Brain-computer interfaces (BCIs) have enabled individuals to control devices, such as spellers, robotic arms, drones, and wheelchairs, but often these BCI applications are restricted to research ...laboratories. With the advent of virtual reality (VR) systems and the Internet of Things (IoT) we can couple these technologies to offer real-time control of a user's virtual and physical environment. Likewise, BCI applications are often single-use with user's having no control outside of the restrictions placed upon the applications at the time of creation. Therefore, there is a need to create a tool that allows users the flexibility to create and modularize aspects of BCI applications for control of IoT devices and VR environments. Using a popular video game engine, Unity, and coupling it with BCI2000, we can create diverse applications that give the end-user additional autonomy during the task at hand. We demonstrate the validity of controlling a Unity-based VR environment and several commercial IoT devices via direct neural interfacing processed through BCI2000.
An easily prepared platinum nanoparticle (PtNP) probe for the sensitive and selective detection of Hg(2+) ions is developed here. The PtNPs with an average size of approximately 2.5 nm were prepared ...by a reduction method with sodium borohydride and trisodium citrate serving as reductant and stabilizer, respectively. The resulting PtNPs could catalyze the reduction of Hg(2+) by surface-capping citrate. The effect of Hg(2+) uptake implies amalgam formation, which leads to remarkable inhibition of the peroxidase-like activity of citrate-capped PtNPs. On the basis of this effect, a colorimetric mercury sensor was established through the use of citrate-capped PtNPs to catalyze the colorimetric system of 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2. The high specificity of the Hg-Pt interaction provides the excellent selectivity for Hg(2+) over interfering metal ions. The sensitivity of this smart probe to Hg(2+) is extremely excellent with a limit of detection (LOD) as low as 8.5 pM. In view of these advantages, as well as the cost-effectiveness, minimized working steps, and naked-eye observation, we expect that this colorimetric sensor will be a promising candidate for the field detection of toxic Hg(2+) ions in environmental, biological, and food samples.
Enterovirus 71 (EV71) can cause hand-foot-and-mouth disease (HFMD) in young children. Severe infection with EV71 can lead to neurological complications and even death. However, the molecular basis of ...viral pathogenesis remains poorly understood. Here, we report that EV71 induces degradation of gasdermin D (GSDMD), an essential component of pyroptosis. Remarkably, the viral protease 3C directly targets GSDMD and induces its cleavage, which is dependent on the protease activity. Further analyses show that the Q193-G194 pair within GSDMD is the cleavage site of 3C. This cleavage produces a shorter N-terminal fragment spanning amino acids 1 to 193 (GSDMD
). However, unlike the N-terminal fragment produced by caspase-1 cleavage, this fragment fails to trigger cell death or inhibit EV71 replication. Importantly, a T239D or F240D substitution abrogates the activity of GSDMD consisting of amino acids 1 to 275 (GSDMD
). This is correlated with the lack of pyroptosis or inhibition of viral replication. These results reveal a previously unrecognized strategy for EV71 to evade the antiviral response.
Recently, it has been reported that GSDMD plays a critical role in regulating lipopolysaccharide and NLRP3-mediated interleukin-1β (IL-1β) secretion. In this process, the N-terminal domain of p30 released from GSDMD acts as an effector in cell pyroptosis. We show that EV71 infection downregulates GSDMD. EV71 3C cleaves GSDMD at the Q193-G194 pair, resulting in a truncated N-terminal fragment disrupted for inducing cell pyroptosis. Notably, GSDMD
(p30) inhibits EV71 replication whereas GSDMD
does not. These results reveal a new strategy for EV71 to evade the antiviral response.
Sirtuins are a class of enzymes originally identified as nicotinamide adenine dinucleotide (NAD)-dependent protein lysine deacetylases. Among the seven mammalian sirtuins, SIRT1-7, only SIRT1-3 ...possess efficient deacetylase activity in vitro, whereas SIRT4-7 possess very weak in vitro deacetylase activity. Several sirtuins that exhibit weak deacetylase activity have recently been shown to possess more efficient activity for the removal other acyl lysine modifications, such as succinyl lysine and palmitoyl lysine. Here, we demonstrate that even the well-known deacetylase SIRT2 possesses efficient activity for the removal of long-chain fatty acyl groups. The catalytic efficiency (kcat/Km) for the removal of a myristoyl group is slightly higher than that for the removal of an acetyl group. The crystal structure of SIRT2 in complex with a thiomyristoyl peptide reveals that SIRT2 possesses a large hydrophobic pocket that can accommodate the myristoyl group. Comparison of the SIRT2 acyl pocket to those of SIRT1, SIRT3, and SIRT6 reveals that the acyl pockets of SIRT1-3 are highly similar, and to a lesser degree, similar to that of SIRT6. The efficient in vitro demyristoylase activity of SIRT2 suggests that this activity may be physiologically relevant and warrants future investigative studies.
Filamentous fungi possess the capacity to produce a wide array of secondary metabolites with diverse biological activities and structures, such as lovastatin and swainsonine. With the advent of the ...post-genomic era, increasing amounts of cryptic or uncharacterized secondary metabolite biosynthetic gene clusters are continually being discovered. However, owing to the longstanding lack of versatile, comparatively simple, and highly efficient genetic manipulation techniques, the broader exploration of industrially important secondary metabolites has been hampered thus far. With the emergence of CRISPR/Cas9-based genome editing technology, this dilemma may be alleviated, as this advanced technique has revolutionized genetic research and enabled the exploitation and discovery of new bioactive compounds from filamentous fungi. In this review, we introduce the CRISPR/Cas9 system in detail and summarize the latest applications of CRISPR/Cas9-mediated genome editing in filamentous fungi. We also briefly introduce the specific applications of the CRISPR/Cas9 system and CRISPRa in the improvement of secondary metabolite contents and discovery of novel biologically active compounds in filamentous fungi, with specific examples noted. Additionally, we highlight and discuss some of the challenges and deficiencies of using the CRISPR/Cas9-based genome editing technology in research on the biosynthesis of secondary metabolites as well as future application of CRISPR/Cas9 strategy in filamentous fungi are highlighted and discussed.
The comprehensively adopted copper-containing intrauterine devices (Cu-IUDs) present typical adverse effects such as bleeding and pain at the initial stage of post-implantation. The replacement of Cu ...material is demanded. Zinc and its alloys, the emerging biodegradable materials, exhibited contraceptive effects since 1969. In this work, we evaluated the feasibility of bulk Zn alloys as IUD active material. Using pure Cu and pure Zn as control groups, we investigated the contraceptive performance of Zn-0.5Cu and Zn-1Cu alloys via in vitro and in vivo tests. The results showed that the main corrosion product of Zn-Cu alloys is ZnO from both in vitro and in vivo studies. CaZn2(PO4)2·2H2O is formed atop after long-term immersion in simulated uterine fluid, whereas CaCO3 is generally formed atop after implantation in the rat uterine environment. The cytocompatibility of the Zn-1Cu alloy was significantly higher than that of the pure Zn and pure Cu to the human endometrial epithelial cell lines. Furthermore, the in vivo results showed that the Zn-1Cu alloy presented much improved histocompatibility, least damage and the fastest recovery on endometrium structure in comparison to pure Zn, Zn-0.5Cu and pure Cu. The systematic and comparing studies suggest that Zn-1Cu alloy can be considered as a possible candidate for IUD with great biochemical and biocompatible properties as well as high contraceptive effectiveness.
The existing adverse effects with the intrinsic properties of copper materials for copper-containing intrauterine devices (Cu-IUD) are of concerns in their employment. Such as burst release of cupric ions (Cu2+) at the initial stage of the Cu-IUD. Zinc and its alloys which have been emerging as a potential biodegradable material exhibited contraceptive effects since 1969. In this study, Zn-1Cu alloys displayed significantly improved biocompatibility with human uterus cells and a decreased inflammatory response within the uterus. Therefore, high antifertility efficacy of the Zn-1Cu alloy was well maintained, while the adverse effects are significantly eased, suggesting that the Zn-1Cu alloy is promising for IUD.
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Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the causative agent of the pandemic disease COVID-19, which is so far without efficacious treatment. The discovery of therapy reagents ...for treating COVID-19 are urgently needed, and the structures of the potential drug-target proteins in the viral life cycle are particularly important. SARS-CoV-2, a member of the Orthocoronavirinae subfamily containing the largest RNA genome, encodes 29 proteins including nonstructural, structural and accessory proteins which are involved in viral adsorption, entry and uncoating, nucleic acid replication and transcription, assembly and release, etc. These proteins individually act as a partner of the replication machinery or involved in forming the complexes with host cellular factors to participate in the essential physiological activities. This review summarizes the representative structures and typically potential therapy agents that target SARS-CoV-2 or some critical proteins for viral pathogenesis, providing insights into the mechanisms underlying viral infection, prevention of infection, and treatment. Indeed, these studies open the door for COVID therapies, leading to ways to prevent and treat COVID-19, especially, treatment of the disease caused by the viral variants are imperative.
In the past few years, several new protein post-translational modifications that use intermediates in metabolism have been discovered. These include various acyl lysine modifications (formylation, ...propionylation, butyrylation, crotonylation, malonylation, succinylation, myristoylation) and cysteine succination. Here, we review the discovery and the current understanding of these modifications. Several of these modifications are regulated by the deacylases, sirtuins, which use nicotinamide adenine dinucleotide (NAD), an important metabolic small molecule. Interestingly, several of these modifications in turn regulate the activity of metabolic enzymes. These new modifications reveal interesting connections between metabolism and protein post-translational modifications and raise many questions for future investigations.
The goal of this study was to develop methods for simultaneously acquiring electrophysiological data during high-definition transcranial direct current stimulation (tDCS) using high-resolution ...electroencephalography (EEG). Previous studies have pointed to the after-effects of tDCS on both motor and cognitive performance, and there appears to be potential for using tDCS in a variety of clinical applications. However, little is known about the real-time effects of tDCS on rhythmic cortical activity in humans due to the technical challenges of simultaneously obtaining electrophysiological data during ongoing stimulation. Furthermore, the mechanisms of action of tDCS in humans are not well understood. We have conducted a simultaneous tDCS-EEG study in a group of healthy human subjects. Significant acute and persistent changes in spontaneous neural activity and event-related synchronization (ERS) were observed during and after the application of high-definition tDCS over the left sensorimotor cortex. Both anodal and cathodal stimulation resulted in acute global changes in broadband cortical activity which were significantly different than the changes observed in response to sham stimulation. For the group of eight subjects studied, broadband individual changes in spontaneous activity during stimulation were apparent both locally and globally. In addition, we found that high-definition tDCS of the left sensorimotor cortex can induce significant ipsilateral and contralateral changes in event-related desynchronization and ERS during motor imagination following the end of the stimulation period. Overall, our results demonstrate the feasibility of acquiring high-resolution EEG during high-definition tDCS and provide evidence that tDCS in humans directly modulates rhythmic cortical synchronization during and after its administration.
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