Salvia miltiorrhiza suppresses cardiomyocyte ferroptosis after myocardial infarction by activating Nrf2 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Ferroptosis, a recently identified non-apoptotic form of cell death reliant on iron, is distinguished by an escalation in lipid reactive oxygen species (ROS) that are iron-dependent. This phenomenon has a strong correlation with irregularities in iron metabolism and lipid peroxidation. Salvia miltiorrhiza Bunge (DS), a medicinal herb frequently utilized in China, is highly esteemed for its therapeutic effectiveness in enhancing blood circulation and ameliorating blood stasis, particularly during the treatment of cardiovascular diseases (CVDs). Numerous pharmacological studies have identified that DS manifests antioxidative stress effects as well as inhibits lipid peroxidation. However, ambiguity persists regarding the potential of DS to impede ferroptosis in cardiomyocytes and subsequently improve myocardial damage post-myocardial infarction (MI). AIM OF THE STUDY: The present work focused on investigating whether DS could be used to prevent the ferroptosis of cardiomyocytes and improve post-MI myocardial damage. MATERIALS AND METHODS: In vivo experiments: Through ligation of the left anterior descending coronary artery, we constructed both a wild-type (WT) and NF-E2 p45-related factor 2 knockout (Nrf2-/-) mouse model of MI. Effects of DS and ferrostatin-1 (Fer-1) on post-MI cardiomyocyte ferroptosis were examined through detecting ferroptosis and myocardial damage-related indicators as well as Nrf2 signaling-associated protein levels. In vitro experiments: Erastin was used for stimulating H9C2 cardiomyocytes to construct an in vitro ferroptosis cardiomyocyte model. Effects of DS and Fer-1 on cardiomyocyte ferroptosis were determined based on ferroptosis-related indicators and Nrf2 signaling-associated protein levels. Additionally, inhibitor and activator of Nrf2 were used for confirming the impact of Nrf2 signaling on DS's effect on cardiomyocyte ferroptosis. RESULTS: In vivo: In comparison to the model group, DS suppressed ferroptosis in cardiomyocytes post-MI and ameliorated myocardial damage by inducing Nrf2 signaling-related proteins (Nrf2, xCT, GPX4), diminishing tissue ferrous iron and malondialdehyde (MDA) content. Additionally, it enhanced glutathione (GSH) levels and total superoxide dismutase (SOD) activity, effects that are aligned with those of Fer-1. Moreover, the effect of DS on alleviating cardiomyocyte ferroptosis after MI could be partly inhibited through Nrf2 knockdown. In vitro: Compared with the erastin group, DS inhibited cardiomyocyte ferroptosis by promoting the expression of Nrf2 signaling-related proteins, reducing ferrous iron, ROS, and MDA levels, but increasing GSH content and SOD activity, consistent with the effect of Fer-1. Additionally, Nrf2 inhibition increased erastin-mediated ferroptosis of cardiomyocytes through decreasing Nrf2 signaling-related protein expressions. Co-treatment with DS and Nrf2 activator failed to further enhance the anti-ferroptosis effect of DS. CONCLUSION: MI is accompanied by cardiomyocyte ferroptosis, whose underlying mechanism is probably associated with Nrf2 signaling inhibition. DS possibly suppresses ferroptosis of cardiomyocytes and improves myocardial damage after MI through activating Nrf2 signaling.

An Adaptive Hammerstein Model for FES-Induced Torque Prediction Based on Variable Forgetting Factor Recursive Least Squares Algorithm.

Modeling the muscle response to functional electrical stimulation (FES) is an important step during model-based FES control system design. The Hammerstein structure is widely used in simulating this nonlinear biomechanical response. However, a fixed relationship cannot cope well with the time-varying property of muscles and muscle fatigue. In this paper, we proposed an adaptive Hammerstein model to predict ankle joint torque induced by electrical stimulation, which used variable forgetting factor recursive least squares (VFFRLS) method to update the model parameters. To validate the proposed model, ten healthy individuals were recruited for short-duration FES experiments, ten for long-duration FES experiments, and three stroke patients for both. The isometric ankle dorsiflexion torque induced by FES was measured, and then the test performance of the fixed-parameter Hammerstein model, the adaptive Hammerstein model based on fixed forgetting factor recursive least squares (FFFRLS) and the adaptive Hammerstein model based on VFFRLS was compared. The goodness of fit, root mean square error, peak error and success rate were applied to evaluate the accuracy and stability of the model. The results indicate a significant improvement in both the accuracy and stability of the proposed adaptive model compared to the fixed-parameter model and the adaptive model based on FFFRLS. The proposed adaptive model enhances the ability of the model to cope with muscle changes.

Hepatocyte nuclear factor 1B deletion, but not intragenic mutation, might be more susceptible to hypomagnesemia.

AIMS: HNF1B syndrome is caused by defects in the hepatocyte nuclear factor 1B (HNF1B) gene, which leads to maturity-onset diabetes of the young type 5 and congenital organ malformations. This study aimed to identify a gene defect in a patient presenting with diabetes and severe diarrhea, while also analyzing the prevalence of hypomagnesemia and its correlation with the HNF1B genotype. MATERIALS AND METHODS: Whole exome sequencing was used to identify responsible point mutations and small indels in the proband and their family members. Multiplex ligation-dependent probe amplification was carried out to identify HNF1B deletions. Furthermore, an analysis of published data on 539 cumulative HNF1B cases, from 29 literature sources, was carried out to determine the correlation between the HNF1B genotype and the phenotype of serum magnesium status. RESULTS: Using multiplex ligation-dependent probe amplification, we identified a de novo heterozygous HNF1B deletion in the patient, who showed dorsal pancreas agenesis and multiple kidney cysts, as detected by magnetic resonance imaging. Magnesium supplementation effectively alleviated the symptoms of diarrhea. Hypomagnesemia was highly prevalent in 192 out of 354 (54.2%) patients with HNF1B syndrome. Compared with patients with intragenic mutations, those with HNF1B deletions were more likely to suffer from hypomagnesemia, with an odds ratio of 3.1 (95% confidence interval 1.8-5.4). CONCLUSIONS: Hypomagnesemia is highly prevalent in individuals with HNF1B syndrome, and those with HNF1B deletion are more susceptible to developing hypomagnesemia compared with those with intragenic mutations. The genotype-phenotype associations in HNF1B syndrome have significant implications for endocrinologists in terms of genotype detection, treatment decisions and prognosis assessment.

Leaf Spot caused by Alternaria alternata on Macleaya cordata in China.

Macleaya cordata is a perennial herb that belongs to the Papaveraceae and is typically prescribed as a traditional antibacterial medicine in China (Kosina et al. 2010). The extract from M. cordata has been widely used in the manufacturing of natural growth promoters as an alternative to antibiotic growth promoters in the livestock industry (Liu et al. 2017), and the products are marketed in 70 countries such as Germany, China, etc (Ikezawa et al. 2009). During the summer of 2019, symptoms of leaf spot were observed on M. cordata (cv. HNXN-001) in two commercial fields (approximately 1, 300 m2 and 2, 100 m2) of Xinning county, Shaoyang City, Hunan Province, China, where approximately 2 to 3% of the plants were affected. The initial symptoms were irregular black and brown spots on the leaves. The lesions expanded and coalesced, eventually leading to leaf blight. Six symptomatic basal leaf sections from six plants from two fields were surface disinfested in 0.5% NaClO for 1 min, then 75% ethanol for 20 s, rinsed in sterile water three times, air dried, and placed onto potato dextrose agar (PDA), one dish for samples from a single leaf. Plates were incubated at 26°C in darkness. Nine strains with similar morphological characters were isolated, and one representative isolate ( BLH-YB-08) was used for morphological and molecular characterization. The colonies on PDA were grayish-green with white round margins. Conidia were typically obclavate to obpyriform, brown to dark brown, and 12.0 to 35.0 × 6.0 to 15.0 µm, and with 1 to 5 transverse septa and 0 to 2 longitudinal septa (n=50). Isolates were identified as Alternaria sp. on the basis of mycelial characteristics, color, and conidial morphology. To confirm identity of the pathogen, DNA was extracted from isolate BLH-YB-08 with the DNAsecure Plant Kit (TIANGEN, Biotech, China). The glyceraldehyde-3-phosphate dehydrogenase (GAPDH), RNA polymerase II second largest subunit (RPB2), actin (ACT), 28S nrDNA (LSU), 18S nuclear ribosomal DNA (SSU), histone 3 (HIS3), internal transcribed spacer (ITS) region of ribosomal DNA, and translation elongation factor 1-α (TEF) genes ( Berbee et al. 1999; Carbone and Kohn. 1999; Glass and Donaldson. 1995; White et al. 1990.) were amplified and sequenced. Sequences were deposited into the GenBank database. They were 100% sequence identity of GAPDH (OQ224996) with A. alternata strain AA2-8 (MH65578; 578/578bp), 100% sequence identity of RPB2 (OQ190460) with A. alternata strain SAX-WN-30-2 ( MK605877; 933/933bp), 100% sequence identity of ACT (OQ923292) with A. alternata strain FCBP0352 (OL830257; 939/939 bp), 100% sequence identity of LSU (OQ891167) with A. alternata XL14 (MG839509 ; 908/908 bp), 100% sequence identity of SSU (OQ139544) with A. alternata strain BJ19.4.1(OM736063; 1,067/1,067 bp), 100% sequence identity of HIS3 (MT454856) with A. alternata YJ-CYC-HC2 (OQ116440 ; 442/442 bp), 100% sequence identity of ITS (MT212225) with A. alternata CS-1-3 (OQ947366; 543/543bp), and 100% sequence identity of TEF (OQ190461) with A. alternata strain YZU 221185 (OQ512730; 252/252 bp). To test pathogenicity, the isolate BLH-YB-08 was cultured on PDA for 7 days to prepare conidial suspensions and the spore concentration adjusted to a final concentration of 1×106 spores/ml. The leaves of five potted 45-day-old M. cordata (cv. HNXN-001) plants were sprayed with conidial suspensions, and five control potted plants were wiped with 75% alcohol and washed five times with sterile distilled water. They were then sprayed with sterile distilled water. Plants were placed in a greenhouse at 25 to 30°C with 90% relative humidity. Pathogenicity tests were conducted twice. Fifteen days after inoculation, lesions were found on inoculated leaves, and the symptoms were the same as those in the field, whereas the controls were healthy. A fungus was consistently isolated from the inoculated leaves and identified as A. alternata by DNA sequencing of the GAPDH, ITS, and HIS3 genes, fulfilling Koch's postulates. To our knowledge, this is the first report of leaf spot on M. cordata caused by A. alternata in China. Understanding its etiology may help to control this fungal pathogen, thus reducing economic losses. Funding: Hunan Provincial Natural Science Foundation General Project (2023JJ30341) Hunan Provincial Natural Science Foundation Youth Fund (2023JJ40367) Seed Industry Innovation Project of Hunan Provincial Science and Technology Department Special project for the construction of Chinese herbal medicine industry technology system in Hunan Province "Xiangjiuwei" Industrial Cluster Project of the Ministry of Agriculture and Rural Affairs.

First report of Fusarium fujikuroi causes leaf spot in Polygonatum odoratum (Mill.) Druce in China.

Polygonatum odoratum (Mill.) Druce, a member of Liliaceae, is one of the traditional Chinese herbal plants mainly used in Jilin, Hubei, Guangxi, Zhejiang, Liaoning, Hunan and Guangdong provinces. Leaf spot disease of P. odoratum was continuously observed in the Planting Demonstration Garden in Changsha (28 °48 N; 113° 34E), Hunan Province of China, in May 2021 and May 2022. The symptoms initially appeared as tiny reddish-brown spots and continued to expand, resulting in round, oval, or irregular tan lesions with necrotic, film-shaped, or perforated central tissues. Leaf spot disease affects approximately 60-70% of plants. For pathogen isolation, symptomatic leaf samples were collected and disinfected with 70% ethanol for 30 s and 3% sodium hypochlorite for 2 min, followed by rinsing with sterile distilled water. Subsequently, small pieces (3 × 3 mm) of diseased tissues were placed on potato dextrose agar (PDA) and incubated in the dark at 25 °C for 24 h to 36 h. The emerging fungal hyphal tips were transferred to PDA and purified by the single-spore method (Yu, et al., 202). In total, 50 disease spots were isolated, and 10 cultures with the same appearance were obtained. Two strains coded as hnxryzy and hnxryzy01 were randomly selected for identification. After 6 days of culture in PDA, dense pink colonies were observed with a mean radial growth rate of 7.5 mm/day. Strains cultured 6 days on synthetic low nutrient medium, microconidia were oval or ovate (7.5-9.67 µm × 2.49-3.57 µm(n = 50)), and macroconidia were sickle-shaped and slightly curved, gradually tapering at both ends, with 2-5 pseudoseptate (10.01-22.14 µm × 2.07-4.22 µm (n = 50)). These morphological characteristics were consistent with the description of Fusarium fujikuroi (Fang, et al., 2021). Furthermore, primers ITS1/ITS4, EF728F/EF986R, Bt2a/Bt2b, RPB1-F5/RPB1-R8 and fRPB2-5F2/fRPB2-7cR (Li, et al., 2013, Xie, et al., 2022) were used to amplify the partial region of the internal transcribed spacer (ITS) , the translation elongation factor EF-1α,ß-tubulin,polymerase II largest subunit (RPB1) and RNA polymerase II second largest subunit (RPB2) genes from strains hnxryzy and hnxryzy01, respectively. Amplicons were sequenced by Tsingke Biotechnology Co., Ltd. The expected sequences of ITS, EF-1α, ß-tubulin, RPB1 and RPB2 of hnxryzy and hnxryzy01 were obtained. The sequence alignment of hnxryzj and hnxryzj01 with the Fusarium ID databased and NCBI shows the following results: The sequences of ITS region, EF-1α, ß-tubulin , RPB1 and RPB2 of strain hnxryzy (GenBank accession nos. ON797440, ON820553, ON820554, OP413443, and OP413445, respectively) and strain hnxryzy01 (GenBank accession nos. ON965284, ON968721, ON968722, OP413444, and OP413446, respectively) were 99% to 100% identical to those of F. fujikuroi (GenBank accession numbers CP023090, KC874784, MN490089, MN193916, and MN193888, respectively). Then a phylogenetic tree based on EF-1α, RPB1, and RPB2 sequences was constructed (Torres-Cruz, et al., 2022). The strains hnxryzy and hnxryzy01 were more closely related to F. fujikuroi ( NRRL13566 GenBank accession nos. AF160279, JX171456, and JX171570, respectively), with bootstrap values of 99%. Two sets (5 plants in each set) of potted plants were used in pathogenicity assays. Wounded leaves were sprayed with conidial suspensions (100 µL, 1 × 107 spores/mL) and sterile water as control. Inoculated plants were covered with plastic bags for 24 h, and maintained at 25 ° C in 12/12 h light/dark conditions in the greenhouse (Yu, et al., 2022). Pathogenicity assays were repeated thrice. Dark brown spots identical to those seen in the field were observed 14 days after inoculation, while the control leaves did not exhibit any symptoms. In this study, the pathogen F. fujikuroi was successfully reisolated from the leaves of inoculated samples showing symptoms, thereby verifying Koch's postulate. To our knowledge, this is the first report of F. fujikuroi inducing leaf spot on P. odoratum in China. Since F. fujikuroi is a common pathogenic fungus that infects different plant species(Qiu, et al., 2020), more attention should be paid to its prevalence in P. odoratum and the potential risk of outbreak in other provinces of China.

First report of Fusarium oxysporum causing stem spots on Polygonatum odoratum in China.

Polygonatum odoratum (Mill.) Druce is a perennial herb in the Liliaceae family and it is one of the traditional Chinese medicinal plants. Modern pharmaceutical studies demonstrate that P. odoratum contains polysaccharides, saponins, alkaloids, flavonoids, volatile oil, and other active components (Jiang-Nan, et al., 2018). From May to June 2022, the stem spot disease was discovered on P. odoratum in the planting demonstration garden in Changsha (28°20N; 113°07E), Hunan province of China. The disease seriously retarded plant growth and was estimated to have affected approximately 40-50% of the plants, significant economic losses to growers. Plants had oval tan spots on the stems, which were light in the center and dark at the margin. The spots in the back expanded and joined together, where the disease was severe, and chlorosis was near the stem spot, while many leaves turned completely yellow and withered before falling to the ground. Finally, the whole plant faded to light green and dried up. In order to isolate pathogens, symptomatic stem samples (5×5 mm) were collected from the edges of the lesions and excised symptomatic tissues consisting of diseased and healthy parts were surface-sterilized with 2% solution of sodium hypochlorite (0.1% active ingredient of chlorine) for 1 min and 75% ethanol for 30 s. The samples were then washed thrice with sterile distilled water, air-dried on the sterile filter papers under aseptic conditions, and finally plated onto Potato Dextrose Agar (PDA) plates, which were incubated at 25 °C for 24 h to 36 h in the dark. Additionally, the emerging fungal hyphal tips were transferred to PDA and purified by the single-spore method. Next, forty plants with stem spots were isolated, and 8 cultures with the same appearance were obtained. Two strains coded hnxryzj and hnxryzj1 were randomly selected, for identification. With a mean radial growth rate of 7.5 mm/day, white and dense colonies were observed after 6 days of culture on PDA. After hnxryzj was cultured on SNA, microconidia were oval or ovate (9.25-14.8µm × 2.18-3.76µm), macroconidia were sickle-shaped and slightly curved, with 2-5 septa (21.52-23.49µm × 2.64-4.51µm (n = 50)). These morphological characteristics were consistent with the description of Fusarium oxysporum (Mirghasempour, et al., 2022) Furthermore, we amplified the partial region of the internal transcribed spacer (ITS) region, the translation elongation factors EF-1α, ß-tubulin, polymerase II largest subunit (RPB1) and RNA polymerase II second largest subunit (RPB2) genes from strain hnxryzj and hnxryzj1, based on the primer pairs ITS1/ITS4, EF728F/EF986R, Bt2a/Bt2b, RPB1-F5/RPB1-R8 and fRPB2-5F2/fRPB2-7cR (Li, et al., 2013, Xie, et al., 2022), and amplicons were sequenced by Tsingke Biotechnology Co. Ltd. By sequence alignment, the ITS, EF-1α, ß-tubulin , RPB1 and RPB2 of hnxryzj and hnxryzj1 were identical, respectively. The sequence alignment of hnxryzj and hnxryzj1 with the Fusarium ID database and NCBI shows the following results: the ITS region, EF-1α, RPB1 and RPB2 sequences of the strain hnxryzj (GenBank accession nos. ON872218, ON897740, OP467556 and OP467557) and hnxryzj1 (GenBank accession nos. OP071248, OP087208, OP467558 and OP467559) were 100% identical to those of F. oxysporum (GenBank accession nos. MZ890536, LC469784 , MT179509 and MW368380, respectively); whereas the ß-tubulin sequences of the strain hnxryzj (GenBank accession nos. ON897741) and hnxryzj1 (GenBank accession nos. OP087207) were 96.9% identical to those of F.oxysporum (CBS144135 GenBank accession nos. MH485136). Subsequently, a phylogenetic tree was established combining EF-1α, RPB1, and RPB2. Strains hnxryzj and hnxryzj1 were F.oxysporum (JW257006 GenBank accession nos. MZ921883, MZ921657 and MZ921752)(Torres-Cruz, et al., 2022), with bootstrap values 100%. The pathogenicity test was carried out by placing mycelial discs obtained from colonies that had been actively growing on PDA for 6 days. In the pathogenicity test, two sets (5 plants in each set) of potted plants, whose stems were wounded, were taken. In one set (5 plants), the PDA cakes with F. oxysporum (d=5mm, the same below) were inoculated on the stems scratched by an inoculation needle (sterilized) (the front of the colony was close to the wound of the stem). In the other set (5 plants), potted plants inoculated with the sterile PDA cakes were served as controls. In a 25 °C greenhouse, each treatment was given a 12h/12h light/dark cycl(Nabi, et al., 2019). The symptoms were observed, and the fungus cake was removed 5 days after inoculation. Then, after 18 days, typical symptoms of oval tan spots similar to original diseased plants in the field were found on the inoculated stems, and 32 days later, the inoculated plant died, while the control stems remained asymptomatic. In addition, F. oxysporum was isolated and identified from the inoculated, symptomatic stems, verifying Koch's postulates. Based on our knowledge, this is the first report of F. oxysporum causing stem spots on P. odoratum in China. Only one other study from China that root rot of Phyllostachys officinalis also resulted from F. oxysporum (Pang, et al., 2022). Furthermore, P. odoratum is an medicinal material in Hunan province. Therefore, comprehensive prevention and control methods are required.

The effects of thermal treatment on emulsifying properties of soy protein isolates: Interfacial rheology and quantitative proteomic analysis.

In this work, the interfacial rheological properties and the quantitative changes of proteins at interfacial protein layers of emulsions stabilized by soy protein isolates (SPI) and heat-treated soy protein isolates (HSPI) were investigated. The quantification results showed that the relative quantities of albumin (2S) and glycinin (11S) in SPI decreased at the oil-water interface, suggesting that they possessed lower interfacial affinities at the interface. Basic 7S globulin presented more adsorption at the oil-water interface due to the well balance of the hydrophobic and hydrophilic groups of its amino acid sequence. The HSPI (95 °C, 20 min) showed a larger apparent diffusion rate (Kdiff) and a shorter equilibrium adsorption time. The results of interfacial rheology of globulins were consistent with their interfacial quantitative changes, which demonstrated that the interfacial behavior and adsorption ability of globulin were improved by thermal treatment. In this research, the interfacial behaviors of SPI and HSPI was illustrated by their interfacial properties and quantitative results of interfacial adsorbed protein layers, would promote a profound comprehension for the interfacial behavior of the protein and the influence of thermal treatment on protein interfacial properties.

Iterative Adjustment of Stimulation Timing and Intensity During FES-Assisted Treadmill Walking for Patients After Stroke.

Functional electric stimulation (FES) is a common intervention to correct foot drop for patients after stroke. Due to the disturbances from internal time-varying muscle characteristics under electrical stimulation and external environmental uncertainties, most of the existing FES system used pre-set stimulation parameters and cannot achieve good gait performances during FES-assisted walking. Therefore, an adaptive FES control system, which used the iterative learning control to adjust the stimulation intensity based on kinematic data and a linear model to modulate the stimulation timing based on walking speed during FES-assisted treadmill walking, was designed and tested on ten patients with foot drop after stroke. In order to examine its orthotic effects, the kinematic data of the patients using the proposed control strategy were collected and compared with the data of the same patients walking using other three FES control strategies, including (1) constant pre-set stimulation intensity and timing, (2) constant pre-set stimulation intensity with speed-adaptive stimulation timing and (3) walking without FES intervention. The error between the maximum ankle dorsiflexion angle during swing phase and the target angle using the proposed control strategy was the smallest among the four conditions. Moreover, there was no significant difference in the ankle plantar flexion angle at the toe-off event and the maximum knee flexion angle during swing phase between the proposed control strategy and walking without FES. In summary, the proposed control strategy can improve FES-assisted walking performances through adaptive modulation of stimulation timing and intensity when coping with variation, and may have good potential in clinic.

[Comparative analysis and comprehensive evaluation for growth and photosynthetic characteristics of different lily species and varieties].

The biological characteristics,agronomic traits,yield traits,stress resistance,quality and photosynthetic characteristics among six lily varieties were compared in order to screen out the excellent lily varieties suitable for spread planting in Hunan province. Lilium longiflorum had the longest growth period,246 days,among these six lily varieties,while others were about 170 days. The leaves of L.longiflorum,self-selected variety,L. lancifolium and L. dauricum had higher chlorophyll content. No obvious difference was found in net photosynthetic rate,stomatal conductance,transpiration rate and intercellular CO2 concentration among all varieties. The self-selected variety had the highest theoretical and actual yield,2 543. 03,1 608. 65 kg per Mu(1 Mu≈666. 7 m2),respectively,but contents of polysaccharides and flavones in bulbs were lower. All of these six lily varieties can sowing,seedling emergence,growth,flowering,mature harvest in Hunan province. L. dauricum and L. lancifolium would be provided for edible lily. L. brownie and the self-selected variety are highly susceptible varieties. L. dauricum and L. lancifolium are suitable to plant widely in disease-prone regions,due to their strong resistance. L. brownie and L. lancifolium are preferred varieties for medicinal and food using for their good quality and higher contents of polysaccharides and flavones. L. davidii had lower theoretical and actual yield,so planting extension of it should be taken into account.

Speed-adaptive control of functional electrical stimulation for dropfoot correction.

BACKGROUND: Functional electrical stimulation is an important therapy technique for dropfoot correction. In order to achieve natural control, the parameter setting of FES should be associated with the activation of the tibialis anterior. METHODS: This study recruited nine healthy subjects and investigated the relations of walking speed with the onset timing and duration of tibialis anterior activation. Linear models were built for the walking speed with respect to these two parameters. Based on these models, the speed-adaptive onset timing and duration were applied in FES-assisted walking for nine healthy subjects and ten subjects with dropfoot. The kinematic performance of FES-assisted walking triggered by speed-adaptive stimulation were compared with those triggered by the heel-off event, and no-stimulation walking at different walking speeds. RESULTS: Higher ankle dorsiflexion angle was observed in heel-off stimulation and speed-adaptive stimulation conditions than that in no-stimulation walking condition at all the speeds. For subjects with stroke, the ankle plantarflexion angle in speed-adaptive stimulation condition was similar to that in no-stimulation walking condition, and it was significant larger than that in heel-off stimulation condition at all speeds. CONCLUSIONS: The improvement in ankle dorsiflexion without worsening ankle plantarflexion in speed-adaptive stimulation condition could be attributed to the appropriate stimulation timing and duration. These results provide evidence that the proposed stimulation system with speed-related parameters is more physiologically appropriate in dropfoot correction, and it may have great potential value in future clinical applications. TRIAL REGISTRATION: Medical Ethics Committee of Guangdong Work Injury Rehabilitation Center, AF/SC-07/2016.22 . Registered 26 May 2016.

Movement Performance of Human-Robot Cooperation Control Based on EMG-Driven Hill-Type and Proportional Models for an Ankle Power-Assist Exoskeleton Robot.

Although the merits of electromyography (EMG)-based control of powered assistive systems have been certified, the factors that affect the performance of EMG-based human-robot cooperation, which are very important, have received little attention. This study investigates whether a more physiologically appropriate model could improve the performance of human-robot cooperation control for an ankle power-assist exoskeleton robot. To achieve the goal, an EMG-driven Hill-type neuromusculoskeletal model (HNM) and a linear proportional model (LPM) were developed and calibrated through maximum isometric voluntary dorsiflexion (MIVD). The two control models could estimate the real-time ankle joint torque, and HNM is more accurate and can account for the change of the joint angle and muscle dynamics. Then, eight healthy volunteers were recruited to wear the ankle exoskeleton robot and complete a series of sinusoidal tracking tasks in the vertical plane. With the various levels of assist based on the two calibrated models, the subjects were instructed to track the target displayed on the screen as accurately as possible by performing ankle dorsiflexion and plantarflexion. Two measurements, the root mean square error (RMSE) and root mean square jerk (RMSJ), were derived from the assistant torque and kinematic signals to characterize the movement performances, whereas the amplitudes of the recorded EMG signals from the tibialis anterior (TA) and the gastrocnemius (GAS) were obtained to reflect the muscular efforts. The results demonstrated that the muscular effort and smoothness of tracking movements decreased with an increase in the assistant ratio. Compared with LPM, subjects made lower physical efforts and generated smoother movements when using HNM, which implied that a more physiologically appropriate model could enable more natural and human-like human-robot cooperation and has potential value for improvement of human-exoskeleton interaction in future applications.

Screening effective parts of combination of Astragali Radix and Angelicae Sinensis Radix (A&A) for its renoprotective effects / 中国中药杂志

<p><b>OBJECTIVE</b>The decoction of Astragali Radix and Angelicae Sinensis Radix (A&A) has shown antifibrotic effects in rats with unilateral ureteral obstruction (UUO). The aim of this study was to track the effective parts of A&A for its renoprotective effects, according to the improvement of renal function and renal tubulointerstitial damage.</p><p><b>METHOD</b>A&A was sequentially extracted by using different solvents for three times and eleven different parts were gained. Wistar rats were randomly divided into Sham, UUO and the treatment groups with A&A or each part of A&A. After administration of A&A or its parts for 10 days, the levels of serum creatinin (Scr) and urea were measured. The morphological changes of kidneys were also semi-quantitatively analyzed by HE, Masson stained tissue sections, which including interstitial cell infiltration, tubular atrophy and interstitial fibrosis.</p><p><b>RESULT</b>The levels of Scr, urea were significantly increased, accompanied with severe renal damage in rats with UUO. As same as A&A, the part I in the first extraction and part IC in the second extraction were all shown to decrease the levels of Scr and urea and the index of renal interstitial damage. However, the following 4 parts extracted from IC in the third extraction were shown no effect on the above indexes.</p><p><b>CONCLUSION</b>The extract part I and part IC could be considered as the predominant parts of A&A for its renoprotective effects, due to their improvement of renal damage in interstitial nephropathy.</p>

[The thresholds comparison of auditory steady-state responses and auditory brain-stem response].

OBJECTIVE: To compare the thresholds of auditory brainstem response (ABR)and auditory steady-state responses (ASSR) in the same group of deaf children and give a clinical evaluation for ASSR after that. METHOD: Both kinds of thresholds have been recorded and analyzed of these deaf children. RESULT: The ABR thresholds are (85.82 +/- 12.39) and (82.70 +/- 14.93) dB nHL for left and right ears. At four testing frequencies of ASSR, the thresholds are (86.91 +/- 16.70), (90.32 +/- 16.11), (91.02 +/- 16.58), (89.80 +/- 17.08) and (85.15 +/- 18.16), (89.32 +/- 17.76), (90.41 +/- 18.87), (85.15 +/- 17.03) dB HL for left and right ears. The correlation coefficients between the ASSR and ABR of left and right ears are 0.622, 0.721, 0.757, 0.714 and 0.613, 0.732, 0.795, 0.739 at these frequencies respectively. These results showed significant correlation exiting. CONCLUSION: Reliable and frequency specific results could be obtained by ASSR so that it could be as a promising audiometry in clinic.

Low-dose therapy with the long-acting erythropoietin analogue darbepoetin alpha persistently activates endothelial Akt and attenuates progressive organ failure.

BACKGROUND: The hematopoietic cytokine erythropoietin has cytoprotective effects in endothelial cells in vitro that are mediated through direct activation of the pro-survival Akt tyrosine kinase signaling pathway. We tested the hypothesis that low-dose therapy with the long-acting recombinant human erythropoietin analogue darbepoetin alpha protects vascular endothelium in vivo in a classic remnant kidney rat model characterized by severe endothelial damage, progressive vascular sclerosis, and ischemia-induced tissue fibrosis. METHODS AND RESULTS: Using a parallel group study design, we randomly assigned animals after 5/6 nephrectomy to treatment with either saline (n=36) or 0.1 microg/kg body wt darbepoetin (n=24) subcutaneously once weekly. We monitored hematocrit, blood pressure, and serum creatinine regularly and obtained renal tissue 6 weeks after nephrectomy for morphological and immunohistochemical analysis. Darbepoetin-treated animals had significantly improved survival compared with saline-treated controls (63% versus 33%; P<0.05), although hematocrit levels were similar in both groups. Darbepoetin treatment ameliorated endothelial damage; attenuated the composite tissue injury score (saline 1.9+/-0.4; darbepoetin 0.4+/-0.2; P<0.001), which included vascular sclerosis, glomerulosclerosis, and tubulointerstitial damage; and preserved renal function. We found persistent activation of the pro-survival Akt signaling pathway in endothelial and epithelial glomerular cells in darbepoetin-treated animals, accompanied by a significant reduction of apoptotic cell death in renal tissue. CONCLUSIONS: Low-dose darbepoetin treatment confers vascular and tissue protection that is associated with persistent stimulation of the pro-survival Akt signaling pathway. The use of recombinant human erythropoietin or analogues may have utility in preventing ischemia-related progressive vascular injury and organ failure.