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1.
Smart Med ; 3(1): e20230045, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-39188514

RESUMO

Recent advancements in soft robotics have been emerging as an exciting paradigm in engineering due to their inherent compliance, safe human interaction, and ease of adaptation with wearable electronics. Soft robotic devices have the potential to provide innovative solutions and expand the horizons of possibilities for biomedical applications by bringing robots closer to natural creatures. In this review, we survey several promising soft robot technologies, including flexible fluidic actuators, shape memory alloys, cable-driven mechanisms, magnetically driven mechanisms, and soft sensors. Selected applications of soft robotic devices as medical devices are discussed, such as surgical intervention, soft implants, rehabilitation and assistive devices, soft robotic exosuits, and prosthetics. We focus on how soft robotics can improve the effectiveness, safety and patient experience for each use case, and highlight current research and clinical challenges, such as biocompatibility, long-term stability, and durability. Finally, we discuss potential directions and approaches to address these challenges for soft robotic devices to move toward real clinical translations in the future.

2.
Phys Rev Lett ; 132(26): 267201, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38996296

RESUMO

A snap-through bifurcation occurs when a bistable structure loses one of its stable states and moves rapidly to the remaining state. For example, a buckled arch with symmetrically clamped ends can snap between an inverted and a natural state as the ends are released. A standard linear stability analysis suggests that the arch becomes unstable to asymmetric perturbations. Surprisingly, our experiments show that this is not always the case: symmetric transitions are also observed. Using experiments, numerics, and a toy model, we show that the symmetry of the transition depends on the rate at which the ends are released, with sufficiently fast loading leading to symmetric snap-through. Our toy model reveals that this behavior is caused by a region of the system's state space in which any initial asymmetry is amplified. The system may not enter this region when loaded fast (hence remaining symmetric), but will traverse it for some interval of time when loaded slowly, causing a transient amplification of asymmetry. Our toy model suggests that this behavior is not unique to snapping arches, but rather can be observed in dynamical systems where both a saddle-node and a pitchfork bifurcation occur in close proximity.

3.
Cancers (Basel) ; 16(12)2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38927940

RESUMO

During the cell life cycle, extracellular vesicles (EVs) transport different cargos, including organelles, proteins, RNAs, DNAs, metabolites, etc., that influence cell proliferation and apoptosis in recipient cells. EVs from metastatic cancer cells remodel the extracellular matrix and cells of the tumor microenvironment (TME), promoting tumor invasion and metastatic niche preparation. Although the process is not fully understood, evidence suggests that EVs facilitate genetic material transfer between cells. In the context of NSCLC, EVs can mediate intercellular mitochondrial (Mt) transfer, delivering mitochondria organelle (MtO), mitochondrial DNA (mtDNA), and/or mtRNA/proteinaceous cargo signatures (MtS) through different mechanisms. On the other hand, certain populations of cancer cells can hijack the MtO from TME cells mainly by using tunneling nanotubes (TNTs). This transfer aids in restoring mitochondrial function, benefiting benign cells with impaired metabolism and enabling restoration of their metabolic activity. However, the impact of transferring mitochondria versus transplanting intact mitochondrial organelles in cancer remains uncertain and the subject of debate. Some studies suggest that EV-mediated mitochondria delivery to cancer cells can impact how cancer responds to radiation. It might make the cancer more resistant or more sensitive to radiation. In our review, we aimed to point out the current controversy surrounding experimental data and to highlight new paradigm-shifting modalities in radiation therapy that could potentially overcome cancer resistance mechanisms in NSCLC.

4.
Adv Mater ; 36(32): e2405440, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38801657

RESUMO

Light-assisted Li-O2 batteries exhibit a high round-trip efficiency attributable to the assistance of light-generated electrons and holes in oxygen reduction and evolution reactions. Nonetheless, the excitonic effect arising from Coulomb interaction between electrons and holes impedes carrier separation, thus hindering efficient utilization of photo-energy. Herein, porphyrinic metal-organic frameworks with (Fe2Ni)O(COO)6 clusters are used as photocathodes to accelerate exciton dissociation into charge carriers for light-assisted Li-O2 batteries. The coupling of Ni 3d and Fe 3d orbitals boosts ligand-to-metal cluster charge transfer, and hence drives exciton dissociation and activates O2 for superoxide (•O2 -) radicals, rather than singlet oxygen (1O2) under photoexcitation. These enable the light-assisted Li-O2 batteries with a low total overvoltage of 0.28 V and round-trip efficiency of 92% under light irradiation of 100 mW cm-2. This work highlights the excitonic effect in photoelectrochemical processes and provides insights into photocathode design for light-assisted Li-O2 batteries.

5.
BMC Genomics ; 25(1): 494, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38764031

RESUMO

BACKGROUND: Mammary gland development is a critical process in mammals, crucial for their reproductive success and offspring nourishment. However, the functional roles of key candidate genes associated with teat number, including ABCD4, VRTN, PROX2, and DLST, in this developmental process remain elusive. To address this gap in knowledge, we conducted an in-depth investigation into the dynamic expression patterns, functional implications, and regulatory networks of these candidate genes during mouse mammary gland development. RESULTS: In this study, the spatial and temporal patterns of key genes were characterized in mammary gland development. Using time-series single-cell data, we uncovered differences in the expression of A bcd4, Vrtn, Prox2, and Dlst in cell population of the mammary gland during embryonic and adult stages, while Vrtn was not detected in any cells. We found that only overexpression and knockdown of Abcd4 could inhibit proliferation and promote apoptosis of HC11 mammary epithelial cells, whereas Prox2 and Dlst had no significant effect on these cells. Using RNA-seq and qPCR, further analysis revealed that Abcd4 can induce widespread changes in the expression levels of genes involved in mammary gland development, such as Igfbp3, Ccl5, Tlr2, and Prlr, which were primarily associated with the MAPK, JAK-STAT, and PI3K-AKT pathways by functional enrichment. CONCLUSIONS: These findings revealed ABCD4 as a candidate gene pivotal for regulating mammary gland development and lactation during pregnancy by influencing PRLR expression.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Glândulas Mamárias Animais , Animais , Feminino , Camundongos , Apoptose/genética , Proliferação de Células , Células Epiteliais/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes , Glândulas Mamárias Animais/crescimento & desenvolvimento , Glândulas Mamárias Animais/metabolismo , Transdução de Sinais , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo
6.
Sensors (Basel) ; 24(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38732965

RESUMO

Although the rapid expansion of urban rail transit offers convenience to citizens, the issue of subway vibration cannot be overlooked. This study investigates the spatial distribution characteristics of vibration in the Fayuan Temple historic and cultural reserve. It involves using a V001 magnetoelectric acceleration sensor capable of monitoring low amplitudes with a sensitivity of 0.298 V/(m/s2), a measuring range of up to 20 m/s2, and a frequency range span from 0.5 to 100 Hz for in situ testing, analyzing the law of vibration propagation in this area, evaluating the impact on buildings, and determining the vibration reduction scheme. The reserve is divided into three zones based on the vertical vibration level measured during the in situ test as follows: severely excessive, generally excessive, and non-excessive vibration. Furthermore, the research develops a dynamic coupling model of vehicle-track-tunnel-stratum-structure to verify the damping effect of the wire spring floating plate track and periodic pile row. It compares the characteristics of three vibration reduction schemes, namely, internal vibration reduction reconstruction, periodic pile row, and anti-vibration reinforcement or reconstruction of buildings, proposing a comprehensive solution. Considering the construction conditions, difficulty, cost, and other factors, a periodic pile row is recommended as the primary treatment measure. If necessary, anti-vibration reinforcement or reconstruction of buildings can serve as supplemental measures.

7.
Materials (Basel) ; 17(3)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38591560

RESUMO

The as-cast (Fe50Mn30Co10Cr10)97C2Mo1 HEA (high entropy alloy) was prepared and cold-rolled at 70%. Subsequently, annealing heat treatment at different temperatures (900 °C, 950 °C, 1000 °C) was carried out. The microstructure evolution and mechanical properties of the HEA were systematically investigated. The results showed that the HEA annealed at 900 °C and 950 °C exhibited uneven grain size and rich σ precipitation phase at grain boundaries. The grains began to grow and complete recrystallization, and no σ phases were observed in HEA annealed at 1000 °C, which resulted in a higher tensile strength of ~885 MPa and elongation of ~68% compared with other annealed HEAs. The higher volume fraction of annealing twins with 60°<111> orientation was produced in HEA annealed at 1000 °C, which enhanced the tensile strength and plasticity via the Twinning-induced plasticity (TWIP) mechanism.

8.
Opt Lett ; 49(6): 1567-1570, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489452

RESUMO

Speckle patterns generated as coherent optical beams are reflected by scattering elements. Multimode fibers (MMFs) can modify the transverse intensity distribution of speckle patterns with macro perturbations, i.e., pressures, providing a simple and low-cost way to achieve equivalent beam-steering for indoor optical wireless communications (OWCs) with divergent optical beams. However, the received optical power (ROP) variance severely limits the mobility of user terminals. In this paper, the issue is alleviated by using the overfilled launch of MMFs and the diversity gain of multi-receivers. By adjusting the axial spatial coupling distance between the MMF and the single mode fiber (SMF) emitting coherent laser, the number of excited modes of MMF can be significantly increased at 1550 nm with negligible coupling and bending losses. In addition, the signal-to-noise ratio (SNR) enhancement obtained by applying two receivers is theoretically analyzed for the case when either thermal noise or shot noise is dominant. The experimental results demonstrate that the proposed scheme can efficiently compensate for the ROP inhomogeneity, and at the same time it can extend the achievable full steering angle up to 12° at a 1.5-m free-space distance for bit error rate (BER) values of less than 3.8 × 10-3.

9.
PLoS Pathog ; 20(3): e1012104, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38512977

RESUMO

The interaction between foot-and-mouth disease virus (FMDV) and the host is extremely important for virus infection, but there are few researches on it, which is not conducive to vaccine development and FMD control. In this study, we designed a porcine genome-scale CRISPR/Cas9 knockout library containing 93,859 single guide RNAs targeting 16,886 protein-coding genes, 25 long ncRNAs, and 463 microRNAs. Using this library, several previously unreported genes required for FMDV infection are highly enriched post-FMDV selection in IBRS-2 cells. Follow-up studies confirmed the dependency of FMDV on these genes, and we identified a functional role for one of the FMDV-related host genes: TOB1 (Transducer of ERBB2.1). TOB1-knockout significantly inhibits FMDV infection by positively regulating the expression of RIG-I and MDA5. We further found that TOB1-knockout led to more accumulation of mRNA transcripts of transcription factor CEBPA, and thus its protein, which further enhanced transcription of RIG-I and MDA5 genes. In addition, TOB1-knockout was shown to inhibit FMDV adsorption and internalization mediated by EGFR/ERBB2 pathway. Finally, the FMDV lethal challenge on TOB1-knockout mice confirmed that the deletion of TOB1 inhibited FMDV infection in vivo. These results identify TOB1 as a key host factor involved in FMDV infection in pigs.


Assuntos
Vírus da Febre Aftosa , Febre Aftosa , Animais , Camundongos , Receptores ErbB/metabolismo , Febre Aftosa/genética , Vírus da Febre Aftosa/genética , Regulação da Expressão Gênica , RNA Guia de Sistemas CRISPR-Cas , Suínos
10.
Jpn J Radiol ; 42(7): 709-719, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38409300

RESUMO

PURPOSE: To investigate the role of magnetic resonance imaging (MRI) based on radiomics using T2-weighted imaging fat suppression (T2WI-FS) and contrast enhanced T1-weighted imaging (CE-T1WI) sequences in differentiating T1-category nasopharyngeal carcinoma (NPC) from nasopharyngeal lymphoid hyperplasia (NPH). MATERIALS AND METHODS: This study enrolled 614 patients (training dataset: n = 390, internal validation dataset: n = 98, and external validation dataset: n = 126) of T1-category NPC and NPH. Three feature selection methods were used, including analysis of variance, recursive feature elimination, and relief. The logistic regression classifier was performed to construct the radiomics signatures of T2WI-FS, CE-T1WI, and T2WI-FS + CE-T1WI to differentiate T1-category NPC from NPH. The performance of the optimal radiomics signature (T2WI-FS + CE-T1WI) was compared with those of three radiologists in the internal and external validation datasets. RESULTS: Twelve, 15, and 15 radiomics features were selected from T2WI-FS, CE-T1WI, and T2WI-FS + CE-T1WI to develop the three radiomics signatures, respectively. The area under the curve (AUC) values for radiomics signatures of T2WI-FS + CE-T1WI and CE-T1WI were significantly higher than that of T2WI-FS (AUCs = 0.940, 0.935, and 0.905, respectively) for distinguishing T1-category NPC and NPH in the training dataset (Ps all < 0.05). In the internal and external validation datasets, the radiomics signatures based on T2WI-FS + CE-T1WI and CE-T1WI outperformed T2WI-FS with no significant difference (AUCs = 0.938, 0.925, and 0.874 for internal validation dataset and 0.932, 0.918, and 0.882 for external validation dataset; Ps > 0.05). The radiomics signature of T2WI-FS + CE-T1WI significantly performed better than three radiologists in the internal and external validation datasets. CONCLUSION: The MRI-based radiomics signature is meaningful in differentiating T1-category NPC from NPH and potentially helps clinicians select suitable therapy strategies.


Assuntos
Hiperplasia , Imageamento por Ressonância Magnética , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Diagnóstico Diferencial , Feminino , Carcinoma Nasofaríngeo/diagnóstico por imagem , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/diagnóstico por imagem , Adulto , Hiperplasia/diagnóstico por imagem , Idoso , Adulto Jovem , Adolescente , Estudos Retrospectivos , Meios de Contraste , Nasofaringe/diagnóstico por imagem , Reprodutibilidade dos Testes , Radiômica
11.
Int J Biol Macromol ; 254(Pt 3): 127940, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37951430

RESUMO

The main challenge in the field of 3D biomimetic skin is to search for a suitable hydrogel matrix with good biocompatibility, appropriate mechanical property and inner porosity that can support the adhesion and proliferation of skin cells. In this study, photocurable chondroitin sulfate methacrylate (CSMA) and collagen methacrylate (CoLMA) synthesized from chondroitin sulfate (CS) and type I collagen I (CoL) in the dermal matrix were used to construct a photo-crosslinked dual-component CSMA-CoLMA hydrogel matrix. Due to the toughening effect of the dual-component, the CSMA-CoLMA hydrogel improved the intrinsic brittleness of the single-component CSMA hydrogel, presented good mechanical tunability. The average storage and elasticity modulus could reach 3.3 KPa and 30.3 KPa, respectively, which were close to those of natural skin. The CSMA-CoLMA hydrogel with a ratio of 8/6 showed suitable porous structure and good biocompatibility, supporting the adhesion and proliferation of skin cells. Furthermore, the expression of characteristic marker proteins was detected in the epidermal and dermal bi-layered models constructed with the hydrogel containing keratinocytes and fibroblasts. These results suggest that the dual-component CSMA-CoLMA hydrogel has promising potential as a matrix to construct 3D biomimetic skin.


Assuntos
Sulfatos de Condroitina , Hidrogéis , Sulfatos de Condroitina/química , Hidrogéis/química , Biomimética , Colágeno/química , Metacrilatos/química , Engenharia Tecidual/métodos
12.
Angew Chem Int Ed Engl ; 63(1): e202315314, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38009311

RESUMO

Aprotic Li-O2 battery has attracted considerable interest for high theoretical energy density, however the disproportionation of the intermediate of superoxide (O2 - ) during discharge and charge leads to slow reaction kinetics and large voltage hysteresis. Herein, the chemically stable ruthenium tris(bipyridine) (RB) cations are employed as a soluble catalyst to alternate the pathway of O2 - disproportionation and its kinetics in both the discharge and charge processes. RB captures O2 - dimer and promotes their intramolecular charge transfer, and it decreases the energy barrier of the disproportionation reaction from 7.70 to 0.70 kcal mol-1 . This facilitates the discharge and charge processes and simultaneously mitigates O2 - and singlet oxygen related side reactions. These endow the Li-O2 battery with reduced discharge/charge voltage gap of 0.72 V and prolonged lifespan for over 230 cycles when coupled with RuO2 catalyst. This work highlights the vital role of superoxide disproportionation for Li-O2 battery.

13.
ACS Appl Mater Interfaces ; 16(1): 998-1004, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38117011

RESUMO

The artificial tactile perception system of this work utilizes a fully connected spiking neural network (SNN) comprising two layers. Its architecture is streamlined and energy-efficient as it directly integrates spiking tactile neurons with piezoresistive sensors and Pt/NbOx/TiN memristors as input neurons. These spiking tactile neurons possess the ability to perceive and integrate pressure stimuli from multiple sensors and encode the information into rate-coded electrical spikes, closely resembling the behavior of a biological tactile neuron. The system's real-time information processing capability is demonstrated through an artificial perceptual learning system that successfully encodes and decodes the Morse code; the artificial perceptual learning system accurately recognizes and displays 26 English letters. Furthermore, the artificial tactile perception system is evaluated for the recognition of the MNIST data set, achieving a classification accuracy of 85.7% with the supervised spiking-rate-dependent plasticity learning rule. The key advantages of this artificial tactile perception system are its simple structure and high efficiency, which contributes to its practicality for various real-world applications.


Assuntos
Redes Neurais de Computação , Percepção do Tato , Aprendizagem/fisiologia , Neurônios/fisiologia , Tato
14.
Mol Ther Nucleic Acids ; 34: 102073, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38074899

RESUMO

The molecular weight of nucleic acid aptamers (20 kDa) is lower than the cutoff threshold of the renal filtration (30-50 kDa), resulting in a very short half-life, which dramatically limits their druggability. To address this, we utilized 3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-(4-hydroxy-2-oxo-2H-chromen-6-yl)propenamide (HC) and 12-((2,5-dioxopyrrolidin-1-yl)oxy)-12-oxododecanoic acid (DA), two newly designed coupling agents, for synergistic binding to human serum albumin (HSA). Both HC and DA are conjugated to a bone anabolic aptamer (Apc001) against sclerostin to form an Apc001OC conjugate with high binding affinity to HSA. Notably, HC and DA could synergistically facilitate prolonging the half-life of the conjugated Apc001 and promoting its bone anabolic potential. Using the designed blocking peptides, the mechanism studies indicate that the synergistic effect of HC-DA on pharmacokinetics and bone anabolic potential of the conjugated Apc001 is achieved via their synergistic binding to HSA. Moreover, biweekly Apc001OC at 50 mg/kg shows comparable bone anabolic potential to the marketed sclerostin antibody given weekly at 25 mg/kg. This proposed bimolecular modification strategy could help address the druggability challenge for aptamers with a short half-life.

16.
J Comput Assist Tomogr ; 47(6): 989-995, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37948376

RESUMO

PURPOSE: This study aimed to evaluate the imaging features of maxillary sinus adenoid cystic carcinoma (ACC) on computed tomography (CT) and magnetic resonance imaging (MRI) and to investigate the imaging differences between solid and nonsolid maxillary sinus ACC. METHODS: We retrospectively reviewed 40 cases of histopathologically confirmed ACC of the maxillary sinus. All the patients underwent CT and MRI. Based on the histopathological characteristics, the patients were classified into 2 groups: ( a ) solid maxillary sinus ACC (n = 16) and ( b ) nonsolid maxillary sinus ACC (n = 24). Imaging features such as tumor size, morphology, internal structure, margin, type of bone destruction, signal intensity, enhancement changes, and perineural tumor spread on CT and MRI, were evaluated. The apparent diffusion coefficient (ADC) was measured. Comparisons of imaging features and ADC values were performed between the solid and nonsolid maxillary sinus ACC using χ 2 and nonparametric tests. RESULTS: The internal structure, margin, type of bone destruction, and degree of enhancement significantly differed between solid and nonsolid maxillary sinus ACC (all P < 0.05). The ADC of the solid maxillary sinus ACC was considerably lower than that of the nonsolid maxillary sinus ( P < 0.05). CONCLUSIONS: Computed tomography and MRI may aid in the differentiation of solid and nonsolid types of maxillary sinus ACC.


Assuntos
Carcinoma Adenoide Cístico , Neoplasias dos Seios Paranasais , Humanos , Carcinoma Adenoide Cístico/diagnóstico por imagem , Carcinoma Adenoide Cístico/patologia , Seio Maxilar/diagnóstico por imagem , Seio Maxilar/patologia , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos
17.
Materials (Basel) ; 16(21)2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37959604

RESUMO

Conventional single-component quantum dots (QDs) suffer from low recombination rates of photogenerated electrons and holes, which hinders their ability to meet the requirements for LED and laser applications. Therefore, it is urgent to design multicomponent heterojunction nanocrystals with these properties. Herein, we used CdSe quantum dot nanocrystals as a typical model, which were synthesized by means of a colloidal chemistry method at high temperatures. Then, CdS with a wide band gap was used to encapsulate the CdSe QDs, forming a CdSe@CdS core@shell heterojunction. Finally, the CdSe@CdS core@shell was modified through the growth of the ZnS shell to obtain CdSe@CdS@ZnS heterojunction nanocrystal hybrids. The morphologies, phases, structures and performance characteristics of CdSe@CdS@ZnS were evaluated using various analytical techniques, including transmission electron microscopy, X-ray diffraction, UV-vis absorption spectroscopy, fluorescence spectroscopy and time-resolved transient photoluminescence spectroscopy. The results show that the energy band structure is transformed from type II to type I after the ZnS growth. The photoluminescence lifetime increases from 41.4 ns to 88.8 ns and the photoluminescence quantum efficiency reaches 17.05% compared with that of pristine CdSe QDs. This paper provides a fundamental study and a new route for studying light-emitting devices and biological imaging based on multicomponent QDs.

18.
Brain Sci ; 13(11)2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-38002558

RESUMO

BACKGROUND: Normal tension glaucoma (NTG) is considered a neurodegenerative disease with glaucomatous damage extending to diffuse brain areas. Therefore, this study aims to explore the abnormalities in the NTG structural network to help in the early diagnosis and course evaluation of NTG. METHODS: The structural networks of 46 NTG patients and 19 age- and sex-matched healthy controls were constructed using diffusion tensor imaging, followed by graph theory analysis and correlation analysis of small-world properties with glaucoma clinical indicators. In addition, the network-based statistical analysis (NBS) method was used to compare structural network connectivity differences between NTG patients and healthy controls. RESULTS: Structural brain networks in both NTG and NC groups exhibited small-world properties. However, the small-world index in the severe NTG group was reduced and correlated with a mean deviation of the visual field (MDVF) and retinal nerve fiber layer (RNFL) thickness. When compared to healthy controls, degree centrality and nodal efficiency in visual brain areas were significantly decreased, and betweenness centrality and nodal local efficiency in both visual and nonvisual brain areas were also significantly altered in NTG patients (all p < 0.05, FDR corrected). Furthermore, NTG patients exhibited increased structural connectivity in the occipitotemporal area, with the left fusiform gyrus (FFG.L) as the hub (p < 0.05). CONCLUSIONS: NTG exhibited altered global properties and local properties of visual and cognitive-emotional brain areas, with enhanced structural connections within the occipitotemporal area. Moreover, the disrupted small-world properties of white matter might be imaging biomarkers for assessing NTG progression.

19.
Nat Commun ; 14(1): 6155, 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37788995

RESUMO

Automating retrosynthesis with artificial intelligence expedites organic chemistry research in digital laboratories. However, most existing deep-learning approaches are hard to explain, like a "black box" with few insights. Here, we propose RetroExplainer, formulizing the retrosynthesis task into a molecular assembly process, containing several retrosynthetic actions guided by deep learning. To guarantee a robust performance of our model, we propose three units: a multi-sense and multi-scale Graph Transformer, structure-aware contrastive learning, and dynamic adaptive multi-task learning. The results on 12 large-scale benchmark datasets demonstrate the effectiveness of RetroExplainer, which outperforms the state-of-the-art single-step retrosynthesis approaches. In addition, the molecular assembly process renders our model with good interpretability, allowing for transparent decision-making and quantitative attribution. When extended to multi-step retrosynthesis planning, RetroExplainer has identified 101 pathways, in which 86.9% of the single reactions correspond to those already reported in the literature. As a result, RetroExplainer is expected to offer valuable insights for reliable, high-throughput, and high-quality organic synthesis in drug development.

20.
Genet Sel Evol ; 55(1): 72, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37853325

RESUMO

BACKGROUND: Although the accumulation of whole-genome sequencing (WGS) data has accelerated the identification of mutations underlying complex traits, its impact on the accuracy of genomic predictions is limited. Reliable genotyping data and pre-selected beneficial loci can be used to improve prediction accuracy. Previously, we reported a low-coverage sequencing genotyping method that yielded 11.3 million highly accurate single-nucleotide polymorphisms (SNPs) in pigs. Here, we introduce a method termed selective linkage disequilibrium pruning (SLDP), which refines the set of SNPs that show a large gain during prediction of complex traits using whole-genome SNP data. RESULTS: We used the SLDP method to identify and select markers among millions of SNPs based on genome-wide association study (GWAS) prior information. We evaluated the performance of SLDP with respect to three real traits and six simulated traits with varying genetic architectures using two representative models (genomic best linear unbiased prediction and BayesR) on samples from 3579 Duroc boars. SLDP was determined by testing 180 combinations of two core parameters (GWAS P-value thresholds and linkage disequilibrium r2). The parameters for each trait were optimized in the training population by five fold cross-validation and then tested in the validation population. Similar to previous GWAS prior-based methods, the performance of SLDP was mainly affected by the genetic architecture of the traits analyzed. Specifically, SLDP performed better for traits controlled by major quantitative trait loci (QTL) or a small number of quantitative trait nucleotides (QTN). Compared with two commercial SNP chips, genotyping-by-sequencing data, and an unselected whole-genome SNP panel, the SLDP strategy led to significant improvements in prediction accuracy, which ranged from 0.84 to 3.22% for real traits controlled by major or moderate QTL and from 1.23 to 11.47% for simulated traits controlled by a small number of QTN. CONCLUSIONS: The SLDP marker selection method can be incorporated into mainstream prediction models to yield accuracy improvements for traits with a relatively simple genetic architecture, however, it has no significant advantage for traits not controlled by major QTL. The main factors that affect its performance are the genetic architecture of traits and the reliability of GWAS prior information. Our findings can facilitate the application of WGS-based genomic selection.


Assuntos
Estudo de Associação Genômica Ampla , Genômica , Animais , Suínos/genética , Masculino , Desequilíbrio de Ligação , Genótipo , Estudo de Associação Genômica Ampla/métodos , Reprodutibilidade dos Testes , Genômica/métodos , Fenótipo , Locos de Características Quantitativas , Polimorfismo de Nucleotídeo Único
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