A review on the usability,flexibility, affinity, and affordability of virtual technology for rehabilitation training of upper limb amputees

(1) Background: Prosthetic rehabilitation is essential for upper limb amputees to regain their ability to work. However, the abandonment rate of prosthetics is higher than 50% due to the high cost of rehabilitation. Virtual technology shows potential for improving the availability and cost-effectiveness of prosthetic rehabilitation. This article systematically reviews the application of virtual technology for the prosthetic rehabilitation of upper limb amputees.(2) Methods: We followed PRISMA review guidance, STROBE, and CASP to evaluate the included articles. Finally, 17 articles were screened from 22,609 articles.(3) Results: This study reviews the possible benefits of using virtual technology from four aspects: usability, flexibility, psychological affinity, and long-term affordability. Three significant challenges are also discussed: realism, closed-loop control, and multi-modality integration.(4) Conclusions: Virtual technology allows for flexible and configurable control rehabilitation, both during hospital admissions and after discharge, at a relatively low cost. The technology shows promise in addressing the critical barrier of current prosthetic training issues, potentially improving the practical availability of prosthesis techniques for upper limb amputees

Crystal structure of the N domain of Lon protease from Mycobacterium avium complex.

Lon protease is evolutionarily conserved in prokaryotes and eukaryotic organelles. The primary function of Lon is to selectively degrade abnormal and certain regulatory proteins to maintain the homeostasis in vivo. Lon mainly consists of three functional domains and the N-terminal domain is required for the substrate selection and recognition. However, the precise contribution of the N-terminal domain remains elusive. Here, we determined the crystal structure of the N-terminal 192-residue construct of Lon protease from Mycobacterium avium complex at 2.4 å resolution，and measured NMR-relaxation parameters of backbones. This structure consists of two subdomains, the β-strand rich N-terminal subdomain and the five-helix bundle of C-terminal subdomain, connected by a flexible linker，and is similar to the overall structure of the N domain of Escherichia coli Lon even though their sequence identity is only 26%. The obtained NMR-relaxation parameters reveal two stabilized loops involved in the structural packing of the compact N domain and a turn structure formation. The performed homology comparison suggests that structural and sequence variations in the N domain may be closely related to the substrate selectivity of Lon variants. Our results provide the structure and dynamics characterization of a new Lon N domain, and will help to define the precise contribution of the Lon N-terminal domain to the substrate recognition

Schistosoma japonicum SjE16.7 Protein Promotes Tumor Development via the Receptor for Advanced Glycation End Products (RAGE).

Schistosome infection contributes to cancer development, but the mechanisms are still not well-understood. SjE16.7 is an EF-hand calcium-binding protein secreted from Schistosoma japonicum eggs. It is a neutrophil attractant and macrophage activator and, as such, plays an important role in the inflammatory granuloma response in schistosomiasis. Here, we show that SjE16.7 binds to host cells by interacting with receptors for advanced glycation end products (RAGE). This ligation leads to activation of the NF-κB signaling pathway, an increase in the generation of reactive oxygen species, and production of the pro-inflammatory cytokines IL-6 and TNF-α. Using a mouse model of colorectal cancer, we demonstrate that intraperitoneal injection of SjE16.7 promotes colorectal cancer progression along with systemic myeloid cell accumulation. Thus, our results identify a new helminth antigen contributing to tumor development in the mammalian host

PRL2 Controls Phagocyte Bactericidal Activity by Sensing and Regulating ROS

Although it is well-recognized that inflammation enhances leukocyte bactericidal activity, the underlying mechanisms are not clear. Here we report that PRL2 is sensitive to oxidative stress at inflamed sites. Reduced PRL2 in phagocytes causes increased respiratory burst activity and enhances phagocyte bactericidal activity. PRL2 (Phosphatase Regenerating Liver 2) is highly expressed in resting immune cells, but is markedly downregulated by inflammation. in vitro experiments showed that PRL2 was sensitive to hydrogen peroxide (H2O2), a common damage signal at inflamed sites. In response to infection, PRL2 knockout (KO) phagocytes were hyper activated, produced more reactive oxygen species (ROS) and exhibited enhanced bactericidal activity. Mice with PRL2 deficiency in the myeloid cell compartment were resistant to lethal listeria infection and cleared the bacteria more rapidly and effectively. Moreover, in vitro experiments demonstrated that PRL2 binds to GTPase Rac and regulates ROS production. Rac GTPases were more active in PRL2 (KO) phagocytes than in wild type cells after bacterium infection. Our findings indicate that PRL2 senses ROS at inflamed sites and regulates ROS production in phagocytes. This positive feedback mechanism promotes bactericidal activity of phagocytes and may play an important role in innate anti-bacterial immunity

(1)H, (13)C, (15)N backbone and side-chain resonance assignments of the human Raf-1 kinase inhibitor protein

Raf-1 kinase inhibitor protein (RKIP) plays a pivotal role in modulating multiple signaling networks. Here we report backbone and side chain resonance assignments of uniformly (15)N, (13)C labeled human RKIP.Natural Science Foundation of China[30900233, 30730026]; Program of Shanghai Subject Chief Scientist[09XD1405100

Suramin Disturbs the Association of the N-Terminal Domain of SARS-CoV-2 Nucleocapsid Protein with RNA

Suramin was originally used as an antiparasitic drug in clinics. Here, we demonstrate that suramin can bind to the N-terminal domain of SARS-CoV-2 nucleocapsid protein (N-NTD) and disturb its interaction with RNA. The BLI experiments showed that N-NTD interacts suramin with a dissociate constant (Kd = 2.74 μM) stronger than that of N-NTD with ssRNA-16 (Kd = 8.37 μM). Furthermore, both NMR titration experiments and molecular docking analysis suggested that suramin mainly binds to the positively charged cavity between the finger and the palm subdomains of N-NTD, and residues R88, R92, R93, I94, R95, K102 and A156 are crucial for N-NTD capturing suramin. Besides, NMR dynamics experiments showed that suramin-bound N-NTD adopts a more rigid structure, and the loop between β2-β3 exhibits fast motion on the ps-ns timescale, potentially facilitating suramin binding. Our findings not only reveal the molecular basis of suramin disturbing the association of SARS-CoV-2 N-NTD with RNA but also provide valuable structural information for the development of drugs against SARS-CoV-2

Structural and Functional Insights into the Stealth Protein CpsY of <i>Mycobacterium tuberculosis</i>

Mycobacterium tuberculosis (Mtb) is an important and harmful intracellular pathogen that is responsible for the cause of tuberculosis (TB). Mtb capsular polysaccharides can misdirect the host’s immune response pathways, resulting in additional challenges in TB treatment. These capsule polysaccharides are biosynthesized by stealth proteins, including CpsY. The structure and functional mechanism of Mtb CpsY are not completely delineated. Here, we reported the crystal structure of CpsY201−520 at 1.64 Å. CpsY201−520 comprises three β-sheets with five α-helices on one side and three on the other. Four conserved regions (CR1–CR4) are located near and at the base of its catalytic cavity, and three spacer segments (S1–S3) surround the catalytic cavity. Site-directed mutagenesis demonstrated the strict conservation of R419 at CR3 and S1–S3 in regulating the phosphotransferase activity of CpsY201−520. In addition, deletion of S2 or S3 (∆S2 or ∆S3) dramatically increased the activity compared to the wild-type (WT) CpsY201−520. Results from molecular dynamics (MD) simulations showed that S2 and S3 are highly flexible. Our study provides new insights for the development of new vaccines and targeted immunotherapy against Mtb.</i

Suramin Targets the Conserved Ligand-Binding Pocket of Human Raf1 Kinase Inhibitory Protein

Suramin was initially used to treat African sleeping sickness and has been clinically tested to treat human cancers and HIV infection in the recent years. However, the therapeutic index is low with numerous clinical side-effects, attributed to its diverse interactions with multiple biological macromolecules. Here, we report a novel binding target of suramin, human Raf1 kinase inhibitory protein (hRKIP), which is an important regulatory protein involved in the Ras/Raf1/MEK/ERK (MAPK) signal pathway. Biolayer interference technology showed that suramin had an intermediate affinity for binding hRKIP with a dissociation constant of 23.8 µM. Both nuclear magnetic resonance technology and molecular docking analysis revealed that suramin bound to the conserved ligand-binding pocket of hRKIP, and that residues K113, W173, and Y181 play crucial roles in hRKIP binding suramin. Furthermore, suramin treatment at 160 µM could profoundly increase the ERK phosphorylation level by around 3 times. Our results indicate that suramin binds to hRKIP and prevents hRKIP from binding with hRaf1, thus promoting the MAPK pathway. This work is beneficial to both mechanistically understanding the side-effects of suramin and efficiently improving the clinical applications of suramin

H-1, C-13, N-15 backbone and side-chain resonance assignments of the human Raf-1 kinase inhibitor protein

Natural Science Foundation of China [30900233, 30730026]; Program of Shanghai Subject Chief Scientist [09XD1405100]Raf-1 kinase inhibitor protein (RKIP) plays a pivotal role in modulating multiple signaling networks. Here we report backbone and side chain resonance assignments of uniformly N-15, C-13 labeled human RKIP

Crystal structure of the polyketide cyclase from Mycobacterium tuberculosis

About 40% of proteins are classified as conserved hypothetical proteins in Mycobacterium tuberculosis (TB). Identification and characterization of these proteins are beneficial to understand the pathogenesis of TB and exploiting novel drugs for TB treatments. The polyketide cyclase, a protein from M. tuberculosis (MtPC) has been annotated as a hypothetical protein in Uniprot database. Sequence analysis shows that the MtPC belongs to the NTF2-like superfamily proteins with diverse functions. Here, we determined the crystal structure of MtPC at a resolution of 2.4 Å and measured backbone relaxation parameters for the MtPC protein. MtPC exists as a dimer in solution, and each subunit contains a six-stranded mixed β-sheet and three α helixes which are arranged in the order α1-α2-β1-β2-α3-β3-β4-β5-β6. The NMR dynamics analysis showed that the overall structure of MtPC is highly rigid on ps-ns time scales. Furthermore, we predicted the potential function of MtPC based on the crystal structure. Our results lay the basis for further exploiting and mechanistically understanding the biological functions of MtPC.<?A3B2 tlsb?