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1.
BME Front ; 5: 0066, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39360181

RESUMEN

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.
BMC Gastroenterol ; 24(1): 353, 2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39375618

RESUMEN

OBJECTIVES: This study examined the potential association between nucleated red blood cell (NRBC) levels and mortality in critically ill patients with acute pancreatitis (AP) in the intensive care unit, due to limited existing research on this correlation. METHODS: This retrospective cohort study utilized data from the MIMIC-IV v2.0 and MIMIC-III v1.4 databases to investigate the potential relationship between NRBC levels and patient outcomes. The study employed restricted cubic splines (RCS) regression analysis to explore non-linear associations. The impact of NRBC on prognosis was assessed using a generalized linear model (GLM) with a logit link, adjusted for potential confounders. Furthermore, four machine learning models, including Gradient Boosting Classifier (GBC), Random Forest, Gaussian Naive Bayes, and Decision Tree Classifier model, were constructed using NRBC data to generate risk scores and evaluate the potential of NRBC in predicting patient prognosis. RESULTS: A total of 354 patients were enrolled in the study, with 162 (45.8%) individuals aged 60 years or older and 204 (57.6%) males. RCS regression analysis demonstrated a non-linear relationship between NRBC levels and 90-day mortality. Receiver Operating Characteristic (ROC) analysis identified a 1.7% NRBC cutoff to distinguish survivor from non-survivor patients for 90-day mortality, yielding an Area Under the Curve (AUC) of 0.599, with a sensitivity of 0.475 and specificity of 0.711. Elevated NRBC levels were associated with increased risks of 90-day mortality in both unadjusted and adjusted models (all Odds Ratios > 1, P < 0.05). Assessment of various machine learning models with nine variables, including NRBC, Sex, Age, Simplified Acute Physiology Score II, Acute Physiology Score III, Congestive Heart Failure, Vasopressin, Norepinephrine, and Mean Arterial Pressure, indicated that the GBC model displayed the highest predictive accuracy for 90-day mortality, with an AUC of 0.982 (95% CI 0.970-0.994). Post hoc power analysis showed a statistical power of 0.880 in the study. CONCLUSIONS: Elevated levels of NRBC are linked to an increased mortality risk in critically ill patients with AP, suggesting its potential for predicting mortality.


Asunto(s)
Enfermedad Crítica , Eritroblastos , Aprendizaje Automático , Pancreatitis , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Pancreatitis/sangre , Pancreatitis/mortalidad , Pronóstico , Anciano , Curva ROC , Unidades de Cuidados Intensivos/estadística & datos numéricos , Adulto
3.
PLoS One ; 19(9): e0309748, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39250466

RESUMEN

Candidemia often poses a diagnostic challenge due to the lack of specific clinical features, and delayed antifungal therapy can significantly increase mortality rates, particularly in the intensive care unit (ICU). This study aims to develop a machine learning predictive model for early candidemia diagnosis in ICU patients, leveraging their clinical information and findings. We conducted this study with a cohort of 334 patients admitted to the ICU unit at Ji Ning NO.1 people's hospital in China from Jan. 2015 to Dec. 2022. To ensure the model's reliability, we validated this model with an external group consisting of 77 patients from other sources. The candidemia to bacteremia ratio is 1:1. We collected relevant clinical procedures and eighteen key examinations or tests features to support the recursive feature elimination (RFE) algorithm. These features included total bilirubin, age, platelet count, hemoglobin, CVC, lymphocyte, Duration of stay in ICU and so on. To construct the candidemia diagnosis model, we employed random forest (RF) algorithm alongside other machine learning methods and conducted internal and external validation with training and testing sets allocated in a 7:3 ratio. The RF model demonstrated the highest area under the receiver operating characteristic (AUC) with values of 0.87 and 0.83 for internal and external validation, respectively. To evaluate the importance of features in predicting candidemia, Shapley additive explanation (SHAP) values were calculated and results revealed that total bilirubin and age were the most important factors in the prediction model. This advancement in candidemia prediction holds significant promise for early intervention and improved patient outcomes in the ICU setting, where timely diagnosis is of paramount crucial.


Asunto(s)
Candidemia , Unidades de Cuidados Intensivos , Aprendizaje Automático , Humanos , Candidemia/diagnóstico , Candidemia/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Algoritmos , Curva ROC , Adulto , China
4.
Arch Biochem Biophys ; 761: 110153, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39271097

RESUMEN

Myocardial infarction (MI) is the primary source of death in cardiovascular diseases. Myricitrin (MYR) is a phenolic compound known for its antioxidant properties. This study aimed to investigate the impact of MYR alone or combined with exercise on a rat model of MI and its underlying mechanism. Sprague-Dawley rats were randomized into 5 groups: sham-operated (Sham), MI-sedentary (MI-Sed), MI-exercise (MI-Ex), MI-sedentary + MYR (MI-Sed-MYR) and MI-exercise + MYR (MI-Ex-MYR). MI was induced through ligation of left anterior descending coronary artery. The treatment with exercise or MYR (30 mg/kg/d) gavage began one week after surgery, either individually or in combination. After 8 weeks, the rats were assessed for cardiac function. Myocardial injuries were estimated using triphenyltetrazolium chloride, sirius red and Masson staining. Changes in reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔΨm), apoptosis and Nrf2/HO-1 pathway were analyzed by ROS kit, JC-1 kit, TUNEL assay, Western blot and immunohistochemistry. Both MYR and exercise treatments improved cardiac function, reduced infarct size, suppressed collagen deposition, and decreased myocardial fibrosis. Additionally, both MYR and exercise treatments lowered ROS production induced by MI, restored ΔΨm, and attenuated oxidative stress and apoptosis in cardiomyocytes. Importantly, the combination of MYR and exercise showed greater efficacy compared to individual treatments. Mechanistically, the combined intervention activated the Nrf2/HO-1 signaling pathway. These findings suggest that the synergistic effect of MYR and exercise may offer a promising therapeutic approach for alleviating MI.

5.
Pharmaceutics ; 16(9)2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39339191

RESUMEN

High-risk BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) is a condition that is typically treated with Bacillus Calmette-Guérin (BCG) therapy. Unfortunately, NMIBC is characterized by high recurrence, with a significant percentage of BCG patients ultimately requiring radical cystectomy. As a consequence, the development of effective new therapies to avoid RC has become a rapidly evolving field to address this unmet clinical need. To date, three biologics-Keytruda, Adstiladrin, and Anktiva-have been approved by the FDA, and multiple drug modalities, particularly gene therapies, have shown promising results in clinical trials. Advances in drug delivery strategies, such as targeted delivery, sustained release, and permeabilization of protective layers, are critical in overcoming the challenges posed by therapeutic intervention in bladder cancer. This review focuses on high-risk BCG-unresponsive NMIBC therapies that have been or are currently being investigated in clinical trials, offering a broad overview of the delivery system designs and up-to-date clinical outcomes that have been reported as of July 2024. It aims to inform the development of future drug delivery systems for second-line therapies in high-risk BCG-unresponsive NMIBC.

6.
Foot Ankle Int ; : 10711007241271247, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39212116

RESUMEN

BACKGROUND: To analyze the feasibility and clinical results of the modified Broström operation (MBO) combined with suture tape augmentation under arthroscopy for chronic lateral ankle instability (CLAI) in patients with generalized joint laxity (GJL). METHODS: From October 2019 to October 2021, a total of 111 patients (111 ankles) treated with MBO combined with suture tape augmentation under arthroscope were retrospectively divided into a GJL group (29 patients) and a control group (82 patients). Mechanical stability of the affected ankle joint was evaluated radiographically preoperatively, at 6 months postoperatively, and the last follow-up. Complications and surgical failures, as well as visual analog scale (VAS) score, the Foot and Ankle Ability Measure (FAAM), and the Karlsson score were also recorded. All statistical analyses were completed using SPSS 20.0. RESULTS: The average follow-up time was 21.7 ± 5.2 months for the GJL group, and 20.9 ± 5.3 months for the control group. Pain and symptoms in both groups were effectively relieved by the procedure reflected by decreased VAS scores, improved FAAM and Karlsson scores at 6 months postoperatively, and the final follow-up (P < .05). Preoperative talar tilt angle and anterior talar translation were significantly greater in the GJL group than those in the control group (P < .05). Postoperatively, both talar tilt angle and anterior talar translation were reduced in both groups at 6 months postoperatively and the last follow-up (P < .05), and we found no significant difference between the two groups (P > .05). Furthermore, we found no significant difference in VAS, FAAM, and Karlsson scores between the 2 groups 6 months postoperatively and at the last follow-up. CONCLUSION: Arthroscopic MBO combined with suture tape augmentation is a reliable procedure for treating CLAI with GJL. At short-term follow-up, we found that the GJL group achieved an equivalent level of stability compared with the control group.

7.
Molecules ; 29(13)2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38998965

RESUMEN

In this study, a self-responsive fluorescence aptasensor was established for the determination of lactoferrin (Lf) in dairy products. Herein, the aptamer itself functions as both a recognition element that specifically binds to Lf and a fluorescent signal reporter in conjunction with fluorescent moiety. In the presence of Lf, the aptamer preferentially binds to Lf due to its specific and high-affinity recognition by folding into a self-assembled and three-dimensional spatial structure. Meanwhile, its reduced spatial distance in the aptamer-Lf complex induces a FRET phenomenon based on the quenching of 6-FAM by amino acids in the Lf protein, resulting in a turn-off of the fluorescence of the system. As a result, the Lf concentration can be determined straightforwardly corresponding to the change in the self-responsive fluorescence signal. Under the optimized conditions, good linearities (R2 > 0.99) were achieved in an Lf concentration range of 2~10 µg/mL for both standard solutions and the spiked matrix, as well as with the desirable detection limits of 0.68 µg/mL and 0.46 µg/mL, respectively. Moreover, the fluorescence aptasensor exhibited reliable recoveries (89.5-104.3%) in terms of detecting Lf in three commercial samples, which is comparable to the accuracy of the HPCE method. The fluorescence aptasensor offers a user-friendly, cost-efficient, and promising sensor platform for point-of-need detection.


Asunto(s)
Aptámeros de Nucleótidos , Técnicas Biosensibles , Productos Lácteos , Lactoferrina , Lactoferrina/análisis , Lactoferrina/química , Aptámeros de Nucleótidos/química , Técnicas Biosensibles/métodos , Productos Lácteos/análisis , Fluorescencia , Límite de Detección , Espectrometría de Fluorescencia/métodos , Análisis de los Alimentos/métodos , Transferencia Resonante de Energía de Fluorescencia/métodos
8.
J Am Soc Mass Spectrom ; 35(8): 1891-1901, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39007842

RESUMEN

Native mass spectrometry (MS) is proving to be a disruptive technique for studying the interactions of proteins, necessary for understanding the functional roles of these biomolecules. Recent research is expanding the application of native MS towards membrane proteins directly from isolated membrane preparations or from purified detergent micelles. The former results in complex spectra comprising several heterogeneous protein complexes; the latter enables therapeutic protein targets to be screened against multiplexed preparations of compound libraries. In both cases, the resulting spectra are increasingly complex to assign/interpret, and the key to these new directions of native MS research is the ability to perform native top-down analysis, which allows unambiguous peak assignment. To achieve this, detergent removal is necessary prior to MS analyzers, which allow selection of specific m/z values, representing the parent ion for downstream activation. Here, we describe a novel, enhanced declustering (ED) device installed into the first pumping region of a cyclic IMS-enabled mass spectrometry platform. The device enables declustering of ions prior to the quadrupole by imparting collisional activation through an oscillating electric field applied between two parallel plates. The positioning of the device enables liberation of membrane protein ions from detergent micelles. Quadrupole selection can now be utilized to isolate protein-ligand complexes, and downstream collision cells enable the dissociation and identification of binding partners. We demonstrate that ion mobility (IM) significantly aids in the assignment of top-down spectra, aligning fragments to their corresponding parent ions by means of IM drift time. Using this approach, we were able to confidently assign and identify a novel hit compound against PfMATE, obtained from multiplexed ligand libraries.


Asunto(s)
Espectrometría de Movilidad Iónica , Proteínas de la Membrana , Proteínas de la Membrana/química , Proteínas de la Membrana/análisis , Espectrometría de Movilidad Iónica/métodos , Micelas , Espectrometría de Masas/métodos , Detergentes/química , Iones/química
9.
Analyst ; 149(14): 3793-3802, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38847183

RESUMEN

Benefitting from the rapid evolution of artificial intelligence and structural biology, an expanding collection of high-resolution protein structures has greatly improved our understanding of protein functions. Yet, proteins are inherently flexible, and these static structures can only offer limited snapshots of their true dynamic nature. The conformational and functional changes of calmodulin (CaM) induced by Ca2+ binding have always been a focus of research. In this study, the conformational dynamics of CaM and its complexes were investigated using a mobility capillary electrophoresis (MCE) and native mass spectrometry (native MS) based method. By analyzing the ellipsoidal geometries of CaM in the solution phase at different Ca2+ concentrations, it is interesting to discover that CaM molecules, whether bound to Ca2+ or not, possess both closed and open conformations. Moreover, each individual CaM molecule actively "jumps" (equilibrium exchange) between these two distinct conformations on a timescale ranging from milli- to micro-seconds. The binding of Ca2+ ions did not affect the structural dynamics of CaM, while the binding of a peptide ligand would stabilize CaM, leading to the observation of a single, compact conformation of the resulting protein complex. A target recognition mechanism was also proposed based on these new findings, suggesting that CaM's interaction with targets may favor a conformational selection model. This enriches our understanding of the binding principles between CaM and its numerous targets.


Asunto(s)
Calcio , Calmodulina , Electroforesis Capilar , Espectrometría de Masas , Calmodulina/química , Calmodulina/metabolismo , Electroforesis Capilar/métodos , Calcio/química , Calcio/metabolismo , Espectrometría de Masas/métodos , Conformación Proteica , Unión Proteica , Animales
10.
Talanta ; 276: 126246, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38796994

RESUMEN

Fluid biopsy technology, characterized by its minimally invasive nature, speed, and continuity, has become a rapidly advancing and widely applied real-time diagnostic technique. Among various biomarkers, proteins represent the most abundant class of disease indicators. The sensitive and accurate detection of protein markers in bodily fluids is significantly influenced by the control exerted by recognition ligands. Aptamers, which are structurally dynamic functional oligonucleotides, exhibit high affinity, specific recognition of targets, and notable characteristics of high editability and modularity. These features make aptamer universal "recognition-capture" components, contribute to a significant leap in their applications within the biosensor domain. In this context, we provide a comprehensive review of the extensive application of aptamer-based biosensors in fluid biopsy. We systematically compile the characteristics and construction strategies of aptamer-based biosensors tailored for fluid biopsy, including aptamer sequences, affinity (KD), fluid background, sensing technologies, sensor construction strategies, incubation time, detection performance, and influencing factors. Furthermore, a comparative analysis of their advantages and disadvantages was conducted. In conclusion, we delineate and deliberate on prospective research trajectories and challenges that lie ahead in the realm of aptamer-based biosensors for fluid biopsy.


Asunto(s)
Aptámeros de Nucleótidos , Biomarcadores , Técnicas Biosensibles , Humanos , Aptámeros de Nucleótidos/química , Técnicas Biosensibles/métodos , Biomarcadores/análisis , Biopsia Líquida/métodos , Proteínas/análisis , Proteínas/química , Líquidos Corporales/química
11.
Se Pu ; 42(5): 401-409, 2024 Apr 08.
Artículo en Chino | MEDLINE | ID: mdl-38736383

RESUMEN

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.


Asunto(s)
Electroforesis Capilar , Electroforesis Capilar/métodos
12.
Front Bioeng Biotechnol ; 12: 1385264, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38798954

RESUMEN

Uphill walking is a common task encountered in daily life, with steeper inclines potentially imposing greater biomechanical and neuromuscular demands on the human body. The heel-to-toe drop (HTD) in footwear may influence the biomechanical and neuromuscular pattern of uphill walking; but the impact remains unclear. Adjustments in HTD can modulate biomechanical and neuromuscular patterns, mitigating the demands and optimizing the body's response to different inclinations. We hypothesize that adjustments in HTD can modulate biomechanical and neuromuscular patterns, mitigating the demands and optimizing the body's response to different inclinations. Nineteen healthy men walked on an adjustable slope walkway, with varied inclinations (6°, 12°, 20°) and HTD shoes (10mm, 25mm, 40 mm), while the marker positions, ground reaction forces and electromyography data were collected. Our study reveals that gait temporo-spatial parameters are predominantly affected by inclination over HTD. Inclination has a more pronounced effect on kinematic variables, while both inclination and HTD significantly modulate kinetic and muscle synergy parameters. This study demonstrates that an increase in the inclination leads to changes in biomechanical and neuromuscular responses during uphill walking and the adjustment of HTD can modulate these responses during uphill walking. However, the present study suggests that an increased HTD may lead to elevated loads on the knee joint and these adverse effects need more attention.

13.
Comput Biol Med ; 176: 108547, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38728994

RESUMEN

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.


Asunto(s)
Imagenología Tridimensional , Humanos , Imagenología Tridimensional/métodos , Aprendizaje Profundo , Algoritmos , Aprendizaje Automático Supervisado
14.
Sensors (Basel) ; 24(8)2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38676055

RESUMEN

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.


Asunto(s)
Electromiografía , Armas de Fuego , Mano , Temblor , Humanos , Temblor/fisiopatología , Masculino , Mano/fisiología , Mano/fisiopatología , Adulto , Adulto Joven , Rendimiento Atlético/fisiología , Músculo Esquelético/fisiopatología , Músculo Esquelético/fisiología
16.
Talanta ; 273: 125837, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38479030

RESUMEN

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.


Asunto(s)
Aptámeros de Nucleótidos , Bacteriófagos , Edición Génica , ADN/química , Proteínas Bacterianas/metabolismo , Aptámeros de Nucleótidos/metabolismo , Técnica SELEX de Producción de Aptámeros
17.
Int J Med Robot ; 20(1): e2619, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38536712

RESUMEN

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.


Asunto(s)
Algoritmos , Imagenología Tridimensional , Humanos , Rayos X , Radiografía , Imagenología Tridimensional/métodos , Tomografía Computarizada por Rayos X/métodos , Procesamiento de Imagen Asistido por Computador/métodos
18.
J Biomech ; 165: 111996, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38377740

RESUMEN

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.


Asunto(s)
Pie , Goma , Dureza , Fenómenos Biomecánicos , Zapatos
20.
Sci Rep ; 14(1): 1724, 2024 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-38242922

RESUMEN

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.


Asunto(s)
Articulación de la Rodilla , Extremidad Inferior , Humanos , Femenino , Movimiento , Articulación del Tobillo , Rango del Movimiento Articular , Fenómenos Biomecánicos , Articulación de la Cadera
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