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To minimize fatigue, sustain workloads, and reduce the risk of injuries, the exoskeleton Carry was developed. Carry combines a soft human–machine interface and soft pneumatic actuation to assist the elbow in load holding and carrying. We hypothesize that the assistance of Carry would decrease, muscle activity, net metabolic rate, and fatigue. With Carry providing 7.2 Nm of assistance, we found reductions of up to 50% for the muscle activity, up to 61% for the net metabolic rate, and up to 99% for fatigue in a group study of 12 individuals. Analyses of operation dynamics and autonomous use demonstrate the applicability of Carry to a variety of use cases, presumably with increased benefits for increased assistance torque. The significant benefits of Carry indicate this device could prevent systemic, aerobic, and/or possibly local muscle fatigue that may increase the risk of joint degeneration and pain due to lifting, holding, or carrying.

Dear Editor, Ginseng has been traditionally used as herbal medicine in Asia for thousands of years to enhance physical performance and to increase resistance to stress and aging, and has been developed into various kinds of dietary supplement with increasing market demand. Its active constituents are ginsenosides, a group of triterpene saponins （ca. 2% in Panax ginseng dried roots） . However,

In December 2019, coronavirus disease 2019 (COVID-19), which is caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in Wuhan (Hubei province, China) 1 ; it soon spread across the world. In this ongoing pandemic, public health concerns and the urgent need for effective therapeutic measures require a deep understanding of the epidemiology, transmissibility and pathogenesis of COVID-19. Here we analysed clinical, molecular and immunological data from 326 patients with confirmed SARS-CoV-2 infection in Shanghai. The genomic sequences of SARS-CoV-2, assembled from 112 high-quality samples together with sequences in the Global Initiative on Sharing All Influenza Data (GISAID) dataset, showed a stable evolution and suggested that there were two major lineages with differential exposure history during the early phase of the outbreak in Wuhan. Nevertheless, they exhibited similar virulence and clinical outcomes. Lymphocytopenia, especially reduced CD4 + and CD8 + T cell counts upon hospital admission, was predictive of disease progression. High levels of interleukin (IL)-6 and IL-8 during treatment were observed in patients with severe or critical disease and correlated with decreased lymphocyte count. The determinants of disease severity seemed to stem mostly from host factors such as age and lymphocytopenia (and its associated cytokine storm), whereas viral genetic variation did not significantly affect outcomes. Genome sequences from 112 patients with confirmed SARS-CoV-2 infection showed two clades of SARS-CoV-2 virus with similar virulence and clinical outcome, and clinical data from 326 cases suggest that T cell depletion and cytokine bursts are associated with a worse prognosis.

Taxol is a widely-applied anticancer drug that inhibits microtubule dynamics in actively replicating cells. Although a minimum 19-step biosynthetic pathway has been proposed and 16 enzymes likely involved have been characterized, stepwise biosynthetic reactions from the well-characterized di-oxygenated taxoids to Taxol tetracyclic core skeleton are yet to be elucidated. Here, we uncover the biosynthetic pathways for a few tri-oxygenated taxoids via confirming the critical reaction order of the second and third hydroxylation steps, unearth a taxoid 9 α -hydroxylase catalyzing the fourth hydroxylation, and identify CYP725A55 catalyzing the oxetane ester formation via a cascade oxidation-concerted acyl rearrangement mechanism. After identifying a acetyltransferase catalyzing the formation of C7-OAc, the pathway producing the highly-oxygenated 1 β -dehydroxybaccatin VI with the Taxol tetracyclic core skeleton is elucidated and its complete biosynthesis from taxa-4(20),11(12)-diene-5 α -ol is achieved in an engineered yeast. These systematic studies lay the foundation for the complete elucidation of the biosynthetic pathway of Taxol. Despite intensive investigation, stepwise reactions from diol to Taxol tetracyclic core skeleton remain unclear. Here, authors fill this gap by identifying two P450s and confirming the reaction order.

On March 30, 2013, a novel avian influenza A H7N9 virus that infects human beings was identified. This virus had been detected in six provinces and municipal cities in China as of April 18, 2013. We correlated genomic sequences from avian influenza viruses with ecological information and did phylogenetic and coalescent analyses to extrapolate the potential origins of the virus and possible routes of reassortment events. We downloaded H7N9 virus genome sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID) database and public sequences used from the Influenza Virus Resource. We constructed phylogenetic trees and did 1000 bootstrap replicates for each tree. Two rounds of phylogenetic analyses were done. We used at least 100 closely related sequences for each gene to infer the overall topology, removed suspicious sequences from the trees, and focused on the closest clades to the novel H7N9 viruses. We compared our tree topologies with those from a bayesian evolutionary analysis by sampling trees (BEAST) analysis. We used the bayesian Markov chain Monte Carlo method to jointly estimate phylogenies, divergence times, and other evolutionary parameters for all eight gene fragments. We used sequence alignment and homology-modelling methods to study specific mutations regarding phenotypes, specifically addressing the human receptor binding properties. The novel avian influenza A H7N9 virus originated from multiple reassortment events. The HA gene might have originated from avian influenza viruses of duck origin, and the NA gene might have transferred from migratory birds infected with avian influenza viruses along the east Asian flyway. The six internal genes of this virus probably originated from two different groups of H9N2 avian influenza viruses, which were isolated from chickens. Detailed analyses also showed that ducks and chickens probably acted as the intermediate hosts leading to the emergence of this virulent H7N9 virus. Genotypic and potential phenotypic differences imply that the isolates causing this outbreak form two separate subclades. The novel avian influenza A H7N9 virus might have evolved from at least four origins. Diversity among isolates implies that the H7N9 virus has evolved into at least two different lineages. Unknown intermediate hosts involved might be implicated, extensive global surveillance is needed, and domestic-poultry-to-person transmission should be closely watched in the future. China Ministry of Science and Technology Project 973, National Natural Science Foundation of China, China Health and Family Planning Commission, Chinese Academy of Sciences.

Formic acid (FA) has emerged as a promising one-carbon feedstock for biorefinery. However, developing efficient microbial hosts for economically competitive FA utilization remains a grand challenge. Here, we discover that the bacterium Vibrio natriegens has exceptional FA tolerance and metabolic capacity natively. This bacterium is remodeled by rewiring the serine cycle and the TCA cycle, resulting in a non-native closed loop (S-TCA) which as a powerful metabolic sink, in combination with laboratory evolution, enables rapid emergence of synthetic strains with significantly improved FA-utilizing ability. Further introduction of a foreign indigoidine-forming pathway into the synthetic V. natriegens strain leads to the production of 29.0 g · L −1 indigoidine and consumption of 165.3 g · L −1 formate within 72 h, achieving a formate consumption rate of 2.3 g · L −1  · h −1 . This work provides an important microbial chassis as well as design rules to develop industrially viable microorganisms for FA biorefinery. Formic acid (FA) is a promising CO2-equivalent feedstock for onecarbon biorefinery, but microbial host that can efficiently utilize FA is unavailable. Here, the authors engineer a non-native closed loop in Vibrio natriegens and demonstrate its application in promoting FA utilization.

Eukaryotic genomes are generally organized in multiple chromosomes. Here we have created a functional single-chromosome yeast from a Saccharomyces cerevisiae haploid cell containing sixteen linear chromosomes, by successive end-to-end chromosome fusions and centromere deletions. The fusion of sixteen native linear chromosomes into a single chromosome results in marked changes to the global three-dimensional structure of the chromosome due to the loss of all centromere-associated inter-chromosomal interactions, most telomere-associated inter-chromosomal interactions and 67.4% of intra-chromosomal interactions. However, the single-chromosome and wild-type yeast cells have nearly identical transcriptome and similar phenome profiles. The giant single chromosome can support cell life, although this strain shows reduced growth across environments, competitiveness, gamete production and viability. This synthetic biology study demonstrates an approach to exploration of eukaryote evolution with respect to chromosome structure and function. Successive fusion of yeast chromosomes is used to produce a single-chromosome strain that is viable, albeit with slightly reduced fitness.

Calorie restriction has been regarded as the only experimental regimen that can effectively lengthen lifespan in various animal models, but the actual mechanism remains controversial. The gut microbiota has been shown to have a pivotal role in host health, and its structure is mostly shaped by diet. Here we show that life-long calorie restriction on both high-fat or low-fat diet, but not voluntary exercise, significantly changes the overall structure of the gut microbiota of C57BL/6 J mice. Calorie restriction enriches phylotypes positively correlated with lifespan, for example, the genus Lactobacillus on low-fat diet, and reduces phylotypes negatively correlated with lifespan. These calorie restriction-induced changes in the gut microbiota are concomitant with significantly reduced serum levels of lipopolysaccharide-binding protein, suggesting that animals under calorie restriction can establish a structurally balanced architecture of gut microbiota that may exert a health benefit to the host via reduction of antigen load from the gut. Calorie restriction has been shown to extend lifespan in diverse model systems, however, the mechanisms underlying this effect remain unclear. Zhang et al. show that calorie restriction changes the structure of the gut microbiota in mice, enriching for phylotypes positively correlated with lifespan.

This study aims to improve our understanding of gait initiation mechanisms and the lower-limb joint mechanical energy contributions. Healthy subjects were instructed to initiate gait on an instrumented track to reach three self-selected target velocities: slow, normal and fast. Lower-limb joint kinematics and kinetics of the first five strides were analyzed. The results show that the initial lateral weight shift is achieved by hip abduction torque on the lifting leg (leading limb). Before the take-off of the leading limb, the forward body movement is initiated by decreasing ankle plantarflexion torque, which results in an inverted pendulum-like passive forward fall. The hip flexion/extension joint has the greatest positive mechanical energy output in the first stride of the leading limb, while the ankle joint contributes the most positive mechanical energy in the first stride of the trailing limb (stance leg). Our results indicate a strong correlation between control of the frontal plane and the sagittal plane joints during gait initiation. The identified mechanisms and the related data can be used as a guideline for improving gait initiation with wearable robots such as exoskeletons and prostheses.