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1.
BME Front ; 5: 0066, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39360181

RESUMO

Objective: We aim to develop a dual-functional bone regeneration scaffold (Qx-D) with antibacterial and osteogenic properties for infected bone defect treatment. Impact Statement: This study provides insights into antibacterial components that could be combined with naturally derived materials through a facile Schiff base reaction, offering a potential strategy to enhance antibacterial properties. Introduction: Naturally derived decalcified bone matrix (DBM) has been reported to be porous and biodegradable. DBM can induce various cell differentiations and participate in immune regulation, making it an ideal bone regeneration scaffold for bone defects. However, DBM does not exhibit antimicrobial properties. Therefore, it is essential to develop antibacterial functionalization method for DBM. Methods: DBM was modified with a macromolecular quaternary ammonium salt (QPEI). A series of Qx-D with tunable feeding ratios were synthesized through Schiff base reaction. The morphology, chemical property, in vitro antibacterial efficiency, in vitro biocompatibility, osteogenic property, and in vivo anti-infection performances were characterized. Results: All Qx-D exhibited marked antibacterial properties. Small adjustments in feed concentration could not induce changes in antibacterial properties. However, cell viability slightly decreased with increasing feed concentration. Q10-D demonstrated significant antibacterial properties and could promote recovery of infected bone defect in an animal model. Conclusion: Qx-D shows marked antibacterial properties and good biocompatibility. Moreover, Q10-D could be a potential choice for infected bone defects.

2.
3.
Plant Cell Environ ; 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39253958

RESUMO

Tree-ring data are pivotal for decoding the age and growth patterns of trees, reflecting the impact of environmental factors over time. Addressing the significant shortcomings of traditional, labour-intensive and resource-demanding methods, we propose an innovative automated technique that utilizes panchromatic images and deep learning for measuring tree rings. The method utilizes convolutional neural networks to enhance image quality, precisely delineate tree rings through segmentation and perform ring counting and width calculation in the post-processing stage. We compiled an extensive data set from diverse sources, including Beijing Forestry University and the Summer Palace, to train our algorithm. The performance of our method was validated empirically, demonstrating its potential to transform tree-ring analysis and provide deeper insights into ecological and climatological research.

4.
Biomaterials ; 314: 122789, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39260030

RESUMO

Chronic diabetic wounds are difficult to treat due to imbalanced inflammatory responses, high blood glucose levels, and bacterial infections. Novel therapeutic approaches based on nucleic acid analogues have been proposed, with unique advantages in improving angiogenesis, increasing collagen synthesis, and exerting anti-inflammatory effects. However, the inherent electronegativity of nucleic acids makes them less susceptible to cellular uptake. In this paper, a kind of near infrared (NIR)-responsive nanocomposite hydrogel loaded with nucleic acid vectors was proposed for promoting wound healing. The redox system composed of molybdenum disulphide nanosheets (MoS2 NSs) initiated the copolymerization of quaternized chitosan containing double bonds and N-isopropylacrylamide (NIPAAm) to form the matrix. In addition, MoS2 NSs with photothermal conversion performance endow the nanocomposite hydrogel to have NIR-response property and act as physical crosslinking points in the matrix. Polydeoxyribonucleotides (PDRN), which have the effect of promoting wound healing, were made into nucleic acid vectors, and loaded into the NIR-responsive hydrogel. MoS2 NSs can convert NIR irradiation into heat, causing phase transitions of temperature-sensitive segments that trigger volume contraction of the hydrogel to extrude the nucleic acid vector. Promoting angiogenesis, slowing inflammation, and guiding tissue regeneration were demonstrated in the diabetic wound model treated with the NIR-responsive nanocomposite hydrogel.

5.
J Obstet Gynaecol ; 44(1): 2389169, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39218008

RESUMO

BACKGROUND: Foetal growth restriction (FGR) occurs when a foetus fails to reach its growth potential. This observational study assessed the expression and significance of cell migration-including protein (CEMIP) and aldosterone synthase (CYP11B2) in the serum of pregnant women with FGR. METHODS: 40 singleton FGR-suffered pregnant women, as well as 40 normal singleton pregnant women, were enrolled. The expression of CEMIP and CYP11B2 in serum was detected in early pregnancy. The correlations between parameters were evaluated. The predictive variables for FGR were determined. The diagnostic value of CEMIP and CYP11B2 for FGR was analysed. RESULTS: CEMIP and CYP11B2 mRNA expression in the serum of pregnant women with FGR decreased (both P < 0.001). CEMIP (95%CI: 0.802-0.921, P < 0.001) and CYP11B2 (95%CI: 0.795-0.907, P < 0.001) mRNA expression in serum and soluble fms like tyrosine kinase-1 (sFLT1)/placental growth factor (PlGF) ratio (95%CI: 0.866-0.974, P < 0.001) were independent predictors of FGR, and CEMIP (r = -0.578, P = 0.001) and CYP11B2 (r = -0.602, P < 0.001) mRNA expression in serum were negatively correlated with sFLT1/PlGF ratio. CEMIP (AUC = 0.741) and CYP11B2 (AUC = 0.764) mRNA expression in serum had good diagnostic value for FGR. CONCLUSION: The expression of CEMIP and CYP11B2 is reduced in the serum of pregnant women with FGR and may become new diagnostic markers for FGR.


Foetal growth restriction is the inability of the foetus to reach its growth potential in the uterus due to various factors. This study aimed to investigate the expression and significance of cell migration-including protein and aldosterone synthase in serum of pregnant women with foetal growth restriction. In our study, we found that the expression of cell migration-including protein and aldosterone synthase in serum of pregnant women with foetal growth restriction were decreased. Cell migration-including protein and aldosterone synthase expression was negatively correlated with soluble fms like tyrosine kinase-1/placental growth factor ratio. In addition, the study also found that cell migration-including protein and aldosterone synthase expression in serum had good diagnostic value for foetal growth restriction.


Assuntos
Citocromo P-450 CYP11B2 , Retardo do Crescimento Fetal , Humanos , Feminino , Retardo do Crescimento Fetal/sangue , Retardo do Crescimento Fetal/diagnóstico , Retardo do Crescimento Fetal/genética , Gravidez , Citocromo P-450 CYP11B2/genética , Citocromo P-450 CYP11B2/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , RNA Mensageiro/sangue
6.
Zhongguo Zhong Yao Za Zhi ; 49(16): 4387-4395, 2024 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-39307775

RESUMO

Aconitum vilmorinianum is an authentic and superior medicinal herbal in Yunnan, which is rich in yunaconitine and other diterpene alkaloids. Diterpene alkaloids are its main active components. Farnesyl pyrophosphate synthase(FPS) is a key enzyme in the terpene biosynthetic pathway and plays an important role in diterpene alkaloid biosynthesis. Functional studies of FPS help to reveal the molecular mechanism of diterpene alkaloid biosynthesis. In this study, one FPS gene(AvFPS) was selected based on the transcriptome data of A. vilmorinianum. Its full-length sequence was cloned, and bioinformatic analysis, functional verification, and gene expression analysis were performed. The open reading frame(ORF) of AvFPS was 1 056 bp, encoding 351 amino acids. Its molecular weight was 41 kDa. AvFPS had two typical conserved functional domains of isopentenyl transferase, " DDIMD" and " DDYXD". The recombinant protein of AvFPS was expressed in Escherichia coli, and purified recombinant protein was used for in vitro enzymatic reaction. The results revealed that AvFPS was able to catalyze the synthesis of farnesyl pyrophosphate(FPP). The results of qRT-PCR analysis showed that AvFPS was expressed in the roots, stems, leaves, and flowers of A. vilmorinianum, with the highest expression level in the roots. The expression level of AvFPS was significantly up-regulated by MeJA induction. This study clarified the catalytic function of AvFPS, revealed the expression pattern of AvFPS in different tissue, as well as at different time induced by MeJA, and provided a reference for a deeper understanding of the function of FPS in the biosynthesis of diterpenoid components.


Assuntos
Aconitum , Clonagem Molecular , Geraniltranstransferase , Proteínas de Plantas , Geraniltranstransferase/genética , Geraniltranstransferase/metabolismo , Geraniltranstransferase/química , Aconitum/genética , Aconitum/enzimologia , Aconitum/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Regulação da Expressão Gênica de Plantas , Sequência de Aminoácidos , Filogenia , Alinhamento de Sequência
7.
RNA ; 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39322276

RESUMO

Uridine residues present at the wobble position of eukaryotic cytosolic tRNAs often carry a 5-carbamoylmethyl (ncm5), 5-methoxycarbonylmethyl (mcm5), or 5-methoxycarbonylhydroxymethyl (mchm5) side-chain. The presence of these side-chains allows proper pairing with cognate codons and they are particularly important in tRNA species where the U34 residue is also modified with a 2-thio (s2) group. The first step in synthesis of the ncm5, mcm5, and mchm5 side-chains is dependent on the six-subunit Elongator complex, whereas the thiolation of the 2-position is catalyzed by the Ncs6/Ncs2 complex. In both yeast and metazoans, allelic variants of Elongator subunit genes show genetic interactions with mutant alleles of SOD1, which encodes the cytosolic Cu,Zn-superoxide dismutase. However, the cause of these genetic interactions remains unclear. Here, we show that yeast sod1 null mutants are impaired in the formation of 2-thio-modified U34 residues. In addition, the lack of Sod1 induces a defect in the biosynthesis of wybutosine, which is a modified nucleoside found at position 37 of tRNAPhe Our results suggest that these tRNA modification defects are caused by superoxide-induced inhibition of the iron-sulfur cluster-containing Ncs6/Ncs2 and Tyw1 enzymes. Since mutations in Elongator subunit genes generate strong negative genetic interactions with mutant ncs6 and ncs2 alleles, our findings at least partially explain why the activity of Elongator can modulate the phenotypic consequences of SOD1/sod1 alleles. Collectively, our results imply that tRNA hypomodification may contribute to impaired proteostasis in Sod1-deficient cells.

8.
ACS Appl Mater Interfaces ; 16(38): 50630-50639, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39264306

RESUMO

Triboelectric nanogenerators (TENGs) have attracted widespread attention as a promising candidate for energy harvesting due to their flexibility and high power density. To meet diverse application scenarios, a highly stretchable (349%), conductive (1.87 S m-1), and antibacterial electrode composed of carbon quantum dots/LiCl/agar-polyacrylamide (CQDs/LiCl/agar-PAAm) dual-network (DN) hydrogel is developed for wearable TENGs. Notably, the concentration of agar alters the pore spacing and pore size of the DN hydrogel, thereby impacting the network cross-linking density and the migration of conductive ions (Li+ and Cl-). This variation further affects the mechanical strength and conductivity of the hydrogel electrode, thus modulating the mechanical stability and electrical output performance of the TENGs. With the optimal agar content, the tensile strength and conductivity of the hydrogel electrode increase by 211 and 719%, respectively. This enhancement ensures the stable output of TENGs during continuous operation (6000 cycles), with open-circuit voltage, short-circuit current, and transferred charge increasing by 200, 530, and 155%, respectively. Additionally, doping with CQDs enables the hydrogel electrode to effectively inhibit the Gram-negative bacterium Escherichia coli. Finally, the TENGs are utilized as a self-power smart ring for efficient and concise information transmission via Morse code. Consequently, this study introduces a creative approach for designing and implementing multifunctional, flexible wearable devices.


Assuntos
Antibacterianos , Eletrodos , Escherichia coli , Hidrogéis , Dispositivos Eletrônicos Vestíveis , Escherichia coli/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Hidrogéis/química , Hidrogéis/farmacologia , Pontos Quânticos/química , Resinas Acrílicas/química , Condutividade Elétrica , Fontes de Energia Elétrica , Ágar/química , Carbono/química , Humanos
9.
Animals (Basel) ; 14(16)2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39199846

RESUMO

Accurate and intelligent identification of rare and endangered individuals of flagship wildlife species, such as Amur tiger (Panthera tigris altaica), is crucial for understanding population structure and distribution, thereby facilitating targeted conservation measures. However, many mathematical modeling methods, including deep learning models, often yield unsatisfactory results. This paper proposes an individual recognition method for Amur tigers based on an improved InceptionResNetV2 model. Initially, the YOLOv5 model is employed to automatically detect and segment facial, left stripe, and right stripe areas from images of 107 individual Amur tigers, achieving a high average classification accuracy of 97.3%. By introducing a dropout layer and a dual-attention mechanism, we enhance the InceptionResNetV2 model to better capture the stripe features of individual tigers at various granularities and reduce overfitting during training. Experimental results demonstrate that our model outperforms other classic models, offering optimal recognition accuracy and ideal loss changes. The average recognition accuracy for different body part features is 95.36%, with left stripes achieving a peak accuracy of 99.37%. These results highlight the model's excellent recognition capabilities. Our research provides a valuable and practical approach to the individual identification of rare and endangered animals, offering significant potential for improving conservation efforts.

10.
Mil Med Res ; 11(1): 60, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39169415

RESUMO

BACKGROUND: The diagnosis of tuberculous pleurisy (TP) presents a significant challenge due to the low bacterial load in pleural effusion (PE) samples. Cell-free Mycobacterium tuberculosis DNA (cf-TB) in PE samples is considered an optimal biomarker for diagnosing TP. This study aimed to evaluate the applicability of cf-TB testing across diverse research sites with a relatively large sample size. METHODS: Patients suspected of TP and presenting with clinical symptoms and radiological evidence of PE were consecutively enrolled by treating physicians from 11 research sites across 6 provinces in China between April 2020 and August 2022. Following centrifugation, sediments obtained from PE were used for Xpert MTB/RIF (Xpert) and mycobacterial culture, while the supernatants were subjected to cf-TB testing. This study employed a composite reference standard to definite TP, which was characterized by any positive result for Mycobacterium tuberculosis (MTB) through either PE culture, PE Xpert, or pleural biopsy. RESULTS: A total of 1412 participants underwent screening, and 1344 (95.2%) were subsequently enrolled in this study. Data from 1241 (92.3%) participants were included, comprising 284 with definite TP, 677 with clinically diagnosed TP, and 280 without TP. The sensitivity of cf-TB testing in definite TP was 73.6% (95% CI 68.2-78.4), significantly higher than both Xpert (40.8%, 95% CI 35.3-46.7, P < 0.001) and mycobacterial culture (54.2%, 95% CI 48.4-59.9, P < 0.001). When clinically diagnosed TP was incorporated into the composite reference standard for sensitivity analysis, cf-TB testing showed a sensitivity of 46.8% (450/961, 95% CI 43.7-50.0), significantly higher than both Xpert (116/961, 12.1%, 95% CI 10.2-14.3, P < 0.001) and mycobacterial culture (154/961, 16.0%, 95% CI 13.8-18.5, P < 0.001). The specificities of cf-TB testing, Xpert, and mycobacterial culture were all 100.0%. CONCLUSIONS: The performance of cf-TB testing is significantly superior to that of Xpert and mycobacterial culture methods, indicating that it can be considered as the primary diagnostic approach for improving TP detection. Trial registration The trial was registered on Chictr.org.cn (ChiCTR2000031680, https://www.chictr.org.cn/showproj.html?proj=49316 ).


Assuntos
DNA Bacteriano , Mycobacterium tuberculosis , Derrame Pleural , Tuberculose Pleural , Humanos , Tuberculose Pleural/diagnóstico , Feminino , Mycobacterium tuberculosis/genética , Estudos Transversais , Masculino , Pessoa de Meia-Idade , Adulto , Derrame Pleural/microbiologia , Derrame Pleural/diagnóstico , China , DNA Bacteriano/análise , Ácidos Nucleicos Livres/análise , Idoso , Sensibilidade e Especificidade
11.
Adv Mater ; 36(40): e2407927, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39185788

RESUMO

The combination of nanoparticles and tumor-targeting bacteria for cancer immunotherapy can overcome the shortcomings of poor nanoparticle accumulation, limited penetration, and restricted distribution. However, it remains a great challenge for the hybrid system to improve therapeutic efficacy through the simultaneous and controllable regulation of immune cells and tumor cells. Herein, a hybrid therapeutic platform is rationally designed to achieve immune cascade-augmented cancer immunotherapy. To construct the hybrids, photothermal nanoparticles responsive to light in the second near-infrared (NIR-II) region are conjugated onto the surface of engineered bacteria through pH-responsive Schiff base bonds. Taking advantage of the hypoxia targeting and deep penetration characteristics of the bacteria, the hybrids can accumulate at tumor sites. Then nanoparticles detach from the bacteria to realize genetic engineering of tumor cells, which induces tumor cell apoptosis and down-regulate the expression of programmed cell death ligand 1 to alleviate immunosuppressive tumor microenvironment. The mild photothermal heating can not only induce tumor-associated antigen release, but also trigger sustainable expression of cytokine interleukin-2. Notably, a synergistic antitumor effect is achieved between the process of p53 transfection and NIR-II light-activated genetic engineering of bacteria. This work proposes a facile strategy for the construction of hybrid system to achieve cascade-augmented cancer immunotherapy.


Assuntos
Engenharia Genética , Imunoterapia , Raios Infravermelhos , Nanopartículas , Animais , Linhagem Celular Tumoral , Nanopartículas/química , Camundongos , Humanos , Neoplasias/terapia , Apoptose , Microambiente Tumoral
12.
PeerJ Comput Sci ; 10: e2025, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38983204

RESUMO

As the diversity and volume of images continue to grow, the demand for efficient fine-grained image retrieval has surged across numerous fields. However, the current deep learning-based approaches to fine-grained image retrieval often concentrate solely on the top-layer features, neglecting the relevant information carried in the middle layer, even though these information contains more fine-grained identification content. Moreover, these methods typically employ a uniform weighting strategy during hash code mapping, risking the loss of critical region mapping-an irreversible detriment to fine-grained retrieval tasks. To address the above problems, we propose a novel method for fine-grained image retrieval that leverage feature fusion and hash mapping techniques. Our approach harnesses a multi-level feature cascade, emphasizing not just top-layer but also intermediate-layer image features, and integrates a feature fusion module at each level to enhance the extraction of discriminative information. In addition, we introduce an agent self-attention architecture, marking its first application in this context, which steers the model to prioritize on long-range features, further avoiding the loss of critical regions of the mapping. Finally, our proposed model significantly outperforms existing state-of-the-art, improving the retrieval accuracy by an average of 40% for the 12-bit dataset, 22% for the 24-bit dataset, 16% for the 32-bit dataset, and 11% for the 48-bit dataset across five publicly available fine-grained datasets. We also validate the generalization ability and performance stability of our proposed method by another five datasets and statistical significance tests. Our code can be downloaded from https://github.com/BJFU-CS2012/MuiltNet.git.

13.
Sensors (Basel) ; 24(14)2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39065947

RESUMO

To investigate the effects of long-term prestress loss on concrete box girders strengthened with external prestressing, a large-span box girder, in service for over 20 years and strengthened with external prestressing, was monitored for four months. Prestress loss in the longitudinal, vertical, and transverse directions of the box girder was calculated according to Chinese code requirements. Magnetic flux rope force transducers were used to monitor the prestress loss in the external prestressing cables. Fiber Bragg Grating (FBG) sensors were used to monitor deflection changes at the mid-span of the bridge. Finally, the effect of prestress loss in the longitudinal, vertical, and transverse tendons on mid-span deflection was investigated through simulations using ABAQUS software. The results show that instantaneous prestress loss accounts for most of the total loss compared to long-term loss, and that longitudinal prestress loss has the most significant effect on mid-span deflection. The impact of longitudinal prestress loss on deflection before and after strengthening was also compared. The downward deflection and up-ward arch caused by longitudinal tendon prestress loss were reduced after strengthening, con-firming the effectiveness of the external prestressing method.

14.
Animals (Basel) ; 14(12)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38929335

RESUMO

Species recognition is a crucial part of understanding the abundance and distribution of various organisms and is important for biodiversity conservation and management. Traditional vision-based deep learning-driven species recognition requires large amounts of well-labeled, high-quality image data, the collection of which is challenging for rare and endangered species. In addition, recognition methods designed based on specific species have poor generalization ability and are difficult to adapt to new species recognition scenarios. To address these issues, zero-shot species recognition based on Contrastive Language-Image Pre-training (CLIP) has become a research hotspot. However, previous studies have primarily utilized visual descriptive information and taxonomic information of species to improve zero-shot recognition performance, and the use of geographic distribution characteristics of species to improve zero-shot recognition performance has not been explored. To fill this gap, we proposed a CLIP-driven zero-shot species recognition method that incorporates knowledge of the geographic distribution of species. First, we designed three prompts based on the species geographic distribution statistical data. Then, the latitude and longitude coordinate information attached to each image in the species dataset was converted into addresses, and they were integrated together to form the geographical distribution knowledge of each species. Finally, species recognition results were derived by calculating the similarity after acquiring features by the trained CLIP image encoder and text encoder. We conducted extensive experiments on multiple species datasets from the iNaturalist 2021 dataset, where the zero-shot recognition accuracies of mammals, mollusks, reptiles, amphibians, birds, and insects were 44.96%, 15.27%, 17.51%, 9.47%, 28.35%, and 7.03%, an improvement of 2.07%, 0.48%, 0.35%, 1.12%, 1.64%, and 0.61%, respectively, as compared to CLIP with default prompt. The experimental results show that the fusion of geographic distribution statistical data can effectively improve the performance of zero-shot species recognition, which provides a new way to utilize species domain knowledge.

15.
Plant J ; 119(2): 879-894, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38923085

RESUMO

Cotton is a globally cultivated crop, producing 87% of the natural fiber used in the global textile industry. The pigment glands, unique to cotton and its relatives, serve as a defense structure against pests and pathogens. However, the molecular mechanism underlying gland formation and the specific role of pigment glands in cotton's pest defense are still not well understood. In this study, we cloned a gland-related transcription factor GhHAM and generated the GhHAM knockout mutant using CRISPR/Cas9. Phenotypic observations, transcriptome analysis, and promoter-binding experiments revealed that GhHAM binds to the promoter of GoPGF, regulating pigment gland formation in cotton's multiple organs via the GoPGF-GhJUB1 module. The knockout of GhHAM significantly reduced gossypol production and increased cotton's susceptibility to pests in the field. Feeding assays demonstrated that more than 80% of the cotton bollworm larvae preferred ghham over the wild type. Furthermore, the ghham mutants displayed shorter cell length and decreased gibberellins (GA) production in the stem. Exogenous application of GA3 restored stem cell elongation but not gland formation, thereby indicating that GhHAM controls gland morphogenesis independently of GA. Our study sheds light on the functional differentiation of HAM proteins among plant species, highlights the significant role of pigment glands in influencing pest feeding preference, and provides a theoretical basis for breeding pest-resistant cotton varieties to address the challenges posed by frequent outbreaks of pests.


Assuntos
Regulação da Expressão Gênica de Plantas , Gossypium , Proteínas de Plantas , Gossypium/genética , Gossypium/parasitologia , Gossypium/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Animais , Giberelinas/metabolismo , Gossipol/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Resistência à Doença/genética , Doenças das Plantas/parasitologia , Doenças das Plantas/imunologia , Mariposas/fisiologia , Larva/crescimento & desenvolvimento
16.
Zool Res ; 45(4): 781-790, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-38894521

RESUMO

Precise targeting of specific regions within the central nervous system (CNS) is crucial for both scientific research and gene therapy in the context of brain diseases. Adeno-associated virus 13 (AAV13) is known for its restricted diffusion range within the CNS, making it an ideal choice for precise labeling and administration within small brain regions. However, AAV13 mediates relatively low expression of target genes. Here, we introduced specifically engineered modifications to the AAV13 capsid protein to enhance its transduction efficiency. We first constructed AAV13-YF by mutating tyrosine to phenylalanine on the surface of the AAV13 capsid. We then inserted the 7m8 peptide, known to enhance cell transduction, into positions 587/588 and 585/586 of the AAV13 capsid, resulting in two distinct variants named AAV13-587-7m8 and AAV13-585-7m8, respectively. We found that AAV13-YF exhibited superior in vitro infectivity in HEK293T cells compared to AAV13, while AAV13-587-7m8 and AAV13-585-7m8 showed enhanced CNS infection capabilities in C57BL/6 mice, with AAV13-587-7m8 infection retaining a limited spread range. These modified AAV13 variants hold promising potential for applications in gene therapy and neuroscience research.


Assuntos
Dependovirus , Camundongos Endogâmicos C57BL , Dependovirus/genética , Animais , Humanos , Camundongos , Células HEK293 , Transdução Genética , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo
17.
Macromol Rapid Commun ; : e2400339, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38925556

RESUMO

Chirality is ubiquitous in nature, and closely related to biological phenomena. Nature-originated nanomaterials such as cellulose nanocrystals (CNCs) are able to self-assemble into hierarchical chiral nematic CNC films and impart handedness to nano and micro scale. However, the effects of the chiral nematic surfaces on cell adhesion are still unknown. Herein, this work presents evidence that the left-handed self-assembled chiral nematic CNC films (L-CNC) significantly improve the adhesion of L929 fibroblasts compared to randomly arranged isotropic CNC films (I-CNC). The fluidic force microscopy-based single-cell force spectroscopy is introduced to assess the cell adhesion forces on the substrates of L-CNC and I-CNC, respectively. With this method, a maximum adhesion force of 133.2 nN is quantified for mature L929 fibroblasts after culturing for 24 h on L-CNC, whereas the L929 fibroblasts exert a maximum adhesion force of 78.4 nN on I-CNC under the same condition. Moreover, the instant SCFS reveals that the integrin pathways are involved in sensing the chirality of substrate surfaces. Overall, this work offers a starting point for the regulation of cell adhesion via the self-assembled nano and micro architecture of chiral nematic CNC films, with potential practical applications in tissue engineering and regenerative medicine.

18.
Heliyon ; 10(11): e32409, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38933950

RESUMO

Identification of novel biomarkers for prediction of disease course and prognosis is needed to reduce morbidity of liver hepatocellular carcinoma (LIHC/HCC) patients. Although dysregulated Periodic tryptophan protein 1 homolog (PWP1/endonuclein) expression has been detected in several tumors, the potential regulatory effect of PWP1 on LIHC remains uncertain. Here we evaluated the expression of PWP1 using multiple online platforms, and demonstrated that PWP1 upregulation was consistently observed in LIHC relative to non-tumor liver tissues and correlated with unfavorable prognosis. Moreover, HCC prognosis was significantly influenced by the methylation status of various CpG sites in the PWP1 gene. Lastly, we provide direct evidence that PWP1 acts as a driver of HCC progression by showing that siRNA-mediated PWP1 silencing significantly suppressed HCC cell proliferation in vitro. These data strongly suggest that PWP1 silencing may be an effective therapeutic strategy to treat LIHC.

19.
Environ Sci Technol ; 58(25): 11185-11192, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38869092

RESUMO

Electrocatalytic hydrogen atom-hydroxyl radical (H*-·OH) redox system is a promising approach for contaminant removal and mineralization. However, its working mechanism, especially the effect of H*, remains unclear, hindering its practical application. Herein, we constructed an electrochemical reactor equipped with our self-made Pd-loaded Ti/TiO2 nanotube cathode and a commercial boron-doped diamond anode. After fulfilling the electrode characterization and free radical detection, we employed coumarin and 7-azido-4-methylcoumarin as probes to confirm the participation of H* in the transformation of organic compounds. A comprehensive study on the degradation kinetics, reaction, and mineralization mechanisms using benzoic acid (BA) and 4-chlorophenol (4-CP) as model compounds was further conducted. The rate constants and total organic carbon removal of BA and 4-CP in the redox system increased compared with those of the individual oxidation and reduction processes. Theoretical calculations demonstrate that H* opens up alternative pathways for BA and 4-CP ring cleavage, forming quinones as reactive intermediates. Furthermore, H* facilitates the mineralization of the typical intermediates, maleic acid and fumaric acid, through C=C bond addition and H-abstraction from the 1,1-diol structure. The presence of H* provides alternative pathways for pollutant transformation, consequently reducing the treatment duration.


Assuntos
Hidrogênio , Oxirredução , Hidrogênio/química , Cinética
20.
Plant Physiol Biochem ; 213: 108808, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38865805

RESUMO

The development of the mining industry and the overuse of inorganic fertilizers have led to an excess of manganese (Mn) in the soil, thereby, contaminating the soil environment and people's health. On heavy metal-contaminated soils, the combined arbuscular mycorrhizal fungi (AMF)-phytoremediation technique becomes a hotspot because of its environmentally friendly, in situ remediation. AMF inoculation often leads to a decrease in host Mn acquisition, which provides a basis for its application in phytoremediation of contaminated soils. Moreover, the utilization value of native AMF is greater than that of exotic AMF, because native AMF can adapt better to Mn-contaminated soils. In addition to the fact that AMF enhance plant Mn tolerance responses such as regionalization, organic matter chelation, limiting uptake and efflux, and so on, AMF also develop plant-independent fungal pathways such as direct biosorption of Mn by mycorrhizal hyphae, fungal Mn transporter genes, and sequestration of Mn by mycorrhizal hyphae, glomalin, and arbuscule-containing root cortical cells, which together mitigate excessive Mn toxicity to plants. Clarifying AMF-plant interactions under Mn stress will provide support for utilizing AMF as a phytoremediation in Mn-contaminated soils. The review reveals in detail how AMF develop its own mechanisms for responding to excess Mn and how AMF enhance plant Mn tolerance, accompanied by perspectives for future research.


Assuntos
Biodegradação Ambiental , Manganês , Micorrizas , Plantas , Micorrizas/metabolismo , Micorrizas/fisiologia , Manganês/metabolismo , Manganês/toxicidade , Plantas/metabolismo , Plantas/efeitos dos fármacos , Plantas/microbiologia , Poluentes do Solo/toxicidade , Poluentes do Solo/metabolismo , Raízes de Plantas/microbiologia , Raízes de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos
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