Backstepping control based on adaptive neural network and disturbance observer for reconfigurable variable stiffness actuator.

Reconfigurable variable stiffness actuator (RVSA) has attracted increasing attention in robotics due to its safety, compliance, and robustness. However, the control of the RVSA is challenging due to nonlinear factors such as high-order nonlinear dynamic, model uncertainties, time-varying model parameters, and disturbances. In this paper, firstly, a lightweight RVSA structure with both passive and active nonlinear variable stiffness characteristic is developed. Secondly, a dynamic surface backstepping control method based on a radial basis neural network and disturbance observer (DSBC-RBFNN-DOB) is proposed to achieve position control of the lightweight RVSA with matched and unmatched uncertainties. To address solve the "complexity explosion" and noise problems in traditional backstepping control, the dynamic surface backstepping control (DSBC) method is used to design the controller. Then, a method based on radial basis neural network (RBFNN) and disturbance observer (DOB) are used to compensate for the matched and unmatched uncertainties in the link and motor. In this method, the matched uncertainties are compensated using RBFNN, and the DOB is integrated to compensate RBFNN approximation errors and unmatched uncertainties. Through Lyapunov stability analysis, the semi-global boundedness of the controller is proven. Finally, the proposed method is simulated and actually implemented, verifying the effectiveness of the method. Simulation and experimental results show that the root mean square error (RMSE) of the proposed method is only 0.97277° and 0.6418°, respectively. Compared with PID, DSBC, and DSBC-RBFNN, the error reduction percentages in simulation (experiment) are 85.6 % (88.9 %), 49.4 % (88.4 %) and 36.1 % (80.0 %) respectively.

Neuroimmune interactions and their roles in neurodegenerative diseases.

The nervous system possesses bidirectional, sophisticated and delicate communications with the immune system. These neuroimmune interactions play a vitally important role in the initiation and development of many disorders, especially neurodegenerative diseases. Although scientific advancements have made tremendous progress in this field during the last few years, neuroimmune communications are still far from being elucidated. By organizing recent research, in this review, we discuss the local and intersystem neuroimmune interactions and their roles in Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Unveiling these will help us gain a better understanding of the process of interplay inside the body and how the organism maintains homeostasis. It will also facilitate a view of the diseases from a holistic, pluralistic and interconnected perspective, thus providing a basis of developing novel and effective methods to diagnose, intervene and treat diseases.

Modulating the Pronociceptive Effect of Sleep Deprivation: A Possible Role for Cholinergic Neurons in the Medial Habenula.

Sleep deprivation has been shown to exacerbate pain sensitivity and may contribute to the onset of chronic pain, yet the precise neural mechanisms underlying this association remain elusive. In our study, we explored the contribution of cholinergic neurons within the medial habenula (MHb) to hyperalgesia induced by sleep deprivation in rats. Our findings indicate that the activity of MHb cholinergic neurons diminishes during sleep deprivation and that chemogenetic stimulation of these neurons can mitigate the results. Interestingly, we did not find a direct response of MHb cholinergic neurons to pain stimulation. Further investigation identified the interpeduncular nucleus (IPN) and the paraventricular nucleus of the thalamus (PVT) as key players in the pro-nociceptive effect of sleep deprivation. Stimulating the pathways connecting the MHb to the IPN and PVT alleviated the hyperalgesia. These results underscore the important role of MHb cholinergic neurons in modulating pain sensitivity linked to sleep deprivation, highlighting potential neural targets for mitigating sleep deprivation-induced hyperalgesia.

Time-delay control scheme with adaptive fixed-time convergent super-twisting fractional-order nonsingular terminal sliding mode for piezoelectric displacement amplifier.

Piezoelectric displacement amplifiers (PDAs) have been widely used in precision positioning fields. However, the inherent hysteresis and creep nonlinear effect of piezoelectric actuators (PEAs) and time-varying lumped disturbances bring extreme challenges to the precise motion control of PDAs. Although various control schemes based on PEAs have been developed and have shown significant results. However, due to the high sensitivity of precision positioning to environmental variations, the development and identification of accurate models and the control timeliness often become obstacles in engineering. To realize precise motion control of PDAs under complex lumped disturbances, a new time-delay control scheme (AFSTA-FONTSM) using an adaptive fixed-time convergent super-twisting algorithm (AFSTA) and a fractional-order nonsingular terminal sliding mode (FONTSM) is proposed. Specifically, the time-delay information obtained by time-delay estimation technology is used to estimate the lumped dynamic characteristic of the system, thus establishing a simple control framework without a system dynamic model. FONSTM is constructed as a sliding mode manifold, and satisfactory error dynamic characteristic is obtained. A new AFSTA is designed as the reaching law in the sliding mode phase. AFSTA has fixed-time convergence when the upper bound of lumped disturbances exists, which ensures the control timeliness. Benefiting from the newly designed adaptive algorithm, the upper bound value of lumped disturbances is no longer needed to determine the control gains, which effectively prevents overestimation of the control gains. Correspondingly, the convergence time of AFSTA is estimated, and the stability of the closed-loop system is analyzed by the Lyapunov theory. Three existing time-delay control schemes, namely MSTA-FONTSM, AMSTA-FONTSM, and ASTA-FONTSM are selected, and four scenes are designed for comparative experiments. The experimental results show that MSTA-FONTSM has the worst control performance among the four control schemes. For the step, and continuous cosine trajectories with periods of T = 1 s and T = 2 s, the root-mean-square error of the proposed AFSTA-FONTSM is reduced by 56.86%, 54.03%, and 50.24% compared with MSTA-FONTSM. For disturbance experiments under different loads, the control performance of the proposed AFSTA-FONTSM is still superior to the other three control schemes without load.

[Therapeutic effect of ß-tricalcium phosphate in mastoid cavity obliterationunder endoscope].

Objective:To investigate the therapeutic effect of ß-tricalcium phosphate in mastoid cavity obliteration for middle ear cholesteatoma under endoscope. Methods:Sixty patients with middle ear cholesteatoma admitted to our department from September 2021 to March 2022 were included in this study. The observation group（n=30） received ß-tricalcium phosphate during mastoid cavity obliteration. The control group（n=30） received autologous tissue during mastoid cavity obliteration. Pure tone audiometry was performed before surgery and after surgery in both groups, and the air conduction thresholds of 500, 1 000, 2 000 and 4 000 Hz were recorded. The external acoustic meatus cross-sectional area within 1 cm of the external acoustic meatus opening was measured during the operation and after the operation. The differences of postoperative ear drying time, hearing change and mastoid cavity healing were compared between the two groups. Results:The duration of postoperative dry ear in the observation group was 2-14 weeks, with an average of （9.4±2.7） weeks, while that in the control group was 4-26 weeks, with an average of（16.0±5.7） weeks. The difference in dry ear time between the two groups was statistically significant（P<0.05）. In the observation group, the threshold change was -19-27 dB, with an average of（6.4±10.7） dB, and in the control group, the threshold change was -9-17 dB, with an average of （4.7±7.1） dB. There was no significant difference in hearing change between the two groups（P>0.05）. In the observation group, the cross-sectional area of 1 cm inside the ear canal opening was -5.9-8.2 mm², with an average of （-0.6±2.6） mm², and in the control group, the cross-sectional area of 1 cm inside the ear canal opening was -5.5-5.2 mm², with an average of （-0.4±2.3） mm². There was no significant difference in intraoperative cavity changes between the two groups（P>0.05）. Conclusion:The application of ß-tricalcium phosphate to fill the mastoid cavity during the operation of endoscopic middle ear cholesteatoma has no adverse effect on the hearing of patients, can shorten the postoperative dry ear time, and results in good postoperative healing, which is worth promoting.

Cordyceps militaris: A novel mushroom platform for metabolic engineering.

Cordyceps militaris, widely recognized as a medicinal and edible mushroom in East Asia, contains a variety of bioactive compounds, including cordycepin (COR), pentostatin (PTN) and other high-value compounds. This review explores the potential of developing C. militaris as a cell factory for the production of high-value chemicals and nutrients. This review comprehensively summarizes the fermentation advantages, metabolic networks, expression elements, and genome editing tools specific to C. militaris and discusses the challenges and barriers to further research on C. militaris across various fields, including computational biology, existing DNA elements, and genome editing approaches. This review aims to describe specific and promising opportunities for the in-depth study and development of C. militaris as a new chassis cell. Additionally, to increase the practicability of this review, examples of the construction of cell factories are provided, and promising strategies for synthetic biology development are illustrated.

Arthroscopic Linear Chain Fixation for the Treatment of Medial Meniscus Posterior Root Tear: A Case Study.

BACKGROUND: The repair and reconstruction of medial meniscus posterior root tears (MMPRTs) is an important issue in the field of orthopedic sports medicine. This study reports the first application of arthroscopic linear chain fixation for the treatment of MMPRTs. CASE PRESENTATION: A 78-year-old female patient presented with a 1.5-month history of right knee pain accompanied by a locked facet joint. The patient underwent surgery with the new linear chain fixation method. In this method, the suture and the loop part of the buckle-strap titanium plate were combined into a linear chain mechanical complex, and the tension of the posterior root stump was gradually increased by pulling on the two attachment lines at the external mouth of the tibial tunnel. The postoperative Lysholm score was 89, and the visual analogue scale score was 0.9, indicating a significant improvement in knee joint function. At the 7-month and 1-year post-surgery follow-up, physical and MRI examinations confirmed satisfactory healing of the MMPRTs. CONCLUSION: This surgical approach offers several benefits, including a simplified instrumentation setup, preservation of natural anatomical structures, and reliable residual stump fixation. It has the potential for clinical implementation.

Water decoction of Pericarpium citri reticulatae and Amomi fructus ameliorates alcohol-induced liver disease involved in the modulation of gut microbiota and TLR4/NF-κB pathway.

Introduction: Alcohol consumption alters the diversity and metabolic activities of gut microbiota, leading to intestinal barrier dysfunction and contributing to the development of alcoholic liver disease (ALD), which is the most prevalent cause of advanced liver diseases. In this study, we investigated the protective effects and action mechanism of an aqueous extraction of Pericarpium citri reticulatae and Amomi fructus (PFE) on alcoholic liver injury. Methods: C57BL/6 mice were used to establish the mouse model of alcoholic liver injury and orally administered 500 and 1,000 mg/kg/d of PFE for 2 weeks. Histopathology, immunohistochemistry, immunofluorescence, Western blotting, qRT-PCR, and 16S rDNA amplicon sequencing were used to analyze the mechanism of action of PFE in the treatment of alcohol-induced liver injury. Results: Treatment with PFE significantly improved alcohol-induced liver injury, as illustrated by the normalization of serum alanine aminotransferase, aspartate aminotransferase, total triglyceride, and cholesterol levels in ALD mice in a dose-dependent manner. Administration of PFE not only maintained the intestinal barrier integrity prominently by upregulating mucous production and tight junction protein expressions but also sensibly reversed the dysregulation of intestinal microecology in alcohol-treated mice. Furthermore, PFE treatment significantly reduced hepatic lipopolysaccharide (LPS) and attenuated oxidative stress as well as inflammation related to the TLR4/NF-κB signaling pathway. The PFE supplementation also significantly promoted the production of short-chain fatty acids (SCFAs) in the ALD mice. Conclusion: Administration of PFE effectively prevents alcohol-induced liver injury and may also regulate the LPS-involved gut-liver axis; this could provide valuable insights for the development of drugs to prevent and treat ALD.

Regulatory mechanism of GA3 application on grape (Vitis vinifera L.) berry size.

Gibberellin A3 (GA3) is often used as a principal growth regulator to increase plant size. Here, we applied Tween-20 (2%)-formulated GA3 (T1:40 mg/L; T2:70 mg/L) by dipping the clusters at the initial expansion phase of 'Red Globe' grape (Vitis vinifera L.) in 2018 and 2019. Tween-20 (2%) was used as a control. The results showed that GA3 significantly increased fruit cell length, cell size, diameter, and volume. The hormone levels of auxin (IAA) and zeatin (ZT) were significantly increased at 2 h (0 d) -1 d after application (DAA0-1) and remained significantly higher at DAA1 until maturity. Conversely, ABA exhibited an opposite trend. The mRNA and non-coding sequencing results yielded 436 differentially expressed mRNA (DE_mRNAs), 79 DE_lncRNAs and 17 DE_miRNAs. These genes are linked to hormone pathways like cysteine and methionine metabolism (ko00270), glutathione metabolism (ko00480) and plant hormone signal transduction (ko04075). GA3 application reduced expression of insensitive dwarf 2 (GID2, VIT_07s0129g01000), small auxin-upregulated RNA (SAUR, VIT_08s0007g03120) and 1-aminocyclopropane-1-carboxylate synthase (ACS, VIT_18s0001g08520), but increased SAUR (VIT_04s0023g00560) expression. These four genes were predicted to be negatively regulated by vvi-miR156, vvi-miR172, vvi-miR396, and vvi-miR159, corresponding to specific lncRNAs. Therefore, miRNAs could affect grape size by regulating key genes GID2, ACS and SAUR. The R2R3 MYB family member VvRAX2 (VIT_08s0007g05030) was upregulated in response to GA3 application. Overexpression of VvRAX2 in tomato transgenic lines increased fruit size in contrast to the wild type. This study provides a basis and genetic resources for elucidating the novel role of ncRNAs in fruit development.

ULK1 confers neuroprotection by regulating microglial/macrophages activation after ischemic stroke.

Microglial activation and autophagy play a critical role in the progression of ischemic stroke and contribute to the regulation of neuroinflammation. Unc-51-like kinase 1 (ULK1) is the primary autophagy kinase involved in autophagosome formation. However, the impact of ULK1 on neuroprotection and microglial activation after ischemic stroke remains unclear. In this study, we established a photothrombotic stroke model, and administered SBI-0206965 (SBI), an ULK1 inhibitor, and LYN-1604 hydrochloride (LYN), an ULK1 agonist, to modulate ULK1 activity in vivo. We assessed sensorimotor deficits, neuronal apoptosis, and microglial/macrophage activation to evaluate the neurofunctional outcome. Immunofluorescence results revealed ULK1 was primarily localized in the microglia of the infarct area following ischemia. Upregulating ULK1 through LYN treatment significantly reduced infarct volume, improved motor function, promoted the increase of anti-inflammatory microglia. In conclusion, ULK1 facilitated neuronal repair and promoted the formation of anti-inflammatory microglia pathway after ischemic injury.

Bowel Stiffness Assessed by Shear-Wave Ultrasound Elastography Predicts Disease Behavior Progression in Patients With Crohn's Disease.

INTRODUCTION: There is a lack of reliable predictors of disease behavior progression in patients with Crohn's disease (CD). Real-time shear-wave elastography (SWE) is a novel method for evaluating tissue stiffness. However, its value for assessing CD has not yet been investigated. We aimed to explore the value of SWE and other ultrasound parameters at diagnosis in predicting CD behavior progression. METHODS: We retrospectively collected data from patients with CD with the nonstenotic nonpenetrating disease (B1 phenotype based on the Montreal classification). All patients underwent intestinal ultrasound at baseline and were followed up. The end point was defined as disease behavior progression to stricturing (B2) or penetrating (B3) disease. Cox regression analysis was performed for the association between baseline characteristics and subsequent end points. In addition, a multivariate nomogram was established to predict the risk of disease behavior progression quantitatively. RESULTS: A total of 130 patients with CD with B1 phenotype were enrolled. Twenty-seven patients (20.8%) developed B2 or B3 disease, with a median follow-up of 33 months. Multivariate analysis identified that SWE was the only independent predictor of disease behavior progression (hazard ratio 1.08, 95% confidence interval 1.03-1.12, P = 0.001). A reverse of the HR appeared at the cutoff 12.75 kPa. The nomogram incorporating SWE and other clinical characteristics showed a good prediction performance (area under the curve = 0.792). DISCUSSION: Intestinal stiffness assessed using SWE is an independent predictor of disease behavior progression in patients with CD. Patients with CD with SWE >12.75 kPa at diagnosis are prone to progress toward stricturing or penetrating diseases.