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1.
Article in English | MEDLINE | ID: mdl-38725372

ABSTRACT

BACKGROUND: Autosomal-recessive mutations in SPEG (striated muscle preferentially expressed protein kinase) have been linked to centronuclear myopathy with or without dilated cardiomyopathy (CNM5). Loss of SPEG is associated with defective triad formation, abnormal excitation-contraction coupling, calcium mishandling and disruption of the focal adhesion complex in skeletal muscles. To elucidate the underlying molecular pathways, we have utilized multi-omics tools and analysis to obtain a comprehensive view of the complex biological processes and molecular functions. METHODS: Skeletal muscles from 2-month-old SPEG-deficient (Speg-CKO) and wild-type (WT) mice were used for RNA sequencing (n = 4 per genotype) to profile transcriptomics and mass spectrometry (n = 4 for WT; n = 3 for Speg-CKO mice) to profile proteomics and phosphoproteomics. In addition, interactomics was performed using the SPEG antibody on pooled muscle lysates (quadriceps, gastrocnemius and triceps) from WT and Speg-CKO mice. Based on the multi-omics results, we performed quantitative real-time PCR, co-immunoprecipitation and immunoblot to verify the findings. RESULTS: We identified that SPEG interacts with myospryn complex proteins CMYA5, FSD2 and RyR1, which are critical for triad formation, and that SPEG deficiency results in myospryn complex abnormalities (protein levels decreased to 22 ± 3% for CMYA5 [P < 0.05] and 18 ± 3% for FSD2 [P < 0.01]). Furthermore, SPEG phosphorylates RyR1 at S2902 (phosphorylation level decreased to 55 ± 15% at S2902 in Speg-CKO mice; P < 0.05), and its loss affects JPH2 phosphorylation at multiple sites (increased phosphorylation at T161 [1.90 ± 0.24-fold], S162 [1.61 ± 0.37-fold] and S165 [1.66 ± 0.13-fold]; decreased phosphorylation at S228 and S231 [39 ± 6%], S234 [50 ± 12%], S593 [48 ± 3%] and S613 [66 ± 10%]; P < 0.05 for S162 and P < 0.01 for other sites). On analysing the transcriptome, the most dysregulated pathways affected by SPEG deficiency included extracellular matrix-receptor interaction (P < 1e-15) and peroxisome proliferator-activated receptor signalling (P < 9e-14). CONCLUSIONS: We have elucidated the critical role of SPEG in the triad as it works closely with myospryn complex proteins (CMYA5, FSD2 and RyR1), it regulates phosphorylation levels of various residues in JPH2 and S2902 in RyR1, and its deficiency is associated with dysregulation of several pathways. The study identifies unique SPEG-interacting proteins and their phosphorylation functions and emphasizes the importance of using a multi-omics approach to comprehensively evaluate the molecular function of proteins involved in various genetic disorders.

2.
J Hazard Mater ; 472: 134581, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38743972

ABSTRACT

Microplastics (MPs) and antibiotic resistance genes (ARGs) are two types of contaminants that are widely present in the soil environment. MPs can act as carriers of microbes, facilitating the colonization and spread of ARGs and thus posing potential hazards to ecosystem safety and human health. In the present study, we explored the microbial networks and ARG distribution characteristics in different soil types (heavy metal (HM)-contaminated soil and agricultural soil planted with different plants: Bidens pilosa L., Ipomoea aquatica F., and Brassica chinensis L.) after the application of MPs and evaluated environmental factors, potential microbial hosts, and ARGs. The microbial communities in the three rhizosphere soils were closely related to each other, and the modularity of the microbial networks was greater than 0.4. Moreover, the core taxa in the microbial networks, including Actinobacteriota, Proteobacteria, and Myxococcota, were important for resisting environmental stress. The ARG resistance mechanisms were dominated by antibiotic efflux in all three rhizosphere soils. Based on the annotation results, the MP treatments induced changes in the relative abundance of microbes carrying ARGs, and the G1-5 treatment significantly increased the abundance of MuxB in Verrucomicrobia, Elusimicrobia, Actinobacteria, Planctomycetes, and Acidobacteria. Path analysis showed that changes in MP particle size and dosage may indirectly affect soil enzyme activities by changing pH, which affects microbes and ARGs. We suggest that MPs may provide surfaces for ARG accumulation, leading to ARG enrichment in plants. In conclusion, our results demonstrate that MPs, as potentially persistent pollutants, can affect different types of soil environments and that the presence of ARGs may cause substantial environmental risks.


Subject(s)
Drug Resistance, Microbial , Ipomoea , Microplastics , Soil Microbiology , Soil Pollutants , Soil Pollutants/toxicity , Microplastics/toxicity , Ipomoea/genetics , Ipomoea/drug effects , Drug Resistance, Microbial/genetics , Rhizosphere , Polyethylene , Genes, Bacterial/drug effects , Brassica/genetics , Brassica/drug effects , Brassica/microbiology , Bacteria/drug effects , Bacteria/genetics , Bacteria/classification , Soil/chemistry , Metals, Heavy/toxicity , Microbiota/drug effects
3.
Sci Rep ; 14(1): 9617, 2024 04 26.
Article in English | MEDLINE | ID: mdl-38671062

ABSTRACT

Brain-computer interfaces (BCIs) that reconstruct and synthesize speech using brain activity recorded with intracranial electrodes may pave the way toward novel communication interfaces for people who have lost their ability to speak, or who are at high risk of losing this ability, due to neurological disorders. Here, we report online synthesis of intelligible words using a chronically implanted brain-computer interface (BCI) in a man with impaired articulation due to ALS, participating in a clinical trial (ClinicalTrials.gov, NCT03567213) exploring different strategies for BCI communication. The 3-stage approach reported here relies on recurrent neural networks to identify, decode and synthesize speech from electrocorticographic (ECoG) signals acquired across motor, premotor and somatosensory cortices. We demonstrate a reliable BCI that synthesizes commands freely chosen and spoken by the participant from a vocabulary of 6 keywords previously used for decoding commands to control a communication board. Evaluation of the intelligibility of the synthesized speech indicates that 80% of the words can be correctly recognized by human listeners. Our results show that a speech-impaired individual with ALS can use a chronically implanted BCI to reliably produce synthesized words while preserving the participant's voice profile, and provide further evidence for the stability of ECoG for speech-based BCIs.


Subject(s)
Amyotrophic Lateral Sclerosis , Brain-Computer Interfaces , Speech , Humans , Amyotrophic Lateral Sclerosis/physiopathology , Amyotrophic Lateral Sclerosis/therapy , Male , Speech/physiology , Middle Aged , Electrodes, Implanted , Electrocorticography
4.
Angiology ; 75(5): 441-453, 2024 May.
Article in English | MEDLINE | ID: mdl-36788038

ABSTRACT

Numerous studies have shown that a low level of high-density lipoprotein cholesterol (HDL-C) is an independent biomarker of cardiovascular disease. High-density lipoprotein (HDL) is considered to be a protective factor for atherosclerosis (AS). Therefore, raising HDL-C has been widely recognized as a promising strategy to treat atherosclerotic cardiovascular diseases (ASCVD). However, several studies have found that increasing HDL-C levels does not necessarily reduce the risk of ASCVD. HDL particles are highly heterogeneous in structure, composition, and biological function. Moreover, HDL particles from atherosclerotic patients exhibit impaired anti-atherogenic functions and these dysfunctional HDL particles might even promote ASCVD. This makes it uncertain that HDL-raising therapy will prevent and treat ASCVD. It is necessary to comprehensively analyze the structure and function of HDL subfractions. We review current advances related to HDL subfractions remodeling and highlight how current lipid-modifying drugs such as niacin, statins, fibrates, and cholesteryl ester transfer protein inhibitors regulate cholesterol concentration of HDL and specific HDL subfractions.


Subject(s)
Atherosclerosis , Cardiovascular Diseases , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Humans , Cardiovascular Diseases/prevention & control , Lipoproteins, HDL , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Cholesterol , Cholesterol, HDL , Atherosclerosis/drug therapy , Atherosclerosis/prevention & control
5.
Microorganisms ; 11(11)2023 Oct 26.
Article in English | MEDLINE | ID: mdl-38004643

ABSTRACT

Fowl adenovirus-induced hepatitis-pericardial effusion syndrome outbreaks have been increasingly reported in China since 2015, resulting in substantial economic losses to the poultry industry. The genetic diversity of indigenous chicken results in different immune traits, affecting the evolution of these viruses. Although the molecular epidemiology of fowl adenovirus serotype 4 (FAdV-4) has been well studied in commercial broiler and layer chickens, the prevalence and genetic characteristics of FAdV-4 in indigenous chickens remain largely unknown. In this study, samples were collected from six indigenous chicken breeds in Yunnan province, China. FAdV-positive samples were identified in five of the six indigenous chicken populations via PCR and 10 isolates were obtained. All FAdVs belonged to serotype FAdV-4 and species FAdV-C. The hexon, fiber, and penton gene sequence comparison analysis demonstrated that the prevalence of FAdV-4 isolates in these chickens might have originated from other provinces that exported chicks and poultry products to Yunnan province. Moreover, several distinct amino acid mutations were firstly identified in the major structural proteins. Our findings highlighted the need to decrease inter-regional movements of live poultry to protect indigenous chicken genetic resources and that the immune traits of these indigenous chickens might result in new mutations of FAdV-4 strains.

6.
Res Sq ; 2023 Sep 25.
Article in English | MEDLINE | ID: mdl-37841873

ABSTRACT

Background: Brain-computer interfaces (BCIs) can restore communication in movement- and/or speech-impaired individuals by enabling neural control of computer typing applications. Single command "click" decoders provide a basic yet highly functional capability. Methods: We sought to test the performance and long-term stability of click-decoding using a chronically implanted high density electrocorticographic (ECoG) BCI with coverage of the sensorimotor cortex in a human clinical trial participant (ClinicalTrials.gov, NCT03567213) with amyotrophic lateral sclerosis (ALS). We trained the participant's click decoder using a small amount of training data (< 44 minutes across four days) collected up to 21 days prior to BCI use, and then tested it over a period of 90 days without any retraining or updating. Results: Using this click decoder to navigate a switch-scanning spelling interface, the study participant was able to maintain a median spelling rate of 10.2 characters per min. Though a transient reduction in signal power modulation interrupted testing with this fixed model, a new click decoder achieved comparable performance despite being trained with even less data (< 15 min, within one day). Conclusion: These results demonstrate that a click decoder can be trained with a small ECoG dataset while retaining robust performance for extended periods, providing functional text-based communication to BCI users.

7.
bioRxiv ; 2023 Oct 20.
Article in English | MEDLINE | ID: mdl-37905068

ABSTRACT

Inherited retinal diseases (IRDs) encompass a genetically diverse group of conditions in which mutations in genes critical to retinal function lead to progressive loss of photoreceptor cells and subsequent visual impairment. A handful of ribosome-associated genes have been implicated in retinal disorders alongside neurological phenotypes. This study focuses on the HBS1L gene, encoding HBS1 Like Translational GTPase which has been recognized as a critical ribosomal rescue factor. Previously, we have reported a female child carrying biallelic HBS1L mutations, manifesting growth restriction, developmental delay, and hypotonia. In this study, we describe her ophthalmologic findings, compare them with the Hbs1ltm1a/tm1a hypomorph mouse model, and evaluate the underlying microscopic and molecular perturbations. The patient was noted to have impaired visual function observed by electroretinogram (ERG), with dampened amplitudes of a- and b-waves in both rod- and cone-mediated responses. Hbs1ltm1a/tm1a mice exhibited profound retinal thinning of the entire retina, specifically of the outer retinal photoreceptor layer, detected using in vivo imaging of optical coherence tomography (OCT) and retinal cross sections. TUNEL assay revealed retinal degeneration due to extensive photoreceptor cell apoptosis. Loss of HBS1L resulted in comprehensive proteomic alterations in mass spectrometry analysis, with169 proteins increased and 480 proteins decreased including many critical IRD-related proteins. GO biological process and GSEA analyses reveal that these downregulated proteins are primarily involved in photoreceptor cell development, cilium assembly, phototransduction, and aerobic respiration. Furthermore, apart from the diminished level of PELO, a known partner protein, HBS1L depletion was accompanied by reduction in translation machinery associated 7 homolog (Tma7), and Endothelial differentiation-related factor 1(Edf1) proteins, the latter of which coordinates cellular responses to ribosome collisions. This novel connection between HBS1L and ribosome collision sensor (EDF1) further highlights the intricate mechanisms underpinning ribosomal rescue and quality control that are essential to maintain homeostasis of key proteins of retinal health, such as rhodopsin.

8.
Adv Sci (Weinh) ; 10(35): e2304853, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37875404

ABSTRACT

Brain-computer interfaces (BCIs) can be used to control assistive devices by patients with neurological disorders like amyotrophic lateral sclerosis (ALS) that limit speech and movement. For assistive control, it is desirable for BCI systems to be accurate and reliable, preferably with minimal setup time. In this study, a participant with severe dysarthria due to ALS operates computer applications with six intuitive speech commands via a chronic electrocorticographic (ECoG) implant over the ventral sensorimotor cortex. Speech commands are accurately detected and decoded (median accuracy: 90.59%) throughout a 3-month study period without model retraining or recalibration. Use of the BCI does not require exogenous timing cues, enabling the participant to issue self-paced commands at will. These results demonstrate that a chronically implanted ECoG-based speech BCI can reliably control assistive devices over long time periods with only initial model training and calibration, supporting the feasibility of unassisted home use.


Subject(s)
Amyotrophic Lateral Sclerosis , Brain-Computer Interfaces , Humans , Speech , Amyotrophic Lateral Sclerosis/complications , Electrocorticography
9.
Sci Adv ; 9(40): eadh0183, 2023 10 06.
Article in English | MEDLINE | ID: mdl-37801508

ABSTRACT

Spinal cord injury (SCI) often leads to physical limitations, persistent pain, and major lifestyle shifts, enhancing the likelihood of prolonged psychological stress and associated disorders such as anxiety and depression. The mechanisms linking stress with regeneration remain elusive, despite understanding the detrimental impact of chronic stress on SCI recovery. In this study, we investigated the effect of chronic stress on primary sensory axon regeneration using a preconditioning lesions mouse model. Our data revealed that chronic stress-induced mitochondrial cristae loss and a decrease in oxidative phosphorylation (OXPHOS) within primary sensory neurons, impeding central axon regrowth. Corticosterone, a stress hormone, emerged as a pivotal player in this process, affecting satellite glial cells by reducing Kir4.1 expression. This led to increased neuronal hyperactivity and reactive oxygen species levels, which, in turn, deformed mitochondrial cristae and impaired OXPHOS, crucial for axonal regeneration. Our study underscores the need to manage psychological stress in patients with SCI for effective sensory-motor rehabilitation.


Subject(s)
Axons , Spinal Cord Injuries , Humans , Mice , Animals , Axons/metabolism , Nerve Regeneration/physiology , Oxidative Phosphorylation , Neurons/metabolism , Spinal Cord Injuries/pathology
10.
J Environ Manage ; 348: 119206, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37898049

ABSTRACT

Improving environmental performance of energy- and carbon-intensive sectors represented by the iron and steel (IS) industry is of utmost importance to address the challenges of resource depletion and climate change worldwide. This article adopts a global-super-Epsilon-Based Measure (EBM) model with undesirable output for IS energy efficiency estimation, identifies efficiency determinants based on Technology-Organization-Environment (TOE) framework, and analyzes various pathways for efficiency improvement by grouping Necessary Condition Analysis (NCA) and fuzzy-set Qualitative Comparative Analysis (fsQCA). Empirical testing using statistical data of the G20 economies during 2010-2020 demonstrates that: 1) energy efficiency in the IS industry in G20 countries has risen amidst fluctuations, with developed countries performing more efficiently than developing countries; 2) individual factors do not constitute a compulsory condition to achieve high energy efficiency in the IS industry; 3) three different paths to achieve high energy performance are found, that is, technology-structure driven, regulation-economy-technology driven, and regulation-technology-production driven. Heterogenous policy recommendations for efficiency gains in the IS sector of different countries with divergent features are proposed accordingly.


Subject(s)
Carbon , Conservation of Energy Resources , Carbon/analysis , Steel , Iron , Climate Change , Efficiency , China , Economic Development , Carbon Dioxide/analysis
11.
Environ Pollut ; 336: 122513, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37673320

ABSTRACT

Enterobacter sp. are widely used in bioremediation, but the mechanism of Cadmium (Cd) toxicity in Enterobacter sp. has been poorly studied. In the present study, we determined the tolerance of Enterobacter sp. FM-1 to Cd by analyzing the physiological and biochemical responses of FM-1 induced under Cd stress. Differentially expressed proteins (DEPs) under exposure to different Cd environments were analyzed by 4D-label-free proteomics to provide a comprehensive understanding of Cd toxicity in FM-1. The greatest total number of DEPs, 1148, was found in the High concentration vs. Control comparison group at 10 h. When protein expression was compared after different incubation times, FM-1 showed the highest Cd tolerance at 48 h. Additionally, with an increasing incubation time, different comparison groups gradually began to show similar growth patterns, which was reflected in the GO enrichment analysis. Notably, only 815 proteins were identified in the High concentration vs. Control group, and KEGG enrichment analysis revealed that these proteins were significantly enriched in the pyruvate metabolism, oxidative phosphorylation, peroxisome, glyoxylate and dicarboxylate metabolism, and citrate cycle pathways. These results suggested that an increased incubation time allows FM-1 adapt and survive in an environment with Cd toxicity, and protein expression significantly increased in response to oxidative stress in a Cd-contaminated environment during the pre-growth period. This study provides new perspectives on bacterial participation in bioremediation and expands our understanding of the mechanism of bacterial resistance under Cd exposure.


Subject(s)
Cadmium , Enterobacter , Cadmium/toxicity , Cadmium/metabolism , Enterobacter/metabolism , Proteomics , Oxidative Stress , Biodegradation, Environmental
12.
J Sep Sci ; 46(19): e2300172, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37528737

ABSTRACT

Chrysanthemum morifolium cv. Fubaiju is rich in phenolic compounds with various benefits such as anti-inflammatory, antioxidant, and cardiovascular protection. In this study, 12 phenolic compounds, including five flavonoid glycosides and seven quinic acid derivatives, were successfully separated from the flowers of Chrysanthemum morifolium cv. Fubaiju by high-speed counter-current chromatography and preparative high-performance liquid chromatography. Ethyl acetate-n-butanol-acetonitrile-water-acetic acid (5:0.5:2.5:5:0.25, v/v/v/v/v) was selected as solvent system to separate six fractions from the flowers of Chrysanthemum morifolium cv. Fubaiju, and 20% aqueous acetonitrile (containing 0.1% formic acid) was chosen to be the elution solvent in preparative high-performance liquid chromatography for purifying the fractions above. Luteolin-7-O-ß-D-glucoside (1), luteolin-7-O-ß-D-glucuronide (2), apigenin-7-O-ß-D-glucoside (3), luteolin-7-O-ß-D-rutinoside (4), diosmetin-7-O-ß-D-glucoside (5), chlorogenic acid (6), 1,5-dicaffeoylquinic acid (7), 1,4-dicaffeoylquinic acid (8), 3,4-dicaffeoylquinic acid (9), 3,4-dicaffeoyl-epi-quinic acid (10), 3,5-dicaffeoylquinic acid (11), and 4,5-dicaffeoylquinic acid (12) were isolated with purities all above 95%, respectively. In addition, all isolates were evaluated for their protective effects on H2 O2 -induced oxidative damage in adult retinal pigment epithelial cells.

13.
J Environ Manage ; 345: 118766, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37579601

ABSTRACT

Soil deficiency, cyclic erosion, and heavy metal pollution have led to fertility loss and ecological function decline in mining areas. Fertilization is an important way to rapidly replenish soil nutrients, which have a major influence on the soil nitrogen cycling process, but different fertilization regimes have different impacts on soil properties and microbial functional potentials. Here, metagenomic sequencing was used to investigate the different responses of key functional genes of microbial nitrogen cycling to fertilization regimes and explore the potential effects of soil physicochemical properties on the key functional genes. The results indicated that AC-HH (ammonium chloride-high frequency and concentration) treatment significantly increased the gene abundance of norC (13.40-fold), nirK (5.46-fold), and napA (5.37-fold). U-HH (urea-high frequency and concentration) treatment significantly increased the gene abundance of hao (6.24-fold), pmoA-amoA (4.32-fold) norC (7.00-fold), nosZ (3.69-fold), and nirK (6.88-fold). Functional genes were distributed differently among the 10 dominant phyla. The nifH and nifK genes were distributed only in Proteobacteria. The hao gene was distributed in Gemmatimonadetes, Nitrospirae and Proteobacteria. Fertilization regimes caused changes in functional redundancy in soil, and nirK and nirB, which are involved in denitrification, were present in different genera. Fertilization regimes with high frequency and high concentration were more likely to increase the gene abundance at the genus level. In summary, this study provides insights into the taxon-specific response of soil nitrogen cycling under different fertilization regimes, where changes in fertilization regimes affect microbial nitrogen cycling by altering soil physicochemical properties in a complex dynamic environment.


Subject(s)
Metagenomics , Soil , Soil/chemistry , Soil Microbiology , Bacteria/genetics , Fertilization , Nitrogen
14.
medRxiv ; 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37425721

ABSTRACT

Recent studies have shown that speech can be reconstructed and synthesized using only brain activity recorded with intracranial electrodes, but until now this has only been done using retrospective analyses of recordings from able-bodied patients temporarily implanted with electrodes for epilepsy surgery. Here, we report online synthesis of intelligible words using a chronically implanted brain-computer interface (BCI) in a clinical trial participant (ClinicalTrials.gov, NCT03567213) with dysarthria due to amyotrophic lateral sclerosis (ALS). We demonstrate a reliable BCI that synthesizes commands freely chosen and spoken by the user from a vocabulary of 6 keywords originally designed to allow intuitive selection of items on a communication board. Our results show for the first time that a speech-impaired individual with ALS can use a chronically implanted BCI to reliably produce synthesized words that are intelligible to human listeners while preserving the participants voice profile.

15.
J Hazard Mater ; 458: 132033, 2023 09 15.
Article in English | MEDLINE | ID: mdl-37453352

ABSTRACT

Metagenomics analysis was performed to determine the effects of Enterobacter sp. FM-1 (FM-1) on key genera as well as functional genes in the rhizosphere of Bidens pilosa L. (B. pilosa L.). Moreover, metabolomics was used to reveal the differences among rhizosphere metabolites after FM-1 inoculation. FM-1 inoculation significantly increased the activity of enzymes associated with the carbon cycle in soil; among them, invertase activity increased by 5.52 units compared to a control. Specifically, the relative abundance of beneficial genera increased significantly, such as Lysobacter (0.45-2.58 unit increase) in low-contamination soils (LC) and Pseudomonas (31.17-45.99 unit increase) in high-contamination soils (HC). Comparison of different transformation processes of the C cycle revealed that inoculation of FM-1 increased the abundance of functional genes related to the carbon cycle in LC soil. In contrast, the nitrogen cycling pathway was significantly elevated in both the LC and HC soils. FM-1 inoculation reduced HM resistance gene abundance in the rhizosphere soil of B. pilosa L. in the LC soil. Moreover, FM-1 and B. pilosa L. interactions promoted the secretion of rhizosphere metabolites, in which lipids and amino acids played important roles in the phytoremediation process. Overall, we explored the rhizosphere effects induced by plantmicrobe interactions, providing new insights into the functional microbes and rhizosphere metabolites involved in phytoremediation.


Subject(s)
Bidens , Metals, Heavy , Soil Pollutants , Rhizosphere , Soil/chemistry , Enterobacter/metabolism , Metagenomics , Soil Pollutants/metabolism , Metals, Heavy/metabolism , Biodegradation, Environmental , Metabolomics , Soil Microbiology , Cadmium/analysis
16.
bioRxiv ; 2023 Apr 24.
Article in English | MEDLINE | ID: mdl-37162921

ABSTRACT

Autosomal-recessive mutations in SPEG (striated muscle preferentially expressed protein kinase) have been linked to centronuclear myopathy. Loss of SPEG is associated with defective triad formation, abnormal excitation-contraction coupling, and calcium mishandling in skeletal muscles. To elucidate the underlying molecular pathways, we have utilized multi-omics tools and analysis to obtain a comprehensive view of the complex biological processes. We identified that SPEG interacts with myospryn complex proteins (CMYA5, FSD2, RyR1), and SPEG deficiency results in myospryn complex abnormalities. In addition, transcriptional and protein profiles of SPEG-deficient muscle revealed defective mitochondrial function including aberrant accumulation of enlarged mitochondria on electron microscopy. Furthermore, SPEG regulates RyR1 phosphorylation at S2902, and its loss affects JPH2 phosphorylation at multiple sites. On analyzing the transcriptome, the most dysregulated pathways affected by SPEG deficiency included extracellular matrix-receptor interaction and peroxisome proliferator-activated receptors signaling, which may be due to defective triad and mitochondrial abnormalities. In summary, we have elucidated the critical role of SPEG in triad as it works closely with myospryn complex, phosphorylates JPH2 and RyR1, and demonstrated that its deficiency is associated with mitochondrial abnormalities. This study emphasizes the importance of using multi-omics techniques to comprehensively analyze the molecular anomalies of rare diseases. Synopsis: We have previously linked mutations in SPEG (striated preferentially expressed protein) with a recessive form of centronuclear myopathy and/or dilated cardiomyopathy and have characterized a striated muscle-specific SPEG-deficient mouse model that recapitulates human disease with disruption of the triad structure and calcium homeostasis in skeletal muscles. In this study, we applied multi-omics approaches (interactomic, proteomic, phosphoproteomic, and transcriptomic analyses) in the skeletal muscles of SPEG-deficient mice to assess the underlying pathways associated with the pathological and molecular abnormalities. SPEG interacts with myospryn complex proteins (CMYA5, FSD2, RyR1), and its deficiency results in myospryn complex abnormalities.SPEG regulates RyR1 phosphorylation at S2902, and its loss affects JPH2 phosphorylation at multiple sites.SPEGα and SPEGß have different interacting partners suggestive of differential function.Transcriptome analysis indicates dysregulated pathways of ECM-receptor interaction and peroxisome proliferator-activated receptor signaling.Mitochondrial defects on the transcriptome, proteome, and electron microscopy, may be a consequence of defective calcium signaling.

17.
bioRxiv ; 2023 Oct 24.
Article in English | MEDLINE | ID: mdl-37066306

ABSTRACT

Neurosurgical procedures that enable direct brain recordings in awake patients offer unique opportunities to explore the neurophysiology of human speech. The scarcity of these opportunities and the altruism of participating patients compel us to apply the highest rigor to signal analysis. Intracranial electroencephalography (iEEG) signals recorded during overt speech can contain a speech artifact that tracks the fundamental frequency (F0) of the participant's voice, involving the same high-gamma frequencies that are modulated during speech production and perception. To address this artifact, we developed a spatial-filtering approach to identify and remove acoustic-induced contaminations of the recorded signal. We found that traditional reference schemes jeopardized signal quality, whereas our data-driven method denoised the recordings while preserving underlying neural activity.

18.
Chemosphere ; 330: 138737, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37084901

ABSTRACT

Microplastic contamination has received much attention, especially in agroecosystems. However, since edible crops with different genetic backgrounds may present different responses to microplastics, more research should be conducted and focused on more edible crops. In the current study, pot experiments were conducted to investigate the potential impact of polyethylene microplastic (PE) (particle sizes: 0.5 µm and 1.0 µm, addition levels: 0 (control), 0.5% and 1.0% (w/w)) addition on the physiological and biochemical variations of I. aquatica F.. The results indicated that PE addition caused an increase in the soil pH and NH4+-N and soil organic matter contents, which increased by 10.1%, 29.9% and 50.1% when PE addition at A10P0.5 level (10 g (PE) kg-1 soil, particle size: 0.5 µm). While, PE exposure resulted in a decrease in soil available phosphorus and total phosphorus contents, which decreased by 53.9% and 10.5% when PE addition at A10P0.5 level. In addition, PE addition altered the soil enzyme activities. Two-way ANOVA indicated that particle size had a greater impact on the variations in soil properties and enzyme activities than the addition level. PE addition had a strong impact on the rhizosphere microbial and root endophyte community diversity and structure of I. aquatica F.. Two-way ANOVA results indicated that the particle size and addition level significantly altered the α-diversity indices of both rhizosphere microbial and root endophyte (P < 0.05, P < 0.01 or P < 0.001). Moreover, PE was adsorbed by I. aquatica F., which was clearly observed in the transverse roots and significantly increased the H2O2, ·O2-, malondialdehyde and ascorbic acid contents in both the roots and aerial parts of I. aquatica F., leading to a decrease in I. aquatica F. biomass. Overall, the current study enriches the understanding of the effect of microplastics on edible crops.


Subject(s)
Ipomoea , Microplastics , Plastics/pharmacology , Endophytes , Polyethylene/pharmacology , Rhizosphere , Hydrogen Peroxide/pharmacology , Soil/chemistry , Phosphorus/pharmacology
19.
Nanomicro Lett ; 15(1): 61, 2023 Mar 03.
Article in English | MEDLINE | ID: mdl-36867262

ABSTRACT

Bulk graphene nanofilms feature fast electronic and phonon transport in combination with strong light-matter interaction and thus have great potential for versatile applications, spanning from photonic, electronic, and optoelectronic devices to charge-stripping and electromagnetic shielding, etc. However, large-area flexible close-stacked graphene nanofilms with a wide thickness range have yet to be reported. Here, we report a polyacrylonitrile-assisted 'substrate replacement' strategy to fabricate large-area free-standing graphene oxide/polyacrylonitrile nanofilms (lateral size ~ 20 cm). Linear polyacrylonitrile chains-derived nanochannels promote the escape of gases and enable macro-assembled graphene nanofilms (nMAGs) of 50-600 nm thickness following heat treatment at 3,000 °C. The uniform nMAGs exhibit 802-1,540 cm2 V-1 s-1 carrier mobility, 4.3-4.7 ps carrier lifetime, and > 1,581 W m-1 K-1 thermal conductivity (nMAG-assembled 10 µm-thick films, mMAGs). nMAGs are highly flexible and show no structure damage even after 1.0 × 105 cycles of folding-unfolding. Furthermore, nMAGs broaden the detection region of graphene/silicon heterojunction from near-infrared to mid-infrared and demonstrate higher absolute electromagnetic interference (EMI) shielding effectiveness than state-of-the-art EMI materials of the same thickness. These results are expected to lead to the broad applications of such bulk nanofilms, especially as micro/nanoelectronic and optoelectronic platforms.

20.
Adv Mater ; 35(22): e2300077, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36930178

ABSTRACT

Excellent through-plane thermally conductive composites are highly demanded for efficient heat dissipation. Giant sheets have large crystalline domain and significantly reduce interface phonon scattering, making them promising to build highly thermally conductive composites. However, realizing vertical orientation of giant sheets remains challenging due to their enormous mass and huge hydrodynamic drag force. Here, we achieve highly vertically ordered liquid crystals of giant graphite oxide (more than 100 µm in lateral dimension) by microwire shearing, which endows the composite with a recorded through-plane thermal conductivity of 94 W m-1 K-1 . Microscale shearing fields induced by vertical motion of microwires conquer huge hydrodynamic energy barrier and vertically reorient giant sheets. The resulting liquid crystals exhibit extremely retarded relaxation and impart large-scale vertical array with bidirectional ordering degree as high as 0.82. The graphite array-based composites demonstrate an ultrahigh thermal enhancement efficiency of over 35 times per unit volume. Furthermore, the composites improve cooling efficiency by 93% for thermal management tests compared to commercial thermal interface materials. This work offers a novel methodology to precisely manipulate the orientation of giant particles and promote large-scale fabrication of vertical array with advanced functionalities.

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