Electroplating of nanoporous Pt (nPt) induces an extremely strong tensile stress, which results in the exfoliation of nPt on flexible polymer substrate despite plasma treatment to improve adhesion. ...Here, we overcame this challenge by modifying flexible stainless-steel, and developed wearable, robust, flexible, and non-enzymatic continuous glucose monitoring system. The flexible stainless-steel was highly effective in improving the adhesion between the metal layer and substrate. The developed wireless system included electrochemical analysis circuits, a microcontroller unit, and a wireless communication module. Finally, we evaluated the continuous glucose monitoring system through two animal testing, by implanting into subcutaneous tissue and measuring interstitial fluid (ISF) glucose values at 5–15-min intervals. Comparison of the measured ISF glucose with blood glucose determined by the Clarke error grid analysis showed that 82.76% of the measured glucose was within zone A. Furthermore, the wearable glucose sensor exhibited bio-compatible to implant through various bio-compatibility tests.
•Stainless steel-based semi-implantable and flexible electrochemical sensor for continuous glucose monitoring.•Highly selective and sensitive electrode using electroplated nanoporous Pt coated with nafion film.•Fabricated enzyme-free sensor showed high sensitivity, fast response, high selectivity, and reliability.•Fabricated sensor was successfully tested in the interstitial fluid of rabbit and showed high accuracy and biological safety.•All measured data was placed on zone A and B of Clarke error grid.
While state‐of‐the‐art skin‐adhering fibrous electrodes have distinct benefits in personal wearable bioelectronics, considerable challenges persist in the production of fibrous‐based soft conductive ...biosensing nanomaterials and their integration into efficient multisensing platforms. Here, an electrochemical‐electrophysiological multimodal biosensing patch based on MXene/fluoropolymer nanofiber‐derived hierarchical porous TiO2 nanocatalyst interconnected 3D fibrous carbon nanohybrid electrodes is reported. The nanohybrid electrode is produced via a one‐step laser carbonaceous thermal oxidation, resulting in excellent elctroconductivity (sheet resistance = 15.6 Ω sq−1), rich active edges for effective electron transmission, and abundant support for enzyme immobilization. The features are attributed to three synergistic effects: i) conductivity of the interior, unoxidized MXene layers, ii) quick heterogeneous electron transmission of the exterior TiO2 nanoparticles, and iii) the porous disordered carbon's electron “bridge” effects. Based on the foregoing, the nanohybrid modified biosensing patch integrated into textile is demonstrated to be capable of simultaneously and precisely monitoring sweat glucose with pH adjustment (sensitivity of 77.12 µA mm−1 cm−2 within physiological concentrations of 0.01–2 × 10−3 m) and electrocardiogram signals (signal‐to‐noise ratio = 37.63 dB). This novel approach paves the way for controlled investigations of the nanohybrid, for several functionalization and design options, and for the mass manufacturing capabilities required in real‐world applications.
Successfully developed MXene/fluoropolymer nanofiber‐derived hierarchical TiO2 nanocatalyst interconnected 3D fibrous carbon nanohybrid electrodes via a one‐step laser carbonaceous thermal oxidation, exhibiting excellent elctroconductivity and flexibility. Based on the TiO2@LCNFs, a flexible, wearable patch‐based soft hybrid bioelectronic textile (HBeT) is developed. The HBeT patch is demonstrated to be capable of simultaneously and precisely monitoring sweat glucose with pH adjustment and electrocardiogram signals.
Current pharmacological treatments for Parkinson’s disease (PD) are focused on symptomatic relief, but not on disease modification, based on the strong belief that PD is caused by irreversible ...dopaminergic neuronal death. Thus, the concept of the presence of dormant dopaminergic neurons and its possibility as the disease-modifying therapeutic target against PD have not been explored. Here we show that optogenetic activation of substantia nigra pars compacta (SNpc) neurons alleviates parkinsonism in acute PD animal models by recovering tyrosine hydroxylase (TH) from the TH-negative dormant dopaminergic neurons, some of which still express DOPA decarboxylase (DDC). The TH loss depends on reduced dopaminergic neuronal firing under aberrant tonic inhibition, which is attributed to excessive astrocytic GABA. Blocking the astrocytic GABA synthesis recapitulates the therapeutic effect of optogenetic activation. Consistently, SNpc of postmortem PD patients shows a significant population of TH-negative/DDC-positive dormant neurons surrounded by numerous GABA-positive astrocytes. We propose that disinhibiting dormant dopaminergic neurons by blocking excessive astrocytic GABA could be an effective therapeutic strategy against PD.
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•Reactive astrocytes in SNpc produce excessive GABA via MAO-B in animal models of PD•Aberrant tonic inhibition causes reduced DA production in neurons and motor deficits•Dormant neurons are rescued by MAO-B inhibition or optogenetic neuronal activation
Heo et al. report that astrocytic GABA-mediated aberrant tonic inhibition of DA neurons leads to a reduction in TH expression and dopamine production, causing dormant DA neurons and motor deficits. Blocking astrocytic GABA synthesis by MAO-B inhibition or optogenetic activation of dormant DA neurons reverses PD pathology.
Currently there is no neuroprotective or neurorestorative therapy for Parkinson's disease. Here we report that transient receptor potential vanilloid 1 (TRPV1) on astrocytes mediates endogenous ...production of ciliary neurotrophic factor (CNTF), which prevents the active degeneration of dopamine neurons and leads to behavioural recovery through CNTF receptor alpha (CNTFRα) on nigral dopamine neurons in both the MPP(+)-lesioned or adeno-associated virus α-synuclein rat models of Parkinson's disease. Western blot and immunohistochemical analysis of human post-mortem substantia nigra from Parkinson's disease suggests that this endogenous neuroprotective system (TRPV1 and CNTF on astrocytes, and CNTFRα on dopamine neurons) might have relevance to human Parkinson's disease. Our results suggest that activation of astrocytic TRPV1 activates endogenous neuroprotective machinery in vivo and that it is a novel therapeutic target for the treatment of Parkinson's disease.
Grade Group assessed using Gleason combined score and tumor extent is a main determinant for risk stratification and therapeutic planning of prostate cancer.
To develop a 3-dimensional magnetic ...resonance imaging (MRI) model regarding Grade Group and tumor extent in collaboration with uroradiologists and uropathologists for optimal treatment planning for prostate cancer.
We studied the data from 83 patients with prostate cancer who underwent multiparametric MRI and subsequent MRI-transrectal ultrasound fusion biopsy and radical prostatectomy. A 3-dimensional MRI model was constructed by integrating topographic information of MRI-based segmented lesions, biopsy paths, and histopathologic information of biopsy specimens. The multiparametric MRI-integrated Grade Group and laterality were assessed by using the 3-dimensional MRI model and compared with the radical prostatectomy specimen.
The MRI-defined index tumor was concordant with radical prostatectomy in 94.7% (72 of 76) of cases. The multiparametric MRI-integrated Grade Group revealed the highest agreement (weighted κ, 0.545) and a significantly higher concordance rate (57.9%) than the targeted (47.8%, P = .008) and systematic (39.4%, P = .01) biopsies. The multiparametric MRI-integrated Grade Group showed significantly less downgrading rates than the combined biopsy (P = .001), without significant differences in upgrading rate (P = .06). The 3-dimensional multiparametric MRI model estimated tumor laterality in 66.2% (55 of 83) of cases, and contralateral clinically significant cancer was missed in 9.6% (8 of 83) of cases. The tumor length measured by multiparametric MRI best correlated with radical prostatectomy as compared with the biopsy-defined length.
The 3-dimensional model incorporating MRI and MRI-transrectal ultrasound fusion biopsy information easily recognized the spatial distribution of MRI-visible and MRI-nonvisible cancer and provided better Grade Group correlation with radical prostatectomy specimens but still requires validation.
* Context.-Grade Group assessed using Gleason combined score and tumor extent is a main determinant for risk stratification and therapeutic planning of prostate cancer. Objective.-To develop a ...3-dimensional magnetic resonance imaging (MRI) model regarding Grade Group and tumor extent in collaboration with uroradiologists and uropathologists for optimal treatment planning for prostate cancer. Design.-We studied the data from 83 patients with prostate cancer who underwent multiparametric MRI and subsequent MRI-transrectal ultrasound fusion biopsy and radical prostatectomy. A 3-dimensional MRI model was constructed by integrating topographic information of MRI-based segmented lesions, biopsy paths, and histopathologic information of biopsy specimens. The multiparametric MRI-integrated Grade Group and laterality were assessed by using the 3-dimensional MRI model and compared with the radical prostatectomy specimen. Results.-The MRI-defined index tumor was concordant with radical prostatectomy in 94.7% (72 of 76) of cases. The multiparametric MRI-integrated Grade Group revealed the highest agreement (weighted к, 0.545) and a significantly higher concordance rate (57.9%) than the targeted (47.8%, P = .008) and systematic (39.4%, P = .01) biopsies. The multiparametric MRI-integrated Grade Group showed significantly less downgrading rates than the combined biopsy (P = .001), without significant differences in upgrading rate (P = .06). The 3-dimensional multiparametric MRI model estimated tumor laterality in 66.2% (55 of 83) of cases, and contralateral clinically significant cancer was missed in 9.6% (8 of 83) of cases. The tumor length measured by multiparametric MRI best correlated with radical prostatectomy as compared with the biopsy-defined length. Conclusions.-The 3-dimensional model incorporating MRI and MRI-transrectal ultrasound fusion biopsy information easily recognized the spatial distribution of MRIvisible and MRI-nonvisible cancer and provided better Grade Group correlation with radical prostatectomy specimens but still requires validation.
Laser‐Carbonization
In article number 2208894, Jae Y. Park and co‐workers, report an electrochemical‐electrophysiological multimodal biosensing patch based on MXene/fluoropolymer nanofibers ...(MFNFs)‐derived hierarchical porous TiO2 nanocatalyst interconnected three‐dimensional fibrous carbon nanohybrid electrodes. The nanohybrid electrode is produced via a one‐step laser carbonaceous thermal oxidation of MFNFs. The nanohybrid modified biosensing patch integrated into textile is demonstrated to be capable of simultaneously and precisely monitoring sweat glucose with pH adjustment and electrocardiogram signals.
Hand–foot skin reaction (HFSR) is the most common adverse event during sorafenib treatment in patients with hepatocellular carcinoma (HCC). In the present study, we aimed to investigate the role of ...urea cream in the prevention of HFSR or amelioration of HFSR severity.
Patients with HCC were treated with either placebo cream or urea cream for 12 weeks concomitantly with sorafenib treatment. HFSR development, the Hand–Foot Skin Reaction and Quality of Life (HF-QoL) questionnaire score, and adverse events were assessed at 2, 4, 8 and 12 weeks.
Of the 288 patients, 247 patients, with 117 patients in the placebo control group and 130 patients in the urea cream group, were analysed. The urea cream group showed a trend towards a lower cumulative incidence of any-grade HFSR (log-rank, P = 0.247) and severe HFSR of grade II or higher (log-rank, P = 0.394) without statistical significance. In the incidence by time point, the incidence of severe HFSR of grade II or higher was significantly lower in the urea cream group than in the placebo control group at 2 weeks (13.8% versus 23.9%, P = 0.042). The urea cream group showed a significantly better HF-QoL questionnaire score than the placebo control group (11.8 versus 19.7, P = 0.014) at 12 weeks.
Treatment with urea cream showed a lower incidence of severe sorafenib-induced HFSR at 2 weeks and reduced the tendency of HFSR development in HCC patients. Therefore, treatment with urea cream may be considered for prophylaxis or improvement of HFSR grade in HCC patients treated with sorafenib.
ClinicalTrials.gov (NCT03212625).
•The urea cream group showed a trend towards a lower cumulative incidence of hand–foot skin reaction (HFSR).•The incidence of severe HFSR (grade ≥II) was reduced by urea cream at 2 weeks.•The urea cream improved score for Hand–Foot Skin Reaction and Quality of Life during sorafenib treatment in HCC patients.
Calpains are a family of calcium-dependent cysteine proteases that are ubiquitously expressed in mammals and play critical roles in neuronal death by catalyzing substrate proteolysis. Here, we ...developed two-dimensional gel electrophoresis-based protease proteomics to identify putative calpain substrates. To accomplish this, cellular lysates from neuronal cells were first separated by pI, and the immobilized sample on a gel strip was incubated with a recombinant calpain and separated by molecular weight. Among 25 altered protein spots that were differentially expressed by at least 2-fold, we confirmed that arsenical pump-driving ATPase, optineurin, and peripherin were cleaved by calpain using in vitro and in vivo cleavage assays. Furthermore, we found that all of these substrates were cleaved in MN9D cells treated with either ionomycin or 1-methyl-4-phenylpyridinium, both of which cause a calcium-mediated calpain activation. Their cleavage was blocked by calcium chelator or calpain inhibitors. In addition, calpain-mediated cleavage of these substrates and its inhibition by calpeptin were confirmed in a middle cerebral artery occlusion model of cerebral ischemia, as well as a stereotaxic brain injection model of Parkinson disease. Transient overexpression of each protein was shown to attenuate 1-methyl-4-phenylpyridinium-induced cell death, indicating that these substrates may confer protection of varying magnitudes against dopaminergic injury. Taken together, the data indicate that our protease proteomic method has the potential to be applicable for identifying proteolytic substrates affected by diverse proteases. Moreover, the results described here will help us decipher the molecular mechanisms underlying the progression of neurodegenerative disorders where protease activation is critically involved.
Background: It is important to assess contribution of calpain activation and identify substrates affected during neurodegeneration.
Results: Gel-based protease proteomics identified novel substrates that were cleaved in neurotoxin-treated culture and rat brain disease models.
Conclusion: These novel calpain substrates may confer protection against neurodegeneration.
Significance: Our findings contribute to better deciphering the molecular mechanism underlying the progression of protease-mediated neurodegeneration.
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