Circular RNAs in tuberculosis and lung cancer.

This review signifies the role of circular RNAs (circRNAs) in tuberculosis (TB) and lung cancer (LC), focusing on pathogenesis, diagnosis, and treatment. CircRNAs, a newly discovered type of non-coding RNA, have emerged as key regulators of gene expression and promising biomarkers in various bodily fluids due to their stability. The current review discusses circRNA biogenesis, highlighting their RNase-R resistance due to their loop forming structure, making them effective biomarkers. It details their roles in gene regulation, including splicing, transcription control, and miRNA interactions, and their impact on cellular processes and diseases. For LC, the review identifies circRNA dysregulation affecting cell growth, motility, and survival, and their potential as therapeutic targets and biomarkers. In TB, it addresses circRNAs' influence on host anti-TB immune responses, proposing their use as early diagnostic markers. The paper also explores the interplay between TB and LC, emphasizing circRNAs as dual biosignatures, and the necessity for differential diagnosis. It concludes that no single circRNA biomarker is universally applicable for both TB and LC. Ultimately, the review highlights the pivotal role of circRNAs in TB and LC, encouraging further research in biomarker identification and therapeutic development concomitant for both diseases.

Spatiotemporally-controlled hydrophobic drug delivery via photosensitizer-driven assembly-disassembly for enhanced triple-negative breast cancer treatment.

Therapeutic approaches for triple-negative breast cancer (TNBC) have been continuously advancing, but inadequate control over release behavior, insufficient tumor selectivity, and limited drug availability continue to impede therapeutic outcomes in nanodrug systems. In this study, we propose a general hydrophobic antineoplastic delivery system, termed spatiotemporally-controlled hydrophobic antineoplastic delivery system (SCHADS) for enhanced TNBC treatment. The key feature of SCHADS is the formation of metastable photosensitive-antineoplastic complexes (PACs) through the self-assembly of hydrophobic drugs driven by photosensitive molecules. With the further decoration of tumor-targeting peptides coupled with the EPR effect, the PACs tend to accumulate in the tumor site tremendously, promoting drug delivery efficiency. Meanwhile, the disassembly behavior of the metastable PACs could be driven by light on demand to achieve in situ drug release, thus promoting chemotherapeutics availability. Furthermore, the abundant ROS generated by the photosensitizer could effectively kill tumor cells, ultimately realizing an effective combination of photodynamic and chemotherapeutic therapy. As an exemplary presentation, chlorin e6 has been chosen to drive the formation of PACs with the system xc- inhibitor sorafenib. Compared with pure drug treatment, the PACs with the above-described preponderances exhibit superior therapeutic effects both in vitro and in vivo and circumvent the side effects due to off-target. By manipulating the laser irradiation, the PACs-treated cell death mechanism could be dynamically regulated, thus providing the potential to remedy intrinsic/acquired resistance of tumor. Collectively, this SCHADS achieves spatio-temporal control of the drug that greatly enhances the availability of anticarcinogen and realizes synergistic antitumor effect in TNBC treatment, even ultimately being extended to the treatment of other types of tumors.

Long-term treatment with ganaxolone for seizures associated with cyclin-dependent kinase-like 5 deficiency disorder: Two-year open-label extension follow-up.

OBJECTIVE: In the placebo-controlled, double-blind phase of the Marigold study (NCT03572933), ganaxolone significantly reduced major motor seizure frequency (MMSF) in patients with cyclin-dependent kinase-like 5 deficiency disorder (CDD). We report 2-year safety and clinical outcomes data from the open-label extension (OLE) phase of Marigold. METHODS: Patients with CDD who completed the double-blind phase were eligible to continue in the OLE. Efficacy assessments included MMSF reduction from prerandomization baseline, responder rates, and Clinical Global Impression-Improvement scores, including assessment of seizure intensity and duration (CGI-CSID). Safety assessments included treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation. RESULTS: Of 101 patients who enrolled in Marigold, 88 (87.1%) entered the OLE (median age = 5 years, 79.5% female). Median 28-day MMSF at baseline was 50.6. At 2 years in the OLE (months 22-24), MMSF was reduced by a median of 48.2% (n = 50); when missing data were imputed, median reduction in MMSF was 43.8% using a mixed effects model and 27.4% using a last observation carried forward model. During months 22-24, 23 of 50 (46.0%) patients experienced reductions in MMSF of ≥50%; 12 of 50 (24.0%) patients experienced MMSF reductions of ≥75%. During months 22-24, 40 of 49 (81.6%) patients were rated by caregivers as having improvement in seizure-related outcomes based on CGI-CSID scores. Thirty-seven patients discontinued ganaxolone due to lack of efficacy (n = 13), withdrawal by caregiver (n = 12), adverse event (n = 10), physician decision (n = 1), or death (n = 1; unrelated to study drug). The most common treatment-related TEAEs were somnolence (17.0%), seizure (11.4%), and decreased appetite (5.7%). Patients reported serious TEAEs (n = 28, 31.8%); those reported in ≥3% of patients were seizure (n = 6), pneumonia (n = 5), acute respiratory failure (n = 3), aspiration pneumonia (n = 3), and dehydration (n = 3). SIGNIFICANCE: Sustained reductions in MMSF at 2 years in the OLE support the efficacy of ganaxolone in seizures associated with CDD. Safety findings in the OLE were consistent with the double-blind phase.

Anchoring a Structurally Editable Proximal Cofactor-like Module to Construct an Artificial Dual-center Peroxygenase.

A recent novel strategy for constructing artificial metalloenzymes (ArMs) that target new-to-nature functions uses dual-functional small molecules (DFSMs) with catalytic and anchoring groups for converting P450BM3 monooxygenase into a peroxygenase. However, this process requires excess DFSMs (1000 equivalent of P450) owing to their low binding affinity for P450, thus severely limiting its practical application. Herein, structural optimization of the DFSM-anchoring group considerably enhanced their binding affinity by three orders of magnitude (Kd ≈10-8  M), thus approximating native cofactors, such as FMN or FAD in flavoenzymes. An artificial cofactor-driven peroxygenase was thus constructed. The co-crystal structure of P450BM3 bound to a DFSM clearly revealed a precatalytic state in which the DFSM participates in H2 O2 activation, thus facilitating peroxygenase activity. Moreover, the increased binding affinity substantially decreases the DFSM load to as low as 2 equivalents of P450, while maintaining increased activity. Furthermore, replacement of catalytic groups showed disparate selectivity and activity for various substrates. This study provides an unprecedented approach for assembling ArMs by binding editable organic cofactors as a co-catalytic center, thereby increasing the catalytic promiscuity of P450 enzymes.

Comparable Encoding, Comparable Perceptual Pattern: Acoustic and Electric Hearing.

Perception with electric neuroprostheses is sometimes expected to be simulated using properly designed physical stimuli. Here, we examined a new acoustic vocoder model for electric hearing with cochlear implants (CIs) and hypothesized that comparable speech encoding can lead to comparable perceptual patterns for CI and normal hearing (NH) listeners. Speech signals were encoded using FFT-based signal processing stages including band-pass filtering, temporal envelope extraction, maxima selection, and amplitude compression and quantization. These stages were specifically implemented in the same manner by an Advanced Combination Encoder (ACE) strategy in CI processors and Gaussian-enveloped Tones (GET) or Noise (GEN) vocoders for NH. Adaptive speech reception thresholds (SRTs) in noise were measured using four Mandarin sentence corpora. Initial consonant (11 monosyllables) and final vowel (20 monosyllables) recognition were also measured. NaÏve NH listeners were tested using vocoded speech with the proposed GET/GEN vocoders as well as conventional vocoders (controls). Experienced CI listeners were tested using their daily-used processors. Results showed that: 1) there was a significant training effect on GET vocoded speech perception; 2) the GEN vocoded scores (SRTs with four corpora and consonant and vowel recognition scores) as well as the phoneme-level confusion pattern matched with the CI scores better than controls. The findings suggest that the same signal encoding implementations may lead to similar perceptual patterns simultaneously in multiple perception tasks. This study highlights the importance of faithfully replicating all signal processing stages in the modeling of perceptual patterns in sensory neuroprostheses. This approach has the potential to enhance our understanding of CI perception and accelerate the engineering of prosthetic interventions. The GET/GEN MATLAB program is freely available athttps://github.com/BetterCI/GETVocoder.

Enabling Peroxygenase Activity in Cytochrome P450 Monooxygenases by Engineering Hydrogen Peroxide Tunnels.

Given prominent physicochemical similarities between H2O2 and water, we report a new strategy for promoting the peroxygenase activity of P450 enzymes by engineering their water tunnels to facilitate H2O2 access to the heme center buried therein. Specifically, the H2O2-driven activities of two native NADH-dependent P450 enzymes (CYP199A4 and CYP153AM.aq) increase significantly (by >183-fold and >15-fold, respectively). Additionally, the amount of H2O2 required for an artificial P450 peroxygenase facilitated by a dual-functional small molecule to obtain the desired product is reduced by 95%-97.5% (with ∼95% coupling efficiency). Structural analysis suggests that mutating the residue at the bottleneck of the water tunnel may open a second pathway for H2O2 to flow to the heme center (in addition to the natural substrate tunnel). This study highlights a promising, generalizable strategy whereby P450 monooxygenases can be modified to adopt peroxygenase activity through H2O2 tunnel engineering, thus broadening the application scope of P450s in synthetic chemistry and synthetic biology.

SENIES: DNA Shape Enhanced Two-Layer Deep Learning Predictor for the Identification of Enhancers and Their Strength.

Identifying enhancers is a critical task in bioinformatics due to their primary role in regulating gene expression. For this reason, various computational algorithms devoted to enhancer identification have been put forward over the years. More features are extracted from the single DNA sequences to boost the performance. Nevertheless, DNA structural information is neglected, which is an essential factor affecting the binding preferences of transcription factors to regulatory elements like enhancers. Here, we propose SENIES, a DNA shape enhanced deep learning predictor, to identify enhancers and their strength. The predictor consists of two layers where the first layer is for enhancer and non-enhancer identification, and the second layer is for predicting the strength of enhancers. Apart from two common sequence-derived features (i.e., one-hot and k-mer), DNA shape is introduced to describe the 3D structures of DNA sequences. Performance comparison with state-of-the-art methods conducted on public datasets demonstrates the effectiveness and robustness of our predictor. The code implementation of SENIES is publicly available at https://github.com/hlju-liye/SENIES.

Emerging albumin hydrogels as personalized biomaterials.

Developing biomaterials-based tissue engineering scaffolds with personalized features and intrinsic biocompatibility is appealing and urgent. Through utilizing various strategies, albumin, as the most abundant protein in plasma, could be fabricated into sustainable, cost-effective, and potentially personalized hydrogels that would display enormous biological applications. To date, much of the albumin-based research is primarily engrossed in using albumin as a therapeutic molecule or a drug carrier, not much as a scaffold for tissue engineering. For this reason, we have come up with a detailed and insightful review of recent progress in albumin-based hydrogels having an emphasis on production techniques, material characteristics, and biological uses. It is envisioned that albumin-based scaffolds would be appealing and useful platforms to meet current tissue engineering needs and achieve the goal of clinical translation to benefit patients. STATEMENT OF SIGNIFICANCE: The creation of autologous material-based scaffolds is a potential method for preventing immunological reactions and obtaining the best therapeutic results. Patient-derived albumin hydrogels may consequently provide improved opportunities for personalized treatment due to their abundant supply and minimal immunogenicity. To provide a detailed and insightful summary on albumin-based hydrogels, this review includes latest comprehensive information on their preparation procedures, features, and applications in 3D printing and other biomedical applications. The challenges, along with the future potential for implementing albumin-based hydrogels in clinics, have also been addressed.

Cochlear-implant Mandarin tone recognition with a disyllabic word corpus.

Despite pitch being considered the primary cue for discriminating lexical tones, there are secondary cues such as loudness contour and duration, which may allow some cochlear implant (CI) tone discrimination even with severely degraded pitch cues. To isolate pitch cues from other cues, we developed a new disyllabic word stimulus set (Di) whose primary (pitch) and secondary (loudness) cue varied independently. This Di set consists of 270 disyllabic words, each having a distinct meaning depending on the perceived tone. Thus, listeners who hear the primary pitch cue clearly may hear a different meaning from listeners who struggle with the pitch cue and must rely on the secondary loudness contour. A lexical tone recognition experiment was conducted, which compared Di with a monosyllabic set of natural recordings. Seventeen CI users and eight normal-hearing (NH) listeners took part in the experiment. Results showed that CI users had poorer pitch cues encoding and their tone recognition performance was significantly influenced by the "missing" or "confusing" secondary cues with the Di corpus. The pitch-contour-based tone recognition is still far from satisfactory for CI users compared to NH listeners, even if some appear to integrate multiple cues to achieve high scores. This disyllabic corpus could be used to examine the performance of pitch recognition of CI users and the effectiveness of pitch cue enhancement based Mandarin tone enhancement strategies. The Di corpus is freely available online: https://github.com/BetterCI/DiTone.

Dual-Stage Irradiation of Size-Switchable Albumin Nanocluster for Cascaded Tumor Enhanced Penetration and Photothermal Therapy.

The triple-negative breast cancer (TNBC) microenvironment makes a feature of aberrant vasculature, high interstitial pressure, and compact extracellular matrix, which combine to reduce the delivery and penetration of therapeutic agents, bringing about incomplete elimination of cancer cells. Herein, employing the tumor penetration strategy of size-shrinkage combined with ligand modification, we constructed a photothermal nanocluster for cascaded deep penetration in tumor parenchyma and efficient eradication of TNBC cells. In our approach, the photothermal agent indocyanine green (ICG) is laded in human serum albumin (HSA), which is cross-linked by a thermally labile azo linker (VA057) and then further modified with a tumor homing/penetrating tLyP-1 peptide (HP), resulting in a TNBC-targeting photothermal-responsive size-switchable albumin nanocluster (ICG@HSA-Azo-HP). Aided by the enhanced permeability and retention effect and guidance of HP, the ca. 149 nm nanoclusters selectively accumulate in the tumor site and then, upon mild irradiation with the 808 nm laser, disintegrate into 11 nm albumin fractions that possess enhanced intratumoral diffusion ability. Meanwhile, HP initiates the CendR pathway among the nutrient-deficient tumor cells and facilitates the transcellular delivery of the nanocluster and its disintegrated fractions for subsequent therapy. By employing this size-shrinkage and peptide-initiated transcytosis strategy, ICG@HSA-Azo-HP possesses excellent penetration capabilities and shows extensive penetration depth in three-dimensional multicellular tumor spheroids after irradiation. Moreover, with a superior photothermal conversion effect, the tumor-penetrating nanocluster can implement effective photothermal therapy throughout the tumor tissue under a second robust irradiation. Both in vivo orthotopic and ectopic TNBC therapy confirmed the efficient tumor inhibition of ICG@HSA-Azo-HP after dual-stage irradiation. The synergistic penetration strategy of on-demanded size-shrinkage and ligand guidance accompanied by clinically feasible NIR irradiation provides a promising approach for deep-penetrating TNBC therapy.

Living Cell Nanoporation and Exosomal RNA Analysis Platform for Real-Time Assessment of Cellular Therapies.

Efficient transfection of therapeutic agents and timely potency testing are two key factors hindering the development of cellular therapy. Here we present a cellular-nanoporation and exosome assessment device, a quantitative platform for nanochannel-based cell electroporation and exosome-based in situ RNA expression analysis. In its application to transfection of anti-miRNAs and/or chemotherapeutics into cells, we have systematically described the differences in RNA expression in secreted exosomes and assessed cellular therapies in real time.

Single-cell immune profiling reveals functional diversity of T cells in tuberculous pleural effusion.

Orchestration of an effective T lymphocyte response at infection sites is critical for protection against Mycobacterium tuberculosis (Mtb) infection. However, the local T cell immunity landscape in human tuberculosis is poorly defined. Tuberculous pleural effusion (TPE), caused by Mtb, is characterized by an influx of leukocytes to the pleural space, providing a platform suitable for delineating complex tissue responses to Mtb infection. Using single-cell transcriptomics and T cell receptor sequencing, we analyzed mononuclear cell populations in paired pleural fluid and peripheral blood of TPE patients. While all major cell clusters were present in both tissues, their relative proportions varied significantly by anatomic location. Lineage tracking analysis revealed subsets of CD8 and CD4 T cell populations with distinct effector functions specifically expanded at pleural sites. Granzyme K-expressing CD8 T cells were preferentially enriched and clonally expanded in pleural fluid from TPE, suggesting that they are involved in the pathogenesis of the disease. The findings collectively reveal the landscape of local T cell immunity in tuberculosis.

Bioinspired Cell Silicification: From Extracellular to Intracellular.

In nature, biosilicification directs the formation of elaborate amorphous silica exoskeletons that provide diatoms mechanically strong, chemically inert, non-decomposable silica armor conferring chemical and thermal stability as well as resistance to microbial attack, without changing the optical transparency or adversely effecting nutrient and waste exchange required for growth. These extraordinary silica/cell biocomposites have inspired decades of biomimetic research aimed at replication of diatoms' hierarchically organized exoskeletons, immobilization of cells or living organisms within silica matrices and coatings to protect them against harmful external stresses, genetic re-programming of cellular functions by virtue of physico-chemical confinement within silica, cellular integration into devices, and endowment of cells with non-native, abiotic properties through facile silica functionalization. In this Perspective, we focus our discussions on the development and concomitant challenges of bioinspired cell silicification ranging from "cells encapsulated within 3D silica matrices" and "cells encapsulated within 2D silica shells" to extra- and intracellular silica replication, wherein all biomolecular interfaces are encased within nanoscopic layers of amorphous silica. We highlight notable examples of advances in the science and technology of biosilicification and consider challenges to advancing the field, where we propose cellular "mineralization" with arbitrary nanoparticle exoskeletons as a generalizable means to impart limitless abiotic properties and functions to cells, and, based on the interchangeability of water and silicic acid and analogies between amorphous ice and amorphous silica, we consider "freezing" cells within amorphous silica as an alternative to cryo-preservation.

Optimization and characterization of poly(lactic-co-glycolic acid) nanoparticles loaded with astaxanthin and evaluation of anti-photodamage effect in vitro.

Astaxanthin is a xanthophyll carotenoid with high beneficial biological activities, such as antioxidant function and scavenging oxygen free radicals, but its application is limited because of poor water solubility and low bioavailability. Here, we prepared and optimized poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with astaxanthin using the emulsion solvent evaporation technique and investigated the anti-photodamage effect in HaCaT cells. The four-factor three-stage Box-Behnken design was used to optimize the nanoparticle formulation. The experimental determination of the optimal nanoparticle size was 154.4 ± 0.35 nm, the zeta potential was 22.07 ± 0.93 mV, encapsulation efficiency was 96.42 ± 0.73% and drug loading capacity was 7.19 ± 0.12%. The physico-chemical properties of the optimized nanoparticles were characterized by dynamic light scattering, scanning electron microscopy, transmission electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry and thermo-gravimetric analyser. In vitro study exhibited the excellent cell viability and cellular uptake of optimized nanoparticles on HaCaT cells. The anti-photodamage studies (cytotoxicity assay, reactive oxygen species content and JC-1 assessment) demonstrated that the optimized nanoparticles were more effective and safer than pure astaxanthin in HaCaT cells. These results suggest that our PLGA-coated astaxanthin nanoparticles synthesis method was highly feasible and can be used in cosmetics or the treatment of skin diseases.

Resveratrol loaded oxidized mesoporous carbon nanoparticles: A promising tool to treat triple negative breast cancer.

Currently, breast cancer has become the most commonly diagnosed malignancy among females and triple negative breast cancer (TNBC) is a highly aggressive and metastatic subtype. The natural polyphenolic compound, resveratrol (3, 4', 5-trihydroxy-trans-stilbene, RES), has drawn great attention for its potential against TNBC. However, due to the poor aqueous solubility, the bioactivity of RES against TNBC is extremely hampered. In this study, oxidized mesoporous carbon nanoparticles (oMCNs) with size below 200 nm and excellent water dispersibility were synthesized using mild oxidation method and RES was successfully encapsulated into the pores of oMCNs with high drug loading efficiency (24.8% w/w). oMCNs exhibited good biocompatibility and excellent cellular uptake efficiency. Compared to pure RES, oMCNs-RES greatly improved the saturated solubility and in vitro release property. In vitro cytoxicity assay and apoptosis analysis showed that oMCNs-RES induced enhanced cytotoxic effect and pro-apoptosis effect mediated via the PARP and Caspase-3 protein cleavage in TNBC cell line, respectively. These results demonstrate oMCNs have the potential to deliver hydrophobic drugs and oMCNs-RES are promising in treating TNBC.

5-hydroxymethylfurfural-embedded poly (vinyl alcohol)/sodium alginate hybrid hydrogels accelerate wound healing.

Treating large acute or chronic wounds remains a challenging task because of a lack of effective methods to accelerate wound healing. Though growth factor-based wound products are found to be effective, they are costly and are potentially associated with increased cancer mortality. Effective, safe, and affordable strategies to tackle large or chronic wounds need to further be designed and developed. Here, we designed a new antioxidant-embedded hydrogel system for speeding up the wound healing process. We prepared multifunctional poly (vinyl alcohol)/sodium alginate (PVA/SA) hydrogels with the incorporation of 5-hydroxymethylfurfural (5-HMF) and silver nanoparticles (Ag-NPs), and investigated their physiochemical and biological properties in vitro and in vivo. PVA, SA, 5-HMF, and Ag-NPs were employed for good mechanical properties, good biocompatibility, anti-inflammation, and anti-bacterial activity, respectively. 5-HMF is commonly found in many food products (e.g. honey, coffee, and black garlic) and is known as an antioxidant. In our in vitro study, 5-HMF was found to effectively facilitate the proliferation and migration of human skin fibroblasts (HSF), and collagen production. Besides, 5-HMF-embedded PVA/SA hybrid hydrogels supported controlled release and good cell compatibility, and more importantly accelerated wound healing in vivo through ameliorated inflammation, enhanced angiogenesis/vascularization, increased collagen production, and promoted re-epithelialization.

CD30 aptamer-functionalized PEG-PLGA nanoparticles for the superior delivery of doxorubicin to anaplastic large cell lymphoma cells.

Nanoparticles (NPs) conjugated with aptamers have been extensively in recent years, which can efficiently target cancer cells that improve the therapeutic effect. Aptamers (Apt) are small oligonucleotide molecule ligands have specific high-affinity. In this work, we developed a PEG-PLGA nanoparticles (NPs) encapsulated with doxorubicin. The NPs were modified with C2NP, a ssDNA aptamer specifically binding to CD30 protein which was over expressed in anaplastic large cell lymphoma (ALCL) cells. PEG-PLGA nanoparticles (NPs) were formed by nanoprecipitation and loaded with doxorubicin, further conjugated C2NP aptamer via an EDC/NHS technique. Obtained results demonstrated that the targeted agent was successfully conjugated confirming by Urea PAGE and XPS. The physicochemical properties of Apt-DOX-NPs like particle size at 168.07 ±â€¯2.72 nm and zeta potential at -30.76 ±â€¯0.153 mV. The time of the release drugs was efficiently increased in targeted formulations and showed higher accumulation in ALCL cells than non-targeted system. Findings from this work demonstrated the potential efficacy of C2NP-functionalized nanoparticles for a therapy in ALCL.

Time-compression thresholds for Mandarin sentences in normal-hearing and cochlear implant listeners.

Faster speech may facilitate more efficient communication, but if speech is too fast it becomes unintelligible. The maximum speeds at which Mandarin words were intelligible in a sentence context were quantified for normal hearing (NH) and cochlear implant (CI) listeners by measuring time-compression thresholds (TCTs) in an adaptive staircase procedure. In Experiment 1, both original and CI-vocoded time-compressed speech from the MSP (Mandarin speech perception) and MHINT (Mandarin hearing in noise test) corpora was presented to 10 NH subjects over headphones. In Experiment 2, original time-compressed speech was presented to 10 CI subjects and another 10 NH subjects through a loudspeaker in a soundproof room. Sentences were time-compressed without changing their spectral profile, and were presented up to three times within a single trial. At the end of each trial, the number of correctly identified words in the sentence was scored. A 50%-word recognition threshold was tracked in the psychophysical procedure. The observed median TCTs were very similar for MSP and MHINT speech. For NH listeners, median TCTs were around 16.7 syllables/s for normal speech, and 11.8 and 8.6 syllables/s respectively for 8 and 4 channel tone-carrier vocoded speech. For CI listeners, TCTs were only around 6.8 syllables/s. The interquartile range of the TCTs within each cohort was smaller than 3.0 syllables/s. Speech reception thresholds in noise were also measured in Experiment 2, and were found to be strongly correlated with TCTs for CI listeners. In conclusion, the Mandarin sentence TCTs were around 16.7 syllables/s for most NH subjects, but rarely faster than 10.0 syllables/s for CI listeners, which quantitatively illustrated upper limits of fast speech information processing with CIs.

5-Hydroxymethylfurfural Mitigates Lipopolysaccharide-Stimulated Inflammation via Suppression of MAPK, NF-κB and mTOR Activation in RAW 264.7 Cells.

5-Hydroxymethylfurfural (5-HMF) is found in many food products including honey, dried fruits, coffee and black garlic extracts. Here, we investigated the anti-inflammatory activity of 5-HMF and its underlying mechanisms in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. 5-HMF pretreatment ranging from 31.5 to 126.0 µg/mL reduced the production of nitric oxide (NO), prostaglandin E2 (PGE2) and pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) in a concentration-dependent manner in LPS-stimulated cells. Moreover, 5-HMF-pretreated cells significantly down-regulated the mRNA expression of two major inflammatory mediators, nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and suppressed the production of pro-inflammatory cytokines, as compared with the only LPS-stimulated cells. 5-HMF suppressed the phosphorylation of extracellular regulated protein kinases (ERK1/2), c-Jun N-terminal kinase (JNK), IκBα, NF-κB p65, the mammalian target of rapamycin (mTOR) and protein kinase B (Akt). Besides, 5-HMF was proved to inhibit NF-κB p65 translocation into nucleus to activate inflammatory gene transcription. These results suggest that 5-HMF could exert the anti-inflammatory activity in the LPS-induced inflammatory response by inhibiting the MAPK, NF-κB and Akt/mTOR pathways. Thus, 5-HMF could be considered as a therapeutic ingredient in functional foods.

Sub-Rayleigh resolution ghost imaging by spatial low-pass filtering.

A sub-Rayleigh resolution ghost imaging experiment is performed via post-detection spatial low-pass filtering of the instantaneous intensity. A super-resolution reconstructed image has been achieved, in which the spatial resolution can exceed the Rayleigh diffraction limit by more than a factor of two. The resolution depends on the filter threshold, and the Rayleigh limit can be exceeded for a wide choice of threshold values. The setup is simple and easy to implement, which is an advantage for practical applications.