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1.
Chemistry ; : e202402536, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39250167

RESUMEN

For the first time, explicit stabilization of all the three conformers, viz. (cis,cis), (cis,trans) and (trans,trans), of a 'nano-sized' highly-flexible urea-bridged Zn(II)porphyrin dimer have been achieved via careful manipulations of external stimuli such as solvent dielectrics, temperature, anionic interactions, axial ligation and surface-induced stabilization. The conformers differ widely in their structures, chemical and photophysical properties and thus have vast potential applicability. X-ray structural characterizations have been reported for the (cis,cis) and (cis,trans)-conformers. While (cis,cis) conformer stabilized exclusively in dichloromethane, more polar solvents resulted in the stabilization of (cis,trans) and (trans,trans)-conformers. Low temperature promotes the stabilization of (cis,trans)-conformer while rise in temperature facilitates flipping to the (cis,cis) one. Significantly, exclusive stabilization of the (trans,trans)-isomer has been illustrated using acetate anion which facilitates H-bonding with the two amide linkages of the urea spacer. Remarkably, HOPG surface facilitates stabilization of the energetically challenging (trans,trans)-conformer via CH···p and p···p interactions with the solid surface to the porphyrinic cores. DFT calculations demonstrate that the relative stability of the conformers can be modulated upon slight external perturbations as also observed in the experiment. Several factors contributing towards the conformational landscape for the highly flexible urea-bridged porphyrin dimers have been mapped.

2.
Hum Mov Sci ; 97: 103273, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39217920

RESUMEN

BACKGROUND: This study examined (i) adaptations in muscle activity following perturbation-based balance training (PBT) using treadmill belt-accelerations or PBT using walkway trips and (ii) whether adaptations during treadmill PBT transfer to a walkway trip. METHODS: Thirty-eight older people (65+ years) undertook two PBT sessions, including 11 treadmill belt-accelerations and 11 walkway trips. Surface electromyography (EMG) was measured bilaterally on the rectus femoris (RF), tibialis anterior (TA), semitendinosus (ST) and gastrocnemius medial head (GM) during the first (T1) and eleventh (T11) perturbations. Adaptations (within-subjects - 1st vs 11th perturbations for treadmill and walkway PBT) and their transfer (between-subjects - 1st walkway trip after treadmill PBT vs 1st walkway trip with no prior training) effects were examined for the EMG parameters. RESULTS: Treadmill PBT reduced post-perturbation peak muscle activation magnitude (left RF, TA, ST, right RF, ST, GM), onset latency (right TA), time to peak (right RF) and co-contraction index (knee muscles) (P < 0.05). Walkway PBT reduced post-trip onset latencies (right TA, ST), peak magnitude (left ST, right GM), time to peak (right RF, ST) and pre-perturbation muscle activity (right TA) (P < 0.05). Those who undertook treadmill PBT were not different to those without prior training during the first walkway trip (P > 0.05). CONCLUSIONS: Both treadmill and walkway PBT induced earlier initiation and peak activation of right limb muscles responsible for the first recovery step. Treadmill PBT also reduced co-contraction of the knee muscles. Adaptations in muscle activity following treadmill PBT did not transfer to a walkway trip.


Asunto(s)
Adaptación Fisiológica , Estudios Cruzados , Electromiografía , Músculo Esquelético , Equilibrio Postural , Humanos , Anciano , Equilibrio Postural/fisiología , Masculino , Femenino , Adaptación Fisiológica/fisiología , Músculo Esquelético/fisiología , Caminata/fisiología , Prueba de Esfuerzo , Aceleración , Anciano de 80 o más Años , Fenómenos Biomecánicos/fisiología
3.
Proc Natl Acad Sci U S A ; 121(37): e2322155121, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39226345

RESUMEN

Utilizing molecular dynamics and free energy perturbation, we examine the relative binding affinity of several covalent polycyclic aromatic hydrocarbon - DNA (PAH-DNA) adducts at the central adenine of NRAS codon-61, a mutational hotspot implicated in cancer risk. Several PAHs classified by the International Agency for Research on Cancer as probable, possible, or unclassifiable as to carcinogenicity are found to have greater binding affinity than the known carcinogen, benzo[a]pyrene (B[a]P). van der Waals interactions between the intercalated PAH and neighboring nucleobases, and minimal disruption of the DNA duplex drive increases in binding affinity. PAH-DNA adducts may be repaired by global genomic nucleotide excision repair (GG-NER), hence we also compute relative free energies of complexation of PAH-DNA adducts with RAD4-RAD23 (the yeast ortholog of human XPC-RAD23) which constitutes the recognition step in GG-NER. PAH-DNA adducts exhibiting the greatest DNA binding affinity also exhibit the least RAD4-RAD23 complexation affinity and are thus predicted to resist the GG-NER machinery, contributing to their genotoxic potential. In particular, the fjord region PAHs dibenzo[a,l]pyrene, benzo[g]chrysene, and benzo[c]phenanthrene are found to have greater binding affinity while having weaker RAD4-RAD23 complexation affinity than their respective bay region analogs B[a]P, chrysene, and phenanthrene. We also find that the bay region PAHs dibenzo[a,j]anthracene, dibenzo[a,c]anthracene, and dibenzo[a,h]anthracene exhibit greater binding affinity and weaker RAD4-RAD23 complexation affinity than B[a]P. Thus, the study of PAH genotoxicity likely needs to be substantially broadened, with implications for public policy and the health sciences. This approach can be broadly applied to assess factors contributing to the genotoxicity of other unclassified compounds.


Asunto(s)
Aductos de ADN , Hidrocarburos Policíclicos Aromáticos , Hidrocarburos Policíclicos Aromáticos/toxicidad , Hidrocarburos Policíclicos Aromáticos/química , Hidrocarburos Policíclicos Aromáticos/metabolismo , Aductos de ADN/química , Aductos de ADN/metabolismo , Aductos de ADN/genética , Humanos , Reparación del ADN , Mutágenos/toxicidad , Mutágenos/química , Simulación de Dinámica Molecular , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/química , Termodinámica , Benzo(a)pireno/toxicidad , Benzo(a)pireno/química , Benzo(a)pireno/metabolismo , ADN/química , ADN/metabolismo , Benzopirenos/toxicidad , Benzopirenos/química , Benzopirenos/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/química
4.
J Neuroeng Rehabil ; 21(1): 161, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39285381

RESUMEN

BACKGROUND: Gait event detection is crucial for assessment, evaluation and provision of biofeedback during rehabilitation of walking. Existing online gait event detection algorithms mostly rely on add-on sensors, limiting their practicality. Instrumented treadmills offer a promising alternative by utilizing the Center of Pressure (CoP) signal for real-time gait event detection. However, current methods have limitations, particularly in detecting cross-step events during perturbed walking conditions. METHODS: We present and validate a CoP-based algorithm to detect gait events and cross-steps in real-time, which combines thresholding and logic techniques. The algorithm was evaluated on CoP datasets from healthy participants (age range 21-61 years), stroke survivors (age range 20-67 years), and people with unilateral transtibial amputation (age range 28-63 years) that underwent perturbation-based balance assessments, encompassing different walking speeds. Detected gait events from a simulated real-time processing operation were compared to offline identified counterparts in order to present related temporal absolute mean errors (AME) and success rate. RESULTS: The proposed algorithm demonstrated high accuracy in detecting gait events during native gait, as well as cross-step events during perturbed walking conditions. It successfully recognized the majority of cross-steps, with a detection success rate of 94%. However, some misclassifications or missed events occurred, mainly due to the complexity of cross-step events. AME for heel strikes (HS) during native gait and cross-step events averaged at 78 ms and 64 ms respectively, while toe off (TO) AME were 126 ms and 111 ms respectively. A statistically significant difference in the algorithm's success rate score in detecting gait events during cross-step intervals was observed across various walking speeds in a sample of 12 healthy participants, while there was no significant difference among groups. CONCLUSION: The proposed algorithm represents an advancement in gait event detection on instrumented treadmills. By leveraging the CoP signal, it successfully identifies gait events and cross-steps in the simulated real-time processing operation, providing valuable insights into human locomotion. The algorithm's ability to accommodate diverse CoP patterns enhance its applicability to a wide range of individuals and gait characteristics. The algorithm's performance was consistent across different populations, suggesting its potential for diverse clinical and research settings, particularly in the domains of gait analysis and rehabilitation practices.


Asunto(s)
Algoritmos , Humanos , Persona de Mediana Edad , Adulto , Anciano , Masculino , Femenino , Adulto Joven , Marcha/fisiología , Rehabilitación de Accidente Cerebrovascular/métodos , Rehabilitación de Accidente Cerebrovascular/instrumentación , Caminata/fisiología , Equilibrio Postural/fisiología , Presión
5.
J Infect Dis ; 230(Supplement_2): S141-S149, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39255394

RESUMEN

Alzheimer's disease (AD) is a neurodegenerative disorder with limited therapeutic options. Accordingly, new approaches for prevention and treatment are needed. One focus is the human microbiome, the consortium of microorganisms that live in and on us, which contributes to human immune, metabolic, and cognitive development and that may have mechanistic roles in neurodegeneration. AD and Alzheimer's disease-related dementias (ADRD) are recognized as spectrum disorders with complex pathobiology. AD/ADRD onset begins before overt clinical signs, but initiation triggers remain undefined. We posit that disruption of the normal gut microbiome in early life leads to a pathological cascade within septohippocampal and cortical brain circuits. We propose investigation to understand how early-life microbiota changes may lead to hallmark AD pathology in established AD/ADRD models. Specifically, we hypothesize that antibiotic exposure in early life leads to exacerbated AD-like disease endophenotypes that may be amenable to specific microbiological interventions. We propose suitable models for testing these hypotheses.


Asunto(s)
Enfermedad de Alzheimer , Microbioma Gastrointestinal , Enfermedad de Alzheimer/microbiología , Humanos , Microbioma Gastrointestinal/fisiología , Animales , Encéfalo/microbiología , Encéfalo/patología , Antibacterianos/uso terapéutico , Microbiota
6.
bioRxiv ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39229108

RESUMEN

Antibiotic resistance presents a significant challenge to public health, as bacteria can develop resistance to antibiotics through random mutations during their life cycles, making the drugs ineffective. Understanding how these mutations contribute to drug resistance at the molecular level is crucial for designing new treatment approaches. Recent advancements in molecular biology tools have made it possible to conduct comprehensive analyses of protein mutations. Computational methods for assessing molecular fitness, such as binding energies, are not as precise as experimental techniques like deep mutational scanning. Although full atomistic alchemical free energy calculations offer the necessary precision, they are seldom used to assess high throughput data as they require significantly more computational resources. We generated a computational library using deep mutational scanning for dihydrofolate reductase (DHFR), a protein commonly studied in antibiotic resistance research. Due to resource limitations, we analyzed 33 out of 159 positions, identifying 16 single amino acid replacements. Calculations were conducted for DHFR in its drug-free state and in the presence of two different inhibitors. We demonstrate the feasibility of such calculations, made possible due to the enhancements in computational resources and their optimized use.

7.
Neuroimage ; : 120835, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39245399

RESUMEN

Working Memory (WM) requires maintenance of task-relevant information and suppression of task-irrelevant/distracting information. Alpha and theta oscillations have been extensively investigated in relation to WM. However, studies that examine both theta and alpha bands in relation to distractors, encompassing not only power modulation but also connectivity modulation, remain scarce. Here, we depicted, at the EEG-source level, the increase in power and connectivity in theta and alpha bands induced by strong relative to weak distractors during a visual Sternberg-like WM task involving the encoding of verbal items. During retention, a strong or weak distractor was presented, predictable in time and nature. Analysis focused on the encoding and retention phases before distractor presentation. Theta and alpha power were computed in cortical regions of interest, and connectivity networks estimated via spectral Granger causality and synthetized using in/out degree indices. The following modulations were observed for strong vs. weak distractors. In theta band during encoding, the power in frontal regions increased, together with frontal-to-frontal and bottom-up occipital-to-temporal-to-frontal connectivity; even during retention, bottom-up theta connectivity increased. In alpha band during retention, but not during encoding, the power in temporal-occipital regions increased, together with top-down frontal-to-occipital and temporal-to-occipital connectivity. From our results, we postulate a proactive cooperation between theta and alpha mechanisms: the first would mediate enhancement of target representation both during encoding and retention, and the second would mediate increased inhibition of sensory areas during retention only, to suppress the processing of imminent distractor without interfering with the processing of ongoing target stimulus during encoding.

8.
Brief Bioinform ; 25(5)2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39226889

RESUMEN

Systematic characterization of biological effects to genetic perturbation is essential to the application of molecular biology and biomedicine. However, the experimental exhaustion of genetic perturbations on the genome-wide scale is challenging. Here, we show TranscriptionNet, a deep learning model that integrates multiple biological networks to systematically predict transcriptional profiles to three types of genetic perturbations based on transcriptional profiles induced by genetic perturbations in the L1000 project: RNA interference, clustered regularly interspaced short palindromic repeat, and overexpression. TranscriptionNet performs better than existing approaches in predicting inducible gene expression changes for all three types of genetic perturbations. TranscriptionNet can predict transcriptional profiles for all genes in existing biological networks and increases perturbational gene expression changes for each type of genetic perturbation from a few thousand to 26 945 genes. TranscriptionNet demonstrates strong generalization ability when comparing predicted and true gene expression changes on different external tasks. Overall, TranscriptionNet can systemically predict transcriptional consequences induced by perturbing genes on a genome-wide scale and thus holds promise to systemically detect gene function and enhance drug development and target discovery.


Asunto(s)
Aprendizaje Profundo , Humanos , Redes Reguladoras de Genes , Perfilación de la Expresión Génica/métodos , Biología Computacional/métodos , Regulación de la Expresión Génica , Interferencia de ARN
9.
Front Neuroinform ; 18: 1451529, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39247901

RESUMEN

Introduction: Gait analysis, an expanding research area, employs non-invasive sensors and machine learning techniques for a range of applications. In this study, we investigate the impact of cognitive decline conditions on gait performance, drawing connections between gait deterioration in Parkinson's Disease (PD) and healthy individuals dual tasking. Methods: We employ Explainable Artificial Intelligence (XAI) specifically Layer-Wise Relevance Propagation (LRP), in conjunction with Convolutional Neural Networks (CNN) to interpret the intricate patterns in gait dynamics influenced by cognitive loads. Results: We achieved classification accuracies of 98% F1 scores for PD dataset and 95.5% F1 scores for the combined PD dataset. Furthermore, we explore the significance of cognitive load in healthy gait analysis, resulting in robust classification accuracies of 90% ± 10% F1 scores for subject cognitive load verification. Our findings reveal significant alterations in gait parameters under cognitive decline conditions, highlighting the distinctive patterns associated with PD-related gait impairment and those induced by multitasking in healthy subjects. Through advanced XAI techniques (LRP), we decipher the underlying features contributing to gait changes, providing insights into specific aspects affected by cognitive decline. Discussion: Our study establishes a novel perspective on gait analysis, demonstrating the applicability of XAI in elucidating the shared characteristics of gait disturbances in PD and dual-task scenarios in healthy individuals. The interpretability offered by XAI enhances our ability to discern subtle variations in gait patterns, contributing to a more nuanced comprehension of the factors influencing gait dynamics in PD and dual-task conditions, emphasizing the role of XAI in unraveling the intricacies of gait control.

10.
J Mot Behav ; : 1-10, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39114919

RESUMEN

Reciprocal inhibition and coactivation are strategies of the central nervous system used to perform various daily tasks. In automatic postural responses (APR), coactivation is widely investigated in the ankle joint muscles, however reciprocal inhibition, although clear in manipulative motor actions, has not been investigated in the context of APRs. The aim was to identify whether reciprocal inhibition can be observed as a strategy in the recruitment of gastrocnemius Medialis (GM), Soleus (So) and Tibialis Anterior (TA) muscles in low- and high-velocity forward and backward perturbations. We applied two balance perturbations with a low and a high velocity of displacement of the movable platform in forward and backward conditions and we evaluated the magnitude and latency time of TA, GM and So activation latency, measured by electromyography (EMG). In forward perturbations, coactivation of the three muscles was observed, with greater activation amplitude of the GM and lesser amplitude of the So and TA muscles. For backward, the pattern of response observed was activation of the TA muscle, a decrease in the EMG signal, which characterizes reciprocal inhibition of the GM muscle and maintenance of the basal state of the So muscle. This result indicates that backward perturbations are more challenging.

11.
Exp Brain Res ; 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39110161

RESUMEN

Proprioception plays an important role in both feedforward and feedback processes underlying movement control. This has been shown with individuals who suffered a profound proprioceptive loss and use vision to partially compensate for the sensory loss. The purpose of this study was to specifically examine the role of proprioception in feedback motor responses to visual perturbations by examining voluntary arm movements in an individual with a rare case of selective peripheral deafferentation (GL). We compared her left and right hand movements with those of age-matched female control participants (70.0 years ± 0.2 SEM) during a reaching task. Participants were asked to move their unseen hand, represented by a cursor on the screen, quickly and accurately to reach a visual target. A visual perturbation could be pseudorandomly applied, at movement onset, to either the target position (target jump) or the cursor position (cursor jump). Results showed that despite the continuous visual feedback that was provided, GL produced larger errors in final position accuracy compared to control participants, with her left nondominant hand being more erroneous after a cursor jump. We also found that the proprioceptively-deafferented individual produced less spatially efficient movements than the control group. Overall, these results provide evidence of a heavier reliance on proprioceptive feedback for movements of the nondominant hand relative to the dominant hand, supporting the view of a lateralization of the feedback processes underlying motor control.

12.
Kurume Med J ; 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39098031

RESUMEN

OBJECTIVES: This study aimed to examine the effects of cognitive tasks during walking with perturbation on the cerebral blood flow. METHODS: The subjects were a total of 20 persons, consisting of 12 healthy adults aged 21-47 years (adult group) and 8 retirement home residents aged 67-85 years who led an independent daily life and could walk independently (elderly group). Oxyhemoglobin was measured using wireless functional near-infrared spectroscopy (fNIRS). An analysis was conducted using the Wilcoxon rank sum test to compare the variation of oxyhemoglobin between walking with perturbation (WP) and walking with perturbation and cognitive tasks (WPC) in each group. In addition, we compared the variation of oxyhemoglobin between groups by analysis of covariance adjusting for the value of WP. RESULTS: In the adult group, the left and right oxyhemoglobin significantly increased under WPC (p=0.0122, 0.0015, respectively). On the other hand, in the elderly group, the right and left oxyhemoglobin did not significantly change under WPC. CONCLUSIONS: These results suggest that the effect of a cognitive task during unstable walking conditions differs between healthy adults and elderly persons, and that this may be important when considering postural control strategies, especially in the elderly.

13.
Med Phys ; 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39153227

RESUMEN

BACKGROUND: Magnetic resonance (MR) imaging devices have been integrated with medical linear accelerators (linac) in radiation therapy. Both perpendicular linac-MR (LMR-B⊥) and parallel (LMR-B∥) systems exist, where due to the MR's magnetic field dose can be perturbed in the patient. Dose perturbations from the electron return effect (ERE) and electron streaming effects (ESEs) are present in LMR-B⊥ systems, where a dose collimating effect has been observed in LMR-B∥ systems . PURPOSE: To report on an asymmetric dose perturbation which is present at the interface between two different materials during treatment in parallel linac-MR (LMR-B∥) systems. To the best of our knowledge, these asymmetric dose effects, "Lateral Scattered Electron Return Effect" (LS-ERE) have not been previously reported. METHODS: BEAMnrc and EGSnrc Monte Carlo (MC) radiation transport codes were used with the EEMF macro to emulate a 6 FFF beam from the 0.5-T Alberta linac-MR (LMR). Simulations were performed at 0.5 and 1.5 T in several different phantom material-interface combinations and field sizes including from modulated MLC-like fields. MC simulations quantified LS-ERE in patient CT datasets for the head, breast, and lung. LS-ERE cancellation techniques were investigated. LS-ERE asymmetries were quantified by subtracting an antiparallel dose from the parallel dose, dividing by two and normalizing to the global 0-T maximum dose. GafChromic film measurements were made in the 0.5-T Alberta LMR-B∥ system using solid water at the water-air interface to validate MC simulations. ERE was simulated for an emulated LMR-B⊥ system and compared to LMR-B∥ dose perturbations. RESULTS: LS-ERE is mostly independent of field size for fields >1 × 1 cm2. For 5 × 5-cm2 fields at 0.5T/1.5T, LS-ERE asymmetries are ≤±6.9%/6.9% at bone-air and ≤±9.0%/7.0% at tissue-air for nonair doses, and ≤±4.1%/5.5% at tissue-lung interfaces. LS-ERE increases as the density gradient increases, where the magnitude and extent of LS-ERE are reduced as field strength increases. For a single 5 × 5-cm2 field at 0.5T/1.5T, the LS-ERE asymmetry is ≤±10.2%/8.5% at the tissue-air sinus interface for head, ≤±4.2%/5.3% at the spine-lung interface for the lung, and ≤±5.7%/4.9% at the skin-air interface for a breast tangent plan at 0.5T/1.5T. POP fields mostly remove LS-ERE asymmetries, with magnetic field reversal during treatment being the most effective method. Skin dose was investigated and compared to 0-T treatments for 0.5T/1.5T LMR-B∥ single field breast and head treatments. Including all dosimetric magnetic field perturbations, a 21%/24% and 22%/22% increase in skin dose to head and breast, respectively, was observed, of which LS-ERE is responsible for approximately 30% of the total. Measured LS-ERE asymmetries and dose enhancements at the water-air interface using GafChromic film were in excellent agreement with MC simulations. ERE in 1.5-T LMR-B⊥ systems are on average 5.5 times larger than total dose perturbations at 0.5 T in LMR-B∥ systems. CONCLUSION: LS-ERE is present at the interface between materials and awareness of LS-ERE is crucial for proper TPS evaluation for LMR-B∥ treatments, especially in areas where large tissue density gradients exist.

14.
ACS Appl Mater Interfaces ; 16(33): 43212-43226, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39106039

RESUMEN

Reactive oxygen species (ROS) hold great potential in tumor pyroptosis therapy, yet they are still limited by short species lifespan and limited diffusion distance. Inducing cells into a metastable state and then applying external energy can effectively trigger pyroptosis, but systemic sensitization still faces challenges, such as limited ROS content, rapid decay, and short treatment windows. Herein, a nanohybrid-based redox homeostasis-perturbator system was designed that synergistically induce early lysosomal escape, autophagy inhibition, and redox perturbation functions to effectively sensitize cells to address these challenges. Specifically, weakly alkaline layered double hydroxide nanosheets (LDH NSs) with pH-responsive degradation properties enabled early lysosomal escape within 4 h, releasing poly(L-dopa) nanoparticles for inducing catechol-quinone redox cycling in the cytoplasm. The intracellular ROS levels were systematically rebounded by 3-4 times in tumor cells and lasted for over 4 h. Subsequently induced lysosomal stress and Ca2+ signaling activation resulted in severe mitochondrial dysfunction, as well as a perilous metastable state. Thereby, sequential near-infrared light was applied to trigger amplified stress through a local photothermal conversion. This led to sufficiently high levels of cleaved caspase-1 and GSDMD activation (2.5-2.8-fold increment) and subsequent pyroptosis response. In addition, OH- released by LDH elevated pH to alleviate the limitation of glutathione depletion by quinones at acidic pH and inhibit protective autophagy. Largely secreted inflammatory factors (2.5-5.6-fold increment), efficient maturation of dendritic cells, and further immune stimulation were boosted for tumor inhibition as a consequence. This study offers a new paradigm and insights into the synergy of internal systematic cellular sensitization and sequential external energy treatment to achieve tumor suppression through pyroptosis.


Asunto(s)
Homeostasis , Lisosomas , Oxidación-Reducción , Piroptosis , Piroptosis/efectos de los fármacos , Lisosomas/metabolismo , Lisosomas/efectos de los fármacos , Humanos , Animales , Ratones , Homeostasis/efectos de los fármacos , Homeostasis/efectos de la radiación , Nanopartículas/química , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/química , Terapia Fototérmica , Hidróxidos/química , Hidróxidos/farmacología , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/terapia , Neoplasias/metabolismo
15.
Front Bioeng Biotechnol ; 12: 1429605, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39161355

RESUMEN

Introduction: The ankle-foot exoskeleton has been demonstrated to help users resist anterior perturbation in the horizontal pelvis plane. However, its effects on perturbations in other directions remain unclear. This paper focuses on how the ankle-foot exoskeleton helps people resist perturbations coming from forward directions within the fan-shaped region in the pelvis horizontal plane. Methods: Firstly, we proposed and validated a hypothesis that the human torque ratio of inversion to plantar flexion torque would change with the perturbation directions of anterior (dir0) and 45° deviating from anterior to left (dir45). Subsequently, based on the regulation demand, we developed an ankle-foot exoskeleton that can adjust the torque ratio delivered to the human body by controlling the forces on two cross-arranged cables. Finally, we evaluated and compared the assistance performance of three powered assistive modes (NM, medBD, and latBD) with the unpowered one (UN) by setting different force pairs in two cables. Results: The results showed that, with the assistance, the margin of stability was increased and the standard deviations of ankle-foot segmental movements were decreased. Meanwhile, the biological inversion torque has a significant difference among the three assistive modes. Compared to the UN, the latBD was shown to reduce the biological inversion torque by 15.8 % and 13.7 % in response to the dir0 and dir45 perturbations, respectively, while the reductions for the NM and medBD were smaller. It was also observed that the torque ratios, generated by the human and the exoskeleton in latBD mode, differed by about 0.1 under dir0 and 0.08 under dir45, while the physiologically similarity of the exoskeleton torque ratio in NM and medBD modes were smaller. Based on the above results, we found that the more physiologically similar the exoskeleton torque ratio, the better the assistive performance. Discussion: The findings demonstrated that the torque-ratio-adjustable exoskeleton could support human resistance to perturbations coming from forward directions within a fan-shaped region in the pelvis horizontal plane and indicated that the exoskeleton's torque ratio should be carefully modulated to match the ratio of the human under various environmental conditions for better assistive performance.

16.
Physiol Meas ; 45(9)2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39197476

RESUMEN

Objective. Time-frequency (T-F) analysis of electroencephalographic (EEG) is a common technique to characterise spectral changes in neural activity. This study explores the limitations of utilizing conventional spectral techniques in examining cyclic event-related cortical activities due to challenges, including high inter-trial variability.Approach. Introducing the cycle-frequency (C-F) analysis, we aim to enhance the evaluation of cycle-locked respiratory events. For synthetic EEG that mimicked cycle-locked pre-motor activity, C-F had more accurate frequency and time localization compared to conventional T-F analysis, even for a significantly reduced number of trials and a variability of breathing rhythm.Main results. Preliminary validations using real EEG data during both unloaded breathing and loaded breathing (that evokes pre-motor activity) suggest potential benefits of using the C-F method, particularly in normalizing time units to cyclic activity phases and refining baseline placement and duration.Significance. The proposed approach could provide new insights for the study of rhythmic neural activities, complementing T-F analysis.


Asunto(s)
Corteza Cerebral , Electroencefalografía , Respiración , Electroencefalografía/métodos , Humanos , Corteza Cerebral/fisiología , Procesamiento de Señales Asistido por Computador , Factores de Tiempo , Masculino
17.
Neuroimage ; 299: 120797, 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39159703

RESUMEN

Attending to heartbeats for interoceptive awareness initiates distinct electrophysiological responses synchronized with the R-peaks of an electrocardiogram (ECG), such as the heartbeat-evoked potential (HEP). Beyond HEP, this study proposes heartbeat-related spectral perturbation (HRSP), a time-frequency map of the R-peak locked electroencephalogram (EEG), and explores its characteristics in identifying interoceptive attention states using a classification approach. HRSPs of EEG brain components specified by independent component analysis (ICA) were used for the offline and online classification of interoceptive states. A convolutional neural network (CNN) designed specifically for HRSP was applied to publicly available data from a binary-state experiment (attending to self-heartbeats and white noise) and data from our four-state classification experiment (attending to self-heartbeats, white noise, time passage, and toe) with diverse input feature conditions of HRSP. From the dynamic state perspective, we evaluated the primary frequency bands of HRSP and the minimal number of averaging epochs required to reflect changing interoceptive attention states without compromising accuracy. We also assessed the utility of group ICA and models for classifying HRSP in new participants. The CNN for trial-by-trial HRSP with actual R-peaks demonstrated significantly higher classification accuracy than HRSP with sham, i.e., randomly positioned, R-peaks. Gradient-weighted class activation mapping highlighted the prominent role of theta and alpha bands between 200-600 ms post-R-peak-features absent in classifications using sham HRSPs. Online classification benefits from employing a group ICA and classification model, ensuring reliable accuracy without individual EEG precollection. These results suggest HRSP's potential to reflect interoceptive attention states, proposing transformative implications for clinical applications.

18.
J Neurophysiol ; 132(3): 1014-1024, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39140589

RESUMEN

We studied simultaneous EMG and midline EEG responses, including over the cerebellum, in 10 standing subjects (35 ± 15 yr; 5 females, 5 males). Recordings were made following repeated taps to the sternum, stimuli known to evoke short-latency EMG responses in leg muscles, consistent with postural reflexes. EEG power had relatively more high-frequency components (>30 Hz) when recorded from electrodes over the cerebellum (Iz and SIz) compared with other midline electrodes. We confirmed a previous report using a similar stimulus that evoked short-latency potentials over the cerebellum. We showed clear midline-evoked EEG potentials occurring at short latency over the cerebellum (P23, N31, N42, and P54) and frontally (N28 and N57) before the previously described perturbation-evoked potential (P1/N1/P2). The P23 response correlated with the subsequent EMG response in the tibialis anterior muscles (r = 0.72, P = 0.018), confirming and extending previous observations. We did not find a correlation with the N1 amplitude. We conclude that early activity occurs from electrodes over the inion in response to a brief tap to the sternum. This is likely to represent cerebellar activity and it appears to modulate short-latency postural EMG responses.NEW & NOTEWORTHY We studied the effects of a brief tap to the sternum in human subjects, known to evoke short-latency postural responses. Using an extended EEG recording system, we showed early evoked responses over the midline cerebellum, including the P23 potential, which correlated with the EMG responses in tibialis anterior, consistent with a cerebellar role in postural reflexes. The stimulus also evoked later EEG responses, including the perturbation potential.


Asunto(s)
Electroencefalografía , Electromiografía , Humanos , Masculino , Femenino , Adulto , Músculo Esquelético/fisiología , Cerebelo/fisiología , Persona de Mediana Edad , Adulto Joven , Postura/fisiología
19.
Neural Netw ; 179: 106564, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39089150

RESUMEN

This study is centered around the dynamic behaviors observed in a class of fractional-order generalized reaction-diffusion inertial neural networks (FGRDINNs) with time delays. These networks are characterized by differential equations involving two distinct fractional derivatives of the state. The global uniform stability of FGRDINNs with time delays is explored utilizing Lyapunov comparison principles. Furthermore, global synchronization conditions for FGRDINNs with time delays are derived through the Lyapunov direct method, with consideration given to various feedback control strategies and parameter perturbations. The effectiveness of the theoretical findings is demonstrated through three numerical examples, and the impact of controller parameters on the error system is further investigated.


Asunto(s)
Redes Neurales de la Computación , Factores de Tiempo , Algoritmos , Retroalimentación , Simulación por Computador , Dinámicas no Lineales
20.
Neural Netw ; 179: 106628, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39168071

RESUMEN

Dictionary learning is an important sparse representation algorithm which has been widely used in machine learning and artificial intelligence. However, for massive data in the big data era, classical dictionary learning algorithms are computationally expensive and even can be infeasible. To overcome this difficulty, we propose new dictionary learning methods based on randomized algorithms. The contributions of this work are as follows. First, we find that dictionary matrix is often numerically low-rank. Based on this property, we apply randomized singular value decomposition (RSVD) to the dictionary matrix, and propose a randomized algorithm for linear dictionary learning. Compared with the classical K-SVD algorithm, an advantage is that one can update all the elements of the dictionary matrix simultaneously. Second, to the best of our knowledge, there are few theoretical results on why one can solve the involved matrix computation problems inexactly in dictionary learning. To fill-in this gap, we show the rationality of this randomized algorithm with inexact solving, from a matrix perturbation analysis point of view. Third, based on the numerically low-rank property and Nyström approximation of the kernel matrix, we propose a randomized kernel dictionary learning algorithm, and establish the distance between the exact solution and the computed solution, to show the effectiveness of the proposed randomized kernel dictionary learning algorithm. Fourth, we propose an efficient scheme for the testing stage in kernel dictionary learning. By using this strategy, there is no need to form nor store kernel matrices explicitly both in the training and the testing stages. Comprehensive numerical experiments are performed on some real-world data sets. Numerical results demonstrate the rationality of our strategies, and show that the proposed algorithms are much efficient than some state-of-the-art dictionary learning algorithms. The MATLAB codes of the proposed algorithms are publicly available from https://github.com/Jiali-yang/RALDL_RAKDL.


Asunto(s)
Algoritmos , Aprendizaje Automático , Inteligencia Artificial , Humanos
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