Prospective Cohort Study

Nanomedicine and nano delivery systems are a relatively new but rapidly developing science where materials in the nanoscale range are employed to serve as means of diagnostic tools or to deliver therapeutic agents to specific targeted sites in a controlled manner Nanotechnology offers multiple benefits in treating chronic human diseases by site-specific, and target-oriented delivery of precise medicines Recently, there are a number of outstanding applications of the nanomedicine (chemotherapeutic agents, biological agents, immunotherapeutic agents etc) in the treatment of various diseases The current review, presents an updated summary of recent advances in the field of nanomedicines and nano based drug delivery systems through comprehensive scrutiny of the discovery and application of nanomaterials in improving both the efficacy of novel and old drugs (eg, natural products) and selective diagnosis through disease marker molecules The opportunities and challenges of nanomedicines in drug delivery from synthetic/natural sources to their clinical applications are also discussed In addition, we have included information regarding the trends and perspectives in nanomedicine area

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Nano based drug delivery systems: recent developments and future prospects

A brain-computer interface (BCI) is a hardware and software communications system that permits cerebral activity alone to control computers or external devices. The immediate goal of BCI research is to provide communications capabilities to severely disabled people who are totally paralyzed or 'locked in' by neurological neuromuscular disorders, such as amyotrophic lateral sclerosis, brain stem stroke, or spinal cord injury. Here, we review the state-of-the-art of BCIs, looking at the different steps that form a standard BCI: signal acquisition, preprocessing or signal enhancement, feature extraction, classification and the control interface. We discuss their advantages, drawbacks, and latest advances, and we survey the numerous technologies reported in the scientific literature to design each step of a BCI. First, the review examines the neuroimaging modalities used in the signal acquisition step, each of which monitors a different functional brain activity such as electrical, magnetic or metabolic activity. Second, the review discusses different electrophysiological control signals that determine user intentions, which can be detected in brain activity. Third, the review includes some techniques used in the signal enhancement step to deal with the artifacts in the control signals and improve the performance. Fourth, the review studies some mathematic algorithms used in the feature extraction and classification steps which translate the information in the control signals into commands that operate a computer or other device. Finally, the review provides an overview of various BCI applications that control a range of devices.

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Brain Computer Interfaces, a Review

Periodic visual stimulation and analysis of the resulting steady-state visual evoked potentials were first introduced over 80 years ago as a means to study visual sensation and perception. From the first single-channel recording of responses to modulated light to the present use of sophisticated digital displays composed of complex visual stimuli and high-density recording arrays, steady-state methods have been applied in a broad range of scientific and applied settings.The purpose of this article is to describe the fundamental stimulation paradigms for steady-state visual evoked potentials and to illustrate these principles through research findings across a range of applications in vision science.

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The steady-state visual evoked potential in vision research: A review.

The past 20 years have witnessed unprecedented progress in brain-computer interfaces (BCIs). However, low communication rates remain key obstacles to BCI-based communication in humans. This study presents an electroencephalogram-based BCI speller that can achieve information transfer rates (ITRs) up to 5.32 bits per second, the highest ITRs reported in BCI spellers using either noninvasive or invasive methods. Based on extremely high consistency of frequency and phase observed between visual flickering signals and the elicited single-trial steady-state visual evoked potentials, this study developed a synchronous modulation and demodulation paradigm to implement the speller. Specifically, this study proposed a new joint frequency-phase modulation method to tag 40 characters with 0.5-s-long flickering signals and developed a user-specific target identification algorithm using individual calibration data. The speller achieved high ITRs in online spelling tasks. This study demonstrates that BCIs can provide a truly naturalistic high-speed communication channel using noninvasively recorded brain activities.

https://www.pnas.org/content/pnas/112/44/E6058.full.pdf

High-speed spelling with a noninvasive brain–computer interface

Brain-computer interface (BCI) systems based on the steady-state visual evoked potential (SSVEP) provide higher information throughput and require shorter training than BCI systems using other brain signals. To elicit an SSVEP, a repetitive visual stimulus (RVS) has to be presented to the user. The RVS can be rendered on a computer screen by alternating graphical patterns, or with external light sources able to emit modulated light. The properties of an RVS (e.g., frequency, color) depend on the rendering device and influence the SSVEP characteristics. This affects the BCI information throughput and the levels of user safety and comfort. Literature on SSVEP-based BCIs does not generally provide reasons for the selection of the used rendering devices or RVS properties. In this paper, we review the literature on SSVEP-based BCIs and comprehensively report on the different RVS choices in terms of rendering devices, properties, and their potential influence on BCI performance, user safety and comfort.

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A survey of stimulation methods used in SSVEP-based BCIs

Conventional chemotherapy for cancer treatment is usually compromised by shortcomings such as insufficient therapeutic outcome and undesired side effects. The past decade has witnessed the rapid development of combination therapy by integrating chemotherapy with hyperthermia for enhanced therapeutic efficacy. Near-infrared (NIR) light-mediated photothermal therapy, which has advantages such as great capacity of heat ablation and minimally invasive manner, has emerged as a powerful approach for cancer treatment. A variety of nanomaterials absorbing NIR light to generate heat have been developed to simultaneously act as carriers for chemotherapeutic drugs, contributing as heat trigger for drug release and/or inducing hyperthermia for synergistic effects. This review aims to summarize the recent development of advanced nanomaterials in chemo-photothermal combination therapy, including metal-, carbon-based nanomaterials and particularly organic nanomaterials. The potential challenges and perspectives for the future development of nanomaterials-based chemo-photothermal therapy were also discussed.

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Recent Advances in Nanomaterials-Based Chemo-Photothermal Combination Therapy for Improving Cancer Treatment.

Focusing of attention on a repetitive visual stimulation (RVS) at a constant frequency, elicits the so called steady-state visual evoked potential (SSVEP). This effect can be advantageously utilized in brain-computer interfaces (BCIs). SSVEP based BCIs can offer higher bitrates and require shorter training time as compared to other BCI modalities. Detection of the SSVEP from the EEG can be facilitated through spatial filtering (linear combination of the signals recorded at several electrodes). Literature offers several options to perform this. In this paper we propose a taxonomy to categorize these methods and we extensively evaluate them using 22 stimulation frequencies. We suggest improvements to existing methods to increase the SSVEP detection performance. We also consider practical aspects in the discussion of results.

Optimal spatial filtering for the steady state visual evoked potential: BCI application

To develop novel therapies for clinical treatments, it increasingly depends on sophisticated delivery systems that facilitate the drugs entry into targeting cells. Profound understanding of cellular uptake routes for transporting carriers promotes the optimization of performance in drug delivery systems. Although endocytic pathway is the most important part of cellular uptake routes for many delivery systems, it suffers the trouble of enzymatic degradation of transporting carriers trapped in endosomes/lysosomes. Therefore, it is desirable to develop alternative transporting methods for delivery systems via non-endocytic pathways to achieve more effective intracellular delivery. In this review, we summarize the literature exploring transporting carriers that mediate intracellular delivery via non-endocytic pathways to present the current research status in this field. Cell-penetrating peptides, pH (low) insertion peptides, and nanoparticles are categorized to exhibit their ability to directly transport various cargos into cytoplasm via non-endocytic uptake in different cell lines. It is hoped that this review can spur the interesting on development of drug delivery systems via non-endocytic uptake pathway.

Transporting carriers for intracellular targeting delivery via non-endocytic uptake pathways.

Hepatocellular carcinoma (HCC) is a common solid tumor worldwide with a poor prognosis. Accumulating evidence has implicated important regulatory roles of epigenetic modifications in the occurrence and progression of HCC. In the present study, we analyzed 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) levels in the tumor tissues and paired adjacent peritumor tissues (APTs) from four individual HCC patients using a (hydroxy)methylated DNA immunoprecipitation approach combined with deep sequencing [(h)MeDIP-Seq]. Bioinformatics analysis revealed that the 5-mC levels in the promoter regions of 2796 genes and the 5-hmC levels in 507 genes differed significantly between HCC tissues and APTs. These differential genes were grouped into various clusters and pathways and found to be particularly enriched in the 'metabolic pathways' that include 'Glycolysis/gluconeogenesis', 'Oxidative phosphorylation' and 'Citrate cycle (TCA cycle)', implicating a potential role of metabolic alterations in HCC. Furthermore, 144 genes had both 5-mC and 5-hmC changes in HCC patients, and 10 of them (PCNA, MDM2, STAG1, E2F4, FGF4, FGF19, RHOBTB2, UBE2QL1, DCN and HSP90AA1) were enriched and interconnected in five pathways including the 'Cell cycle', 'Pathway in cancer', 'Ubiquitin mediated proteolysis', 'Melanoma' and 'Prostate cancer' pathways. The genome-wide mapping of 5-mC and 5-hmC in HCC tissues and APTs indicated that both 5-mC and 5-hmC epigenetic modifications play important roles in the regulation of HCC, and there may be some interconnections between them. Taken together, in the present study we conducted the first genome-wide mapping of DNA methylation combined with hydroxymethylation in HBV-related HCC and provided a series of potential novel epigenetic biomarkers for HCC.

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Danhua Zhu

Papers

A survey of stimulation methods used in SSVEP-based BCIs

Recent Advances in Nanomaterials-Based Chemo-Photothermal Combination Therapy for Improving Cancer Treatment.

Optimal spatial filtering for the steady state visual evoked potential: BCI application

Transporting carriers for intracellular targeting delivery via non-endocytic uptake pathways.

Whole-genome DNA methylation and hydroxymethylation profiling for HBV-related hepatocellular carcinoma.