Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 310
Filter
1.
Comput Biol Med ; 176: 108547, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38728994

ABSTRACT

Self-supervised pre-training and fully supervised fine-tuning paradigms have received much attention to solve the data annotation problem in deep learning fields. Compared with traditional pre-training on large natural image datasets, medical self-supervised learning methods learn rich representations derived from unlabeled data itself thus avoiding the distribution shift between different image domains. However, nowadays state-of-the-art medical pre-training methods were specifically designed for downstream tasks making them less flexible and difficult to apply to new tasks. In this paper, we propose grid mask image modeling, a flexible and general self-supervised method to pre-train medical vision transformers for 3D medical image segmentation. Our goal is to guide networks to learn the correlations between organs and tissues by reconstructing original images based on partial observations. The relationships are consistent within the human body and invariant to disease type or imaging modality. To achieve this, we design a Siamese framework consisting of an online branch and a target branch. An adaptive and hierarchical masking strategy is employed in the online branch to (1) learn the boundaries or small contextual mutation regions within images; (2) to learn high-level semantic representations from deeper layers of the multiscale encoder. In addition, the target branch provides representations for contrastive learning to further reduce representation redundancy. We evaluate our method through segmentation performance on two public datasets. The experimental results demonstrate our method outperforms other self-supervised methods. Codes are available at https://github.com/mobiletomb/Gmim.

2.
Se Pu ; 42(5): 401-409, 2024 Apr 08.
Article in Chinese | MEDLINE | ID: mdl-38736383

ABSTRACT

This paper serves as an annual review of capillary electrophoresis (CE) technology for 2023. The journals were selected based on their impact factor (IF), a universally recognized academic performance metric, combined with experimental work closely related to CE technology, to facilitate the rapid acquisition of significant research and application advancements in CE technology in 2023. A thematic search of the ISI Web of Science database yielded 669 research papers on CE technology published in 2023. This review highlights five experimental papers published in journals with IFs greater than 10.0, including Nature Communications, Nucleic Acids Research, Engineering, Journal of Medical Virology, and Carbohydrate Polymers, and 31 experimental papers from representative journals with IFs between 5.0 and 10.0, such as Analytical Chemistry, Analytica Chimica Acta, Talanta, and Food Chemistry. It also provides an overview of experimental research in journals with focused reporting on CE technology but with IFs less than 5.0, such as Journal of Chromatography A and Electrophoresis, as well as significant experimental research from key domestic Chinese core journals (Peking University). In 2023, all the latest scientific advancements reported in journals with an IF greater than 10.0 utilized previously reported CE methods, offering new breakthroughs for the promotion and application of CE technology. Additionally, new applications of CE in conjunction with mass spectrometry remained a hot topic. An increase in reports on the hardware aspects of CE, such as 3D printing and underwater systems, and significant breakthroughs in the analysis of non-solution samples, such as solid particles, cell vesicles, cells, viruses, and bacteria, was noted. CE is advantageous for the analysis of drugs and their components. In Chinese journals, the number of papers on CE applications exceeded that in previous years, with particular focus on the field of printing for new applications.


Subject(s)
Electrophoresis, Capillary , Electrophoresis, Capillary/methods
3.
Sensors (Basel) ; 24(8)2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38676055

ABSTRACT

Physiologic hand tremors are a critical factor affecting the aim of air pistol shooters. However, the extent of the effect of hand tremors on shooting performance is unclear. In this study, we aim to explore the relationship between hand tremors and shooting performance scores as well as investigate potential links between muscle activation and hand tremors. In this study, 17 male air pistol shooters from China's national team and the Air Pistol Sports Center were divided into two groups: the elite group and the sub-elite group. Each participant completed 40 shots during the experiment, with shooters' hand tremors recorded using three-axis digital accelerometers affixed to their right hands. Muscle activation was recorded using surface electromyography on the right anterior deltoid, posterior deltoid, biceps brachii (short head), triceps brachii (long head), flexor carpi radialis, and extensor carpi radialis. Our analysis revealed weak correlations between shooting scores and hand tremor amplitude in multiple directions (middle-lateral, ML: r2 = -0.22, p < 0.001; vertical, VT: r2 = -0.25, p < 0.001), as well as between shooting scores and hand tremor complexity (ML: r2 = -0.26, p < 0.001; VT: r2 = -0.28, p < 0.001), across all participants. Notably, weak correlations between shooting scores and hand tremor amplitude (ML: r2 = -0.27, p < 0.001; VT: r2 = -0.33, p < 0.001) and complexity (ML: r2 = -0.31, p < 0.001) were observed in the elite group but not in the sub-elite group. Moderate correlation were found between the biceps brachii (short head) RMS and hand tremor amplitude in the VT and ML directions (ML: r2 = 0.49, p = 0.010; VT: r2 = 0.44, p = 0.025) in all shooters, with a moderate correlation in the ML direction in elite shooters (ML: r2 = 0.49, p = 0.034). Our results suggest that hand tremors in air pistol shooters are associated with the skill of the shooters, and muscle activation of the biceps brachii (long head) might be a factor affecting hand tremors. By balancing the agonist and antagonist muscles of the shoulder joint, shooters might potentially reduce hand tremors and improve their shooting scores.


Subject(s)
Electromyography , Firearms , Hand , Tremor , Humans , Tremor/physiopathology , Male , Hand/physiology , Hand/physiopathology , Adult , Young Adult , Athletic Performance/physiology , Muscle, Skeletal/physiopathology , Muscle, Skeletal/physiology
4.
Int J Med Robot ; 20(1): e2619, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38536712

ABSTRACT

BACKGROUND: 2D/3D medical image registration is one of the key technologies for surgical navigation systems to perform pose estimation and achieve accurate positioning, which still remains challenging. The purpose of this study is to introduce a new method for X-ray to CT 2D/3D registration and conduct a feasibility study. METHODS: In this study, a 2D/3D affine registration method based on feature point detection is investigated. It combines the morphological and edge features of spinal images to accurately extract feature points from the images, and uses graph neural networks to aggregate anatomical features of different points to increase the local detail information. Meanwhile, global and positional information are extracted by the Swin Transformer. RESULTS: The results indicate that the proposed method has shown improvements in both accuracy and success ratio compared with other methods. The mean target registration error value reached up to 0.31 mm; meanwhile, the runtime overhead was much lower, achieving an average runtime of about 0.6 s. This ultimately improves the registration accuracy and efficiency, demonstrating the effectiveness of the proposed method. CONCLUSIONS: The proposed method can provide more comprehensive image information and shows good prospects for pose estimation and achieving accurate positioning in surgical navigation systems.


Subject(s)
Algorithms , Imaging, Three-Dimensional , Humans , X-Rays , Radiography , Imaging, Three-Dimensional/methods , Tomography, X-Ray Computed/methods , Image Processing, Computer-Assisted/methods
6.
Talanta ; 273: 125837, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38479030

ABSTRACT

CRISPR/Cas9 is a natural immune system of archaea and bacteria, which has been widely used in gene editing. In order to better control and improve the accuracy and safety of the system, inhibitors for SpyCas9 as "switches" have been selected for several years. The available inhibitors currently are all natural polypeptides inhibitors derived from phages, except one small molecule inhibitor. These natural inhibitors are challenging to obtain and are available in limited quantities, and the small molecule inhibitor is cytotoxic. Herein, we discover aptamers against the SpyCas9 protein, by coupling CE-SELEX within one-round pressure controllable selection strategy. One of the identified aptamers, Apt2, shows high affinity at the nanomolar level and leads for effective SpyCas9 enzymatic inhibition in vitro. It is predicted that Apt2 interacts with the HNH and RuvC domains of SpyCas9, competitively inhibiting the binding of substrate DNA to SpyCas9. The proposed aptamer inhibitor is the oligonucleotide inhibitor of SpyCas9, which has the potential in construction of the universal, simple and precise CRISPR-Cas9 system activity control strategy. Meanwhile, these aptamers could also be valuable tools for study of the functions of CRISPR/Cas9 and the related functional mechanisms.


Subject(s)
Aptamers, Nucleotide , Bacteriophages , Gene Editing , DNA/chemistry , Bacterial Proteins/metabolism , Aptamers, Nucleotide/metabolism , SELEX Aptamer Technique
7.
J Biomech ; 165: 111996, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38377740

ABSTRACT

High loading impact associated with heel strikes causes running injuries. This study aimed to investigate how loading impact is affected by midsole hardness and running surface type. Twelve young rear-foot runners ran at a fixed speed along an 18 m runway wearing shoes with different midsole hardness (Asker C-45, C-50, C-55, C-60, from soft to hard) and on two different surfaces (rubber and concrete). We quantified vertical average loading rate (VALR) and vertical impact peak force (VIPF). We conducted midsole × surface repeated-measures ANOVA on loading impact measures, and one-sample t-tests to compare VALR with a threshold value (80 BW·s-1). Midsole hardness and surface type mainly affected VALR. Although no significant effect of these variables was observed for VIPF magnitude, there were effects on time to VIPF and steps with VIPF. Several combinations of midsole and surface hardness reduced VALR below 80 BW·s-1: Asker C-45 with both surfaces, and Asker C-50 with a rubber surface. The combination of softer midsole and surface effectively reduced loading rates as shown by increased time to VIPF and reduced VALR. Combining softer midsole and surface results in the greatest cushioning, which demonstrates the benefit of considering both factors in reducing running injuries.


Subject(s)
Foot , Rubber , Hardness , Biomechanical Phenomena , Shoes
9.
Sci Rep ; 14(1): 1724, 2024 01 19.
Article in English | MEDLINE | ID: mdl-38242922

ABSTRACT

We aimed to examine the changes in balance performance, kinematic variables, and joint coordination of the lower extremities during the Y-balance learning task. Twenty female university students completed five consecutive blocks of Y-balance learning from days 3 to 7 (135 trials). Pre-tests and tests were performed on days 1 and 9. Maximum reach distance, peak joint angle, and joint coordination in the anterior (AL), posterolateral (PL), and posteromedial (PM) directions were measured to determine the efficacy of Y-balance performance. A repeated measures ANOVA was performed for the maximum reach distance across learning blocks to confirm whether learning had occurred. Our results indicated that the maximum reach distance on day 5 was longer than that on other learning days. The maximum reach distance significantly increased in the PL and PM directions after learning. The hip flexion (PL/PM), abduction (PM), internal rotation (PM), and external rotation (PL) angles increased after learning. The knee joint flexion angle increased in both AL and PL directions. Only the ankle dorsiflexion angle increased in the AL direction. Joint coordination indicated that the knee and hip joints performed simultaneously during internal rotation. Ankle-knee joint coordination was performed using dorsiflexion and flexion strategies. Statistical parametric mapping analysis indicated significant differences in the ankle sagittal plane in the AL direction, hip horizontal and hip/knee sagittal planes in the PL direction, and hip/knee sagittal and hip frontal/horizontal planes in the PM direction. These data suggest that the dynamic balance ability of the novice participants improved in relation to changes in coordination patterns after learning. The results of this study can be applied to other populations to improve their dynamic balance and prevent fall injuries.


Subject(s)
Knee Joint , Lower Extremity , Humans , Female , Movement , Ankle Joint , Range of Motion, Articular , Biomechanical Phenomena , Hip Joint
10.
Appl Physiol Nutr Metab ; 49(3): 360-374, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-37944128

ABSTRACT

This study investigated the effects of amygdalin (AMY, a cyanogenic glycoside widely distributed in the fruits and seeds of Rosaceae plants) on cardiac performance and ventricular remodeling in a rat model of myocardial infarction (MI). We also investigated whether the combination of AMY with exercise training (ExT) has a beneficial synergistic effect in treating MI rats. MI was induced by the ligation of the left anterior descending coronary artery in male SD rats. ExT or AMY treatment was started 1 week after MI and continued for 1 week (short-term) or 8 weeks (long-term). Cardiac function was evaluated by echocardiographic and hemodynamic parameters. Heart tissues were harvested and subjected to 2,3,5-triphenyl-tetrazolium chloride, Masson's trichrome, hematoxylin-eosin, and immunohistochemical staining. Gene expression was determined by quantitative polymerase chain reaction. Western blot gave a qualitative assessment of protein levels. AMY or ExT improved cardiac function and reduced infarct size in MI rats. AMY or ExT also suppressed myocardial fibrosis and attenuated inflammation in the infarct border zone of hearts from MI rats, as evidenced by inhibition of collagen deposition, inflammatory cell infiltration, and pro-inflammatory markers (interleukin 1ß, interleukin 6, tumor necrosis factor-α, and cyclooxygenase 2). Notably, the effects of AMY combined with ExT were superior to those of AMY alone or ExT alone. Mechanistically, these beneficial functions were correlated with the inhibition of MI-induced activation of the transforming growth factor-ß/Smad pathway. Collectively, AMY and ExT exert a synergistic effect on improving cardiac performance and ameliorating cardiac inflammation and fibrosis after MI, and the effects of long-term intervention were better than short-term intervention.


Subject(s)
Amygdalin , Myocardial Infarction , Animals , Rats , Rats, Sprague-Dawley , Amygdalin/pharmacology , Myocardial Infarction/therapy , Inflammation/therapy , Fibrosis
11.
Commun Chem ; 6(1): 219, 2023 Oct 12.
Article in English | MEDLINE | ID: mdl-37828292

ABSTRACT

Despite recent advances in cryo-electron microscopy and artificial intelligence-based model predictions, a significant fraction of structure determinations by macromolecular crystallography still requires experimental phasing, usually by means of single-wavelength anomalous diffraction (SAD) techniques. Most synchrotron beamlines provide highly brilliant beams of X-rays of between 0.7 and 2 Å wavelength. Use of longer wavelengths to access the absorption edges of biologically important lighter atoms such as calcium, potassium, chlorine, sulfur and phosphorus for native-SAD phasing is attractive but technically highly challenging. The long-wavelength beamline I23 at Diamond Light Source overcomes these limitations and extends the accessible wavelength range to λ = 5.9 Å. Here we report 22 macromolecular structures solved in this extended wavelength range, using anomalous scattering from a range of elements which demonstrate the routine feasibility of lighter atom phasing. We suggest that, in light of its advantages, long-wavelength crystallography is a compelling option for experimental phasing.

12.
Front Bioeng Biotechnol ; 11: 1241135, 2023.
Article in English | MEDLINE | ID: mdl-37720321

ABSTRACT

Introduction: Musculoskeletal simulation has been widely used to analyze athletes' movements in various competitive sports, but never in ski jumping. Aerodynamic forces during ski jumping take-off have been difficult to account for in dynamic simulation. The purpose of this study was to establish an efficient approach of musculoskeletal simulation of ski jumping take-off considering aerodynamic forces and to analyze the muscle function and activity. Methods: Camera-based marker-less motion capture was implemented to measure the take-off kinematics of eight professional jumpers. A suitable full-body musculoskeletal model was constructed for the simulation. A method based on inverse dynamics iteration was developed and validated to estimate the take-off ground reaction force. The aerodynamic forces, which were calculated based on body kinematics and computational fluid dynamics simulations, were exerted on the musculoskeletal model as external forces. The activation and joint torque contributions of lower extremity muscles were calculated through static optimization. Results: The estimated take-off ground reaction forces show similar trend with the results from past studies. Although overall inconsistencies between simulated muscle activation and EMG from previous studies were observed, it is worth noting that the activation of the tibialis anterior, gluteus maximus, and long head of the biceps femoris was similar to specific EMG results. Among lower extremity extensors, soleus, vastus lateralis, biceps femoris long head, gluteus maximus, and semimembranosus showed high levels of activation and joint extension torque contribution. Discussion: Results of this study advanced the understanding of muscle action during ski jumping take-off. The simulation approach we developed may help guide the physical training of jumpers for improved take-off performance and can also be extended to other phases of ski jumping.

13.
PLoS Pathog ; 19(8): e1011395, 2023 08.
Article in English | MEDLINE | ID: mdl-37578959

ABSTRACT

Viruses with single-stranded, positive-sense (+) RNA genomes incur high numbers of errors during replication, thereby creating diversified genome populations from which new, better adapted viral variants can emerge. However, a definitive error rate is known for a relatively few (+) RNA plant viruses, due to challenges to account for perturbations caused by natural selection and/or experimental set-ups. To address these challenges, we developed a new approach that exclusively profiled errors in the (-)-strand replication intermediates of turnip crinkle virus (TCV), in singly infected cells. A series of controls and safeguards were devised to ensure errors inherent to the experimental process were accounted for. This approach permitted the estimation of a TCV error rate of 8.47 X 10-5 substitution per nucleotide site per cell infection. Importantly, the characteristic error distribution pattern among the 50 copies of 2,363-base-pair cDNA fragments predicted that nearly all TCV (-) strands were products of one replication cycle per cell. Furthermore, some of the errors probably elevated error frequencies by lowering the fidelity of TCV RNA-dependent RNA polymerase, and/or permitting occasional re-replication of progeny genomes. In summary, by profiling errors in TCV (-)-strand intermediates incurred during replication in single cells, this study provided strong support for a stamping machine mode of replication employed by a (+) RNA virus.


Subject(s)
Carmovirus , RNA Viruses , Carmovirus/genetics , RNA, Viral/genetics , RNA, Viral/metabolism , Mutation Rate , RNA Viruses/genetics , RNA-Dependent RNA Polymerase/metabolism , Virus Replication/genetics
14.
Viruses ; 15(7)2023 06 28.
Article in English | MEDLINE | ID: mdl-37515147

ABSTRACT

Superinfection exclusion (SIE) is an antagonistic interaction between identical or closely related viruses in host cells. Previous studies by us and others led to the hypothesis that SIE was elicited by one or more proteins encoded in the genomes of primary viruses. Here, we tested this hypothesis using Turnip mosaic virus (TuMV), a member of the genus Potyvirus of the family Potyviridae, with significant economic consequences. To this end, individual TuMV-encoded proteins were transiently expressed in the cells of Nicotiana benthamiana leaves, followed by challenging them with a modified TuMV expressing the green fluorescent protein (TuMV-GFP). Three days after TuMV-GFP delivery, these cells were examined for the replication-dependent expression of GFP. Cells expressing TuMV P1, HC-Pro, 6K1, CI, 6K2, NIa-VPg, NIb, or CP proteins permitted an efficient expression of GFP, suggesting that these proteins failed to block the replication of a superinfecting TuMV-GFP. By contrast, N. benthamiana cells expressing TuMV P3 or NIa-Pro did not express visible GFP fluorescence, suggesting that both of them could elicit potent SIE against TuMV-GFP. The SIE elicitor activity of P3 and NIa-Pro was further confirmed by their heterologous expression from a different potyvirus, potato virus A (PVA). Plants systemically infected with PVA variants expressing TuMV P3 or NIa-Pro blocked subsequent infection by TuMV-GFP. A +1-frameshift mutation in P3 and NIa-Pro cistrons facilitated superinfection by TuMV-GFP, suggesting that the P3 and NIa-Pro proteins, but not the RNA, are involved in SIE activity. Additionally, deletion mutagenesis identified P3 amino acids 3 to 200 of 352 and NIa-Pro amino acids 3 to 40 and 181 to 242 of 242 as essential for SIE elicitation. Collectively, our study demonstrates that TuMV encodes two spatially separated proteins that act independently to exert SIE on superinfecting TuMV. These results lay the foundation for further mechanistic interrogations of SIE in this virus.


Subject(s)
Potyviridae , Potyvirus , Superinfection , Potyvirus/genetics , Plant Diseases , Nicotiana
15.
Connect Tissue Res ; 64(5): 479-490, 2023 09.
Article in English | MEDLINE | ID: mdl-37287279

ABSTRACT

BACKGROUND: Tendon-derived stem cells (TDSCs) are proposed as a potential cell-seed for the treatment of tendon injury due to their tenogenic differentiation potential. In this work, we defined the action of long non-coding RNA (lncRNA) muscle differentiation 1 (LINCMD1) in tenogenic differentiation of human TDSCs (hTDSCs). METHODS: Quantitative real-time PCR (qRT-PCR) was used to assess the levels of LINCMD1, microRNA (miR)-342-3p, and early growth response-1 (EGR1) mRNA. Cell proliferation was detected by the XTT colorimetric assay. Protein expression was quantified by western blot. hTDSCs were grown in an osteogenic medium to induce osteogenic differentiation, and the extent of osteogenic differentiation was assessed by Alizarin Red Staining (ARS). The activity of alkaline phosphatase (ALP) was measured by the ALP Activity Assay Kit. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to evaluate the direct relationship between miR-342-3p and LINCMD1 or EGR1. RESULTS: Our results showed that enforced expression of LINCMD1 or suppression of miR-342-3p accelerated the proliferation and tenogenic differentiation and reduced osteogenic differentiation of hTDSCs. LINCMD1 regulated miR-342-3p expression by binding to miR-342-3p. EGR1 was identified as a direct and functional target of miR-342-3p, and knockdown of EGR1 reversed the effects of miR-342-3p suppression on cell proliferation and tenogenic and osteogenic differentiation. Furthermore, the miR-342-3p/EGR1 axis mediated the regulation of LINCMD1 on hTDSC proliferation and tenogenic and osteogenic differentiation. CONCLUSION: Our study suggests the induction of LINCMD1 in tenogenic differentiation of hTDSCs through miR-342-3p/EGR1 axis.


Subject(s)
MicroRNAs , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Osteogenesis/genetics , Stem Cells/metabolism , Cell Differentiation/genetics , Tendons/metabolism , Cells, Cultured , Early Growth Response Protein 1/genetics , Early Growth Response Protein 1/metabolism
16.
Environ Sci Pollut Res Int ; 30(34): 82094-82106, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37318733

ABSTRACT

Globally, air pollution is the fourth leading risk factor for death, while lung cancer (LC) is the leading cause of cancer-related death. The aim of this study was to explore the prognostic factors of LC and the influence of high fine particulate matter (PM2.5) on LC survival. Data on LC patients were collected from 133 hospitals across 11 cities in Hebei Province from 2010 to 2015, and survival status was followed up until 2019. The personal PM2.5 exposure concentration (µg/m3) was matched according to the patient's registered address, calculated from a 5-year average for every patient, and stratified into quartiles. The Kaplan-Meier method was used to estimate overall survival (OS), and Cox's proportional hazard regression model was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). The 1-, 3-, and 5-year OS rates of the 6429 patients were 62.9%, 33.2%, and 15.2%, respectively. Advanced age (75 years or older: HR = 2.34, 95% CI: 1.25-4.38), subsite at overlapping (HR = 4.35, 95% CI: 1.70-11.1), poor/undifferentiated differentiation (HR = 1.71, 95% CI: 1.13-2.58), and advanced stages (stage III: HR = 2.53, 95% CI: 1.60-4.00; stage IV: HR = 4.00, 95% CI: 2.63-6.09) were risk factors for survival, while receiving surgical treatment was a protective factor (HR = 0.60, 95% CI: 0.44-0.83). Patients exposed to light pollution had the lowest risk of death with a 26-month median survival time. The risk of death in LC patients was greatest at PM2.5 concentrations of 98.7-108.9 µg/m3, especially for patients at advanced stage (HR = 1.43, 95% CI: 1.29-1.60). Our study indicates that the survival of LC is severely affected by relatively high levels of PM2.5 pollution, especially in those with advanced-stage cancer.


Subject(s)
Air Pollutants , Air Pollution , Lung Neoplasms , Humans , Aged , Air Pollutants/analysis , Particulate Matter/analysis , Air Pollution/analysis , Lung Neoplasms/chemically induced , China/epidemiology , Cohort Studies , Environmental Exposure/adverse effects
17.
Molecules ; 28(9)2023 Apr 30.
Article in English | MEDLINE | ID: mdl-37175248

ABSTRACT

Low-density lipoprotein receptor-related protein 6 (LRP6), a member of the low-density lipoprotein receptor (LDLR) family, displays a unique structure and ligand-binding function. As a co-receptor of the Wnt/ß-catenin signaling pathway, LRP6 is a novel therapeutic target that plays an important role in the regulation of cardiovascular disease, lipid metabolism, tumorigenesis, and some classical signals. By using capillary electrophoresis-systematic evolution of ligands by exponential enrichment (CE-SELEX), with recombinant human LRP-6 as the target, four candidate aptamers with a stem-loop structure were selected from an ssDNA library-AptLRP6-A1, AptLRP6-A2, AptLRP6-A3, and AptLRP6-A4. The equilibrium dissociation constant KD values between these aptamers and the LRP6 protein were in the range of 0.105 to 1.279 µmol/L, as determined by CE-LIF analysis. Their affinities and specificities were further determined by the gold nanoparticle (AuNP) colorimetric method. Among them, AptLRP6-A3 showed the highest affinity with LRP6-overexpressed human breast cancer cells. Therefore, the LRP6 aptamer identified in this study constitutes a promising modality for the rapid diagnosis and treatment of LRP6-related diseases.


Subject(s)
Aptamers, Nucleotide , Metal Nanoparticles , Humans , Low Density Lipoprotein Receptor-Related Protein-6/genetics , Low Density Lipoprotein Receptor-Related Protein-6/metabolism , Lipoproteins, LDL , Gold , DNA, Single-Stranded , Aptamers, Nucleotide/chemistry
18.
PLoS Pathog ; 19(5): e1011365, 2023 05.
Article in English | MEDLINE | ID: mdl-37126519

ABSTRACT

Viruses are constantly subject to natural selection to enrich beneficial mutations and weed out deleterious ones. However, it remains unresolved as to how the phenotypic gains or losses brought about by these mutations cause the viral genomes carrying the very mutations to become more or less numerous. Previous investigations by us and others suggest that viruses with plus strand (+) RNA genomes may compel such selection by bottlenecking the replicating genome copies in each cell to low single digits. Nevertheless, it is unclear if similarly stringent reproductive bottlenecks also occur in cells invaded by DNA viruses. Here we investigated whether tomato yellow leaf curl virus (TYLCV), a small virus with a single-stranded DNA genome, underwent population bottlenecking in cells of its host plants. We engineered a TYLCV genome to produce two replicons that express green fluorescent protein and mCherry, respectively, in a replication-dependent manner. We found that among the cells entered by both replicons, less than 65% replicated both, whereas at least 35% replicated either of them alone. Further probability computation concluded that replication in an average cell was unlikely to have been initiated with more than three replicon genome copies. Furthermore, sequential inoculations unveiled strong mutual exclusions of these two replicons at the intracellular level. In conclusion, the intracellular population of the small DNA virus TYLCV is actively bottlenecked, and such bottlenecking may be a virus-encoded, evolutionarily conserved trait that assures timely selection of new mutations emerging through error-prone replication.


Subject(s)
Begomovirus , Begomovirus/genetics , Genome, Viral , Plant Diseases/genetics
19.
J Chem Inf Model ; 63(9): 2783-2793, 2023 05 08.
Article in English | MEDLINE | ID: mdl-37074785

ABSTRACT

The presence of cadmium ions (Cd2+) in environmental samples demands a fast, sensitive, and selective analytical method that can measure toxic levels. Biosensors based on aptamers (aptasensors) have been developed, but some of them suffer from poor sensitivity and specificity due to the immobilization of aptamers. Here, we employed circular dichroism, molecular docking, and molecular dynamics simulation to reveal that the aptamer gradually undergoes significant conformational changes upon Cd2+ binding. This fact highlights the advantages of biosensors based on free aptamers. So, keeping these results, an analytical method was established for the detection of Cd2+ by utilizing capillary zone electrophoresis (CZE), which is adapted for the free aptamer. So, CZE equipped with aptamer as a detection probe can detect Cd2+ within 4 min in the range from 5 to 250 nM with R2 = 0.994, limit of detection 5 nM (signal-to-noise ratio = 3), and recovery from 92.6 ± 1.6 to 107.4 ± 1.0% in river water samples. Furthermore, the detected concentration in water samples is below the harmful levels (267 nM) recommended by World Health Organization standards in drinking water. This method displays a high sensitivity and specificity for Cd2+. It is found to be superior to existing methods, which use immobilized aptamers, and can be readily expanded to design aptasensors for other targets.


Subject(s)
Aptamers, Nucleotide , Cadmium , Aptamers, Nucleotide/chemistry , Molecular Docking Simulation , Electrophoresis, Capillary , Water
20.
Se Pu ; 41(5): 377-385, 2023 May 08.
Article in Chinese | MEDLINE | ID: mdl-37087603

ABSTRACT

This article provides a detailed review of capillary electrophoresis (CE) technology in 2022, summarizing a total of 881 CE technology-related articles searched from ISI Web of Science using the keywords "capillary electrophoresis mass spectrometry" or "capillary isoelectric focusing" or "micellar electrokinetic chromatography" or "capillary electrophoresis" (excluding "capillary electrochromatography""microchip" "microfluidic" "capillary monolithic column"). The review focuses on 16 articles published in Lancet Global Health, ACS Central Science, Microbiome, Trends in Food Science & Technology, TrAC-Trends in Analytical Chemistry, Journal of Pharmaceutical Analysis, Journal of Cachexia, Sarcopenia and Muscle, Food Hydrocolloids, Science of the Total Environment, and Carbohydrate Polymers with impact factors (IFs) greater than 10.0, and 46 articles published in Analytical Chemistry, Analytica Chimica Acta, Talanta, and Food Chemistry with IFs between 5.0 and 10.0. A comprehensive overview of representative CE works published in Journal of Chromatography A, Electrophoresis, and important Chinese core journals (Peking University) with IFs<5.0 is also provided. Based on IFs, this review introduces representative works on CE to facilitate readers' understanding of important research advances in CE technology over the last year.


Subject(s)
Capillary Electrochromatography , Chromatography , Humans , Mass Spectrometry/methods , Chromatography/methods , Capillary Isoelectric Focusing , Polymers
SELECTION OF CITATIONS
SEARCH DETAIL
...