The contest between artificial management and natural environment determines the adaptive strategies of leaf morphogenesis in Sabina chinensis.

Sabina chinensis is a typically heteromorphic leaf evergreen tree worldwide with both ornamental and ecological value. However, the shaping mechanism of heteromorphic leaves of S. chinensis and its adaptability to environment are important factors determining its morphology. The morphological change of S. chinensis under different habitats (tree around) and treatments (light, pruning and nutrients) was investigated. Our findings suggested that the prickle leaves proportion was associated with low light intensity and soil nutrient scarcity. Stems and leaves are pruned together to form clusters of large prickle leaves, while only pruning leaves often form alternately growing small prickle leaves and scale leaves, and the length of the prickle leaves is between 0.5 cm and 1 cm. The gene expression of prickle leaves is higher than that of scale leaves under adverse environmental conditions, and the gene expression correlations between small prickle leaf and scale leaf were the highest. Homologous and heterologous mutants of gene structure in prickle leaves were larger than those in scale leaves. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway showed that phenylpropanone and flavonoid biosynthesis were common enrichment pathways, and that the enrichment genes were mainly related to metabolism, genetic information processing and organismal systems. Therefore, we concluded that the occurrence of the heteromorphic leaf phenomenon was related to the changes in photosynthesis, mechanical damage and nutrient supplementation. The organic matter in the S. chinensis prickle leaves was reduced under environmental stresses, and it will be allocated to the expression of prickle leaf or protective cuticles formation.

Hippocampal proteome comparison of infant and adult Fmr1 deficiency mice reveals adult-related changes associated with postsynaptic density.

Deficiency in fragile X mental retardation 1 (Fmr1) leads to loss of its encoded protein FMRP and causes fragile X syndrome (FXS) by dysregulating its target gene expression in an age-related fashion. Using comparative proteomic analysis, this study identified 105 differentially expressed proteins (DEPs) in the hippocampus of postnatal day 7 (P7) Fmr1-/y mice and 306 DEPs of P90 Fmr1-/y mice. We found that most DEPs in P90 hippocampus were not changed in P7 hippocampus upon FMRP absence, and some P90 DEPs exhibited diverse proteophenotypes with abnormal expression of protein isoform or allele variants. Bioinformatic analyses showed that the P7 DEPs were mainly enriched in fatty acid metabolism and oxidoreductase activity and nutrient responses; whereas the P90 PEPs (especially down-regulated DEPs) were primarily enriched in postsynaptic density (PSD), neuronal projection development and synaptic plasticity. Interestingly, 25 of 30 down-regulated PSD proteins present in the most enriched protein to protein interaction network, and 6 of them (ANK3, ATP2B2, DST, GRIN1, SHANK2 and SYNGAP1) are both FMRP targets and autism candidates. Therefore, this study suggests age-dependent alterations in hippocampal proteomes upon loss of FMRP that may be associated with the pathogenesis of FXS and its related disorders. SIGNIFICANCE: It is well known that loss of FMRP resulted from Fmr1 deficiency leads to fragile X syndrome (FXS), a common neurodevelopmental disorder accompanied by intellectual disability and autism spectrum disorder (ASD). FMRP exhibits distinctly spatiotemporal patterns in the hippocampus between early development and adulthood, which lead to distinct dysregulations of gene expression upon loss of FMRP at the two age stages potentially linked to age-related phenotypes. Therefore, comparison of hippocampal proteomes between infancy and adulthood is valuable to provide insights into the early causations and adult-dependent consequences for FXS and ASD. Using a comparative proteomic analysis, this study identified 105 and 306 differentially expressed proteins (DEPs) in the hippocampi of postnatal day 7 (P7) and P90 Fmr1-/y mice, respectively. Few overlapping DEPs were identified between P7 and P90 stages, and the P7 DEPs were mainly enriched in the regulation of fatty acid metabolism and oxidoreduction, whereas the P90 DEPs were preferentially enriched in the regulation of synaptic formation and plasticity. Particularly, the up-regulated P90 proteins are primarily involved in immune responses and neurodegeneration, and the down-regulated P90 proteins are associated with postsynaptic density, neuron projection and synaptic plasticity. Our findings suggest that distinctly changed proteins in FMRP-absence hippocampus between infancy and adulthood may contribute to age-dependent pathogenesis of FXS and ASD.

Motor Imagery Performance through Embodied Digital Twins in a Virtual Reality-Enabled Brain-Computer Interface Environment.

This study introduces an innovative framework for neurological rehabilitation by integrating brain-computer interfaces (BCI) and virtual reality (VR) technologies with the customization of three-dimensional (3D) avatars. Traditional approaches to rehabilitation often fail to fully engage patients, primarily due to their inability to provide a deeply immersive and interactive experience. This research endeavors to fill this gap by utilizing motor imagery (MI) techniques, where participants visualize physical movements without actual execution. This method capitalizes on the brain's neural mechanisms, activating areas involved in movement execution when imagining movements, thereby facilitating the recovery process. The integration of VR's immersive capabilities with the precision of electroencephalography (EEG) to capture and interpret brain activity associated with imagined movements forms the core of this system. Digital Twins in the form of personalized 3D avatars are employed to significantly enhance the sense of immersion within the virtual environment. This heightened sense of embodiment is crucial for effective rehabilitation, aiming to bolster the connection between the patient and their virtual counterpart. By doing so, the system not only aims to improve motor imagery performance but also seeks to provide a more engaging and efficacious rehabilitation experience. Through the real-time application of BCI, the system allows for the direct translation of imagined movements into virtual actions performed by the 3D avatar, offering immediate feedback to the user. This feedback loop is essential for reinforcing the neural pathways involved in motor control and recovery. The ultimate goal of the developed system is to significantly enhance the effectiveness of motor imagery exercises by making them more interactive and responsive to the user's cognitive processes, thereby paving a new path in the field of neurological rehabilitation.

Electro-oxidative quinylation of sulfides to sulfur ylides in batch and continuous flow.

An unprecedented strategy for preparing a series of sulfur ylides through electro-oxidative quinylation of sulfides in batch and continuous flow has been developed. Good to excellent yields were obtained with excellent functional group compatibility and good concentration tolerance under exogenous oxidant- and transition metal-free conditions. Advantageously, this electrosynthesis methodology was scalable with higher daily production and steady production was achieved attributing to the use of micro-flow cells.

Monitoring soil moisture in winter wheat with crop water stress index based on canopy-air temperature time lag effect.

Crop water stress index (CWSI) has been widely used in soil moisture monitoring. However, the influence of the time lag effect between canopy temperature and air temperature on the accuracy of soil moisture monitoring with different CWSI models has not been further investigated. Therefore, based on the continuous record of canopy temperature and air temperature, this study explored the influence of canopy-air temperature hysteresis on the diagnosis of soil moisture with three CWSI models (CWSIT-theoretical, CWSIE-empirical, CWSIH-hybrid). The results show (1) the peak time of canopy temperature was ahead of that of air temperature, and the lag time varied under different soil moisture conditions. When the soil moisture was seriously deficient, the lag time decreased. However, from jointing-heading period to filling-ripening period, the lag time became longer. (2) The values of CWSIT, CWSIE, and CWSIH decreased when the time lag effect was considered. In jointing-heading period, heading-filling period, and filling-ripening period, CWSIT had the highest accuracy in soil moisture monitoring without the consideration of the time lag effect. When the time lag effect was considered, the monitoring accuracy of CWSIE and CWSIH was greatly improved and higher than that of CWSIT, while that of CWSIT was reduced. The findings provided a basis for further improving the accuracy of soil moisture monitoring with CWSI models.

Five similar anthocyanidin molecules display distinct disruptive effects and mechanisms of action on Aß1-42 protofibril: A molecular dynamic simulation study.

Alzheimer's disease (AD) is associated with the deposition of amyloid-ß (Aß) fibrillary aggregates. Disaggregation of Aß fibrils is considered as one of the promising AD treatments. Recent experimental studies showed that anthocyanidins, one type of flavonoids abundant in fruits/vegetables, can disaggregate Aß fibrillary aggregates. However, their relative disruptive capacities and underlying mechanisms are largely unknown. Herein, we investigated the detailed interactions between five most common anthocyanidins (cyanidin, aurantinidin, peonidin, delphinidin, and pelargonidin) and Aß protofibril (an intermediate of Aß fibrillization) by performing microsecond molecular dynamic simulations. We found that all five anthocyanidins can destroy F4-L34-V36 hydrophobic core and K28-A42 salt bridge, leading to Aß protofibril destabilization. Aurantinidin exhibits the strongest damage to Aß protofibril (with the most severe disruption on K28-A42 salt bridges), followed by cyanidin (with the most destructive effect on F4-L34-V36 core). Detailed analyses reveal that the protofibril-destruction capacities of anthocyanidins are subtly modulated by the interplay of anthocyanidin-protofibril hydrogen bonding, hydrophobic, aromatic stacking interactions, which are dictated by the number or location of hydroxyl/methyl groups of anthocyanidins. These findings provide important mechanistic insights into Aß protofibril disaggregation by anthocyanidins, and suggest that aurantinidin/cyanidin may serve as promising starting-points for the development of new drug candidates against AD.

Feasibility and usability of a virtual-reality-based sensorimotor activation apparatus for carpal tunnel syndrome patients.

PURPOSE: This study aimed to assess the usability of a virtual reality-assisted sensorimotor activation (VRSMA) apparatus for individual digit rehabilitation. The study had two main objectives: Firstly, to collect preliminary data on the expectations and preferences of patients with carpal tunnel syndrome (CTS) regarding virtual reality (VR) and an apparatus-assisted therapy for their affected digits. Secondly, to evaluate the usability of the VRSMA apparatus that was developed. METHODS: The VRSMA system consists of an apparatus that provides sensory and motor stimulation via a vibratory motor and pressure sensor attached to a button, and a virtual reality-based visual cue provided by texts overlaid on top of a 3D model of a hand. The study involved 10 CTS patients who completed five blocks of VRSMA with their affected hand, with each block corresponding to the five digits. The patients were asked to complete a user expectations questionnaire before experiencing the VRSMA, and a user evaluation questionnaire after completing the VRSMA. Expectations for VRSMA were obtained from the questionnaire results using a House of Quality (HoQ) analysis. RESULTS: In the survey for expectations, participants rated certain attributes as important for a rehabilitation device for CTS, with mean ratings above 4 for attributes such as ease of use, ease of understanding, motivation, and improvement of hand function based on clinical evidence. The level of immersion and an interesting rehabilitation regime received lower ratings, with mean ratings above 3.5. The survey evaluating VRSMA showed that the current prototype was overall satisfactory with a mean rating of 3.9 out of 5. Based on the HoQ matrix, the highest priority for development of the VRSMA was to enhance device comfort and usage time. This was followed by the need to perform more clinical studies to provide evidence of the efficacy of the VRSMA. Other technical characteristics, such as VRSMA content and device reliability, had lower priority scores. CONCLUSION: The current study presents a potential for an individual digit sensorimotor rehabilitation device that is well-liked by CTS patients.

The effect of combining action observation in virtual reality with kinesthetic motor imagery on cortical activity.

Introduction: In the past, various techniques have been used to improve motor imagery (MI), such as immersive virtual-reality (VR) and kinesthetic rehearsal. While electroencephalography (EEG) has been used to study the differences in brain activity between VR-based action observation and kinesthetic motor imagery (KMI), there has been no investigation into their combined effect. Prior research has demonstrated that VR-based action observation can enhance MI by providing both visual information and embodiment, which is the perception of oneself as part of the observed entity. Additionally, KMI has been found to produce similar brain activity to physically performing a task. Therefore, we hypothesized that utilizing VR to offer an immersive visual scenario for action observation while participants performed kinesthetic motor imagery would significantly improve cortical activity related to MI. Methods: In this study, 15 participants (9 male, 6 female) performed kinesthetic motor imagery of three hand tasks (drinking, wrist flexion-extension, and grabbing) both with and without VR-based action observation. Results: Our results indicate that combining VR-based action observation with KMI enhances brain rhythmic patterns and provides better task differentiation compared to KMI without action observation. Discussion: These findings suggest that using VR-based action observation alongside kinesthetic motor imagery can improve motor imagery performance.

Evaluation of EEG Oscillatory Patterns and Classification of Compound Limb Tactile Imagery.

Objective: The purpose of this study was to investigate the cortical activity and digit classification performance during tactile imagery (TI) of a vibratory stimulus at the index, middle, and thumb digits within the left hand in healthy individuals. Furthermore, the cortical activities and classification performance of the compound TI were compared with similar compound motor imagery (MI) with the same digits as TI in the same subjects. Methods: Twelve healthy right-handed adults with no history of upper limb injury, musculoskeletal condition, or neurological disorder participated in the study. The study evaluated the event-related desynchronization (ERD) response and brain-computer interface (BCI) classification performance on discriminating between the digits in the left-hand during the imagery of vibrotactile stimuli to either the index, middle, or thumb finger pads for TI and while performing a motor activity with the same digits for MI. A supervised machine learning technique was applied to discriminate between the digits within the same given limb for both imagery conditions. Results: Both TI and MI exhibited similar patterns of ERD in the alpha and beta bands at the index, middle, and thumb digits within the left hand. While TI had significantly lower ERD for all three digits in both bands, the classification performance of TI-based BCI (77.74 ± 6.98%) was found to be similar to the MI-based BCI (78.36 ± 5.38%). Conclusions: The results of this study suggest that compound tactile imagery can be a viable alternative to MI for BCI classification. The study contributes to the growing body of evidence supporting the use of TI in BCI applications, and future research can build on this work to explore the potential of TI-based BCI for motor rehabilitation and the control of external devices.

Naphthoquinone-dopamine hybrids disrupt α-synuclein fibrils by their intramolecular synergistic interactions with fibrils and display a better effect on fibril disruption.

α-Synuclein (αSyn) is an intrinsically disordered protein and its abnormal aggregation into amyloid fibrils is the main hallmark of Parkinson's disease (PD). The disruption of preformed αSyn fibrils using small molecules is considered as a potential strategy for PD treatment. Recent experiments have reported that naphthoquinone-dopamine hybrids (NQDA), synthesized by naphthoquinone (NQ) and dopamine (DA) molecules, can significantly disrupt αSyn fibrils and cross the blood-brain barrier. To unravel the fibril-disruptive mechanisms at the atomic level, we performed microsecond molecular dynamics simulations of αSyn fibrils in the absence and presence of NQDA, NQ, DA, or NQ+DA molecules. Our simulations showed that NQDA reduces the ß-sheet content, disrupts K45-E57 and E46-K80 salt-bridges, weakens the inter-protofibril interaction, and thus destabilizes the αSyn fibril structure. NQDA has the ability to form cation-π and H-bonding interactions with K45/K80, and form π-π stacking interactions with Y39/F94. Those interactions between NQDA and αSyn fibrils play a crucial role in disaggregating αSyn fibrils. Moreover, we found that NQDA has a better fibril destabilization effect than that of NQ, DA, and NQ+DA molecules. This is attributed to the synergistic fibril-binding effect between NQ and DA groups in NQDA molecules. The DA group can form strong π-π stacking interactions with aromatic residues Y39/F94 of the αSyn fibril, while the DA molecule cannot. In addition, NQDA can form stronger cation-π interactions with residues K45/K80 than those of both NQ and DA molecules. Our results provide the molecular mechanism underlying the disaggregation of the αSyn fibril by NQDA and its better performance in fibril disruption than NQ, DA, and NQ+DA molecules, which offers new clues for the screening and development of promising drug candidates to treat PD.

The relationship between shear wave velocity in transverse carpal ligament and carpal tunnel pressure: A finite element analysis.

Elevated carpal tunnel pressure in carpal tunnel syndrome (CTS) patients is one of the major causes of nerve damage but cannot be measured non-invasively. This study proposed to use shear wave velocity (SWV) in the transverse carpal ligament (TCL) to measure the surrounding carpal tunnel pressure. The relationship between the carpal tunnel pressure and the SWV in the TCL was investigated through a subject-specific carpal tunnel finite element model reconstrued by MRI imaging. Parametric analysis was conducted to study the effect of TCL Young's modulus and carpal tunnel pressure on the TCL SWV. The SWV in TCL was found to be strongly dependent on the carpal tunnel pressure and TCL Young's modulus. The calculated SWV ranged from 8.0 m/s to 22.6 m/s under a combination of carpal tunnel pressure (0-200 mmHg) and TCL Young's modulus (1.1-11 MPa). An empirical equation was used to fit the relationship between the SWV in TCL and carpal tunnel pressure, with TCL Young's modulus as a confounding factor. The equation proposed in this study provided an approach to estimate carpal tunnel pressure by measuring the SWV in the TCL for a potential non-invasive diagnosis of CTS and may shed light on the mechanical nerve damage mechanism.

The effect of thickness and elastic modulus of the anterior talofibular ligament on anterior ankle joint stiffness: A subject-specific finite element study.

Ankle sprain is a frequent type of sports injury leading to lateral ligament injury. The anterior talofibular ligament (ATFL) is a primary ligamentous stabilizer of the ankle joint and typically the most vulnerable ligament injured in a lateral ankle sprain (LAS). This study aimed to quantitively investigate the effect of the thickness and elastic modulus of ATFL on anterior ankle joint stiffness (AAJS) by developing nine subject-specific finite element (FE) models under acute injury, chronic injury, and control conditions of ATFL. A 120 N forward force was applied at the posterior calcaneus leading to an anterior translation of the calcaneus and talus to simulate the anterior drawer test (ADT). In the results, the ratio of the forward force to the talar displacement was used to assess the AAJS, which increased by 5.85% in the acute group and decreased by 19.78% in the chronic group, compared to those of the control group. An empirical equation described the relationship between AAJS, thickness, and elastic modulus (R-square 0.98). The equation proposed in this study provided an approach to quantify AAJS and revealed the effect of the thickness and the elastic modulus of ATFL on ankle stability, which may shed light on the potential diagnosis of lateral ligament injury.

A finite element analysis of the carpal arch with various locations of carpal tunnel release.

Objective: The purpose of this study was to investigate the effects of the location of transverse carpal ligament (TCL) transection on the biomechanical property of the carpal arch structure. It was hypothesized that carpal tunnel release would lead to an increase of the carpal arch compliance (CAC) in a location-dependent manner. Methods: A pseudo-3D finite element model of the volar carpal arch at the distal carpal tunnel was used to simulate arch area change under different intratunnel pressures (0-72 mmHg) after TCL transection at different locations along the transverse direction of the TCL. Results: The CAC of the intact carpal arch was 0.092 mm2/mmHg, and the simulated transections ranging from 8 mm ulnarly to 8 mm radially from the center point of the TCL led to increased CACs that were 2.6-3.7 times of that of the intact carpal arch. The CACs after radial transections were greater than those ulnarly transected carpal arches. Conclusion: The TCL transection in the radial region was biomechanically favorable in reducing carpal tunnel constraint for median nerve decompression.

Inoculation with Azorhizobium caulinodans ORS571 enhances plant growth and salt tolerance of switchgrass (Panicum virgatum L.) seedlings.

BACKGROUND: Switchgrass (Panicum virgatum L.) is an important biofuel crop that may contribute to replacing petroleum fuels. However, slow seedling growth and soil salinization affect the growth and development of switchgrass. An increasing number of studies have shown that beneficial microorganisms promote plant growth and increase tolerance to salinity stress. However, the feasibility of inoculating switchgrass with Azorhizobium caulinodans ORS571 to enhance the growth and salt tolerance of its seedlings is unclear. Our previous study showed that A. caulinodans ORS571 could colonize wheat (Triticum aestivum L.) and thereby promote its growth and development and regulate the gene expression levels of microRNAs (miRNAs). RESULTS: In this study, we systematically studied the impact of A. caulinodans ORS571 on switchgrass growth and development and the response to salinity stress; we also studied the underlying mechanisms during these biological processes. Inoculation with A. caulinodans ORS571 significantly alleviated the effect of salt stress on seedling growth. Under normal conditions, A. caulinodans ORS571 significantly increased fresh plant weight, chlorophyll a content, protein content, and peroxidase (POD) activity in switchgrass seedlings. Under salt stress, the fresh weight, dry weight, shoot and root lengths, and chlorophyll contents were all significantly increased, and some of these parameters even recovered to normal levels after inoculation with A. caulinodans ORS571. Soluble sugar and protein contents and POD and superoxide dismutase (SOD) activities were also significantly increased, contrary to the results for proline. Additionally, A. caulinodans ORS571 may alleviate salt stress by regulating miRNAs. Twelve selected miRNAs were all upregulated to different degrees under salt stress in switchgrass seedlings. However, the levels of miR169, miR171, miR319, miR393, miR535, and miR854 were decreased significantly after inoculation with A. caulinodans ORS571 under salt stress, in contrast to the expression level of miR399. CONCLUSION: This study revealed that A. caulinodans ORS571 increased the salt tolerance of switchgrass seedlings by increasing their water content, photosynthetic efficiency, osmotic pressure maintenance, and reactive oxygen species (ROS) scavenging abilities and regulating miRNA expression. This work provides a new, creative idea for improving the salt tolerance of switchgrass seedlings.

Hydrogen peroxide preconditioning is of dual role in cardiac ischemia/reperfusion.

Moderate reactive oxygen species (ROS) at reperfusion would trigger cardioprotection and various antioxidants for pharmacological preconditioning failed to achieve cardioprotection. The causes for different roles of preischemic ROS during cardiac ischemia/reperfusion (I/R) require reevaluation. We investigated the precise role of ROS and its working model in this study. Different doses of hydrogen peroxide (H2O2, the most stable form of ROS) were added 5 min before ischemia using isolated perfused rat hearts, only moderate-dose H2O2 preconditioning (H2O2PC) achieved contractile recovery, whereas the low dose and high dose led to injury. Similar results were observed in isolated rat cardiomyocytes on cytosolic free Ca2+ concentration ([Ca2+]c) overload, ROS production, the recovery of Ca2+ transient, and cell shortening. Based on the data mentioned above, we set up a mathematics model to describe the effects of H2O2PC with the fitting curve by the percentage of recovery of heart function and Ca2+ transient in I/R. Besides, we used the two models to define the initial thresholds of H2O2PC achieving cardioprotection. We also detected the expression of redox enzymes and Ca2+ signaling toolkits to explain the mathematics models of H2O2PC in a biological way. The expression of tyrosine 705 phosphorylation of STAT3, Nuclear factor E2-related factor 2, manganese superoxide dismutase, phospholamban, catalase, ryanodine receptors, and sarcoendoplasmic reticulum calcium ATPase 2 were similar with the control I/R and low-dose H2O2PC but were increased in the moderate H2O2PC and decreased in the high-dose H2O2PC. Thus, we concluded that preischemic ROS are of dual role in cardiac I/R.

The Effects of Subthreshold Vibratory Noise on Cortical Activity During Motor Imagery.

Previous studies have demonstrated that both visual and proprioceptive feedback play vital roles in mental practice of movements. Tactile sensation has been shown to improve with peripheral sensory stimulation via imperceptible vibratory noise by stimulating the sensorimotor cortex. With both proprioception and tactile sensation sharing the same population of posterior parietal neurons encoding within high-level spatial representations, the effect of imperceptible vibratory noise on motor imagery-based brain-computer interface is unknown. The objective of this study was to investigate the effects of this sensory stimulation via imperceptible vibratory noise applied to the index fingertip in improving motor imagery-based brain-computer interface performance. Fifteen healthy adults (nine males and six females) were studied. Each subject performed three motor imagery tasks, namely drinking, grabbing, and flexion-extension of the wrist, with and without sensory stimulation while being presented a rich immersive visual scenario through a virtual reality headset. Results showed that vibratory noise increased event-related desynchronization during motor imagery compared with no vibration. Furthermore, the task classification percentage was higher with vibration when the tasks were discriminated using a machine learning algorithm. In conclusion, subthreshold random frequency vibration affected motor imagery-related event-related desynchronization and improved task classification performance.

Stiffening of the gluteal muscle increased the intramuscular stress: An in-silico implication of deep tissue injury.

Objectives: Deep tissue injury is a common form of pressure ulcers in muscle tissues under bony prominences caused by sustained pressure or shear, which has a great impact on patients with restricted mobility such as spinal cord injury. Frequent spasms in spinal cord injury patients featured by muscle stiffening may be one of the factors leading to deep tissue injury. The purpose of this study was to investigate the relationship between the gluteal muscle shear modulus and intramuscular compressive/shear stress/strain. Methods: A semi-3D finite element model of the human buttock was established using COMSOL software and the acquired biomechanical data were analyzed through Pearson correlation and Spearman correlation. Results: Results showed that the compressive stress, strain energy density, and average von Mises stress increased with the increase of the gluteal muscle shear modulus. Conclusion: These results may indicate muscle stiffening caused by muscle spasms could lead to higher deep tissue injury development risk as well as shed light on effective treatments for relieving muscular sclerosis mechanically.

EGCG attenuates α-synuclein protofibril-membrane interactions and disrupts the protofibril.

The fibrillary aggregates of α-synuclein (α-syn) are closely associated with the etiology of Parkinson's disease (PD). Mounting evidence shows that the interaction of α-syn with biological membranes is a culprit for its aggregation and cytotoxicity. While some small molecules can effectively inhibit α-syn fibrillization in solution, their potential roles in the presence of membrane are rarely studied. Among them, green tea extract epigallocatechin gallate (EGCG) is currently under active investigation. Herein, we investigated the effects of EGCG on α-syn protofibril (an intermediate of α-syn fibril formation) in the presence of a model membrane and on the interactions between α-syn protofibril and the membrane, as well as the underlying mechanisms, by performing microsecond all-atom molecular dynamics simulations. The results show that EGCG has destabilization effects on α-syn protofibril, albeit to a lesser extent than that in solution. Intriguingly, we find that EGCG forms overwhelming H-bonding and cation-π interactions with membrane and thus attenuates protofibril-membrane interactions. Moreover, the decreased protofibril-membrane interactions impede the membrane damage by α-syn protofibril and enable the membrane integrity. These findings provide atomistic understanding towards the attenuation of α-syn protofibril-induced cytotoxicity by EGCG in cellular environment, which is helpful for the development of EGCG-based therapeutic strategies against PD.

Cationic micelles as nanocarriers for enhancing intra-cartilage drug penetration and retention.

There is a tremendous unmet medical need for osteoarthritis (OA) treatment around the world, and pharmacological management is the most common option but presents a limited and short efficacy. Insufficient drug delivery to articular cartilage is the key cause. It is widely accepted that the complex structure of articular cartilage and the rapid clearance of joint liquids largely hinder drug penetration and retention in the cartilage. To address these obstacles, we designed and prepared a positively charged micellar system that can effectively deliver a model drug to the deep zone of the cartilage and prolong the drug retention time. In this work, a triblock copolymer composed of cationic poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) and poly(ε-caprolactone) (PCL), denoted as PDMAEMA-PCL-PDMAEMA, was synthesized. A triblock copolymer composed of brush poly[poly(ethylene glycol) methacrylate] (pPEGMA) and PCL, denoted as pPEGMA-PCL-pPEGMA, was prepared for comparison. The two types of triblock copolymers were self-assembled in an aqueous environment to form cationic and neutral micelles, respectively. A hydrophobic fluorescent dye as a model drug was loaded into micelle cores, and the dye-loaded micelles were evaluated for intra-cartilage penetration and retention using porcine knee cartilage explants. The PDMAEMA-PCL-PDMAEMA cationic micelles were found to significantly enhance the intra-cartilage penetration and retention capability due to the electrostatic interaction between the micelles and the negatively charged cartilage extracellular matrix. The confocal microscopy study showed that the cationic micelles could penetrate the full-thickness porcine cartilage explants (around 1.5 mm) within 24 hours. Up to 87% of the cationic micelles were taken up by porcine cartilage explants, and 71% of the absorbed micelles were retained in the tissue for at least 4 days. Although the pPEGMA-PCL-pPEGMA neutral micelles were able to penetrate the full-thickness cartilage, this type of micelle showed lower uptake (44%) and retention (44%) rates. This observation implied that the surface charge of micelles could play an important role in efficient intra-cartilage drug delivery. This study verified the feasibility and effectiveness of the PDMAEMA-PCL-PDMAEM cationic micelles in intra-cartilage drug delivery, showing that cationic micelles could be promising carriers for OA treatment.

Precision agriculture management based on a surrogate model assisted multiobjective algorithmic framework.

Sustainable intensification needs to optimize irrigation and fertilization strategies while increasing crop yield. To enable more precision and effective agricultural management, a bi-level screening and bi-level optimization framework is proposed. Irrigation and fertilization dates are obtained by upper-level screening and upper-level optimization. Subsequently, due to the complexity of the problem, the lower-level optimization uses a data-driven evolutionary algorithm, which combines the fast non-dominated sorting genetic algorithm (NSGA-II), surrogate-assisted model of radial basis function and Decision Support System for Agrotechnology Transfer to handle the expensive objective problem and produce a set of optimal solutions representing a trade-off between conflicting objectives. Then, the lower-level screening quickly finds better irrigation and fertilization strategies among thousands of solutions. Finally, the experiment produces a better irrigation and fertilization strategy, with water consumption reduced by 44%, nitrogen application reduced by 37%, and economic benefits increased by 7 to 8%.