Biodegradable polyvinyl alcohol/nano-hydroxyapatite composite membrane enhanced by MXene nanosheets for guided bone regeneration.

MXene, as a new category of two-dimensional nanomaterials, exhibits a promising prospect in biomedical applications due to its ultrathin structure and morphology, as well as a range of remarkable properties such as biological, chemical, electronic, and optical properties. In this work, different concentrations of MXene (M) were added to polyvinyl alcohol (PVA, P)/nano-hydroxyapatite (n-HA, H) mixed solution, and series of PVA/n-HA/MXene (PHM) composite membranes were obtained by combining sol-gel and freeze-drying processes. Morphology, chemical composition, surface, and mechanical properties of the prepared PHM membranes were characterized by various techniques. Subsequently, the swelling and degradation performances of the composite membranes were tested by swelling and degradation tests. In addition, in vitro studies like cell adhesion, cytotoxicity, proliferation, osteogenic differentiation, and antibacterial properties of MC3T3-E1 were also evaluated. The results showed that the addition of MXene could apparently improve the composite membranes' physicochemical properties, bioactivity, and osteogenic differentiation. Specially, PHM membrane had the best comprehensive properties when the concentration of MXene was set as 2.0% w/v. In a word, the addition of MXene has a positive effect on improving the mechanical properties, osteogenic induction, and antibacterial properties of PH composite membranes, and the prepared PHM composite membranes possess potential applications for guided bone regeneration.

Green synthetic sodium alginate-glycerol-MXene nanocomposite membrane with excellent flexibility and mineralization ability for guided bone regeneration.

Developing a novel bioactive material as a barrier membrane for guided bone regeneration (GBR) surgery remains challenging. As a new member of two-dimensional (2D) material family, MXene is a promising candidate component for barrier membranes due to its high specific surface area and osteogenic differentiation ability. In this work, a green and simple SA/glycerol/MXene (SgM) composite membrane was prepared via solvent casting method by using sodium alginate (SA) and MXene (M) as raw materials while employing glycerol (g) as a plasticizer. The addition of glycerol significantly increased the elongation at the break of SA from 10%-20% to 240%-360%, while the introduction of MXene promoted the deposition of calcium and phosphorus to form hydroxyapatite. At the same time, the roughness of the SgM composite membrane is apparently improved, which is conducive to cell adhesion and proliferation. This work provides a basis for further research on SgM composite membrane as GBR membrane for the treatment of bone defects.

The impact of echinococcosis interventions on economic outcomes in Qinghai Province of China: Evidence from county-level panel data.

Introduction: Echinococcosis can incur substantial economic losses for the livestock industry by causing organ condemnation, delayed growth, and reduced meat and wool output and quality in sheep and cattle, as well as increased surgery costs, hospital care, and decreased productivity in humans. Yet echinococcosis could be prevented and controlled by interventions, such as dog management and deworming, lamb vaccination, slaughter management, and training and public education. Methods: Exploiting temporal and spatial variations in the number of intervention measures implemented in 39 counties in Qinghai province of China in 2015-2020, this study assesses the economic impact of echinococcosis interventions using a dynamic difference-in-differences model. Results: The results suggest that echinococcosis interventions brought about substantial economic gains measured by per capita net income of rural residents and per capita gross output of animal husbandry. These economic gains are greater in non-pastoral counties (with a gain in per capita net income of rural residents of 3,308 yuan and a gain per capita gross output of animal husbandry of 1,035 yuan) than in pastoral counties (with a gain in per capita net income of rural residents of 1,372 yuan and a gain per capita gross output of animal husbandry of 913 yuan). They are also greater in counties with echinococcosis infection level-2 (with a human infection rate of 0.1-1% or a dog infection rate of 1-5%) than infection level-1 counties (with a human prevalence rate ≥1% or a dog infection rate ≥5%). Discussion: Not only will these economic gains encourage livestock farmers to strengthen their echinococcosis prevention and control practices, but they will also inform public policy on zoonotic disease prevention and control in China and other countries alike.

Biodegradable and biocompatible alginate/gelatin/MXene composite membrane with efficient osteogenic activity and its application in guided bone regeneration.

Guided bone regeneration (GBR) utilizes a barrier membrane to maintain the osteogenic space and promote osseointegration of the implants. Developing a novel biomaterial to meet the mechanical and biological performance requirements of GBR membrane (GBRM) remains a huge challenge. Here, the sodium alginate (SA, S)/gelatin (G)/MXene (M) composite membrane (SGM) was prepared by combining sol-gel and freeze-drying processes. The incorporation of MXene improved the mechanical properties and hydrophilicity of the SA/G (SG) membrane, and also enhanced its cell proliferation and osteogenic differentiation. More importantly, when the concentration of MXene is 0.25%W/V, the SGM composite membrane exhibited the best tensile strength (40 MPa), high swelling rate (1012%), and appropriate degradation rate (40%). Meanwhile, the biological improvements were more significant. Therefore, the appropriate amount addition of MXene has a positive and obvious effect on the improvements of the mechanical properties, biocompatibility, and osteogenic induction of the SG composite membranes. This work provides a more extendable development idea for the application of SGM composite membrane as GBRM.

Amplification-Free COVID-19 Detection by Digital Droplet REVEALR.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, exposed a pressing need for new public health tools for pathogen detection, disease diagnosis, and viral genotyping. REVEALR (RNA-encoded viral nucleic acid analyte reporter) is an isothermal DNAzyme-based point-of-care diagnostic that functions with a detection limit of ∼10 copies/µL when coupled with a preamplification step and can be utilized for viral genotyping of SARS-CoV-2 variants of concern through base pair mismatch recognition in a competitive binding format. Here, we describe an advanced REVEALR platform, termed digital droplet REVEALR (ddREVEALR), that can achieve direct viral detection and absolute sample quantitation utilizing a signal amplification strategy that relies on chemical modifications, DNAzyme multiplexing, and volume compression. Using an AI-assisted image-based readout, ddREVEALR was found to achieve 95% positive predictive agreement from a set of 20 nasal pharyngeal swabs collected at UCI Medical Center in Orange, California. We propose that the combination of amplification-free and protein-free analysis makes ddREVEALR a promising application for direct viral RNA detection of clinical samples.

Intracellular hemin is a potent inhibitor of the voltage-gated potassium channel Kv10.1.

Heme, an iron-protoporphyrin IX complex, is a cofactor bound to various hemoproteins and supports a broad range of functions, such as electron transfer, oxygen transport, signal transduction, and drug metabolism. In recent years, there has been a growing recognition of heme as a non-genomic modulator of ion channel functions. Here, we show that intracellular free heme and hemin modulate human ether à go-go (hEAG1, Kv10.1) voltage-gated potassium channels. Application of hemin to the intracellular side potently inhibits Kv10.1 channels with an IC50 of about 4 nM under ambient and 63 nM under reducing conditions in a weakly voltage-dependent manner, favoring inhibition at resting potential. Functional studies on channel mutants and biochemical analysis of synthetic and recombinant channel fragments identified a heme-binding motif CxHx8H in the C-linker region of the Kv10.1 C terminus, with cysteine 541 and histidines 543 and 552 being important for hemin binding. Binding of hemin to the C linker may induce a conformational constraint that interferes with channel gating. Our results demonstrate that heme and hemin are endogenous modulators of Kv10.1 channels and could be exploited to modulate Kv10.1-mediated cellular functions.

REVEALR-Based Genotyping of SARS-CoV-2 Variants of Concern in Clinical Samples.

The SARS-CoV-2 virus has evolved into new strains that increase viral transmissibility and reduce vaccine protection. The rapid circulation of these more harmful strains across the globe has created a pressing need for alternative public health screening tools. REVEALR (RNA-encoded viral nucleic acid analytic reporter), a rapid and highly sensitive DNAzyme-based detection system, functions with perfect accuracy against patient-derived clinical samples. Here, we design REVEALR into a novel genotyping assay that detects single-base mismatches corresponding to each of the major SARS-CoV-2 strains found in the United States. Of 34 sequence-verified patient samples collected in early, mid, and late 2021 at the UCI Medical Center in Orange, California, REVEALR identified the correct variant [Wuhan-Hu-1, alpha (B.1.1.7), gamma (P.1), epsilon (B.1.427/9), delta (B.1.617.2), and omicron (B.1.1.529)] with 100% accuracy. The assay, which is programmable and amenable to multiplexing, offers an important new approach to personalized diagnostics.

REVEALR: A Multicomponent XNAzyme-Based Nucleic Acid Detection System for SARS-CoV-2.

Isothermal amplification strategies capable of rapid, inexpensive, and accurate nucleic acid detection provide new options for large-scale pathogen detection, disease diagnosis, and genotyping. Here we report a highly sensitive multicomponent XNA-based nucleic acid detection platform that combines analyte preamplification with X10-23-mediated catalysis to detect the viral pathogen responsible for COVID-19. The platform, termed RNA-Encoded Viral Nucleic Acid Analyte Reporter (REVEALR), functions with a detection limit of ≤20 aM (∼10 copies/µL) using conventional fluorescence and paper-based lateral flow readout modalities. With a total assay time of 1 h, REVEALR provides a convenient nucleic acid alternative to equivalent CRISPR-based approaches, which have become popular methods for SARS-CoV-2 detection. The assay shows no cross-reactivity for other in vitro transcribed respiratory viral RNAs and functions with perfect accuracy against COVID-19 patient-derived clinical samples.

Following replicative DNA synthesis by time-resolved X-ray crystallography.

The mechanism of DNA synthesis has been inferred from static structures, but the absence of temporal information raises longstanding questions about the order of events in one of life's most central processes. Here we follow the reaction pathway of a replicative DNA polymerase using time-resolved X-ray crystallography to elucidate the order and transition between intermediates. In contrast to the canonical model, the structural changes observed in the time-lapsed images reveal a catalytic cycle in which translocation precedes catalysis. The translocation step appears to follow a push-pull mechanism where the O-O1 loop of the finger subdomain acts as a pawl to facilitate unidirectional movement along the template with conserved tyrosine residues 714 and 719 functioning as tandem gatekeepers of DNA synthesis. The structures capture the precise order of critical events that may be a general feature of enzymatic catalysis among replicative DNA polymerases.

SFU-store-nav: A multimodal dataset for indoor human navigation.

This article describes a dataset collected in a set of experiments that involves human participants and a robot. The set of experiments was conducted in the computing science robotics lab in Simon Fraser University, Burnaby, BC, Canada, and its aim is to gather data containing common gestures, movements, and other behaviours that may indicate humans' navigational intent relevant for autonomous robot navigation. The experiment simulates a shopping scenario where human participants come in to pick up items from his/her shopping list and interact with a Pepper robot that is programmed to help the human participant. We collected visual data and motion capture data from 108 human participants. The visual data contains live recordings of the experiments and the motion capture data contains the position and orientation of the human participants in world coordinates. This dataset could be valuable for researchers in the robotics, machine learning and computer vision community.

Reading and Writing Digital Information in TNA.

DNA has become a popular soft material for low energy, high-density information storage, but it is susceptible to damage through oxidation, pH, temperature, and nucleases in the environment. Here, we describe a new molecular chemotype for data archiving based on the unnatural genetic framework of α-l-threofuranosyl nucleic acid (TNA). Using a simple genetic coding strategy, 23 kilobytes of digital information were stored in DNA-primed TNA oligonucleotides and recovered with perfect accuracy after exposure to biological nucleases that destroyed equivalent DNA messages. We suggest that these results extend the capacity for nucleic acids to function as a soft material for low energy, high-density information storage by providing a safeguard against information loss caused by nuclease digestion.

Impact of intracellular hemin on N-type inactivation of voltage-gated K+ channels.

N-type inactivation of voltage-gated K+ channels is conferred by the N-terminal "ball" domains of select pore-forming α subunits or of auxiliary ß subunits, and influences electrical cellular excitability. Here, we show that hemin impairs inactivation of K+ channels formed by Kv3.4 α subunits as well as that induced by the subunits Kvß1.1, Kvß1.2, and Kvß3.1 when coexpressed with α subunits of the Kv1 subfamily. In Kvß1.1, hemin interacts with cysteine and histidine residues in the N terminus (C7 and H10) with high affinity (EC50 100 nM). Similarly, rapid inactivation of Kv4.2 channels induced by the dipeptidyl peptidase-like protein DPP6a is also sensitive to hemin, and the DPP6a mutation C13S eliminates this dependence. The results suggest a common mechanism for a dynamic regulation of Kv channel inactivation by heme/hemin in N-terminal ball domains of Kv α and auxiliary ß subunits. Free intracellular heme therefore has the potential to regulate cellular excitability via modulation of Kv channel inactivation.

Modulation of K+ channel N-type inactivation by sulfhydration through hydrogen sulfide and polysulfides.

Fast N-type inactivation of voltage-gated K+ (Kv) channels is important in fine-tuning of cellular excitability. To serve diverse cellular needs, N-type inactivation is regulated by numerous mechanisms. Here, we address how reactive sulfur species-the gaseous messenger H2S and polysulfides-affect N-type inactivation of the mammalian Kv channels Kv1.4 and Kv3.4. In both channels, the H2S donor NaHS slowed down inactivation with varying potency depending on the "aging" of NaHS solution. Polysulfides were > 1000 times more effective than NaHS with the potency increasing with the number of sulfur atoms (Na2S2 < Na2S3 < Na2S4). In Kv1.4, C13 in the N-terminal ball domain mediates the slowing of inactivation. In recombinant protein exposed to NaHS or Na2S4, a sulfur atom is incorporated at C13 in the protein. In Kv3.4, the N terminus harbors two cysteine residues (C6, C24), and C6 is of primary importance for channel regulation by H2S and polysulfides, with a minor contribution from C24. To fully eliminate the dependence of N-type inactivation on sulfhydration, both cysteine residues must be removed (C6S:C24S). Sulfhydration of a single cysteine residue in the ball-and-chain domain modulates the speed of inactivation but does not remove it entirely. In both Kv1.4 and Kv3.4, polysulfides affected the N-terminal cysteine residues when assayed in the whole-cell configuration; on-cell recordings confirmed that polysulfides also modulate K+ channel inactivation with undisturbed cytosol. These findings have collectively identified reactive sulfur species as potent modulators of N-type inactivation in mammalian Kv channels.

Different gap junction-propagated effects on cisplatin transfer result in opposite responses to cisplatin in normal cells versus tumor cells.

Previous work has shown that gap junction intercellular communication (GJIC) enhances cisplatin (Pt) toxicity in testicular tumor cells but decreases it in non-tumor testicular cells. In this study, these different GJIC-propagated effects were demonstrated in tumor versus non-tumor cells from other organ tissues (liver and lung). The downregulation of GJIC by several different manipulations (no cell contact, pharmacological inhibition, and siRNA suppression) decreased Pt toxicity in tumor cells but enhanced it in non-tumor cells. The in vivo results using xenograft tumor models were consistent with those from the above-mentioned cells. To better understand the mechanism(s) involved, we studied the effects of GJIC on Pt accumulation in tumor and non-tumor cells from the liver and lung. The intracellular Pt and DNA-Pt adduct contents clearly increased in non-tumor cells but decreased in tumor cells when GJIC was downregulated. Further analysis indicated that the opposite effects of GJIC on Pt accumulation in normal versus tumor cells from the liver were due to its different effects on copper transporter1 and multidrug resistance-associated protein2, membrane transporters attributed to intracellular Pt transfer. Thus, GJIC protects normal organs from cisplatin toxicity while enhancing it in tumor cells via its different effects on intracellular Pt transfer.