and morbidity, using joinpoint regression, age-period-cohort (APC) model, and Bayesian APC approach. Finally, we analyzed the attributable burden of CVD. In 2019, the prevalence of CVD in China was 120 million, representing a 140.02% increase since 1990. The number of DALYs attributed to CVD increased by 52.56% compared to 1990. Joinpoint showed a fluctuating incidence downward, while mortality significantly declined. The APC fitting results indicated that recent generations have a higher prevalence than the past, and the prevalence has increased among individuals of the same age group. The BAPC predicted that CVD's prevalence and mortality in the Chinese would stabilize and decline between 2020 and 2030, with a significant decline among males. The main CVD-attributable burdens in 2019 were metabolic risks, especially high blood pressure. CONCLUSION: Given China's large and rapidly aging population, the burden of CVD is a major concern. Practical strategies to prevent and manage CVD are urgently needed to address this public health challenge.


Assuntos
Doenças Cardiovasculares , Masculino , Humanos , Idoso , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Expectativa de Vida , Anos de Vida Ajustados por Qualidade de Vida , Teorema de Bayes , Fatores de Risco , Saúde Global
20.
Childs Nerv Syst ; 39(11): 3281-3288, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37318613

RESUMO

OBJECTIVE: Subdural osteoma (SO) is a rarely reported benign tumor, and there is no report of SO manifested with epileptic seizures. We aim to further the understanding of SO-related epilepsy. METHODS: Here, we report a meaningful case of epilepsy secondary to SO. A systematic review of the literature about SO using the electronic database PubMed and Web of science up to December 2022 was conducted. RESULTS: A 15-year-old girl presented with epileptic seizures for 8 years. Magnetic resonance imaging revealed an irregular lesion with heterogeneous signal in the right frontal convexity. Right frontal craniotomy was performed to remove the lesion. The pathological diagnosis was SO. Histological analysis revealed that the mechanosensitive ion channels Piezo 1/2 were upregulated in the brain tissue compressed by the osteoma, compared with the levels in the osteoma-free region. Seizure freedom was obtained during the 6-month follow-up after the surgery. We identified 24 cases of SO in 23 articles. With our case, a total of 25 cases with 32 SOs was included. Of 25 cases, 24 are adults, and 1 is a child. Seizure has been reported only in our case. Frontal osteoma was found in 76% of the patients. Symptoms were cured in 56% of the patients after surgery. CONCLUSION: Surgery is a safe and effective approach to the treatment of symptomatic osteoma. Mechanical compression on cerebral cortex may be a predisposing factor of the epileptogenesis caused by the SO.


Assuntos
Epilepsia , Osteoma , Adulto , Criança , Feminino , Humanos , Adolescente , Epilepsia/cirurgia , Epilepsia/complicações , Imageamento por Ressonância Magnética/métodos , Córtex Cerebral/patologia , Convulsões/complicações , Osteoma/diagnóstico , Osteoma/patologia , Osteoma/cirurgia
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