Plasmonic Near-Infrared Photoconductor Based on Hot Hole Collection in the Metal-Semiconductor-Metal Junction.

Harvesting energetic carriers from plasmonic resonance has been a hot topic in the field of photodetection in the last decade. By interfacing a plasmonic metal with a semiconductor, the photoelectric conversion mechanism, based on hot carrier emission, is capable of overcoming the band gap limitation imposed by the band-to-band transition of the semiconductor. To date, most of the existing studies focus on plasmonic structural engineering in a single metal-semiconductor (MS) junction system and their responsivities are still quite low in comparison to conventional semiconductor, material-based photodetection platforms. Herein, we propose a new architecture of metal-semiconductor-metal (MSM) junctions on a silicon platform to achieve efficient hot hole collection at infrared wavelengths with a photoconductance gain mechanism. The coplanar interdigitated MSM electrode's configuration forms a back-to-back Schottky diode and acts simultaneously as the plasmonic absorber/emitter, relying on the hot-spots enriched on the random Au/Si nanoholes structure. The hot hole-mediated photoelectric response was extended far beyond the cut-off wavelength of the silicon. The proposed MSM device with an interdigitated electrode design yields a very high photoconductive gain, leading to a photocurrent responsivity up to several A/W, which is found to be at least 1000 times higher than that of the existing hot carrier based photodetection strategies.

Ultrasound Deep Brain Stimulation Modulates Body Temperature in Mice.

Body temperature plays a critical role in rehabilitation, and numerous studies proved that the regulation of body temperature contributes to the sensorimotor recovery of patients with brain diseases such as stroke. The hypothalamus plays a key role in thermoregulation. Ultrasound deep brain stimulation (UDBS) can noninvasively modulate deep brain nuclei and have potential applications in the treatment of Parkinson's disease, Alzheimer's disease, and depression, among others. The purpose of this study was to investigate whether ultrasound stimulation of the hypothalamus could regulate body temperature in free-moving mice. Results showed that thermoregulation was related to ultrasonic parameters (pulse repetition frequency (PRF), duty cycle, total time, and acoustic pressure). UDBS of the preoptic area of the anterior hypothalamus at 500 Hz PRF could significantly reduce body temperature ( [Formula: see text] at t = 5 min, [Formula: see text] at t = 10 min, [Formula: see text] at t = 15 min). Meanwhile, UDBS of the dorsomedial hypothalamus at 10 Hz PRF triggered a significant increase in body temperature ( [Formula: see text] at t = 5 min, [Formula: see text] at t = 10 min). These results suggest that UDBS, as a noninvasive neuromodulation tool, may play a key role in the future clinical treatment of malignant hyperthermia and hypothermia.

Closed-loop wearable ultrasound deep brain stimulation system based on EEG in mice.

Objective. Epilepsy is one of the most common severe brain disorders. Ultrasound deep brain stimulation (UDBS) has shown a potential capability to suppress seizures. However, because seizures occur sporadically, it is necessary to develop a closed-loop system to suppress them. Therefore, we developed a closed-loop wearable UDBS system that delivers ultrasound to the hippocampus to suppress epileptic seizures.Approach.Mice were intraperitoneally injected with 10 mg kg-1kainic acid and divided into sham and UDBS groups. Epileptic seizures were detected by applying both long short-term memory (LSTM) and bidirectional LSTM (BILSTM) networks according to EEG signal characteristics. When epileptic seizures were detected, the closed-loop UDBS system automatically activated a trigger switch to stimulate the hippocampus for 10 min and continuously record EEG signals until 20 min after ultrasonic stimulation. EEG signals were analyzed using the MATLAB software. After EEG recording, we observed the survival rate of the experimental mice for 72 h.Main results.The BiLSTM network was found to have preferable classification performance over the LSTM network. The closed-loop UDBS system with BiLSTM could automatically detect epileptic seizures using EEG signals and effectively reduce epileptic EEG power spectral density and seizure duration by 10.73%, eventually improving the survival rate of early epileptic mice from 67.57% in the sham group to 88.89% in the UDBS group.Significance.The closed-loop UDBS system developed in this study could be an effective clinical tool for the control of epilepsy.

MicroRNA 223 Targeting ATG16L1 Affects Microglial Autophagy in the Kainic Acid Model of Temporal Lobe Epilepsy.

This study aimed to explore whether microRNA (miR) 223 affects microglial autophagy by targeting autophagy-related 16-like 1 (ATG16L1) in the kainic acid (KA) model of temporal lobe epilepsy (TLE). The miRNA and mRNA expression levels were quantified using quantitative real-time polymerase chain reaction (qRT-PCR), and the protein expression was investigated using western blotting. A dual-luciferase reporter assay was used to test the direct interaction between miR 223 and ATG16L1. In situ hybridization was performed to measure the hippocampal expression of miR 223. We used immunofluorescence staining to assess the expression of ATG16L1 and microtubule-associated protein light chain 3 (LC3) in the murine hippocampal microglia. Inhibitor of miR 223 was utilized to investigate the role of miR 223 in TLE, and the epileptic activity was assessed using electroencephalography (EEG). The autophagosomes were observed by transmission electron microscopy. In patients with TLE, the murine KA model of TLE, and the KA-stimulated BV2 cells, miR 223, and sequestosome 1 (SQSTM1/P62) expressions were remarkably increased, whereas ATG16L1 and LC3 levels were significantly decreased. Using a dual-luciferase reporter assay, ATG16L1 was determined as a direct target of miR 223. Treatment with antagomir 223 alleviated epilepsy, prevented abnormalities in EEG recordings and increased the ATG16L1 and LC3 levels in KA-treated mice. Inhibition of miR 223 induced increased autophagy in BV2 cells upon Rapamycin stimulation. These findings show that miR 223 affects microglial autophagy via ATG16L1 in the KA model of TLE. The miR 223/ATG16L1 pathway may offer a new treatment option for TLE.

Immune response in glioma's microenvironment.

OBJECTIVES: Glioma is the most common tumor of the central nervous system. In this review, we outline the immunobiological factors that interact with glioma cells and tumor microenvironment (TME), providing more potential targets for clinical inhibition of glioma development and more directions for glioma treatment. CONTENT: Recent studies have shown that glioma cells secrete a variety of immune regulatory factors and interact with immune cells such as microglial cells, peripheral macrophages, myeloid-derived suppressor cells (MDSCs), and T lymphocytes in the TME. In particular, microglia plays a key role in promoting glioma growth. Infiltrating immune cells induce local production of cytokines, chemokines and growth factors. Further leads to immune escape of malignant gliomas. SUMMARY AND OUTLOOK: The complex interaction of tumor cells with the TME has largely contributed to tumor heterogeneity and poor prognosis. We review the immunobiological factors, immune cells and current immunotherapy of gliomas, provide experimental evidence for future research and treatment of gliomas.

DNA nanotetrahedron linked dual-aptamer based voltammetric aptasensor for cardiac troponin I using a magnetic metal-organic framework as a label.

An ultrasensitive voltammetric aptasensor was constructed to analyze cardiac troponin I (cTnI). It is based on DNA nanotetrahedron (NTH) linked dual-aptamer (dAPT) and magnetic metal organic frameworks (mMOFs) of type Fe3O4@UiO-66. Firstly, the DNA NTH linked dAPT (Tro4 and Tro6) were immobilized on a gold electrode for improving the capture efficiency of cTnI. The novel mMOFs Fe3O4@UiO-66 was then decorated by Au@Pt nanoparticles (Au@PtNPs), horseradish peroxidase (HRP), G-quadruplex/hemin (GQH) DNAzyme, and two types of aptamers to form signaling nanoprobes. In the presence of cTnI, an aptamer-protein-nanoprobe sandwich-type structure is formed. Afterward, the nanoprobes including enzyme, GQH DNAzyme and Fe3O4@UiO-66/Au@PtNP were utilized to catalyze the oxidation of hydroquinone by hydrogen peroxide for the electrochemical signals amplification, typically at a working potential of -0.1 V (vs. Ag/AgCl). The voltammetric signal increases linearly in the 0.01 to 100 ng·mL-1 cTnI concentration range, and the detection limit is 5.7 pg·mL-1. Graphical abstract An ultrasensitive voltammetric aptasensor was constructed to analyze cardiac troponin I (cTnI) based on DNA nanotetrahedron linked dual-aptamer and magnetic metal organic frameworks of type Fe3O4@UiO-66. The results indicated the aptasensor has a wide linear response range (0.01 to 100 ng/mL) and low detection limit (5.74 pg/mL) for cTnI. GE: gold electrode; MCH: 6-Mmercapto-1-hexanol; HRP: horseradish peroxidase; HQ: hydroquinone; BQ: benzoquinone.

Identification of co-expression modules and pathways correlated with osteosarcoma and its metastasis.

BACKGROUND: Osteosarcoma is the most common bone tumor that occurs in children. METHODS: To identify co-expression modules and pathways correlated with osteosarcoma and its clinical characteristics, we performed weighted gene co-expression network analysis (WGCNA) on RNA-seq data of osteosarcoma with 52 samples. Then we performed pathway enrichment analysis on genes from significant modules. RESULTS: A total of 5471 genes were included in WGCNA, and 16 modules were identified. Module-trait analysis identified that a module involved in microtubule bundle formation, drug metabolism-cytochrome P450, and IL-17 signaling pathway was negatively correlated with osteosarcoma and positively correlated with metastasis; a module involved in DNA replication was positively correlated with osteosarcoma; a module involved in cell junction was positively correlated with metastasis; and a module involved in heparin binding negatively correlated with osteosarcoma. Moreover, expression levels in four of the top ten differentially expressed genes were validated in another independent dataset. CONCLUSIONS: Our analysis might provide insight for molecular mechanisms of osteosarcoma.

Investigating age­induced differentially expressed genes and potential molecular mechanisms in osteosarcoma based on integrated bioinformatics analysis.

Osteosarcoma (OS) is the most common primary bone malignancy. It predominantly occurs in adolescents, but can develop at any age. The age at diagnosis is a prognostic factor of OS, but the molecular basis of this remains unknown. The current study aimed to identify age­induced differentially expressed genes (DEGs) and potential molecular mechanisms that contribute to the different outcomes of patients with OS. Microarray data (GSE39058 and GSE39040) obtained from the Gene Expression Omnibus database and used to analyze age­induced DEGs to reveal molecular mechanism of OS among different age groups (<20 and >20 years old). Differentially expressed mRNAs (DEMs) were divided into up and downregulated DEMs (according to the expression fold change), then Gene Ontology function enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed. Furthermore, the interactions among proteins encoded by DEMs were integrated with prediction for microRNA­mRNA interactions to construct a regulatory network. The key subnetwork was extracted and Kaplan­Meier survival analysis for a key microRNA was performed. DEMs within the subnetwork were predominantly involved in 'ubiquitin protein ligase binding', 'response to growth factor', 'regulation of type I interferon production', 'response to decreased oxygen levels', 'voltage­gated potassium channel complex', 'synapse part', 'regulation of stem cell proliferation'. In summary, integrated bioinformatics was applied to analyze the potential molecular mechanisms leading to different outcomes of patients with OS among different age groups. The hub genes within the key subnetwork may have crucial roles in the different outcomes associated with age and require further analysis.

Galectin-3 deficiency protects lipopolysaccharide-induced chondrocytes injury via regulation of TLR4 and PPAR-γ-mediated NF-κB signaling pathway.

The aim of the present study was to identify the functional role of galectin-3 (Gal-3) in lipopolysaccharide (LPS)-induced injury in ATDC5 cells and to explore the probable molecular mechanisms. Here, we identified that LPS is sufficient to enhance the expression of Gal-3 in ATDC5 cells. In addition, repression of Gal-3 obviously impeded LPS-stimulated inflammation damage as exemplified by a reduction in the release of inflammatory mediators interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α, as well as the production of nitric oxide and prostaglandin E2 (PGE2) concomitant with the downregulation of matrix metalloproteinases (MMP)-13 and MMP-3 expression in ATDC5 cells after LPS administration. Moreover, ablation of Gal-3 dramatically augmented cell ability and attenuated cell apoptosis accompanied by an increase in the expression of antiapoptotic protein Bcl-2 and a decrease in the expression of proapoptotic protein Bax and caspase-3 in ATDC5 cells subjected with LPS. Importantly, we observed that forced expression of TLR4 or blocked PPAR-γ with the antagonist GW9662 effectively abolished Gal-3 inhibition-mediated anti-inflammatory and antiapoptosis effects triggered by LPS. Mechanistically, depletion of Gal-3 prevents the NF-κB signaling pathway. Taken together, these findings indicated that the absence of Gal-3 exerted chondroprotective properties dependent on TLR4 and PPAR-γ-mediated NF-κB signaling, indicating that Gal-3 functions as a protector in the development and progression of osteoarthritis.

Retinoic acid retards fetal and hindlimb skeletal development asymmetrically in a retinoic acid-induced clubfoot model.

Retinoic acid (RA) has been shown to induce congenital clubfoot in animal models, but it is unknown whether the effect of RA on the formation of clubfoot in vivo results from generalized growth retardation or from the specific effects of hindlimb skeletal development. Our experimental research was based on a clubfoot model treated by maternal administration of RA (120, 130 or 140 mg/kg body weight) as an intragastric dose on embryonic day 10 (E10), and a control group was administered with an equivalent dose of solvent. Prenatal RA exposure reduced fetal body weight, length and skeletal ossification of the hindlimb compared with the control fetuses in a dose-dependent manner. The normal development curves indicated that the RA-exposed fetuses showed delayed increase in body weight and skeletal ossification development. However, there was no uniform effect on the skeletons of the hindlimb, not least retardation in ossification and induction malformation on the talus and calcaneus. Our results demonstrated that prenatal RA exposure had retardation effects on the developing hindlimb skeleton that was independent of those on the overall fetal growth. The normal skeletal ossification showed that the talus and calcaneus were poorly ossified and they were delayed by almost one day in the RA 120 mg/kg group. Therefore, during the susceptible stages, different regions of the limb bud responded differently to the teratogenic effects of RA.

Quantitative evaluation in vivo of the degree of differentiation of hindlimb cartilage in a rat clubfoot model.

The Limb Morphogenetic Differentiation Scoring system introduced by Neubert and Barrach in 1977 has been used in drug testing as a measure of the degree of cartilage growth inhibition especially for forelimb in vitro. There is no scoring system to quantify the degree of hindlimb bud cartilage differentiation in vivo. A total of 60 female Sprague-Dawley rats weighing 220-250 g were assigned at random to six control groups and six experimental groups on day 0 of pregnancy. The experimental groups were treated with all-trans-retinoic acid (ATRA). A new limb morphogenetic differentiation scoring system was developed and used to quantify the degree of development of the hindlimb buds from the fetuses at embryonic days E13 to E18. The differentiation of cartilages assessed by the new scoring system showed a statistically significant difference between the experimental group and the control group from E13 to E18 (T-test, p < 0.05). Cartilage growth (the proximodistal length) in the control group increased gradually from E14, reaching its peak at E17, but in the experimental group the growth at E13, E16, E17, and E18 was significantly shorter (p < 0.05). In conclusion, the new limb morphogenetic differentiation scoring system described here can be used to quantify the degree of inhibition of the hindlimb bud development by teratogenic drugs or materials, and morphogenetic differentiation in vivo.