Establishing a Three-Dimensional Coculture Module of Epithelial Cells Using Nanofibrous Membranes.

Technical hurdles in a culture of epithelial cells include dedifferentiation and loss of function. Biomimetic three-dimensional (3D) cell culture methods can enhance cell culture efficiency. This study introduces an advanced two-layered culture system intended to cultivate epithelial cells as tissue-like layers with the culture of fibroblasts within a 3D environment.

A dental intraoral image dataset of gingivitis for image captioning.

One of the most striking topics in Artificial Intelligence (AI) is Image captioning that aims to integrate computer vision and natural language processing to create descriptions for each image. In this paper, we propose a new dataset designed specifically for image captioning in gingivitis diagnosis using deep learning. It includes 1,096 high-resolution intraoral images of 12 anterior teeth and surrounding gingival tissue that were collected under controlled conditions with professional-grade photography equipment.

Synthetic Extracellular Matrix of Polyvinyl Alcohol Nanofibers for Three-Dimensional Cell Culture.

An ideal extracellular matrix (ECM) replacement scaffold in a three-dimensional cell (3D) culture should induce in vivo-like interactions between the ECM and cultured cells. Highly hydrophilic polyvinyl alcohol (PVA) nanofibers disintegrate upon contact with water, resulting in the loss of their fibrous morphology in cell cultures. This can be resolved by using chemical crosslinkers and post-crosslinking.

Assessing the impact of stricter drink driving policy on alcohol consumption in a population of Hanoi, Vietnam using wastewater analysis.

Introduction: On 1 January 2020, Vietnam introduced a new law with harsher fines and penalties for driving under the influence of alcohol. Reports of empty beer restaurants following this implementation suggested the new law has the potential to reduce population-level alcohol consumption. This pilot study aims to quantify short-term changes in alcohol consumption levels after the implementation of the new law and assess whether it could lead to a reduction in total alcohol consumption in the population.

A giant metaplastic breast carcinoma with osseous differentiation: A rare case report and review of the literature.

Introduction: Metaplastic breast carcinoma (MBC) is a rare form of breast cancer, comprising less than 1 % of all breast malignancies. Osseous differentiation is an extremely rare subtype of MBC, accounting for only 0.003-0.

Potent Apoptosis Induction by a Novel Trispecific B7-H3xCD16xTIGIT 2+1 Common Light Chain Natural Killer Cell Engager.

Valued for their ability to rapidly kill multiple tumor cells in succession as well as their favorable safety profile, NK cells are of increasing interest in the field of immunotherapy. As their cytotoxic activity is controlled by a complex network of activating and inhibiting receptors, they offer a wide range of possible antigens to modulate their function by antibodies. In this work, we utilized our established common light chain (cLC)-based yeast surface display (YSD) screening procedure to isolate novel B7-H3 and TIGIT binding monoclonal antibodies.

Evaluation of Peptide Ligation Strategies for the Synthesis of the Bivalent Acid-Sensing Ion Channel Inhibitor Hi1a.

Hi1a is a naturally occurring bivalent spider-venom peptide that is being investigated as a promising molecule for limiting ischemic damage in strokes, myocardial infarction, and organ transplantation. However, the challenges associated with the synthesis and production of the peptide in large quantities have slowed the progress in this area; hence, access to synthetic Hi1a is an essential milestone for the development of Hi1a as a pharmacological tool and potential therapeutic.

Pain-causing stinging nettle toxins target TMEM233 to modulate Na1.7 function.

Voltage-gated sodium (Na) channels are critical regulators of neuronal excitability and are targeted by many toxins that directly interact with the pore-forming α subunit, typically via extracellular loops of the voltage-sensing domains, or residues forming part of the pore domain. Excelsatoxin A (ExTxA), a pain-causing knottin peptide from the Australian stinging tree Dendrocnide excelsa, is the first reported plant-derived Na channel modulating peptide toxin. Here we show that TMEM233, a member of the dispanin family of transmembrane proteins expressed in sensory neurons, is essential for pharmacological activity of ExTxA at Na channels, and that co-expression of TMEM233 modulates the gating properties of Na1.

µ-Conotoxins Targeting the Human Voltage-Gated Sodium Channel Subtype Na1.7.

µ-Conotoxins are small, potent, peptide voltage-gated sodium (Na) channel inhibitors characterised by a conserved cysteine framework. Despite promising in vivo studies indicating analgesic potential of these compounds, selectivity towards the therapeutically relevant subtype Na1.7 has so far been limited.

Assessing changes in nicotine consumption over two years in a population of Hanoi by wastewater analysis with benchmarking biomarkers.

Monitoring the actual change in consumption of nicotine (a proxy for smoking) in the population is essential for formulating tobacco control policies. In recent years, wastewater-based epidemiology (WBE) has been applied as an alternative method to estimate changes in consumption of tobacco and other substances in different communities around the world, with high potential to be used in resource-scarce settings. This study aimed to conduct a WBE analysis in Hanoi, Vietnam, a lower-middle-income-country setting known for high smoking prevalence.

Preparation of MnO/MIL-100(Fe) composite and its mechanism for enhancing the photocatalytic removal of rhodamine B in water.

In this study, MnO/MIL-100(Fe) composite was successfully synthesized by the hydrothermal method and applied for photocatalytic removal of rhodamine B (RhB) in water. The physical and chemical properties of the synthesized materials were characterized by XRD, FTIR, SEM, UV-visible, and BET analyses. Experimental results showed a great enhancement in the photocatalytic ability of the MnO/MIL-100(Fe) composite as compared to individual MnO or MIL-100(Fe) under visible light and persulfate activation.

On the Utility of Chemical Strategies to Improve Peptide Gut Stability.

Inherent susceptibility of peptides to enzymatic degradation in the gastrointestinal tract is a key bottleneck in oral peptide drug development. Here, we present a systematic analysis of (i) the gut stability of disulfide-rich peptide scaffolds, orally administered peptide therapeutics, and well-known neuropeptides and (ii) medicinal chemistry strategies to improve peptide gut stability. Among a broad range of studied peptides, cyclotides were the only scaffold class to resist gastrointestinal degradation, even when grafted with non-native sequences.

Prevalence of illicit drug consumption in a population of Hanoi: an estimation using wastewater-based epidemiology.

Illicit drug use is a serious issue in Vietnam, but information about their prevalence is scarce, mainly based on seizure data. Wastewater-based epidemiology (WBE) is an alternative tool for obtaining such information, especially when stigma related to drug use can hinder survey approaches. The study aimed to apply WBE to assess the prevalence of use of a range of illicit drugs in an urban population of Vietnam.

The Allosteric Activation of α7 nAChR by α-Conotoxin MrIC Is Modified by Mutations at the Vestibular Site.

α-conotoxins are 13-19 amino acid toxin peptides that bind various nicotinic acetylcholine receptor (nAChR) subtypes. α-conotoxin Mr1.7c (MrIC) is a 17 amino acid peptide that targets α7 nAChR.

Chemical Synthesis of TFF3 Reveals Novel Mechanistic Insights and a Gut-Stable Metabolite.

TFF3 regulates essential gastro- and neuroprotective functions, but its molecular mode of action remains poorly understood. Synthetic intractability and lack of reliable bioassays and validated receptors are bottlenecks for mechanistic and structure-activity relationship studies. Here, we report the chemical synthesis of TFF3 and its homodimer native chemical ligation followed by oxidative folding.

Improving the Gastrointestinal Stability of Linaclotide.

High susceptibility to proteolytic degradation in the gastrointestinal tract limits the therapeutic application of peptide drugs in gastrointestinal disorders. Linaclotide is an orally administered peptide drug for the treatment of irritable bowel syndrome with constipation (IBS-C) and abdominal pain. Linaclotide is however degraded in the intestinal environment within 1 h, and improvements in gastrointestinal stability might enhance its therapeutic application.

Discovery, Pharmacological Characterisation and NMR Structure of the Novel µ-Conotoxin SxIIIC, a Potent and Irreversible Na Channel Inhibitor.

Voltage-gated sodium (Na) channel subtypes, including Na1.7, are promising targets for the treatment of neurological diseases, such as chronic pain. Cone snail-derived µ-conotoxins are small, potent Na channel inhibitors which represent potential drug leads.

Genetic interaction between two VNTRs in the MAOA gene is associated with the nicotine dependence.

The present study combined the analysis of two transcriptional regulators, uVNTR and dVNTR, in the MAOA gene that is an enzyme responsible for the monoamine degradation and identified genetic interaction between these VNTRs in association with the nicotine dependence. The main impact is that when analyzing different populations in the genetic studies, the functionally meaningful variants should be combined rather than addressing individual elements separately (a mini polygenic risk score for a particular gene/locus). This combination is very rarely analyzed and therefore the study sets an example.

Manipulation of a spider peptide toxin alters its affinity for lipid bilayers and potency and selectivity for voltage-gated sodium channel subtype 1.7.

Huwentoxin-IV (HwTx-IV) is a gating modifier peptide toxin from spiders that has weak affinity for the lipid bilayer. As some gating modifier toxins have affinity for model lipid bilayers, a tripartite relationship among gating modifier toxins, voltage-gated ion channels, and the lipid membrane surrounding the channels has been proposed. We previously designed an HwTx-IV analogue (gHwTx-IV) with reduced negative charge and increased hydrophobic surface profile, which displays increased lipid bilayer affinity and activity at the voltage-gated sodium channel subtype 1.

Enzymatic Ligation of a Pore Blocker Toxin and a Gating Modifier Toxin: Creating Double-Knotted Peptides with Improved Sodium Channel Na1.7 Inhibition.

Disulfide-rich animal venom peptides targeting either the voltage-sensing domain or the pore domain of voltage-gated sodium channel 1.7 (Na1.7) have been widely studied as drug leads and pharmacological probes for the treatment of chronic pain.

Evaluation of chloroplast genome annotation tools and application to analysis of the evolution of coffee species.

Chloroplast sequences are widely used for phylogenetic analysis due to their high degree of conservation in plants. Whole chloroplast genomes can now be readily obtained for plant species using new sequencing methods, giving invaluable data for plant evolution However new annotation methods are required for the efficient analysis of this data to deliver high quality phylogenetic analyses. In this study, the two main tools for chloroplast genome annotation were compared.