Comparison of biomechanical analysis results using different musculoskeletal models for children with cerebral palsy

Introduction: Musculoskeletal model-based simulations have gained popularity as a tool for analyzing human movement biomechanics. However, when examining the same gait, different models with varying anatomical data and assumptions may produce inconsistent biomechanical results. This inconsistency is particularly relevant for children with cerebral palsy, who often exhibit multiple pathological gait patterns that can impact model outputs.Methods: The aim of this study was to investigate the effect of selecting musculoskeletal models on the biomechanical analysis results in children with cerebral palsy. Gait data were collected from multiple participants at slow, medium, and fast velocities. Joint kinematics, joint dynamics, and muscle activation were calculated using six popular musculoskeletal models within a biomechanical simulation environment.Results: The degree of inconsistency, measured as the root-mean-square deviation, in kinematic and kinetic results produced by the different models ranged from 4% to 40% joint motion range and 0%–28% joint moment range, respectively. The correlation between the results of the different models (both kinematic and kinetic) was good (R>0.85, P<0.01), with a stronger correlation observed in the kinetic results. Four of the six models showed a positive correlation between the simulated muscle activation of rectus femoris and the surface EMG, while all models exhibited a positive correlation between the activation of medial gastrocnemius and the surface EMG (P<0.01).Discussion: These results provide insights into the consistency of model results, factors influencing consistency, characteristics of each model’s outputs, mechanisms underlying these characteristics, and feasible applications for each model. By elucidating the impact of model selection on biomechanical analysis outcomes, this study advances the field’s understanding of musculoskeletal modeling and its implications for clinical gait analysis model decision-making in children with cerebral palsy

Deciphering of interactions between platinated DNA and HMGB1 by hydrogen/deuterium exchange mass spectrometry

A high mobility group box 1 (HMGB1) protein has been reported to recognize both 1,2-intrastrand crosslinked DNA by cisplatin (1,2-cis-Pt-DNA) and monofunctional platinated DNA using trans-[PtCl2(NH3)(thiazole)] (1-trans-PtTz-DNA). However, the molecular basis of recognition between the trans-PtTz-DNA and HMGB1 remains unclear. In the present work, we described a hydrogen/deuterium exchange mass spectrometry (HDX-MS) method in combination with docking simulation to decipher the interactions of platinated DNA with domain A of HMGB1. The global deuterium uptake results indicated that 1-trans-PtTz-DNA bound to HMGB1a slightly tighter than the 1,2-cis-Pt-DNA. The local deuterium uptake at the peptide level revealed that the helices I and II, and loop 1 of HMGB1a were involved in the interactions with both platinated DNA adducts. However, docking simulation disclosed different H-bonding networks and distinct DNA-backbone orientations in the two Pt-DNA-HMGB1a complexes. Moreover, the Phe37 residue of HMGB1a was shown to play a key role in the recognition between HMGB1a and the platinated DNAs. In the cis-Pt-DNA-HMGB1a complex, the phenyl ring of Phe37 intercalates into a hydrophobic notch created by the two platinated guanines, while in the trans-PtTz-DNA-HMGB1a complex the phenyl ring appears to intercalate into a hydrophobic crevice formed by the platinated guanine and the opposite adenine in the complementary strand, forming a penta-layer π–π stacking associated with the adjacent thymine and the thiazole ligand. This work demonstrates that HDX-MS associated with docking simulation is a powerful tool to elucidate the interactions between platinated DNAs and proteins

Adversarial Robustness of Deep Code Comment Generation

Deep neural networks (DNNs) have shown remarkable performance in a variety of domains such as computer vision, speech recognition, or natural language processing. Recently they also have been applied to various software engineering tasks, typically involving processing source code. DNNs are well-known to be vulnerable to adversarial examples, i.e., fabricated inputs that could lead to various misbehaviors of the DNN model while being perceived as benign by humans. In this paper, we focus on the code comment generation task in software engineering and study the robustness issue of the DNNs when they are applied to this task. We propose ACCENT, an identifier substitution approach to craft adversarial code snippets, which are syntactically correct and semantically close to the original code snippet, but may mislead the DNNs to produce completely irrelevant code comments. In order to improve the robustness, ACCENT also incorporates a novel training method, which can be applied to existing code comment generation models. We conduct comprehensive experiments to evaluate our approach by attacking the mainstream encoder-decoder architectures on two large-scale publicly available datasets. The results show that ACCENT efficiently produces stable attacks with functionality-preserving adversarial examples, and the generated examples have better transferability compared with baselines. We also confirm, via experiments, the effectiveness in improving model robustness with our training method

Xiaoaiping Induces Developmental Toxicity in Zebrafish Embryos Through Activation of ER Stress, Apoptosis and the Wnt Pathway

The aim of the study was to determine the developmental toxicity of the traditional Chinese medicine Xiaoaiping (XAP) and to investigate its underlying mechanism of action. Zebrafish embryos were incubated with 0.4, 0.8, 1.2, and 1.6 mg/mL XAP. Endpoints such as mortality, hatching rate, malformation, body length, morphology score, swimming behavior, histological changes, reactive oxygen species (ROS) production, total superoxide dismutase (T-SOD) activity, and the mRNA expression of genes related to oxidative stress, endoplasmic reticulum (ER) stress, apoptosis, and the Wnt pathway were evaluated. Our results demonstrated that XAP exposure increased mortality and malformation and reduced the hatching rate. XAP resulted in severe malformation, including swim bladder deficiency, yolk retention, pericardial edema, and tail curvature. Histopathological analysis showed that XAP induced liver, heart and muscle injury. High doses (≥1.2 mg/mL) of XAP notably decreased the locomotor capacity of zebrafish. ROS generation was remarkably increased and T-SOD activity was decreased, confirming that oxidative stress was induced by XAP. The mRNA expression levels of ER stress-related genes (chop, hspa5, hsp90b1, and perk), apoptosis-related genes (caspase-3, bax, and p53) and wnt11 were significantly upregulated by XAP exposure. The expression levels of the oxidative stress-related genes (cat, sod1, and gstp2), Wnt pathway-related genes (β-catenin, wnt3a, and wnt8a) and bcl-2 initially increased and then decreased as the XAP exposure dose increased. In conclusion, we provide evidence for the first time that XAP can induce dose-related developmental toxicity, and ER stress, apoptosis and the Wnt pathway participate in the toxicity regulation

Rheological properties and structural features of coconut milk emulsions stabilized with maize kernels and starch

peer-reviewedIn this study, maize kernels and starch with different amylose contents at the same concentration were added to coconut milk. The nonionic composite surfactants were used to prepare various types of coconut milk beverages with optimal stability, and their fluid properties were studied. The steady and dynamic rheological property tests show that the loss modulus (G″) of coconut milk is larger than the storage modulus (G′), which is suitable for the pseudoplastic fluid model and has a shear thinning effect. As the droplet size of the coconut milk fluid changed by the addition of maize kernels and starch, the color intensity, ζ-potential, interfacial tension and stability of the sample significantly improved. The addition of the maize kernels significantly reduced the size of the droplets (p < 0.05). The potential values of zeta (ζ) and the surface tension of the coconut milk increased. Based on the differential scanning calorimetry (DSC) measurement, the addition of maize kernels leads to an increase in the transition temperature, especially in samples with a high amylose content. The higher transition temperature can be attributed to the formation of some starches and lipids and the partial denaturation of proteins in coconut milk, but phase separation occurs. These results may be helpful for determining the properties of maize kernels in food-containing emulsions (such as sauces, condiments, and beverages) that achieve the goal of physical stability

High-efficiency in vitro and in vivo detection of Zn2+ by dye-assembled upconversion nanoparticles

10.1021/ja5115248Journal of the American Chemical Society13762336-234

Distinct lesion features and underlying mechanisms in patients with acute multiple infarcts in multiple cerebral territories

ObjectiveTo determine the etiology spectrum and lesion distribution patterns of patients with acute multiple infarcts in multiple cerebral territories (AMIMCT) and provide guidance for treatment and prevention strategies in these patients.MethodsPatients with acute ischemic stroke diagnosed using diffusion-weighted imaging (DWI) were consecutively included in this study between June 2012 and Apr 2022. AMIMCT was defined as non-contiguous focal lesions located in more than one cerebral territory with acute neurological deficits. We retrospectively analyzed the clinical and imaging characteristics, etiology spectra and underlying mechanisms in patients with and without AMIMCT. Infarct lesion patterns on DWI and their relevance to etiology were further discussed.ResultsA total of 1,213 patients were enrolled, of whom 145 (12%) were diagnosed with AMIMCT. Patients with AMIMCT tended to be younger (P = 0.016), more often female (P = 0.001), and exhibited less common conventional vascular risk factors (P &lt; 0.05) compared to those without AMIMCT. The constitution of the Trial of Org 10,172 in Acute Stroke Treatment classification was significantly different between patients with and without AMIMCT (P = 0.000), with a higher proportion of stroke of other determined causes (67.6% vs. 12.4%). For detailed etiologies, autoimmune or hematologic diseases were the most common (26.2%) etiologies of AMIMCT, followed by periprocedural infarcts (15.2%), cardioembolism (12.4%), tumor (12.4%), large artery atherosclerosis (10.3%), and sudden drop in blood pressure (8.3%). Hypercoagulability and systemic hypoperfusion are common underlying mechanisms of AMIMCT. Distinctive lesion distribution patterns were found associated with stroke etiologies and mechanisms in AMIMCT. Most of patients with large artery atherosclerosis (73.3%), autoimmune/hematologic diseases (57.9%) manifested the disease as multiple infarct lesions located in bilateral supratentorial regions. However, 66.7% of cardioembolism and 83.8% of cardiovascular surgery related stroke presented with both supratentorial and infratentorial infarct lesions.ConclusionThe etiologies and mechanisms of patients with AMIMCT were more complex than those without AMIMCT. The distribution characteristics of infarct lesions might have important implications for the identification of etiology and mechanism in the future, which could further guide and optimize clinical diagnostic strategies

Mesenchymal Stem Cells: A Double-edged Sword in Regulating Immune Responses

Mesenchymal stem cells (MSCs) have been employed successfully to treat various immune disorders in animal models and clinical settings. Our previous studies have shown that MSCs can become highly immunosuppressive upon stimulation by inflammatory cytokines, an effect exerted through the concerted action of chemokines and nitric oxide (NO). Here, we show that MSCs can also enhance immune responses. This immune-promoting effect occurred when proinflammatory cytokines were inadequate to elicit sufficient NO production. When inducible nitric oxide synthase (iNOS) production was inhibited or genetically ablated, MSCs strongly enhance T-cell proliferation in vitro and the delayed-type hypersensitivity response in vivo. Furthermore, iNOS-/- MSCs significantly inhibited melanoma growth. It is likely that in the absence of NO, chemokines act to promote immune responses. Indeed, in CCR5-/- CXCR3-/- mice, the immune-promoting effect of iNOS-/- MSCs is greatly diminished. Thus, NO acts as a switch in MSC-mediated immunomodulation. More importantly, the dual effect on immune reactions was also observed in human MSCs, in which indoleamine 2,3-dioxygenase (IDO) acts as a switch. This study provides novel information about the pathophysiological roles of MSCs. © 2012 Macmillan Publishers Limited All rights reserved