Prediction of Spasticity through Upper Limb Active Range of Motion in Stroke Survivors: A Generalized Estimating Equation Model.

BACKGROUND: We aim to study the association between spasticity and active range of motion (ROM) during four repetitive functional tasks such as cone stacking (CS), fast flexion-extension (FFE), fast ball squeezing (FBS), and slow ball squeezing (SBS), and predicted spasticity models. METHODS: An experimental study with control and stroke groups was conducted in a Medical Center. A total of sixty-four participants, including healthy control (n = 22; average age (years) = 54.68 ± 9.63; male/female = 12/10) and chronic stroke survivors (n = 42; average age = 56.83 ± 11.74; male/female = 32/10) were recruited. We employed a previously developed smart glove device mounted with multiple inertial measurement unit (IMU) sensors on the upper limbs of healthy and chronic stroke individuals. The recorded ROMs were used to predict subjective spasticity through generalized estimating equations (GEE) for the affected side. RESULTS: The models have significant (p ≤ 0.05 *) prediction of spasticity for the elbow, thumb, index, middle, ring, and little fingers. Overall, during SBS and FFE activities, the maximum number of upper limb joints attained the greater average ROMs. For large joints, the elbow during CS and the wrist during FFE have the highest average ROMs, but smaller joints and the wrist have covered the highest average ROMs during FFE, FBS, and SBS activities. CONCLUSIONS: Thus, it is concluded that CS can be used for spasticity assessment of the elbow, FFE for the wrist, and SBS, FFE, and FBS activities for the thumb and finger joints in chronic stroke survivors.

Development of AAV-delivered broadly neutralizing anti-human ACE2 antibodies against SARS-CoV-2 variants.

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in the emergence of new variants that are resistant to existing vaccines and therapeutic antibodies, has raised the need for novel strategies to combat the persistent global COVID-19 epidemic. In this study, a monoclonal anti-human angiotensin-converting enzyme 2 (hACE2) antibody, ch2H2, was isolated and humanized to block the viral receptor-binding domain (RBD) binding to hACE2, the major entry receptor of SARS-CoV-2. This antibody targets the RBD-binding site on the N terminus of hACE2 and has a high binding affinity to outcompete the RBD. In vitro, ch2H2 antibody showed potent inhibitory activity against multiple SARS-CoV-2 variants, including the most antigenically drifted and immune-evading variant Omicron. In vivo, adeno-associated virus (AAV)-mediated delivery enabled a sustained expression of monoclonal antibody (mAb) ch2H2, generating a high concentration of antibodies in mice. A single administration of AAV-delivered mAb ch2H2 significantly reduced viral RNA load and infectious virions and mitigated pulmonary pathological changes in mice challenged with SARS-CoV-2 Omicron BA.5 subvariant. Collectively, the results suggest that AAV-delivered hACE2-blocking antibody provides a promising approach for developing broad-spectrum antivirals against SARS-CoV-2 and potentially other hACE2-dependent pathogens that may emerge in the future.

Identification of the perpetrator imperatorin in Xin-yi-san-theophylline interaction: observed and predicted herb-drug interaction in rats.

OBJECTIVES: Theophylline is a bronchodilator with a narrow therapeutic index and primarily metabolised by cytochrome P450 (CYP) 1A2. Xin-yi-san (XYS) is a herbal formula frequently used to ameliorate nasal inflammation. This study aimed to investigate the effects of XYS and its ingredient, imperatorin, on theophylline pharmacokinetics in rats. METHODS: The kinetics of XYS- and imperatorin-mediated inhibition of theophylline oxidation were determined. Pharmacokinetics of theophylline were analysed. Comparisons were made with the CYP1A2 inhibitor, fluvoxamine. KEY FINDINGS: XYS extract and its ingredient, imperatorin, non-competitively inhibited theophylline oxidation. Fluvoxamine (50 and 100 mg/kg) and XYS (0.5 and 0.9 g/kg) significantly prolonged the time to reach the maximum plasma concentration (tmax) of theophylline by 3-10 fold. In a dose-dependent manner, XYS and imperatorin (0.1-10 mg/kg) treatments significantly decreased theophylline clearance by 27-33% and 19-56%, respectively. XYS (0.9 g/kg) and imperatorin (10 mg/kg) significantly prolonged theophylline elimination half-life by 29% and 142%, respectively. Compared with the increase (51-112%) in the area under curve (AUC) of theophylline by fluvoxamine, the increase (27-57%) by XYS was moderate. CONCLUSIONS: XYS decreased theophylline clearance primarily through imperatorin-suppressed theophylline oxidation. Further human studies are essential for the dose adjustment in the co-medication regimen.

Oral ellagic acid attenuated LPS-induced neuroinflammation in rat brain: MEK1 interaction and M2 microglial polarization.

Ellagic acid, the marker component of peels of Punica granatum L., is known traditionally to treat traumatic hemorrhage. In this study, the cellular mechanism underlying ellagic acid-induced anti-inflammation was investigated using lipopolysaccharides (LPSs) as a neuroinflammation inducer. Our in vitro data showed that LPS (1 µg/mL) consistently phosphorylated ERK and induced neuroinflammation, such as elevation in tumor necrosis factor-α (TNF-α) and nitric oxide production in treated BV-2 cells. Incubation of ellagic acid significantly inhibited LPS-induced ERK phosphorylation and subsequent neuroinflammation in treated BV-2 cells. Furthermore, our in vivo study of neuroinflammation employed an intranigral infusion of LPS that resulted in a time-dependent elevation in phosphorylated ERK levels in the infused substantia nigra (SN). Oral administration of ellagic acid (100 mg/kg) significantly attenuated LPS-induced ERK phosphorylation. A four-day treatment of ellagic acid did not alter LPS-induced ED-1 elevation but ameliorated LPS-induced reduction in CD206 and arginase-1 (two biomarkers of M2 microglia). A seven-day treatment of ellagic acid abolished LPS-induced increases in heme-oxygenase-1, cyclo-oxygenase 2, and α-synuclein trimer levels (a pathological hallmark) in the infused SN. At the same time, ellagic acid attenuated LPS-induced increases in active caspase 3 and receptor-interacting protein kinase-3 levels (respective biomarkers of apoptosis and necroptosis) as well as reduction in tyrosine hydroxylase-positive cells in the infused SN. In silico analysis showed that ellagic acid binds to the catalytic site of MEK1. Our data suggest that ellagic acid is capable of inhibiting MEK1-ERK signaling and then attenuated LPS-induced neuroinflammation, protein aggregation, and programmed cell deaths. Moreover, M2 microglial polarization is suggested as a novel antineuroinflammatory mechanism in the ellagic acid-induced neuroprotection.

System Based on Artificial Intelligence Edge Computing for Detecting Bedside Falls and Sleep Posture.

Bedside falls and pressure ulcers are crucial issues in geriatric care. Although many bedside monitoring systems have been proposed, they are limited by the computational complexity of their algorithms. Moreover, most of the data collected by the sensors of these systems must be transmitted to a back-end server for calculation. With an increase in the demand for the Internet of Things, problems such as higher cost of bandwidth and overload of server computing are faced when using the aforementioned systems. To reduce the server workload, certain computing tasks must be offloaded from cloud servers to edge computing platforms. In this study, a bedside monitoring system based on neuromorphic computing hardware was developed to detect bedside falls and sleeping posture. The artificial intelligence neural network executed on the back-end server was simplified and used on an edge computing platform. An integer 8-bit-precision neural network model was deployed on the edge computing platform to process the thermal image captured by the thermopile array sensing element to conduct sleep posture classification and bed position detection. The bounding box of the bed was then converted into the features for posture classification correction to correct the posture. In an experimental evaluation, the accuracy rate, inferencing speed, and power consumption of the developed system were 94.56%, 5.28 frames per second, and 1.5 W, respectively. All the calculations of the developed system are conducted on an edge computing platform, and the developed system only transmits fall events to the back-end server through Wi-Fi and protects user privacy.

A receptor-binding domain-based nanoparticle vaccine elicits durable neutralizing antibody responses against SARS-CoV-2 and variants of concern.

Numerous vaccines have been developed to address the current COVID-19 pandemic, but safety, cross-neutralizing efficacy, and long-term protectivity of currently approved vaccines are still important issues. In this study, we developed a subunit vaccine, ASD254, by using a nanoparticle vaccine platform to encapsulate the SARS-CoV-2 spike receptor-binding domain (RBD) protein. As compared with the aluminum-adjuvant RBD vaccine, ASD254 induced higher titers of RBD-specific antibodies and generated 10- to 30-fold more neutralizing antibodies. Mice vaccinated with ASD254 showed protective immune responses against SARS-CoV-2 challenge, with undetectable infectious viral loads and reduced typical lesions in lung. Besides, neutralizing antibodies in vaccinated mice lasted for at least one year and were effective against various SARS-CoV-2 variants of concern, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Furthermore, particle size, polydispersity index, and zeta-potential of ASD254 remained stable after 8-month storage at 4°C. Thus, ASD254 is a promising nanoparticle vaccine with good immunogenicity and stability to be developed as an effective vaccine option in controlling upcoming waves of COVID-19.

SRT1720 as an SIRT1 activator for alleviating paraquat-induced models of Parkinson's disease.

Epidemiological studies have linked herbicides and Parkinson's disease (PD), with the strongest associations resulting from long exposure durations. Paraquat (PQ), an herbicide, induces PD-like syndromes and has widely been accepted as a PD mimetic. Currently, there is still no cure to prevent the progression of PD, and the search for effective therapeutic ways is urgent. Recently, the impairing activity of sirtuins (SIRTs), such as SIRT1, may correlate with PD etiology. However, the nonspecificity of SIRT1 agonists has made the protective mechanisms against PD unclear and hampered the therapeutic application of SIRT1. Thus, this study investigated the protective mechanism and therapeutic potential of SRT1720, a more specific agonist for SIRT1 synthesized by Sirtris, in alleviating the toxicity of PQ-induced cellular and animal models of PD. Here we show that SRT1720 alleviates PQ-induced toxicity in cell and animal models. Genetic silencing and pharmacological inhibition of SIRT1 attenuated SRT1720's protection against PQ-induced toxicity. Moreover, SRT1720 not only attenuated PQ-induced increased oxidative stress and mitochondrial free radical formations but also decreased mitochondrial membrane potential. Furthermore, SRT1720 reversed PQ-induced decreased PGC-1α levels and mitochondrial biogenesis. Although PQ and SRT1720 elevated NRF2 and antioxidative enzyme levels, only PQ decreased antioxidative enzyme activity but not SRT1720. NRF2 and PGC-1α silencing attenuated SRT1720 protection against PQ-induced toxicity. SRT1720 targeted SIRT1 and activated downstream PGC-1α and NRF2 signalings to prevent PQ-induced toxicity involving oxidative stress and mitochondrial dysfunction. Thus, SRT1720 might have therapeutic potential in preventing PD.

AI-Based Automatic System for Assessing Upper-Limb Spasticity of Patients with Stroke Through Voluntary Movement.

Spasticity is a common complication for patients with stroke, but only few studies investigate the relation between spasticity and voluntary movement. This study proposed a novel automatic system for assessing the severity of spasticity (SS) of four upper-limb joints, including the elbow, wrist, thumb, and fingers, through voluntary movements. A wearable system which combined 19 inertial measurement units and a pressure ball was proposed to collect the kinematic and force information when the participants perform four tasks, namely cone stacking (CS), fast flexion and extension (FFE), slow ball squeezing (SBS), and fast ball squeezing (FBS). Several time and frequency domain features were extracted from the collected data, and two feature selection approaches based on recursive feature elimination were adopted to select the most influential features. The selected features were input into five machine learning techniques for assessing the SS for each joint. The results indicated that using CS task to assess the SS of elbow and fingers and using FBS task to assess the SS of thumb and wrist can reach the highest weighted-average F1-score. Furthermore, the study also concluded that FBS is the optimal task for assessing all the four upper-limb joints. The overall result shown that the proposed automatic system can assess four upper-limb joints through voluntary movements accurately, which is a breakthrough of finding the relation between spasticity and voluntary movement.

Design of a Multi-Sensor System for Exploring the Relation between Finger Spasticity and Voluntary Movement in Patients with Stroke.

A novel wearable multi-sensor data glove system is developed to explore the relation between finger spasticity and voluntary movement in patients with stroke. Many stroke patients suffer from finger spasticity, which is detrimental to their manual dexterity. Diagnosing and assessing the degrees of spasticity require neurological testing performed by trained professionals to estimate finger spasticity scores via the modified Ashworth scale (MAS). The proposed system offers an objective, quantitative solution to assess the finger spasticity of patients with stroke and complements the manual neurological test. In this work, the hardware and software components of this system are described. By requiring patients to perform five designated tasks, biomechanical measurements including linear and angular speed, acceleration, and pressure at every finger joint and upper limb are recorded, making up more than 1000 features for each task. We conducted a preliminary clinical test with 14 subjects using this system. Statistical analysis is performed on the acquired measurements to identify a small subset of features that are most likely to discriminate a healthy patient from patients suffering from finger spasticity. This encouraging result validates the feasibility of this proposed system to quantitatively and objectively assess finger spasticity.

Development of a Smartphone-Based mHealth Platform for Telerehabilitation.

Telerehabilitation is becoming increasingly valuable as a method for expanding medical services. The smartphone-based mHealth platform (SMPT) has been developed to provide high-quality remote rehabilitation through a smartphone and inertial measurement units. The SMPT uses smartphone as a main platform with connection to medical backend server to provide telerehabilitation. Patients would be referred to therapists to receive a tutorial of exercise technique prior to conducting their home exercise. Once patients begin their home exercises, they can report any problems instantly through the SMPT. The medical staff can adjust the exercise program according to patient feedback and the data collected by the SMPT. After completing the exercise program, patients visit their clinician for re-evaluation. A Service User Technology Acceptability Questionnaire from both medical professional and public perspective revealed a high level of agreement on enhanced care, increased accessibility, and satisfaction and a moderate level of agreement on the use of this platform as a substitute for traditional rehabilitation. Concerns about privacy and discomfort were low in the medical professional and public groups. Concerns about care personnel were also significantly different between the two groups. The SMPT is a promising system for providing telerehabilitation as an adjunct to traditional rehabilitation, which may result in improved outcomes compared with those achieved when using traditional rehabilitation alone.

A critical overview of current progress for COVID-19: development of vaccines, antiviral drugs, and therapeutic antibodies.

The novel coronavirus disease (COVID-19) pandemic remains a global public health crisis, presenting a broad range of challenges. To help address some of the main problems, the scientific community has designed vaccines, diagnostic tools and therapeutics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The rapid pace of technology development, especially with regard to vaccines, represents a stunning and historic scientific achievement. Nevertheless, many challenges remain to be overcome, such as improving vaccine and drug treatment efficacies for emergent mutant strains of SARS-CoV-2. Outbreaks of more infectious variants continue to diminish the utility of available vaccines and drugs. Thus, the effectiveness of vaccines and drugs against the most current variants is a primary consideration in the continual analyses of clinical data that supports updated regulatory decisions. The first two vaccines granted Emergency Use Authorizations (EUAs), BNT162b2 and mRNA-1273, still show more than 60% protection efficacy against the most widespread current SARS-CoV-2 variant, Omicron. This variant carries more than 30 mutations in the spike protein, which has largely abrogated the neutralizing effects of therapeutic antibodies. Fortunately, some neutralizing antibodies and antiviral COVID-19 drugs treatments have shown continued clinical benefits. In this review, we provide a framework for understanding the ongoing development efforts for different types of vaccines and therapeutics, including small molecule and antibody drugs. The ripple effects of newly emergent variants, including updates to vaccines and drug repurposing efforts, are summarized. In addition, we summarize the clinical trials supporting the development and distribution of vaccines, small molecule drugs, and therapeutic antibodies with broad-spectrum activity against SARS-CoV-2 strains.

A booster dose of Delta × Omicron hybrid mRNA vaccine produced broadly neutralizing antibody against Omicron and other SARS-CoV-2 variants.

BACKGROUND: With the continuous emergence of new SARS-CoV-2 variants that feature increased transmission and immune escape, there is an urgent demand for a better vaccine design that will provide broader neutralizing efficacy. METHODS: We report an mRNA-based vaccine using an engineered "hybrid" receptor binding domain (RBD) that contains all 16 point-mutations shown in the currently prevailing Omicron and Delta variants. RESULTS: A booster dose of hybrid vaccine in mice previously immunized with wild-type RBD vaccine induced high titers of broadly neutralizing antibodies against all tested SARS-CoV-2 variants of concern (VOCs). In naïve mice, hybrid vaccine generated strong Omicron-specific neutralizing antibodies as well as low but significant titers against other VOCs. Hybrid vaccine also elicited CD8+/IFN-γ+ T cell responses against a conserved T cell epitope present in wild type and all VOCs. CONCLUSIONS: These results demonstrate that inclusion of different antigenic mutations from various SARS-CoV-2 variants is a feasible approach to develop cross-protective vaccines.

Dendrobium nobile protects retinal cells from UV-induced oxidative stress damage via Nrf2/HO-1 and MAPK pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Excessive UV irradiation and ROS exposure are the main contributors of ocular pathologies. Pseudobulb of Dendrobium nobile Lindl. is one of the sources of Shihu and has long been used in traditional Chinese medicine as a tonic to nourish stomach, replenish body fluid, antipyretic and anti-inflammation. AIM OF STUDY: This study aimed to investigate whether D. nobile could protect ocular cells against oxidative stress damage. MATERIALS AND METHODS: Retinal-related cell lines, ARPE-19 and RGC-5 cells, were pretreated with D. nobile extracts before H2O2- and UV-treatment. Cell viability and the oxidative stress were monitored by sulforhodamine B (SRB) and SOD1 and CAT assay kits, respectively. The oxidative stress related proteins were measured by Western blotting. RESULTS: Under activity-guided fractionation, a sesquiterpene-enriched fraction (DN-2) and a major component (1) could ameliorate H2O2- and UV-induced cytotoxicity and SOD1 and CAT activity, but not dendrobine, the chemical marker of D. nobile. Western blotting showed both DN-2 and compound 1 protected ARPE-19 cells against UV-induced oxidative stress damage by regulating MAPK and Nrf2/HO-1 signaling. CONCLUSION: Our results suggest D. nobile extract protects retinal pigment epithelia cells from UV- and oxidative stress-damage, which may have a beneficial effect on eye diseases.

The impact of aging and reaching movements on grip stability control during manual precision tasks.

BACKGROUND: Operating an object by generating stable hand-grip force during static or dynamic posture control of the upper extremities simultaneously is an important daily activity. Older adults require different attentional resources during grip strength control and arm movements. However, the impact of aging and reaching movements on precise grip strength and stability control among older adults is not well understood. This study investigated the impact of aging and reaching movements on grip strength and stability control in both hands of the upper extremities. METHODS: Fifty healthy young adults (age: 28.8 ± 14.0 years) and 54 healthy older adults (73.6 ± 6.3 years) were recruited to perform isometric grip strength test at 20% maximal voluntary contraction as the target force during three manual precision tasks simultaneously: stationary task (without arm movements), forward-reach task, and backward-reach task. The average grip force (in kg) and coefficient of variation values (expressed as a percentage) during manual precision tasks were calculated to determine the quality of participants' grip strength. The deviation error, absolute error, and force-stability index values were calculated to determine the strength control relative to the target force. RESULTS: For both the young and older groups, the force-stability index values in both hands were significantly higher during forward- and backward-reaching movements than in the stationary condition (p < 0.05). The older group exhibited a significantly lower hand-grip strength and stability of strength control in both hands than the young group (p < 0.05). CONCLUSIONS: Aging and reaching task performance reduced the grip strength of participants and increased the variations in strength control of both hands relative to the target force, indicating that older adults exhibit poor grip strength and stability control when performing arm-reaching movements. These findings may help clinical therapists in establishing objective indexes for poor grip-stability control screening and developing appropriate rehabilitation programs or health-promotion exercises that can improve grip strength and stability control in older people.

Targeting conserved N-glycosylation blocks SARS-CoV-2 variant infection in vitro.

BACKGROUND: Despite clinical success with anti-spike vaccines, the effectiveness of neutralizing antibodies and vaccines has been compromised by rapidly spreading SARS-CoV-2 variants. Viruses can hijack the glycosylation machinery of host cells to shield themselves from the host's immune response and attenuate antibody efficiency. However, it remains unclear if targeting glycosylation on viral spike protein can impair infectivity of SARS-CoV-2 and its variants. METHODS: We adopted flow cytometry, ELISA, and BioLayer interferometry approaches to assess binding of glycosylated or deglycosylated spike with ACE2. Viral entry was determined by luciferase, immunoblotting, and immunofluorescence assays. Genome-wide association study (GWAS) revealed a significant relationship between STT3A and COVID-19 severity. NF-κB/STT3A-regulated N-glycosylation was investigated by gene knockdown, chromatin immunoprecipitation, and promoter assay. We developed an antibody-drug conjugate (ADC) that couples non-neutralization anti-spike antibody with NGI-1 (4G10-ADC) to specifically target SARS-CoV-2-infected cells. FINDINGS: The receptor binding domain and three distinct SARS-CoV-2 surface N-glycosylation sites among 57,311 spike proteins retrieved from the NCBI-Virus-database are highly evolutionarily conserved (99.67%) and are involved in ACE2 interaction. STT3A is a key glycosyltransferase catalyzing spike glycosylation and is positively correlated with COVID-19 severity. We found that inhibiting STT3A using N-linked glycosylation inhibitor-1 (NGI-1) impaired SARS-CoV-2 infectivity and that of its variants [Alpha (B.1.1.7) and Beta (B.1.351)]. Most importantly, 4G10-ADC enters SARS-CoV-2-infected cells and NGI-1 is subsequently released to deglycosylate spike protein, thereby reinforcing the neutralizing abilities of antibodies, vaccines, or convalescent sera and reducing SARS-CoV-2 variant infectivity. INTERPRETATION: Our results indicate that targeting evolutionarily-conserved STT3A-mediated glycosylation via an ADC can exert profound impacts on SARS-CoV-2 variant infectivity. Thus, we have identified a novel deglycosylation method suitable for eradicating SARS-CoV-2 variant infection in vitro. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Hyperglycosylated spike of SARS-CoV-2 gamma variant induces breast cancer metastasis.

SARS-CoV-2 exploits the host cellular machinery for virus replication leading to the acute syndrome of coronavirus disease 2019 (COVID-19). Growing evidence suggests SARS-CoV-2 also exacerbates many chronic diseases, including cancers. As mutations on the spike protein (S) emerged as dominant variants that reduce vaccine efficacy, little is known about the relation between SARS-CoV-2 virus variants and cancers. Compared to the SARS-CoV-2 wild-type, the Gamma variant contains two additional NXT/S glycosylation motifs on the S protein. The hyperglycosylated S of Gamma variant is more stable, resulting in more significant epithelial-mesenchymal transition (EMT) potential. SARS-CoV-2 infection promoted NF-κB signaling activation and p65 nuclear translocation, inducing Snail expression. Pharmacologic inhibition of NF-κB activity by nature food compound, I3C suppressed viral replication and Gamma variant-mediated breast cancer metastasis, indicating that NF-κB inhibition can reduce chronic disease in COVID-19 patients. Our study revealed that the Gamma variant of SARS-CoV-2 activates NF-κB and, in turn, triggers the pro-survival function for cancer progression.

Rapid generation of mouse model for emerging infectious disease with the case of severe COVID-19.

Since the pandemic of COVID-19 has intensely struck human society, small animal model for this infectious disease is in urgent need for basic and pharmaceutical research. Although several COVID-19 animal models have been identified, many of them show either minimal or inadequate pathophysiology after SARS-CoV-2 challenge. Here, we describe a new and versatile strategy to rapidly establish a mouse model for emerging infectious diseases in one month by multi-route, multi-serotype transduction with recombinant adeno-associated virus (AAV) vectors expressing viral receptor. In this study, the proposed approach enables profound and enduring systemic expression of SARS-CoV-2-receptor hACE2 in wild-type mice and renders them vulnerable to SARS-CoV-2 infection. Upon virus challenge, generated AAV/hACE2 mice showed pathophysiology closely mimicking the patients with severe COVID-19. The efficacy of a novel therapeutic antibody cocktail RBD-chAbs for COVID-19 was tested and confirmed by using this AAV/hACE2 mouse model, further demonstrating its successful application in drug development.

Depth-Camera Based Energy Expenditure Estimation System for Physical Activity Using Posture Classification Algorithm.

Insufficient physical activity is common in modern society. By estimating the energy expenditure (EE) of different physical activities, people can develop suitable exercise plans to improve their lifestyle quality. However, several limitations still exist in the related works. Therefore, the aim of this study is to propose an accurate EE estimation model based on depth camera data with physical activity classification to solve the limitations in the previous research. To decide the best location and amount of cameras of the EE estimation, three depth cameras were set at three locations, namely the side, rear side, and rear views, to obtain the kinematic data and EE estimation. Support vector machine was used for physical activity classification. Three EE estimation models, namely linear regression, multilayer perceptron (MLP), and convolutional neural network (CNN) models, were compared and determined the model with optimal performance in different experimental settings. The results have shown that if only one depth camera is available, optimal EE estimation can be obtained using the side view and MLP model. The mean absolute error (MAE), mean square error (MSE), and root MSE (RMSE) of the classification results under the aforementioned settings were 0.55, 0.66, and 0.81, respectively. If higher accuracy is required, two depth cameras can be set at the side and rear views, the CNN model can be used for light-to-moderate activities, and the MLP model can be used for vigorous activities. The RMSEs for estimating the EEs of standing, walking, and running were 0.19, 0.57, and 0.96, respectively. By applying the different models on different amounts of cameras, the optimal performance can be obtained, and this is also the first study to discuss the issue.

Effects of Shengmai San on key enzymes involved in hepatic and intestinal drug metabolism in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Shengmai San (SMS) has been commonly used as a traditional Chinese medicine for the treatment of cardiovascular disorders, of which drug interactions need to be assessed for the safety concern. There is little evidence for the alterations of hepatic and intestinal drug-metabolizing enzymes after repeated SMS treatments to assess drug interactions. AIM OF THE STUDY: The studies aim to illustrate the effects of repeated treatments with SMS on cytochrome P450s (CYPs), reduced nicotinamide adenine dinucleotide (phosphate)-quinone oxidoreductase (NQO), uridine diphosphate-glucuronosyltransferase (UGT), and glutathione S-transferase (GST) using in vivo rat model. MATERIALS AND METHODS: The SMS was prepared using Schisandrae Fructus, Ginseng Radix, and Ophiopogonis Radix (OR) (1:2:2). Chromatographic analyses of decoctions were performed using ultra-performance liquid chromatography (UPLC) and LC-mass spectrometry. Sprague-Dawley rats were orally treated with the SMS and its component herbal decoctions for 2 or 3 weeks. Hepatic and intestinal enzyme activities were determined. CYP3A expression and the kinetics of intestinal nifedipine oxidation (NFO, a CYP3A marker reaction) were determined. RESULTS: Schisandrol A, schisandrin B, ginsenoside Rb1 and ophiopogonin D were identified in SMS. SMS selectively suppressed intestinal, but not hepatic, NFO activity in a dose- and time-dependent manner. Hepatic and intestinal UGT, NQO and GST activities were not affected. A 3-week SMS treatment decreased the maximal velocity of intestinal NFO by 50%, while the CYP3A protein level remained unchanged. Among SMS component herbs, the decoction of OR decreased intestinal NFO activity. CONCLUSIONS: These findings demonstrate that 3-week treatment with SMS and OR suppress intestinal, but not hepatic CYP3A function. It suggested that the potential interactions of SMS with CYP 3A drug substrates should be noticed, especially the drugs whose bioavailability depends heavily on intestinal CYP3A.

Huang Lian Jie Du Tang attenuates paraquat-induced mitophagy in human SH-SY5Y cells: A traditional decoction with a novel therapeutic potential in treating Parkinson's disease.

Huang Lian Jie Du Tang (HLJDT) is a traditional Chinese medical decoction for heat-fire clearing and detoxication. Theoretically, the cause of Parkinson's disease (PD) has been attributed to the dysregulations of internal wind, phlegm, fire, and stasis. Thus, HLJDT has been used to treat PD. However, the molecular mechanism is unknown. Besides, paraquat (PQ) as an herbicide has been known to impair midbrain dopaminergic neurons, resemblance to the pathology of PD. Thus, the molecular mechanism of HLJDT in treating PD and PQ-induced in vitro PD model was investigated in this study. Primarily, the dose-response of PQ (0.1∼1 mM)-induced neurotoxicity for 24 h was performed in the human neuroblastoma SH-SY5Y cells. The LD50 of PQ is around 0.3 mM and was applied throughout the following experiments. The neutral red assay was used to estimate cell viability. Co-transfection of the mitochondrial marker and proapoptotic factor genes were applied to measure the release of mitochondrial proapoptotic factors during PQ intoxication and HLJDT protection. The fluorescent dyes were used to detect mitochondrial membrane potential and free radical formation. Western blot and dot-blot analysis and immunocytochemistry were used to estimate the level of proteins related to apoptosis and mitophagy. PINK1 gene silencing was used to determine the significance of mitophagy during PQ intoxication. In this study, HLJDT attenuated PQ-induced apoptosis in SH-SY5Y cells. HLJDT reversed PQ-induced decreased mitochondrial membrane potential and suppressed PQ-induced increased cytosolic and mitochondrial free radical formations and mitochondrial proapoptotic factor releases. Furthermore, HLJDT mitigated PQ-induced increases in full-length PINK1, phosphorylations of Parkin and ubiquitin, mitochondrial translocation of phosphorylated Parkin, and mitophagy. PINK1 gene silencing attenuated PQ-induced neurotoxicity. Therefore, HLJDT attenuated PQ-induced cell death by regulating mitophagy.