Effect of Wearable Sensor-Based Exercise on Musculoskeletal Disorders in Individuals With Neurodegenerative Diseases: A Systematic Review and Meta-Analysis

BackgroundThe application of wearable sensor technology in an exercise intervention provides a new method for the standardization and accuracy of intervention. Considering that the deterioration of musculoskeletal conditions is of serious concern in patients with neurodegenerative diseases, it is worthwhile to clarify the effect of wearable sensor-based exercise on musculoskeletal disorders in such patients compared with traditional exercise.MethodsFive health science-related databases, including PubMed, Cochrane Library, Embase, Web of Science, and Ebsco Cumulative Index to Nursing and Allied Health, were systematically searched. The protocol number of the study is PROSPERO CRD42022319763. Randomized controlled trials (RCTs) that were published up to March 2022 and written in English were included. Balance was the primary outcome measure, comprising questionnaires on postural stability and computerized dynamic posturography. The secondary outcome measures are motor symptoms, mobility ability, functional gait abilities, fall-associated self-efficacy, and adverse events. Stata version 16.0 was used for statistical analysis, and the weighted mean difference (WMD) was selected as the effect size with a 95% confidence interval (CI).ResultsFifteen RCTs involving 488 participants with mean ages ranging from 58.6 to 81.6 years were included in this review, with 14 of them being pooled in a quantitative meta-analysis. Only five included studies showed a low risk of bias. The Berg balance scale (BBS) was used in nine studies, and the pooled data showed a significant improvement in the wearable sensor-based exercise group compared with the traditional exercise group after 3–12-week intervention (WMD = 1.43; 95% CI, 0.50 to 2.36, P = 0.003). A significant change in visual score was found both post-assessment and at 1-month follow-up assessment (WMD = 4.38; 95% CI, 1.69 to 7.07, P = 0.001; I2 = 0.0%). However, no significant differences were found between the two groups in the secondary outcome measures (all p > 0.05). No major adverse events were reported.ConclusionThe wearable sensor-based exercise had advantages in improving balance in patients with neurodegenerative diseases, while there was a lack of evidence in motor symptoms, mobility, and functional gait ability enhancement. Future studies are recommended to construct a comprehensive rehabilitation treatment system for the improvement in both postural control and quality of life.Systematic Review Registrationhttp://www.crd.york.ac.uk/prospero/, identifier CRD42022319763

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

Heterologous Replicase from Cucumoviruses can Replicate Viral RNAs, but is Defective in Transcribing Subgenomic RNA4A or Facilitating Viral Movement

Interspecific exchange of RNA1 or RNA2 between the cucumoviruses cucumber mosaic virus (CMV) and tomato aspermy virus (TAV) was reported to be non-viable in plants previously. Here we investigated viability of the reassortants between CMV and TAV in Nicotiana benthamiana plants by Agrobacterium-mediated viral inoculation. The reassortants were composed of CMV RNA1 and TAV RNA2 plus RNA3 replicated in the inoculated leaves, while they were defective in viral systemic movement at the early stage of infection. Interestingly, the reassortant containing TAV RNA1 and CMV RNA2 and RNA3 infected plants systemically, but produced RNA4A (the RNA2 subgenome) at an undetectable level. The defect in production of RNA4A was due to the 1a protein encoded by TAV RNA1, and partially restored by replacing the C-terminus (helicase domain) in TAV 1a with that of CMV 1a. Collectively, exchange of the replicase components between CMV and TAV was acceptable for viral replication, but was defective in either directing transcription of subgenomic RNA4A or facilitating viral long-distance movement. Our finding may shed some light on evolution of subgenomic RNA4A in the family Bromoviridae

CONSTANS-Like 9 (OsCOL9) Interacts with Receptor for Activated C-Kinase 1(OsRACK1) to Regulate Blast Resistance through Salicylic Acid and Ethylene Signaling Pathways

<div><p>In a previous transcriptome analysis of early response genes in rice during <i>Magnaporthe oryzae</i> infection, we identified a CONSTANS-like (<i>COL</i>) gene <i>OsCOL9</i>. In the present study, we investigated the functional roles of <i>OsCOL9</i> in blast resistance. <i>OsCOL9</i> belonged to group II of the COL protein family, and it contained a BB-box and a C-terminal CCT (CONSTANS, COL and TOC1) domain. <i>OsCOL9</i> was found in the nucleus of rice cells, and it exerted transcriptional activation activities through its middle region (MR). <i>Magnaporthe oryzae</i> infection induced <i>OsCOL9</i> expression, and transgenic <i>OsCOL9</i> knock-out rice plants showed increased pathogen susceptibility. <i>OsCOL9</i> was a critical regulator of pathogen-related genes, especially <i>PR1b</i>, which were also activated by exogenous salicylic acid (SA) and 1-aminocyclopropane-1-carboxylicacid (ACC), the precursor of ethylene (ET). Further analysis indicated that <i>OsCOL9</i> over-expression increased the expressions of phytohormone biosynthetic genes, <i>NPR1</i>, <i>WRKY45</i>, <i>OsACO1</i> and <i>OsACS1</i>, which were related to SA and ET biosynthesis. Interestingly, we found that OsCOL9 physically interacted with the scaffold protein OsRACK1 through its CCT domain, and the <i>OsRACK1</i> expression was induced in response to exogenous SA and ACC as well as <i>M</i>. <i>oryzae</i> infection. Taken together, these results indicated that the COL protein OsCOL9 interacted with OsRACK1, and it enhanced the rice blast resistance through SA and ET signaling pathways.</p></div

Expression of <i>OsRACK1</i> when induced by <i>M</i>. <i>oryzae</i> infection as well as SA and ACC treatments.

<p>(A), (B) and (C) represents the relative expression of <i>OsRACK1</i> treated by <i>M</i>. <i>oryzae</i>, SA and ACC after 48 h, respectively. H₂O was used as control. Values shown are means±SD from three independent experiments. (D), Quantitative real-time PCR analyses of <i>OsRACK1</i> expression in WT and <i>OsCOL9</i> transgenic plants. Error bars indicate the SD and asterisks indicate a significant difference according to the t-test (*P<0.05) compared with the corresponding controls.</p

Nuclear localization and transcriptional activity of OsCOL9.

<p>(A) Subcellular localization of OsCOL9 in rice protoplast cells. 35S:GFP served as control and 35S:OsMADS3-mCherry served as a nuclear marker. Cell fluorescence was observed using confocal microscope at 12 h post-transformation. OsCOL9-GFP signals are green, and the nuclear signals are red. Merged images of GFP, mCherry and bright-fields are shown. Scale bar is 5 μm. (B) Transcriptional activation analysis of OsCOL9 and three truncated mutants (B-box, MR and CCT) fused with the yeast GAL4 DNA-binding domain. Full-length OsCOL9 and the truncated mutants were fused with pGBKT7, and the constructs were transformed into Y2H Gold yeast cells. Transcriptional activation activity was determined according to the ability to activate the expression of His, Ade and X-α-Gal reporter genes in yeast. BD-OsCOL9 and BD-MR transformants were selected on SD/-Trp/-His/-Ade plates containing X-α-Gal and 100 mM 3-AT. OsCOL9 and its MR domain contained the transcriptional activity by a positive (+) reaction in the X-α-Gal assay.</p

The expression of SA and ET pathway-related genes in <i>OsCOL9-OX</i> and <i>oscol9-ko</i> lines.

<p>(A) The relative expressions of <i>NPR1</i> and <i>WRKY45</i> in <i>OsCOL9-OX</i>, <i>oscol9-ko</i> and wild-type plants. (B) Gene expressions of enzymes that restrict ACC synthesis: <i>OsACS1</i>, <i>OsACO2</i>, <i>OsACO7</i> and <i>OsACO1</i>. Values shown are means±SD from three independent experiments. Error bars indicate the SD and asterisks indicate a significant difference according to the t-test (*P<0.05) compared with the wild-type plants.</p

Identification of <i>OsCOL9</i> transgenic plants.

<p>(A) Schematic structure of transgenic vector construction. (B) Target sequence alignment of <i>OsCOL9</i> CRISPR/Cas9 splice sites. The blue sequence of wild-type is the PAM sequence, and the red sequence is a paired gRNA binding site compared with wild-type. Blue and red regions were spliced by the CRISPR/CAs9 endonuclease in the <i>OsCOL9</i> genome sequence. (C) Expression analysis of <i>OsCOL9</i> in over-expression and knock-out lines was measured by RT-PCR and compared with the wild-type line. Values shown are means±SD from three independent experiments (**P<0.01). (D) Morphologies of wild-type, <i>OsCOL9-OX</i> (left) and <i>oscol9-ko</i> (right). The photograph was taken 50 days after heading of transgenic plants (T1 generation) and wild-type plants. The scale bar is 8 cm.</p

Identification of OsCOL9 and OsRACK1 interactions.

<p>(A). Yeast two-hybrid assay showed interaction between OsCOL9 CCT domain and OsRACK1. (B). Bimolecular fluorescence complementation (BiFC) assays showed the interaction between OsCOL9 and OsRACK1 in rice protoplasts. Scale bars are 5 μm. C. <i>In vitro</i> pull-down assay suggested the direct interaction between the OsCOL9 CCT domain and OsRACK1.</p