An Operating Stiffness Controller for the Medical Continuum Robot Based on Impedance Control.

Continuum manipulators can conform to curvilinear paths and manipulate objects in complex environments, which makes it emerging to be applied in minimally invasive surgery (MIS). However, different and controllable operating stiffness of the continuum manipulator is required during different stages of surgery to achieve safe access or stable and precise operation. This work proposes an operating stiffness controller (OSC) for the typical tendon-driven continuum manipulator based on the variable impedance control method with Lagrangian dynamic modeling. This controller can adjust the operating stiffness by modifying the driving forces along the driving tendons of the continuum manipulator without changing its material or structure. The proposed OSC converts the damping and stiffness matrices of the impedance control into variable parameters. This merit allows it to dynamically adjust the operating stiffness of the continuum manipulator according to the desired constant or time-varying stiffness. Furthermore, the OSC stability can be proven based on a Lyapunov function, and its stiffness control performances have been analyzed and evaluated in both simulations and experiments. The OSC controller generated average relevant error values of 7.82% and 3.09% for the operating stiffness control experiments with constant and time-varying desired stiffness, respectively. These experimental results indicate that the OSC has high accuracy, stability, and strong robustness in the operating stiffness control tasks.

A stacked transmembrane electro-chemisorption system connected by hydrophobic gas permeable membranes for on-site utilization of authigenic acid and base to enhance ammonia recovery from wastewater.

The ammonia recovery from wastewater via electrochemical technologies represents a promising way for wastewater treatment, resource recovery, and carbon emissions reduction. However, chemicals consumption and reactors scalability of the existing electrochemical systems have become the key challenges for their development and application. In this study, a stacked transmembrane electro-chemisorption (sTMECS) system was developed to utilize authigenic acid and base on site for enhancing ammonia recovery from wastewater. The easily scaled up system was achieved via innovatively connecting the cathode chamber in a unit with the anode chamber in the adjacent unit by a hydrophobic gas permeable membrane (GPM). Thus, authigenic base at cathodes and authigenic acid at anodes could be utilized as stripper and absorbent on site to enhance the transmembrane chemisorption of ammonia. Continuous power supply, reducing the distances of electrodes to GPM and moderate aeration of the catholyte could promote ammonia recovery. Applied to the ammonia recovery from the simulated urine, the sTMECS under the current density 62.5 A/cm2 with a catholyte aeration rate of 3.2 L/(L⋅min) for operation time 4 h showed the transmembrane ammonia flux of 26.00 g N/(m2·h) and the system energy consumption of 10.5 kWh/kg N. Accordingly, the developed sTMECS system with chemicals saving, easy scale-up and excellent performance shows good prospects in recovering ammonia from wastewater.

Results of a Pilot External Quality Assessment Scheme for Genetic Testing of Newborns with Spinal Muscular Atrophy.

BACKGROUND: This study aims to evaluate the ability of laboratories to perform spinal muscular atrophy (SMA) genetic testing in newborns based on dried blood spot (DBS) samples, and to provide reference data and advance preparation for establishing the pilot external quality assessment (EQA) scheme for SMA genetic testing of newborns in China. METHODS: The pilot EQA scheme contents and evaluation principles of this project were designed by National Center for Clinical Laboratories (NCCL), National Health Commission. Two surveys were carried out in 2022, and 5 batches of blood spots were submitted to the participating laboratory each time. All participating laboratories conducted testing upon receiving samples, and test results were submitted to NCCL within the specified date. RESULTS: The return rates were 75.0% (21/28) and 95.2% (20/21) in the first and second surveys, respectively. The total return rate of the two examinations was 83.7% (41/49). Nineteen laboratories (19/21, 90.5%) had a full score passing on the first survey, while in the second survey twenty laboratories (20/20, 100%) scored full. CONCLUSIONS: This pilot EQA survey provides a preliminary understanding of the capability of SMA genetic testing for newborns across laboratories in China. A few laboratories had technical or operational problems in testing. It is, therefore, of importance to strengthen laboratory management and to improve testing capacity for the establishment of a national EQA scheme for newborn SMA genetic testing.

Gas permeable membrane electrode assembly with in situ utilization of authigenic acid and base for transmembrane electro-chemisorption to enhance ammonia recovery from wastewater.

Ammonia recovery from wastewater is of great significance for aquatic ecology safety, human health and carbon emissions reduction. Electrochemical methods have gained increasing attention since the authigenic base and acid of electrochemical systems can be used as stripper and absorbent for transmembrane chemisorption of ammonia, respectively. However, the separation of electrodes and gas permeable membrane (GPM) significantly restricts the ammonia transfer-transformation process and the authigenic acid-base utilization. To break the restrictions, this study developed a gas permeable membrane electrode assembly (GPMEA), which innovatively integrated anode and cathode on each side of GPM through easy phase inversion of polyvinylidene fluoride binder, respectively. With the GPMEA assembled in a stacked transmembrane electro-chemisorption (sTMECS) system, in situ utilization of authigenic acid and base for transmembrane electro-chemisorption of ammonia was achieved to enhance the ammonia recovery from wastewater. At current density of 60 A/m2, the transmembrane ammonia flux of the GPMEA was 693.0 ± 15.0 g N/(m2·d), which was 86 % and 28 % higher than those of separate GPM and membrane cathode, respectively. The specific energy consumption of the GPMEA was 9.7∼16.1 kWh/kg N, which were about 50 % and 25 % lower than that of separate GPM and membrane cathode, respectively. Moreover, the application of GPMEA in the ammonia recovery from wastewater is easy to scale up in the sTMECS system. Accordingly, with the features of excellent performance, energy saving and easy scale-up, the GPMEA showed good prospects in electrochemical ammonia recovery from wastewater.

Association Between Sleep Quality and Cognitive Symptoms in Patients with Major Depressive Disorder.

Cognitive symptoms and sleep disturbance (SD) are common non-mood-related symptoms of major depressive disorder (MDD). In clinical practice, both cognitive symptoms and SD are related to MDD progression. However, there are only a few studies investigating the connection between cognitive symptoms and SD in patients with MDD, and only preliminary evidence suggests a significant association between cognitive symptoms and SD in patients with mood disorders. This study investigates the relationship between cognitive symptoms and sleep quality in patients with major depressive disorder. Patients (n = 20) with MDD were enrolled; their mean Hamilton Depression Scale-17 score was 21.95 (±2.76). Gold standard polysomnography (PSG) was used to assess sleep quality, and the validated THINC-integrated tool (the cognitive screening tool) was used to evaluate cognitive function in MDD patients. Overall, the results showed significant correlations between the cognitive screening tool's total score and sleep latency, wake-after-sleep onset, and sleep efficiency. These findings indicate that cognitive symptoms are associated with poor sleep quality among patients with MDD.

Epigenetic priming by hypomethylation enhances the immunogenic potential of tolinapant in T-cell lymphoma.

Programmed cell death mechanisms are important for the regulation of tumor development and progression. Evasion of and resistance to apoptosis are significant factors in tumorigenesis and drug resistance. Bypassing apoptotic pathways and eliciting another form of regulated cell death, namely necroptosis, an immunogenic cell death (ICD), may override apoptotic resistance. Here, we present the mechanistic rationale for combining tolinapant, an antagonist of the inhibitor of apoptosis proteins (IAP), with decitabine, a hypomethylating agent (HMA), in T-cell lymphoma (TCL). Tolinapant treatment alone of TCL cells in vitro and in syngeneic in vivo models demonstrated that ICD markers can be upregulated, and we have shown that epigenetic priming with decitabine further enhances this effect. The clinical relevance of ICD markers was confirmed by the direct measurement of plasma proteins from peripheral TCL patients treated with tolinapant. We showed increased levels of necroptosis in TCL lines, along with the expression of cancer-specific antigens (such as cancer testis antigens) and increases in genes involved in interferon signaling induced by HMA treatment, together deliver a strong adaptive immune response to the tumor. These results highlight the potential of a decitabine and tolinapant combination for TCL and could lead to clinical evaluation.

Starch and sucrose metabolism plays an important role in the stem development in Medicago sativa.

The forage quality of alfalfa (Medicago sativa ) stems is greater than the leaves. Sucrose hydrolysis provides energy for stem development, with starch being enzymatically converted into sucrose to maintain energy homeostasis. To understand the physiological and molecular networks controlling stem development, morphological characteristics and transcriptome profiles in the stems of two alfalfa cultivars (Zhungeer and WL168) were investigated. Based on transcriptome data, we analysed starch and sugar contents, and enzyme activity related to starch-sugar interconversion. Zhungeer stems were shorter and sturdier than WL168, resulting in significantly higher mechanical strength. Transcriptome analysis showed that starch and sucrose metabolism were significant enriched in the differentially expressed genes of stems development in both cultivars. Genes encoding INV , bglX , HK , TPS and glgC downregulated with the development of stems, while the gene encoding was AMY upregulated. Weighted gene co-expression network analysis revealed that the gene encoding glgC was pivotal in determining the variations in starch and sucrose contents between the two cultivars. Soluble carbohydrate, sucrose, and starch content of WL168 were higher than Zhungeer. Enzyme activities related to sucrose synthesis and hydrolysis (INV, bglX, HK, TPS) showed a downward trend. The change trend of enzyme activity was consistent with gene expression. WL168 stems had higher carbohydrate content than Zhungeer, which accounted for more rapid growth and taller plants. WL168 formed hollow stems were formed during rapid growth, which may be related to the redistribution of carbohydrates in the pith tissue. These results indicated that starch and sucrose metabolism play important roles in the stem development in alfalfa.

Connectome reorganization associated with temporal lobe pathology and its surgical resection.

Network neuroscience offers a unique framework to understand the organizational principles of the human brain. Despite recent progress, our understanding of how the brain is modulated by focal lesions remains incomplete. Resection of the temporal lobe is the most effective treatment to control seizures in pharmaco-resistant temporal lobe epilepsy (TLE), making this syndrome a powerful model to study lesional effects on network organization in young and middle-aged adults. Here, we assessed the downstream consequences of a focal lesion and its surgical resection on the brain's structural connectome, and explored how this reorganization relates to clinical variables at the individual patient level. We included adults with pharmaco-resistant TLE (n = 37) who underwent anterior temporal lobectomy between two imaging time points, as well as age- and sex-matched healthy controls who underwent comparable imaging (n = 31). Core to our analysis was the projection of high-dimensional structural connectome data-derived from diffusion MRI tractography from each subject-into lower-dimensional gradients. We then compared connectome gradients in patients relative to controls before surgery, tracked surgically-induced connectome reconfiguration from pre- to postoperative time points, and examined associations to patient-specific clinical and imaging phenotypes. Before surgery, individuals with TLE presented with marked connectome changes in bilateral temporo-parietal regions, reflecting an increased segregation of the ipsilateral anterior temporal lobe from the rest of the brain. Surgery-induced connectome reorganization was localized to this temporo-parietal subnetwork, but primarily involved postoperative integration of contralateral regions with the rest of the brain. Using a partial least-squares analysis, we uncovered a latent clinical-imaging signature underlying this pre- to postoperative connectome reorganization, showing that patients who displayed postoperative integration in bilateral fronto-occipital cortices also had greater preoperative ipsilateral hippocampal atrophy, lower seizure frequency, and secondarily generalized seizures. Our results bridge the effects of focal brain lesions and their surgical resections with large-scale network reorganization and inter-individual clinical variability, thus offering new avenues to examine the fundamental malleability of the human brain.

Efficacy Analysis of Pneumocystoscopic Cohen Surgery for Lower Ureteral Lesions in Children.

Objective: This study aims to evaluate the clinical effects, safety, and recovery associated with minimally invasive pneumocystoscopic ureterovesical reimplantation (Cohen) compared to open surgery for treating lower ureteral lesions in children. Methods: The data of 60 sick children with lower ureteral lesions were retrospectively analyzed, who underwent ureterovesical reimplantation in our hospital from January 2017 to June 2022. All of them went through a Cohen procedure. Sixty children were divided into two groups according to surgical approaches: open surgery group (n=30) and pneumocystoscopic group (n=30). There were 26 boys and 4 girls in the open surgery group, aged from 3 months and 7 days old to 8 years and 5 months old, with 18 cases of lower ureteral stenosis and 12 cases of ureteral reflux, while there were 20 boys and 10 girls in the pneumocystoscopic group, aged from 7 months and 2 days old to 10 years and 9 months old, with 18 cases of lower ureteral stenosis and 12 cases of ureteral reflux. We retrospectively analyzed data from 60 children, comparing outcomes such as intraoperative complications, postoperative recovery, and long-term efficacy between open surgery and pneumocystoscopic approaches. Results: The pneumocystoscopic group exhibited smaller surgical incisions, reduced intraoperative bleeding, and shorter hospital stays compared to the open surgery group, although the operation duration was longer. Both groups showed similar postoperative ureter diameters and long-term recovery, with minimal occurrences of ureteral reflux relapse. Conclusion: Pneumocystoscopic ureterovesical reimplantation (Cohen) demonstrated safety, efficacy, minimal invasiveness, and faster recovery in treating lower ureteral lesions in children, with aesthetic benefits and fewer complications, making it a promising approach for pediatric urological surgeries.

Comparison of the efficacy of Aeromonas veronii ΔhisJ vaccine in Carassius auratus via different immunization routes.

Introdction: Aeromonas veronii is a significant pathogen to various aquatic life. Infections in fish can lead to high mortality rates, causing substantial economic losses in aquaculture. Vaccination is proposed as a substitute for antibiotics in aquaculture to decrease disease-related mortality and morbidity. Our study previously constructed a hisJ-deleted strain of A. veronii, which provided protective effect to Loach. Methods: To further assess the vaccine's applicability, this study evaluated its genetic stability and safety, and the immune protective effects in Carassius auratus through four distinct administration routes: intraperitoneal injection, intramuscular injection, oral administration, and immersion, to determine the efficacy of these administration routes. Results: The results showed that the vaccine remained genetically stable after 45 generations. Immunization via these administration routes was safe for Carassius auratus, with intraperitoneal and intramuscular injections causing stronger adverse reactions. Immersion immunization resulted in mild adverse reactions, and no significant adverse reactions were observed following oral immunization. Immunizing Carassius auratus at safe concentrations via these routes enhanced the phagocytic activity in serum, increased the levels of non-specific immune-related enzymes (ACP, AKP, C3, C4, LZM, SOD, and IgM), and improved specific serum antibody levels. It also elevated levels of cytokines related to inflammatory responses (IL-1ß, IL-10, TNF-α, TGF-ß) in organ tissues (liver, spleen, kidney, mid-post intestine, and gills). The survival rates of Carassius auratus were measured after challenging with the virulent strain A. veronii TH0426, resulting in the relative survival rates of 64% for Intraperitoneal vaccine group, 56% for Intramuscular vaccine group, 52% for oral vaccine group, and 48% for immersion vaccine group. Analysis of bacterial load in the liver, spleen, and kidney post-challenge showed a decreasing trend in the control group, indicating that the vaccine strain ΔhisJ could gradually restrict the rapid proliferation of bacteria in these tissues, thereby providing a certain level of immune protection against A. veronii. Discussion: In brief, the vaccine strain ΔhisJ can serve as a safe live attenuated vaccine for Carassius auratus, and this study lays the foundation for the development of live attenuated vaccines against Aeromonas veronii.

Phenylspirodrimane with Moderate Reversal Effect of Multidrug Resistance Isolated from the Deep-Sea Fungus Stachybotrys sp. 3A00409.

Two new phenylspirodrimanes, stachybotrins K and L (1 and 2), together with eight known analogues (3-10), were isolated from deep-sea-derived Stachybotrys sp. MCCC 3A00409. Their structures were determined by extensive NMR data and mass spectroscopic analysis. Absolute configurations of new compounds were determined through a comparison of their circular dichroism (CD) spectra with other reported compounds. The possible reversal effects of all compounds were assayed in the resistant cancer cell lines. Stachybotrysin B (8) can reverse multidrug resistance (MDR) in ABCB1-overexpression cells (KBv200, Hela/VCR) at the non-cytotoxic concentration. Doxorubicin accumulation assay and molecular-docking analysis reveal that the mechanism of its reversal MDR effect may be related to the increase in the intracellular concentration of substrate anticancer drugs.

Seasonal characterization of chemical and optical properties of water-soluble organic aerosol in Beijing.

Water-soluble organic aerosol (WSOA) plays a crucial role in altering radiative forcing and impacting human health. However, our understanding of the seasonal variations of WSOA in Chinese megacities after the three-year clean air action plan is limited. In this study, we analyzed PM2.5 filter samples collected over one year (2020-2021) in Beijing to characterize the seasonal changes in the chemical and optical properties of WSOA using an offline aerosol mass spectrometer along with spectroscopy techniques. The mean mass concentration of WSOA during the observation period was 8.84 ± 7.12 µg m-3, constituting approximately 64-67 % of OA. Our results indicate the contribution of secondary OA (SOA) increased by 13-28 % due to a substantial reduction in primary emissions after the clean air action plan. The composition of WSOA exhibited pronounced seasonal variations, with a predominant contribution from less oxidized SOA in summer (61 %) and primary OA originating from coal combustion and biomass burning during the heating season (34 %). The mass absorption efficiency of WSOA at 365 nm in winter was nearly twice that in summer, suggesting that WSOA from primary emissions possesses a stronger light-absorbing capability than SOA. On average, water-soluble brown carbon accounted for 33-48 % of total brown carbon absorption. Fluorescence analysis revealed humic-like substances as the most significant fluorescence component of WSOA, constituting 82 %. Furthermore, both absorption and fluorescence chromophores were associated with nitrogen-containing compounds, highlighting the role of nitrogen-containing species in influencing the optical properties of WSOA. The results are important for chemical transport models to accurately simulate the WSOA and its climate effects.

Dual targetable drug delivery system based on cell membrane camouflaged liposome for enhanced tumor targeting and improved anti-tumor efficiency.

Receptor and ligand binding mediated targeted drug delivery systems (DDS) sometimes fail to target to tumor sites, and cancer cell membrane (CCM) coating can overcome the dilemma of immune clearance and nonspecific binding of DDS in vivo. In order to enhance the targeting ability and improve the anti-tumor effect, a dual targeting DDS was established based on U87MG CCM mediated homologous targeting and cyclic peptide RGD mediated active targeting. The DDS was prepared by coating RGD doped CCM onto doxorubicin (DOX) loaded liposomes. The homologous and active dual targeting ability endowed the DDS (RGD-CCM-LP-DOX) exhibited superior cancer cell affinity, improved tissue distribution and enhanced anti-tumor effects. In vivo pharmacodynamic studies revealed that RGD-CCM-LP-DOX exhibited superior therapeutic effect compared with homologous targeting CCM-LP-DOX and non-targetable LP-DOX injection. H&E staining, Ki 67 staining and TUNEL staining confirmed that RGD-CCM-LP-DOX not only increased anti-tumor efficacy, but also reduced tissue toxicity by changing the distribution in vivo. The experimental results showed that the RGD doped CCM camouflaged liposome DDS is a better choice for chemotherapeutics delivery.

Atypical connectome topography and signal flow in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common pharmaco-resistant epilepsy in adults. While primarily associated with mesiotemporal pathology, recent evidence suggests that brain alterations in TLE extend beyond the paralimbic epicenter and impact macroscale function and cognitive functions, particularly memory. Using connectome-wide manifold learning and generative models of effective connectivity, we examined functional topography and directional signal flow patterns between large-scale neural circuits in TLE at rest. Studying a multisite cohort of 95 patients with TLE and 95 healthy controls, we observed atypical functional topographies in the former group, characterized by reduced differentiation between sensory and transmodal association cortices, with most marked effects in bilateral temporo-limbic and ventromedial prefrontal cortices. These findings were consistent across all study sites, present in left and right lateralized patients, and validated in a subgroup of patients with histopathological validation of mesiotemporal sclerosis and post-surgical seizure freedom. Moreover, they were replicated in an independent cohort of 30 TLE patients and 40 healthy controls. Further analyses demonstrated that reduced differentiation related to decreased functional signal flow into and out of temporolimbic cortical systems and other brain networks. Parallel analyses of structural and diffusion-weighted MRI data revealed that topographic alterations were independent of TLE-related cortical thinning but partially mediated by white matter microstructural changes that radiated away from paralimbic circuits. Finally, we found a strong association between the degree of functional alterations and behavioral markers of memory dysfunction. Our work illustrates the complex landscape of macroscale functional imbalances in TLE, which can serve as intermediate markers bridging microstructural changes and cognitive impairment.

Procyanidin B2 alleviates oxidized low-density lipoprotein-induced cell injury, inflammation, monocyte chemotaxis, and oxidative stress by inhibiting the nuclear factor kappa-B pathway in human umbilical vein endothelial cells.

BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) can initiate and affect almost all atherosclerotic events including endothelial dysfunction. In this text, the role and underlying molecular basis of procyanidin B2 (PCB2) with potential anti-oxidant and anti-inflammatory activities in ox-LDL-induced HUVEC injury were examined. METHODS: HUVECs were treated with ox-LDL in the presence or absence of PCB2. Cell viability and apoptotic rate were examined by CCK-8 assay and flow cytometry, respectively. The mRNA and protein levels of genes were tested by RT-qPCR and western blot assays, respectively. Potential downstream targets and pathways of apple procyanidin oligomers were examined by bioinformatics analysis for the GSE9647 dataset. The effect of PCB2 on THP-1 cell migration was examined by recruitment assay. The effect of PCB2 on oxidative stress was assessed by reactive oxygen species (ROS) level, malondialdehyde (MDA) content, and mitochondrial membrane potential (MMP). RESULTS: ox-LDL reduced cell viability, induced cell apoptosis, and facilitated the expression of oxidized low-density lipoprotein receptor 1 (LOX-1), C-C motif chemokine ligand 2 (MCP-1), vascular cell adhesion protein 1 (VCAM-1) in HUVECs. PCB2 alleviated ox-LDL-induced cell injury in HUVECs. Apple procyanidin oligomers triggered the differential expression of 592 genes in HUVECs (|log2fold-change| > 0.58 and adjusted p-value < 0.05). These dysregulated genes might be implicated in apoptosis, endothelial cell proliferation, inflammation, and monocyte chemotaxis. PCB2 inhibited C-X-C motif chemokine ligand 1/8 (CXCL1/8) expression and THP-1 cell recruitment in ox-LDL-stimulated HUVECs. PCB2 inhibited ox-LDL-induced oxidative stress and nuclear factor kappa-B (NF-κB) activation in HUVECs. CONCLUSION: PCB2 weakened ox-LDL-induced cell injury, inflammation, monocyte recruitment, and oxidative stress by inhibiting the NF-κB pathway in HUVECs.

The effect of electromyographic feedback functional electrical stimulation on the plantar pressure in stroke patients with foot drop.

Purpose: The purpose of this study was to observe, using Footscan analysis, the effect of electromyographic feedback functional electrical stimulation (FES) on the changes in the plantar pressure of drop foot patients. Methods: This case-control study enrolled 34 stroke patients with foot drop. There were 17 cases received FES for 20 min per day, 5 days per week for 4 weeks (the FES group) and the other 17 cases only received basic rehabilitations (the control group). Before and after 4 weeks, the walking speed, spatiotemporal parameters and plantar pressure were measured. Results: After 4 weeks treatments, Both the FES and control groups had increased walking speed and single stance phase percentage, decreased step length symmetry index (SI), double stance phase percentage and start time of the heel after 4 weeks (p < 0.05). The increase in walking speed and decrease in step length SI in the FES group were more significant than the control group after 4 weeks (p < 0.05). The FES group had an increased initial contact phase, decreased SI of the maximal force (Max F) and impulse in the medial heel after 4 weeks (p < 0.05). Conclusion: The advantages of FES were: the improvement of gait speed, step length SI, and the enhancement of propulsion force were more significant. The initial contact phase was closer to the normal range, which implies that the control of ankle dorsiflexion was improved. The plantar dynamic parameters between the two sides of the foot were more balanced than the control group. FES is more effective than basic rehabilitations for stroke patients with foot drop based on current spatiotemporal parameters and plantar pressure results.

Influences of Heat Stress on Glutamate Transmission-Dependent Expression Levels of IL-1ß and IL-18 in BV-2 Microglial Cells.

OBJECTIVE: This study aimed to explore the impact of heat stress (HS) on glutamate transmission-dependent expression levels of interleukin-1ß (IL-1ß) and IL-18 in BV-2 microglial cells. METHODS: BV-2 microglial cells were cultured in vitro, with cells maintained at 37 °C serving as the control. The HS group experienced incubation at 40 °C for 1 h, followed by further culturing at 37 °C for 6 or 12 h. The experimental group was pre-incubated with glutamate, the glutamate antagonist riluzole, or the mGluR5 agonist, 2-Chloro-5-hydroxyphenylglycine (CHPG), before HS. Glutamate content in BV-2 culture supernatant was assessed using colorimetric assay. Moreover, mRNA expression levels of EAAT3 and/or mGluR5 in BV-2 cells were determined via quantitative polymerase chain reaction. Interleukins (IL-1ß and IL-18) in cell culture supernatant were measured using enzyme-linked immunosorbent assay. Western blot analysis was employed to assess protein levels of IL-1ß and IL-18 in BV-2 cells. RESULTS: HS induced a significant release of glutamate and increased the expression levels of mGluR5 and EAAT3 in BV-2 cells. It also triggered the expression levels and release of pro-inflammatory factors, such as IL-1ß and IL-18, synergizing with the effects of glutamate treatment. Preincubation with both riluzole and CHPG significantly reduced HS-induced glutamate release and mitigated the increased expression levels and release of IL-1ß and IL-18 induced by HS. CONCLUSION: The findings confirmed that microglia could be involved in HS primarily through glutamate metabolisms, influencing the expression levels and release of IL-1ß and IL-18.

Continuous Motion Intention Prediction Using sEMG for Upper-Limb Rehabilitation: A Systematic Review of Model-Based and Model-Free Approaches.

Upper limb functional impairments persisting after stroke significantly affect patients' quality of life. Precise adjustment of robotic assistance levels based on patients' motion intentions using sEMG signals is crucial for active rehabilitation. This paper systematically reviews studies on continuous prediction of upper limb single joints and multi-joint combinations motion intention using Model-Based (MB) and Model-Free (MF) approaches over the past decade, based on 186 relevant studies screened from six major electronic databases. The findings indicate ongoing challenges in terms of subject composition, algorithm robustness and generalization, and algorithm feasibility for practical applications. Moreover, it suggests integrating the strengths of both MB and MF approaches to improve existing algorithms. Therefore, future research should further explore personalized MB-MF combination methods incorporating deep learning, attention mechanisms, muscle synergy features, motor unit features, and closed-loop feedback to achieve precise, real-time, and long-duration prediction of multi-joint complex movements, while further refining the transfer learning strategy for rapid algorithm deployment across days and subjects. Overall, this review summarizes the current research status, significant findings, and challenges, aiming to inspire future research on predicting upper limb motion intentions based on sEMG.

The Recognition Pathway of the SARS-CoV-2 Spike Receptor-Binding Domain to Human Angiotensin-Converting Enzyme 2.

COVID-19 caused by SARS-CoV-2 has spread around the world. The receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 is a critical component that directly interacts with host ACE2. Here, we simulate the ACE2 recognition processes of RBD of the WT, Delta, and OmicronBA.2 variants using our recently developed supervised Gaussian accelerated molecular dynamics (Su-GaMD) approach. We show that RBD recognizes ACE2 through three contact regions (regions I, II, and III), which aligns well with the anchor-locker mechanism. The higher binding free energy in State d of the RBDOmicronBA.2-ACE2 system correlates well with the increased infectivity of OmicronBA.2 in comparison with other variants. For RBDDelta, the T478K mutation affects the first step of recognition, while the L452R mutation, through its nearby Y449, affects the RBDDelta-ACE2 binding in the last step of recognition. For RBDOmicronBA.2, the E484A mutation affects the first step of recognition, the Q493R, N501Y, and Y505H mutations affect the binding free energy in the last step of recognition, mutations in the contact regions affect the recognition directly, and other mutations indirectly affect recognition through dynamic correlations with the contact regions. These results provide theoretical insights for RBD-ACE2 recognition and may facilitate drug design against SARS-CoV-2.