The HEAT repeat protein HPO-27 is a lysosome fission factor.

Lysosomes are degradation and signalling centres crucial for homeostasis, development and ageing1. To meet diverse cellular demands, lysosomes remodel their morphology and function through constant fusion and fission2,3. Little is known about the molecular basis of fission. Here we identify HPO-27, a conserved HEAT repeat protein, as a lysosome scission factor in Caenorhabditis elegans. Loss of HPO-27 impairs lysosome fission and leads to an excessive tubular network that ultimately collapses. HPO-27 and its human homologue MROH1 are recruited to lysosomes by RAB-7 and enriched at scission sites. Super-resolution imaging, negative-staining electron microscopy and in vitro reconstitution assays reveal that HPO-27 and MROH1 self-assemble to mediate the constriction and scission of lysosomal tubules in worms and mammalian cells, respectively, and assemble to sever supported membrane tubes in vitro. Loss of HPO-27 affects lysosomal morphology, integrity and degradation activity, which impairs animal development and longevity. Thus, HPO-27 and MROH1 act as self-assembling scission factors to maintain lysosomal homeostasis and function.

Distinct roles of two myosins in C. elegans spermatid differentiation.

During spermatogenesis, interconnected haploid spermatids segregate undesired cellular contents into residual bodies (RBs) before detaching from RBs. It is unclear how this differentiation process is controlled to produce individual spermatids or motile spermatozoa. Here, we developed a live imaging system to visualize and investigate this process in C. elegans. We found that non-muscle myosin 2 (NMY-2)/myosin II drives incomplete cytokinesis to generate connected haploid spermatids, which are then polarized to segregate undesired cellular contents into RBs under the control of myosin II and myosin VI. NMY-2/myosin II extends from the pseudo-cleavage furrow formed between two haploid spermatids to the spermatid poles, thus promoting RB expansion. In the meantime, defective spermatogenesis 15 (SPE-15)/myosin VI migrates from spermatids towards the expanding RB to promote spermatid budding. Loss of myosin II or myosin VI causes distinct cytoplasm segregation defects, while loss of both myosins completely blocks RB formation. We found that the final separation of spermatids from RBs is achieved through myosin VI-mediated cytokinesis, while myosin II is dispensable at this step. SPE-15/myosin VI and F-actin form a detergent-resistant actomyosin VI ring that undergoes continuous contraction to promote membrane constriction between spermatid and RB. We further identified that RGS-GAIP-interacting protein C terminus (GIPC)-1 and GIPC-2 cooperate with myosin VI to regulate contractile ring formation and spermatid release. Our study reveals distinct roles of myosin II and myosin VI in spermatid differentiation and uncovers a novel myosin VI-mediated cytokinesis process that controls spermatid release.

MEX3A promotes triple negative breast cancer proliferation and migration via the PI3K/AKT signaling pathway.

Triple-negative breast cancer (TNBC) has the characteristics of fast growth, easy invasion, metastasis, poor prognosis, low tumor-free survival rate and overall survival rate. In this study, the RNA-binding protein MEX3A was selected by using the methods of TCGA database analysis, mRNA microarrays, and tissue chip immunohistochemistry experiments. The high expression of MEX3A is associated with malignancy and poor prognosis of TNBC. In addition, MEX3A knockdown can inhibit the growth and migration of TNBC cells while MEX3A overexpression shows the opposite effect. In vivo experiments, we also demonstrated that downregulating MEX3A can inhibit the tumorigenicity of TNBC cells. The mRNA microarrays and Ingenuity pathway analysis (IPA) were used to explore the downstream of MEX3A, and verified the relationship between PI3K/AKT signaling pathway and MEX3A. Additionally, we have simultaneously up-regulated MEX3A and treated with pathway inhibitors in vitro experiments and found that it can slow down the growth of TNBC cells. In short, we identified MEX3A as a tumor promoter, potential prognostic indicator and therapeutic target for TNBC, may function through the regulation of the PI3K/AKT signaling pathway.

Impairments of cortico-cortical connectivity in fine tactile sensation after stroke.

BACKGROUND: Fine tactile sensation plays an important role in motor relearning after stroke. However, little is known about its dynamics in post-stroke recovery, principally due to a lack of effective evaluation on neural responses to fine tactile stimulation. This study investigated the post-stroke alteration of cortical connectivity and its functional structure in response to fine tactile stimulation via textile fabrics by electroencephalogram (EEG)-derived functional connectivity and graph theory analyses. METHOD: Whole brain EEG was recorded from 64 scalp channels in 8 participants with chronic stroke and 8 unimpaired controls before and during the skin of the unilateral forearm contacted with a piece of cotton fabric. Functional connectivity (FC) was then estimated using EEG coherence. The fabric stimulation induced FC (SFC) was analyzed by a cluster-based permutation test for the FC in baseline and fabric stimulation. The functional structure of connectivity alteration in the brain was also investigated by assessing the multiscale topological properties of functional brain networks according to the graph theory. RESULTS: In the SFC distribution, an altered hemispheric lateralization (HL) (HL degree, 14%) was observed when stimulating the affected forearm in the stroke group, compared to stimulation of the unaffected forearm of the stroke group (HL degree, 53%) and those of the control group (HL degrees, 92% for the left and 69% for the dominant right limb). The involvement of additional brain regions, i.e., the distributed attention networks, was also observed when stimulating either limb of the stroke group compared with those of the control. Significantly increased (P < 0.05) global and local efficiencies were found when stimulating the affected forearm compared to the unaffected forearm. A significantly increased (P < 0.05) degree of inter-hemisphere FC (interdegree) mainly within ipsilesional somatosensory region and a significantly diminished degree of intra-hemisphere FC (intradegree) (P < 0.05) in ipsilesional primary somatosensory region were observed when stimulating the affected forearm, compared with the unaffected forearm. CONCLUSIONS: The alteration of cortical connectivity in fine tactile sensation post-stroke was characterized by the compensation from the contralesional hemisphere and distributed attention networks related to involuntary attention. The interhemispheric connectivity could implement the compensation from the contralateral hemisphere to the ipsilesional somatosensory region. Stroke participants also exerted increased cortical activities in fine tactile sensation.

Rotation velocity detection with orbital angular momentum light spot completely deviated out of the rotation center.

Based on the rotational Doppler effect, an orbital angular momentum beam can measure the lateral rotation velocity of an object, which has broad application prospects. However, all existing research focus on the light spot center coinciding with the rotation center, or only with small center offset. This is difficult to ensure in remote detection applications. In this paper, the rotational Doppler frequency shifts under three cases, including no center offset, small center offset and large center offset, are analyzed theoretically. Through theoretical research results, a novel method of measuring rotation velocity is proposed, with the light spot completely deviated out of the rotation center. A laboratory verification experiment shows that this proposed method breaks the limit of center offset of lateral rotation velocity measurement and is of great significance to the remote detection of non-cooperative rotation object.

Super-resolved angular displacement estimation based upon a Sagnac interferometer and parity measurement.

Super-resolved angular displacement estimation is of crucial significance to the field of quantum information processing. Here we report an estimation protocol based on a Sagnac interferometer fed by a coherent state carrying orbital angular momentum. In a lossless scenario, through the use of parity measurement, our protocol can achieve a 4ℓ-fold super-resolved output with quantum number ℓ; meanwhile, a shot-noise-limited sensitivity saturating the quantum Cramér-Rao bound is reachable. We also consider the effects of several realistic factors, including nonideal state preparation, photon loss, and inefficient measurement. Finally, with mean photon number N¯=2.297 and ℓ = 1 taken, we experimentally demonstrate a super-resolved effect of angular displacement with a factor of 7.88.

Hysteresis Modelling and Feedforward Control of Piezoelectric Actuator Based on Simplified Interval Type-2 Fuzzy System.

The piezoelectric actuator is indispensable for driving the micro-manipulator. In this paper, a simplified interval type-2 (IT2) fuzzy system is proposed for hysteresis modelling and feedforward control of a piezoelectric actuator. The partial derivative of the output of IT2 fuzzy system with respect to the modelling parameters can be analytically computed with the antecedent part of IT2 fuzzy rule specifically designed. In the experiments, gradient based optimization was used to identify the IT2 fuzzy hysteresis model. Results showed that the maximum error of model identification is 0.42% with only 3 developed IT2 fuzzy rules. Moreover, the model validation was conducted to demonstrate the generalization performance of the identified model. Based on the analytic inverse of the developed model, feedforward control experiment for tracking sinusoidal trajectory of 20 Hz was carried out. As a result, the hysteresis effect of the piezoelectric actuator was reduced with the maximum tracking error being 4.6%. Experimental results indicated an improved performance of the proposed IT2 fuzzy system for hysteresis modelling and feedforward control of the piezoelectric actuator.

Tried-and-true binary strategy for angular displacement estimation based upon fidelity appraisal.

We demonstrate a tried-and-true binary strategy for angular displacement estimation, of which the measuring system is a modified Mach-Zehnder interferometer fed by a coherent state carrying orbital angular momentum, and two Dove prisms are embedded in two arms. Unlike previous protocols, in this paper, we use fidelity instead of standard deviation to evaluate the detection strategies. Two binary strategy candidates, parity detection and Z detection, are considered and compared. In addition, we study the effects of several realistic scenarios on the estimation protocol, including transmission loss, detection efficiency, dark counts, and those which are a combination thereof. Finally, we exhibit a proof-of-principle experiment, the results suggest a resolution enhancement effect with a factor of 3.72.

Super-sensitive angular displacement estimation via an SU(1,1)-SU(2) hybrid interferometer.

In this paper, we propose a protocol for the estimation of angular displacement based upon orbital angular momentum and an SU(1,1)-SU(2) hybrid interferometer. This interferometer consists of an optical parametric amplifier, a beam splitter, and reflection mirrors; the balanced homodyne detection is used as the detection strategy. The results indicate that super-resolution and super-sensitivity can be achieved with an ideal scenario. Additionally, we study the effect of photon loss on resolution and sensitivity, and the robustness of our protocol is also discussed. Finally, the advantage of our protocol compared with an SU(1,1) protocol is demonstrated, and the merits of orbital angular momentum-enhanced protocol are summarized.

A Neuromuscular Electrical Stimulation (NMES) and robot hybrid system for multi-joint coordinated upper limb rehabilitation after stroke.

BACKGROUND: It is a challenge to reduce the muscular discoordination in the paretic upper limb after stroke in the traditional rehabilitation programs. METHOD: In this study, a neuromuscular electrical stimulation (NMES) and robot hybrid system was developed for multi-joint coordinated upper limb physical training. The system could assist the elbow, wrist and fingers to conduct arm reaching out, hand opening/grasping and arm withdrawing by tracking an indicative moving cursor on the screen of a computer, with the support from the joint motors and electrical stimulations on target muscles, under the voluntary intention control by electromyography (EMG). Subjects with chronic stroke (n = 11) were recruited for the investigation on the assistive capability of the NMES-robot and the evaluation of the rehabilitation effectiveness through a 20-session device assisted upper limb training. RESULTS: In the evaluation, the movement accuracy measured by the root mean squared error (RMSE) during the tracking was significantly improved with the support from both the robot and NMES, in comparison with those without the assistance from the system (P < 0.05). The intra-joint and inter-joint muscular co-contractions measured by EMG were significantly released when the NMES was applied to the agonist muscles in the different phases of the limb motion (P < 0.05). After the physical training, significant improvements (P < 0.05) were captured by the clinical scores, i.e., Modified Ashworth Score (MAS, the elbow and the wrist), Fugl-Meyer Assessment (FMA), Action Research Arm Test (ARAT), and Wolf Motor Function Test (WMFT). CONCLUSIONS: The EMG-driven NMES-robotic system could improve the muscular coordination at the elbow, wrist and fingers. TRIAL REGISTRATION: ClinicalTrials.gov. NCT02117089 ; date of registration: April 10, 2014.

Effects of body-mapping-designed clothing on heat stress and running performance in a hot environment.

To investigate clothing-induced differences in human thermal response and running performance, eight male athletes participated in a repeated-measure study by wearing three sets of clothing (CloA, CloB, and CloC). CloA and CloB were body-mapping-designed with 11% and 7% increased capacity of heat dissipation respectively than CloC, the commonly used running clothing. The experiments were conducted by using steady-state running followed by an all-out performance running in a controlled hot environment. Participants' thermal responses such as core temperature (Tc), mean skin temperature ([Formula: see text]), heat storage (S), and the performance running time were measured. CloA resulted in shorter performance time than CloC (323.1 ± 10.4 s vs. 353.6 ± 13.2 s, p = 0.01), and induced the lowest [Formula: see text], smallest ΔTc, and smallest S in the resting and running phases. This study indicated that clothing made with different heat dissipation capacities affects athlete thermal responses and running performance in a hot environment. Practitioner Summary: A protocol that simulated the real situation in running competitions was used to investigate the effects of body-mapping-designed clothing on athletes' thermal responses and running performance. The findings confirmed the effects of optimised clothing with body-mapping design and advanced fabrics, and ensured the practical advantage of developed clothing on exercise performance.

Temperature induced modulation of lipid oxidation and lipid accumulation in palmitate-mediated 3T3-L1 adipocytes and 3T3-L1 adipocytes.

Human skin temperature can vary widely depending on anatomical location and ambient temperature. It is also known that local changes in skin and subcutaneous temperature can affect fat metabolism. This study aimed to explore the potential effects of surrounding thermal environment on fat by investigating cell viability, lipid oxidation, and lipid accumulation in 3T3-L1 adipocytes and palmitate-treated adipocytes after 4h incubation. No significant differences of viability in 3T3-L1 adipocytes were detected under different temperature conditions. Despite no significant increase being observed under warm temperature (39°C) conditions, a similarly significant suppression of intracellular reactive oxygen species (ROS) and lipid peroxidation were found in 3T3-L1 adipocytes and palmitate-treated adipocytes under 4h exposure to cooler temperatures of 31-33°C (P<0.01). ROS, chemically reactive molecules containing oxygen, are currently understood to be a major contributor to oxidantive stress in obesity. Additionally, cooler temperatures (31-33°C) could improve the size of lipid droplets in 3T3-L1 adipocytes (P<0.01), but no significant effect was generated by temperature change on lipid droplets in palmitate-treated adipocytes. In the palmitate-induced adiposity model, although excessive ROS and lipid peroxidation has been attenuated by temperature decrease (P<0.01), it still does not positively modulate lipid droplet size (P>0.05) and remedy the palmitate damage induced cell death (P<0.01). These findings provide preliminary support for potential interventions based on temperature manipulation for cell metabolism of adipocytes.

Overexpression of MALT1-A20-NF-κB in adult B-cell acute lymphoblastic leukemia.

BACKGROUND: A20 is a dual inhibitor of NF-κB activation and apoptosis in the tumor necrosis factor receptor 1 signaling pathway, and both are related to tumorigenesis. A20 is frequently inactivated by deletions and/or mutations in several B and T cell lymphoma subtypes; however, knowledge of the role of A20 in B-cell acute lymphoblastic leukemia (B-ALL) remains limited. In this study, we characterized the A20 gene expression pattern, the expression level of its upstream regulating factor MALT1, and its downstream target NF-κB in adult B-ALL. METHODS: The expression level of MALT1, A20 and NF-κB1 was detected in peripheral blood mononuclear cells (PBMCs) from 20 patients with adult B-ALL (including 12 de novo B-ALL and 8 refractory/relapse B-ALL cases), and nine patients with B-ALL in complete remission (CR) using real-time PCR. Sixteen healthy individuals served as controls. RESULTS: Significant A20 overexpression was found in the B-ALL (median: 13.489) compared with B-ALL CR (median: 3.755) (P = 0.003) patients and healthy individuals (median: 8.748) (P = 0.002), while there was no significant difference in A20 expression between B-ALL CR patients and healthy individuals (P = 0.107). Interestingly, the A20 expression level in the B-ALL samples was relatively different with approximately 50% of the B-ALL cases showing a relatively high A20 expression level, while the remaining 50% cases demonstrated slight upregulation or a similar expression level as the healthy controls. However, there was no significant difference in the A20 expression level between de novo B-ALL (median 12.252) and refractory/relapse B-ALL patients (median 21.342) (P = 0.616). Similarly, a significantly higher expression level of NF-κB1 was found in the B-ALL (median 1.062) patients compared with healthy individuals (median 0.335) (P < 0.0001), while the NF-κB1 expression level was downregulated in the B-ALL CR group (median 0.339), which was significantly lower than that in those with B-ALL (P = 0.001). Moreover, the MALT1 expression level in B-ALL was upregulated (median 1.938) and significantly higher than that in healthy individuals (median 0.677) (P = 0.002) and B-ALL CR patients (median 0.153) (P = 0.008). The correlation of the expression levels of all three genes was lost in B-ALL. CONCLUSIONS: We found that MALT1-A20-NF-κB is overexpressed in adult B-ALL, which may be related to the pathogenesis of B-ALL, and this pathway may be considered a potentially attractive target for the development of B-ALL therapeutics.

Whole-Genome Resequencing-Based Qualitative Trait Locus Mapping Correlated yellow with the Mutant Color in Honeybees, Apis cerana cerana.

The honeybee, Apis cerana cerana (Ac), is an important pollinator and has adapted to the local ecological environment with relevant coloration. The cuticle coloration of the brown (br) mutant is brown instead of black in wild-type individuals. Therefore, this study aimed to identify and characterize the gene responsible for the br mutation. Genome resequencing with allele segregation measurement using Euclidean distance followed by Lowess regression analysis revealed that the color locus linked to the mutation was located on chromosome 11. A 2-base deletion on exon 4 was identified in the g7628 (yellow) gene after genome assembly and sequence cloning. In addition, the cuticle color of the abdomen of worker bees changed from black to brown when a defect was induced in the yellow gene using short interfering RNA (siRNA); however, the survival rate did not decrease significantly. These results indicate that the yellow gene participated in the body pigmentation, and its defect was responsible for the br mutation. This study promotes the understanding of the molecular basis of body coloration in honeybees, enriching the molecular mechanisms underlying insect pigmentation.

Viral infection and spread are inhibited by the polyubiquitination and downregulation of TRPV2 channel by the interferon-stimulated gene TRIM21.

Interferon (IFN) contributes to the host's antiviral response by inducing IFN-stimulated genes (ISGs). However, their functional targets and the mechanism of action remain elusive. Here, we report that one such ISG, TRIM21, interacts with and degrades the TRPV2 channel in myeloid cells, reducing its expression and providing host protection against viral infections. Moreover, viral infection upregulates TRIM21 in paracrine and autocrine manners, downregulating TRPV2 in neighboring cells to prevent viral spread to uninfected cells. Consistently, the Trim21-/- mice are more susceptible to HSV-1 and VSV infection than the Trim21+/+ littermates, in which viral susceptibility is rescued by inhibition or deletion of TRPV2. Mechanistically, TRIM21 catalyzes the K48-linked ubiquitination of TRPV2 at Lys295. TRPV2K295R is resistant to viral-infection-induced TRIM21-dependent ubiquitination and degradation, promoting viral infection more profoundly than wild-type TRPV2 when reconstituted into Lyz2-Cre;Trpv2fl/fl myeloid cells. These findings characterize targeting the TRIM21-TRPV2 axis as a conducive strategy to control viral spread to bystander cells.

Causal analysis of coach and bus accidents in China based on road alignments.

Given the complexity and the difficulty of controlling contributors effectively, road passenger transport often results in serious injuries and fatalities. The purpose of this study is to identify the main contributors to coach and bus accidents and to provide policy recommendations for making improvements in accident prevention. The Driving Reliability and Error Analysis Method 3.0 (DREAM 3.0) was modified and used to analyze the contributing factors (i.e. phenotypes and genotypes in DREAM) and their casual mechanisms. By having statistical analysis and social network analysis (SNA) adopted, the main genotypes and phenotypes of the DREAM charts were identified. The results of the study showed that A2.1 (too high speed) was the key phenotype and the main genotypic process chain leading to the phenotype was "inadequate safety management â†’ inadequate training â†’ inadequate skills/knowledge â†’ misjudgment of the situation â†’ too high speed" on all types of road. For A2.1 (too high speed), C2 (misjudgment of the situation) was the dominant genotype, while N5 (inadequate safety management) was the root cause of most genotypes. This suggests that road passenger transport companies, as the responsible parties, often fail to implement or violate safety prevention and control systems. Government regulators should promote the policy system and incentivize them to fulfil their safety management responsibilities. The government should also educate the public and improve the road environment to reduce passenger-related risks and the impact of environmental factors on drivers.

The differential expression pattern of the BMI-1, SALL4 and ABCA3 genes in myeloid leukemia.

BACKGROUND AND METHODS: In order to characterize the expression pattern of SALL4, BMI-1 and ABCA3 genes in patients with myeloid leukemia and those who achieved complete remission (CR) after chemotherapy. Real-time PCR was used to determine the expression level of these genes in peripheral blood mononuclear cells from 24 patients with AML, eight patients with AML-CR, 13 patients with CML in the chronic phase (CML-CP), 12 patients with CML in blast crisis (CML-BC), 13 patients with CML-CR and 11 healthy individuals (HI). RESULTS: Overexpression of the BMI-1 gene was found in the AML, CML-CP and CML-BC groups as compared with HI group, while the BMI-1 expression level was lower in patients who achieved CR. In contrast, significantly increased SALL4 expression was only found in AML group, additionally, SALL4 expression was lower in the CML-CP and CML-CR groups compared with the HI group, while the SALL4 expression level in the CML-BC group was higher and significantly greater than that in the CML-CP and CML-CR groups. Moreover, a positive correlation between the expression of SALL4 and BMI-1 genes was found in samples from most groups. There was no significant difference of ABCA3 expression level in AML and CML-BC group in comparison with HI group. Interestingly, the ABCA3 expression level was significantly decreased in the CML-CP, AML-CR and CML-CR in comparison with the HI group. Moreover, the ABCA3 expression level in all of the CR groups was lower than that in their corresponding groups. CONCLUSIONS: These results describe the altered SALL4, ABCA3 and BMI-1 expression pattern in different phases of myeloid leukemia, which may relate to the development and progression to different diseases. SALL4 expression was strongly correlated with BMI-1 in most of the myeloid leukemia patient groups, providing a potential link between SALL4 and BMI-1 in leukemogenesis.

Electroencephalographic Measurement on Post-stroke Sensory Deficiency in Response to Non-painful Cold Stimulation.

Background: Reduced elementary somatosensation is common after stroke. However, the measurement of elementary sensation is frequently overlooked in traditional clinical assessments, and has not been evaluated objectively at the cortical level. This study designed a new configuration for the measurement of post-stroke elementary thermal sensation by non-painful cold stimulation (NPCS). The post-stroke cortical responses were then investigated during elementary NPCS on sensory deficiency via electroencephalography (EEG) when compared with unimpaired persons. Method: Twelve individuals with chronic stroke and fifteen unimpaired controls were recruited. A 64-channel EEG system was used to investigate the post-stroke cortical responses objectively during the NPCS. A subjective questionnaire of cold sensory intensity was also administered via a numeric visual analog scale (VAS). Three water samples with different temperatures (i.e., 25, 10, and 0°C) were applied to the skin surface of the ventral forearm for 3 s via glass beaker, with a randomized sequence on either the left or right forearm of a participant. EEG relative spectral power (RSP) and topography were used to evaluate the neural responses toward NPCS with respect to the independent factors of stimulation side and temperature. Results: For unimpaired controls, NPCS initiated significant RSP variations, mainly located in the theta band with the highest discriminative resolution on the different temperatures (P < 0.001). For stroke participants, the distribution of significant RSP spread across all EEG frequency bands and the temperature discrimination was lower than that observed in unimpaired participants (P < 0.05). EEG topography showed that the NPCS could activate extensive and bilateral sensory cortical areas after stroke. Significant group differences on RSP intensities were obtained in each EEG band (P < 0.05). Meanwhile, significant asymmetry cortical responses in RSP toward different upper limbs were observed during the NPCS in both unimpaired controls and participants with stroke (P < 0.05). No difference was found between the groups in the VAS ratings of the different temperatures (P > 0.05). Conclusion: The post-stroke cortical responses during NPCS on sensory deficiency were characterized by the wide distribution of representative RSP bands, lowered resolution toward different temperatures, and extensive activated sensory cortical areas.

Engineering a Synthetic Pathway for Tyrosol Synthesis in Escherichia coli.

Tyrosol is an aromatic compound with great value that is widely used in the food and pharmaceutical industry. In this study, we reported a synthetic pathway for converting p-coumaric acid (p-CA) into tyrosol in Escherichia coli. We found that the enzyme cascade comprising ferulic acid decarboxylase (FDC1) from Saccharomyces cerevisiae, styrene monooxygenase (SMO), styrene oxide isomerase (SOI) from Pseudomonas putida, and phenylacetaldehyde reductase (PAR) from Solanum lycopersicum could efficiently synthesize tyrosol from p-CA with a conversion rate over 90%. To further expand the range of substrates, we also introduced tyrosine ammonia-lyase (TAL) from Flavobacterium johnsoniae to connect the synthetic pathway with the endogenous l-tyrosine metabolism. We found that tyrosol could be efficiently produced from glycerol, reaching 545.51 mg/L tyrosol in a tyrosine-overproducing strain under shake flasks. In summary, we have established alternative routes for tyrosol synthesis from p-CA (a potential lignin-derived biomass), glucose, and glycerol.

An Exoneuromusculoskeleton for Self-Help Upper Limb Rehabilitation After Stroke.

This article presents a novel electromyography (EMG)-driven exoneuromusculoskeleton that integrates the neuromuscular electrical stimulation (NMES), soft pneumatic muscle, and exoskeleton techniques, for self-help upper limb training after stroke. The developed system can assist the elbow, wrist, and fingers to perform sequential arm reaching and withdrawing tasks under voluntary effort control through EMG, with a lightweight, compact, and low-power requirement design. The pressure/torque transmission properties of the designed musculoskeletons were quantified, and the assistive capability of the developed system was evaluated on patients with chronic stroke (n = 10). The designed musculoskeletons exerted sufficient mechanical torque to support joint extension for stroke survivors. Compared with the limb performance when no assistance was provided, the limb performance (measured as the range of motion in joint extension) significantly improved when mechanical torque and NMES were provided (p < 0.05). A pilot trial was conducted on patients with chronic stroke (n = 15) to investigate the feasibility of using the developed system in self-help training and the rehabilitation effects of the system. All the participants completed the self-help device-assisted training with minimal professional assistance. After a 20-session training, significant improvements were noted in the voluntary motor function and release of muscle spasticity at the elbow, wrist, and fingers, as indicated by the clinical scores (p < 0.05). The EMG parameters (p < 0.05) indicated that the muscular coordination of the entire upper limb improved significantly after training. The results suggested that the developed system can effectively support self-help upper limb rehabilitation after stroke. ClinicalTrials.gov Register Number NCT03752775.