ABSTRACT
BACKGROUND: Convolutional neural network (CNN) can capture the structural features changes of brain aging based on MRI, thus predict brain age in healthy individuals accurately. However, most studies use single feature to predict brain age in healthy individuals, ignoring adding information from multiple sources and the changes in brain aging patterns after mild traumatic brain injury (mTBI) were still unclear. METHODS: Here, we leveraged the structural data from a large, heterogeneous dataset (N = 1464) to implement an interpretable 3D combined CNN model for brain-age prediction. In addition, we also built an atlas-based occlusion analysis scheme with a fine-grained human Brainnetome Atlas to reveal the age-sstratified contributed brain regions for brain-age prediction in healthy controls (HCs) and mTBI patients. The correlations between brain predicted age gaps (brain-PAG) following mTBI and individual's cognitive impairment, as well as the level of plasma neurofilament light were also examined. RESULTS: Our model utilized multiple 3D features derived from T1w data as inputs, and reduced the mean absolute error (MAE) of age prediction to 3.08 years and improved Pearson's r to 0.97 on 154 HCs. The strong generalizability of our model was also validated across different centers. Regions contributing the most significantly to brain age prediction were the caudate and thalamus for HCs and patients with mTBI, and the contributive regions were mostly located in the subcortical areas throughout the adult lifespan. The left hemisphere was confirmed to contribute more in brain age prediction throughout the adult lifespan. Our research showed that brain-PAG in mTBI patients was significantly higher than that in HCs in both acute and chronic phases. The increased brain-PAG in mTBI patients was also highly correlated with cognitive impairment and a higher level of plasma neurofilament light, a marker of neurodegeneration. The higher brain-PAG and its correlation with severe cognitive impairment showed a longitudinal and persistent nature in patients with follow-up examinations. CONCLUSION: We proposed an interpretable deep learning framework on a relatively large dataset to accurately predict brain age in both healthy individuals and mTBI patients. The interpretable analysis revealed that the caudate and thalamus became the most contributive role across the adult lifespan in both HCs and patients with mTBI. The left hemisphere contributed significantly to brain age prediction may enlighten us to be concerned about the lateralization of brain abnormality in neurological diseases in the future. The proposed interpretable deep learning framework might also provide hope for testing the performance of related drugs and treatments in the future.
Subject(s)
Aging , Brain Concussion , Brain , Magnetic Resonance Imaging , Neural Networks, Computer , Humans , Adult , Male , Female , Middle Aged , Magnetic Resonance Imaging/methods , Brain Concussion/diagnostic imaging , Brain/diagnostic imaging , Young Adult , Aged , Cognitive Dysfunction/diagnostic imaging , Deep LearningABSTRACT
Blood proteins are emerging as potential biomarkers for mild traumatic brain injury (mTBI). Molecular pathology of mTBI underscores the critical roles of neuronal injury, neuroinflammation, and vascular health in disease progression. However, the temporal profile of blood biomarkers associated with the aforementioned molecular pathology after CT-negative mTBI, their diagnostic and prognostic potential, and their utility in monitoring white matter integrity and progressive brain atrophy remain unclear. Thus, we investigated serum biomarkers and neuroimaging in a longitudinal cohort, including 103 CT-negative mTBI patients and 66 matched healthy controls (HCs). Angiogenic biomarker vascular endothelial growth factor (VEGF) exhibited the highest area under the curve of 0.88 in identifying patients from HCs. Inflammatory biomarker interleukin-1ß and neuronal cell body injury biomarker ubiquitin carboxyl-terminal hydrolase L1 were elevated in acute-stage patients and associated with deterioration of cognitive function from acute-stage to 6-12 mo post-injury period. Notably, axonal injury biomarker neurofilament light (NfL) was elevated in acute-stage patients, with higher levels associated with impaired white matter integrity in acute-stage and progressive gray and white matter atrophy from 3- to 6-12 mo post-injury period. Collectively, our findings emphasized the potential clinical value of serum biomarkers, particularly NfL and VEGF, in diagnosing mTBI and monitoring disease progression.
Subject(s)
Brain Concussion , Humans , Brain Concussion/diagnostic imaging , Vascular Endothelial Growth Factor A , Neurofilament Proteins , Disease Progression , Biomarkers , Atrophy/pathology , Tomography, X-Ray Computed , Brain/diagnostic imaging , Brain/pathologyABSTRACT
Mild traumatic brain injury (mTBI) disrupts the integrity of white matter microstructure, which affects brain functional connectivity supporting cognitive function. Although the relationship between structural and functional connectivity (SC and FC), here called SC-FC coupling, has been studied on global level in brain disorders, the long-term disruption of SC-FC coupling in mTBI at regional scale was still unclear. The current study investigated the alteration pattern of regional SC-FC coupling in 104 acute mTBI patients (41 with 6-12 months of follow-up) and 56 healthy controls (HCs). SC and FC networks were constructed to measure regional, intra-network, and inter-network SC-FC coupling. Compared with HCs, acute mTBI exhibited altered SC-FC coupling of the sensorimotor network (SMN). The coupling laterality indicators of the SMN can identify mTBI from controls. The persistent SC-FC decoupling of the SMN and the additional decoupling of the default mode network (DMN) were observed in chronic mTBI. Crucially, decoupling of the SMN and DMN predicted better cognitive outcomes. The findings revealed the SC-FC coupling alternations exhibited hierarchical trend originating from the sensorimotor cortex to high-order cognitive regions with the progression of mTBI. The regional and hierarchical SC-FC coupling may be a prognostic biomarker to provide insights into the pathophysiology mechanism of mTBI.
Subject(s)
Brain Concussion , Cognitive Dysfunction , Humans , Brain Concussion/complications , Brain Concussion/diagnostic imaging , Magnetic Resonance Imaging , Nerve Net/diagnostic imaging , Brain/diagnostic imaging , Brain MappingABSTRACT
The DNA damage response (DDR) plays crucial roles in cancer prevention and therapy. Poly(ADP-ribose) polymerase 1 (PARP1) mediates multiple signal transduction in the DDR as a master regulator. Uncovering the regulatory factors of PARP1 contributes to a more comprehensive view of tumorigenesis and treatment strategies. Here, we reveal that MARVELD1 acts as a mediator of DDR to perform early events and maintain genome stability. Mechanistically, PARP1 PARylates MARVELD1 at D102, D118 and D130, and in turn, MARVELD1 stabilizes PARP1 by enhancing NAA50-mediated acetylation, thus forming a positive feedback loop. MARVELD1 knockout mice and their embryo fibroblasts exhibit genomic instability and shorter half-life of PARP1. Moreover, MARVELD1 partnering with PARP1 facilitates resistance to genotoxic drugs and disrupts PARP inhibitor (PARPi) effect in PDX model of colorectal cancer (CRC). Overall, our results underline the link between MARVELD1 and PARP1 in therapeutic resistance based on DDR and provide new insights for clinical tumor therapy of PARPi.
Subject(s)
DNA Damage , Genomic Instability , Animals , Mice , Carcinogenesis , DNA Repair , Poly (ADP-Ribose) Polymerase-1/genetics , Poly (ADP-Ribose) Polymerase-1/metabolism , Protein Processing, Post-TranslationalABSTRACT
Traumatic brain injury (TBI) disrupt the coordinated activity of triple-network and produce impairments across several cognitive domains. The triple-network model posits a key role of the salience network (SN) that regulates interactions with the central executive network (CEN) and default mode network (DMN). However, the aberrant dynamic interactions among triple-network and associations with neurobehavioral symptoms in mild TBI was still unclear. In present study, we used brain network interaction index (NII) and dynamic functional connectivity to examine the time-varying cross-network interactions among the triple-network in 109 acute patients, 41 chronic patients, and 65 healthy controls. Dynamic cross-network interactions were significantly increased and more variable in mild TBI compared to controls. Crucially, mild TBI exhibited an increased NII as enhanced integrations between the SN and CEN while reduced coupling of the SN with DMN. The increased NII also implied much severer and multiple domains of cognitive impairments at both acute and chronic mild TBI. Abnormities in time-varying engagement of triple-network is a clinically relevant neurobiological signature of psychopathology in mild TBI. The findings provided align with and advance an emerging perspective on the importance of aberrant brain dynamics associated with highly disparate cognitive and behavioral outcomes in trauma.
Subject(s)
Brain Concussion , Cognitive Dysfunction , Humans , Brain Concussion/complications , Brain Concussion/diagnostic imaging , Magnetic Resonance Imaging , Brain/diagnostic imaging , Brain Mapping , Nerve Net , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/etiology , Cognitive Dysfunction/pathologyABSTRACT
Transition metal carbonates/hydroxides have attracted much attention as appealing anode materials due to their considerable reversible electrochemical catalytic conversion capacity. However, their serious positive or negative trends with cycles caused by the electrochemical catalytic conversion seriously affect their practical applications. Herein, novel one-dimensional cobalt hydroxide carbonate (CHC) nanomaterials are tightly anchored on reduced graphene oxide (RGO) sheets via a facile one-pot hydrothermal synthesis, forming surface-confined domains to further restrict the electrochemical catalytic conversion process. The analysis on the cycled electrodes at varied potentials confirms that the added capacity of CHC arises from the step-by-step reversible reactions of Li2CO3 and LiOH under the electrochemical catalysis of Co metal generated by the conversion reaction of CHC. The reversible reaction of Li2CO3 is followed closely by that of LiOH in the discharge process, while the order is opposite in the charge process. Such a step-by-step electrochemical catalytic conversion process could confine each other to accommodate the volume change and avoid side reactions. The confined effect is further enhanced by limiting the width and length of the CHC, which are determined by regulating the nucleation and growth of CHC on the surface of RGO, leading to an extraordinary cyclability. The optimized CHC/RGO hybrid maintains a high reversible capacity of 1110 mA h g-1 after 100 cycles at 0.1 A g-1, which is much higher than the theoretical value of CHC (506 mA h g-1) on the basis of the recognized conversion reaction. Furthermore, it keeps high reversible capacities of 755 and 506 mA h g-1 after 200 cycles at 1 and 2 A g-1, respectively, exhibiting a high-rate cyclability with the lowest coefficient of variance of 9.4% among the reported ones. The confined step-by-step electrochemical catalytic conversion process facilitates high lithium storage capacity and satisfactory cyclability with a pretty low variance coefficient.
ABSTRACT
Due to its poor water solubility, the herbicide cyanazine is usually dissolved in organic reagents when used, which poses a great threat to the environment. Poor water solubility also causes limited herbicidal activity. In our study, the water solubility of cyanazine was increased by forming a cyanazine/hydroxypropyl beta-cyclodextrin (HPßCD) inclusion complex. The formation of the inclusion complex was confirmed by FT-IR, XRD, SEM and other characterization methods. Phase solubility study showed that HPßCD could improve the water solubility of cyanazine. Thermogravimetric analysis indicated that the thermal stability of cyanazine was improved by forming inclusion complex and the biological activity test showed that better herbicidal activity was obtained on the inclusion complex compared with the cyanazine. The results showed that the formation of inclusion complex could improve the application of cyanazine in agricultural production and reduce the risk to the environment.
ABSTRACT
Although the electrochemical catalytic conversion process is effective in increasing the reversible capacity of lithium-ion batteries, the low contact efficiency between metal catalyst and substrate and pulverization of the solid electrolyte interface (SEI) film without protection are not beneficial for the electrochemical reactions. Herein, Fe7 S8 nanoparticles are confined by both reduced graphene oxide (RGO) and in-situ-formed amorphous carbon (C) to form dual-carbon-confined Fe7 S8 as a lithium-ion anode. The dual-carbon-confined structure provides a confined space to prevent pulverization of the SEI film and increases the local concentration of intermediate phases, which could be electrocatalytically decomposed by Fe nanoparticles formed in situ to increase the reversibility of the electrochemical reactions and gain high reversible capacity. In addition, the dual-carbon-confined structure ensures fast transfer of electrons and boosts transport of lithium ions due to the highly conductive dual-carbon shell. Thus, the Fe7 S8 /C/RGO anode delivers an excellent rate performance and long cycling stability. At current densities of 2000 and 5000â mA g-1 , the reversible capacities are 520â mA h g-1 over 1500â cycles and 294â mA h g-1 over 2000â cycles, respectively.
ABSTRACT
Increasing demands for lithium-ion batteries (LIBs) with high energy density and high power density require highly reversible electrochemical reactions to enhance the cyclability and capacities of electrodes. As the reversible formation/decomposition of the solid electrolyte interface (SEI) film during the lithiation/delithiation process of Fe3S4 could bring about a higher capacity than its theoretical value, in the present work, synthesized Fe3S4 nanoparticles are sandwich-wrapped with reduced graphene oxide (RGO) to fabricate highly reversible and long cycling life anode materials for high-performance LIBs. The micron-sized long slit between sandwiched RGO sheets effectively prevents the aggregation of intermediate phases during the discharge/charge process and thus increases cycling capacity because of the reversible formation/decomposition of the SEI film driven by Fe nanoparticles. Furthermore, the RGO sheets interconnect with each other by a face-to-face mode to construct a more efficiently conductive network, and the maximum interfacial oxygen bridge bonds benefit the fast electron hopping from RGO to Fe3S4, improving the depth of the electrochemical reactions and facilitating the highly reversible lithiation/delithiation of Fe3S4. Thus, the resultant Fe3S4/RGO hybrid shows a highly reversible charge capacity of 1324 mA h g-1 over 275 cycles at a current density of 100 mA g-1, even retains 480 mA h g-1 over 500 cycles at 1000 mA g-1, which are much higher than reported values.
ABSTRACT
The conventional rapid detection method for AIDS is testing HIV-1 antibody in blood. Urine HIV-1 antibody testing is a new means with great potential for development because of its safe, convenient and low cost. In this paper, HIV-1 antibody in urine, the merits of urine HIV-1 testing and factors that effect the result of test were reviewed, the application and product actuality of urine testing production were briefly introduced, and the development prospect of urine HIV-1 testing was viewed.