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A simple, rapid, and convenient colorimetric chemosensor of a specific target toward the end user is still required for on-site detection and real-time monitoring applications. In this study, we developed a rapid in situ colorimetric assay for cobalt detection using the naked eye. Interestingly, a yellow to light orange visual color transition was observed within 3 s when a Chrysoidine G (CG) chemosensor was exposed to cobalt. Surprisingly, the CG chemosensor had great selectivity toward cobalt without any interference of other metal ions. Under optimized conditions, a lower detection limit of 0.1 ppm via a spectrophotometer and a visual detection limit of 2 ppm with a linear range from 0.4 to 1 ppm (R2 = 0.97) were determined. Moreover, the CG chemosensor is reversible and maintains its functionality after treatment with chelating agents. In conclusion, we show the superior capabilities of the CG chemosensor, which has the potential to provide extremely facile handling, high sensitivity, and a fast response time for applications of on-site detection to real-time cobalt monitoring for the general public. [ABSTRACT FROM AUTHOR]

Most agricultural traits are controlled by quantitative trait loci (QTLs); however, there are fewstudies on QTLmapping of horticultural traits in pepper (Capsicumspp.) due to the lack of high-densitymolecular maps and the sequence information. In this study, an ultra-high-density map and 120 recombinant inbred lines (RILs) derived from a cross between C. annuum 'Perennial' and C. annuum 'Dempsey' were used for QTL mapping of horticultural traits. Parental lines and RILs were resequenced at 18× and 1× coverage, respectively. Using a sliding window approach, an ultra-high-density bin map containing 2,578 bins was constructed. The total map length of the map was 1,372 cM, and the average interval between binswas 0.53 cM. A total of 86 significant QTLs controlling 17 horticultural traitswere detected. Among these, 32 QTLs controlling 13 traits were major QTLs. Our research shows that the construction of bin maps using low-coverage sequence is a powerful method for QTL mapping, and that the short intervals between bins are helpful for fine-mapping of QTLs. Furthermore, bin maps can be used to improve the quality of reference genomes by elucidating the genetic order of unordered regions and anchoring unassigned scaffolds to linkage groups. [ABSTRACT FROM AUTHOR]

Free-standing thin nanoplates of Bi2Te3 and Bi2Se3 were synthesized by solvothermal method. It was demonstrated that the thickness of the nanoplates can be controlled by introducing a controlled amount of polyvinylpyrrolidone (PVP) in the synthesis reaction. PVP bonds to the polar basal planes of hexagonal crystal structure of Bi2Te3 and Bi2Se3, and they suppress the growth (speed) of the hexagonal crystals in the c-axis direction. Highly anisotropic growth yielded the formation of 2-dimensional nanostructures of nanoplates. The plates were examined directly with transmission electron microscopy (TEM) with in-situ heating. These crystalline nanoplates with extremely high width to thickness ratios were found to exhibit much lower thermal stability compared to the bulk counterpart or the conventional nanoparticles as represented by the reduced melting temperature. The melting temperature of a nanoplate decreased by more than 100° C compared to the melting temperature of the bulk material. While it is widely known that the meting temperature decreases for nanoparticles with reduced sizees in all three spatial dimensions, we demonstrate that the reduction in one dimension, i.e. thickness of the platelets in the present study, is effective enough to induce much greater decrease of the melting point than the decrease as observed for the case of nanoparticles. [ABSTRACT FROM AUTHOR]

Background: Breast metastasis from extramammary malignancy is uncommon and often presents diagnostic challenges. Herein, we report a case of a patient with metachronous isolated breast metastasis from pulmonary adenocarcinoma with micropapillary component. Case presentation: A 47-year-old woman presented with left breast nodule detected on a screening breast ultrasonography. She had surgery for pulmonary adenocarcinoma 3 years ago, and was disease-free state in the follow up studies. The patient was diagnosed with invasive micropapillary carcinoma of the breast by core needle biopsy. She underwent left breast lumpectomy and sentinel lymph node biopsy, and the histologic findings revealed micropapillary carcinoma. Based on the immunohistochemical study, the final diagnosis was solitary breast metastasis from pulmonary adenocarcinoma with micropapillary component. Conclusions: The diagnosis of metastasis to the breast from extramammary malignancies is difficult but important for proper management and prediction of prognosis. A careful clinical history with a thorough clinical examination is needed to make the correct diagnosis. [ABSTRACT FROM AUTHOR]

Intratesticular cysts, once thought to be a rarity, are now being reported with an increasing prevalence as a result of the wider use of scrotal ultrasound scanning. Despite greater understanding of intratesticular cysts, their management remains unclear. Treatment has included enucleation and even radical orchiectomy over fear of the possibility of an associated malignancy. A more conservative approach with serial ultrasound scanning has been advocated if a clear distinction can be made between neoplastic and non-neoplastic testicular cysts. However, in view of the benign nature of such cysts, even repeated ultrasound scanning may not be necessary and may be considered over-treatment. In this study we present clinical and morphological characteristics of multiple cysts in the right testicle in a 62-year-old patient, where a slightly nodular lesion in the right testicle was detected. [ABSTRACT FROM AUTHOR]

The article provides information on a study which analyzed the iron (Fe)(III)/polydopamine (pDA)-mediated capture and release of catecholic compounds using a method developed from mussel byssus cuticle. Topics discussed include the capture and release of pyrocatechol violet (PCV), use of ethylenediaminetetraacetic acid (EDTA) treatment to demonstrate the release of captured PCV, and pDA coating on silica beads.

Binding behaviors of streptavidin were investigated with different lateral packing densities of biotin-functionalized, non-biofouling pOEGMA brushes, synthesized by surface-initiated polymerization from mixed SAMs with different mole fractions of the polymerization initiator on gold surfaces. [ABSTRACT FROM AUTHOR]

The individual encapsulation of living cells has a great impact on the area of cell-based sensors and devices as well as fundamental studies in cell biology. In this work, living yeast cells were individually encapsulated with functionalizable, artificial polydopamine shells, inspired by an adhesive protein in mussels. Yeast cells maintained their viability within polydopamine, and the cell cycle was controlled by the thickness of the shells. In addition, the artificial shells aided the cell in offering much stronger resistance against foreign aggression, such as lyticase. After formation of the polydopamine shells, the shells were functionalized with streptavidin by utilizing the chemical reactivity of polydopamine, and the fun ctionalized cells were biospecifically immobilized onto the defined surfaces. Our work suggests a biomimetic approach to the encapsulation and functionalization of individual living cells with covalently bonded, artificial shells. [ABSTRACT FROM AUTHOR]

Abstract Clinical outcome after traumatic brain injury (TBI) is closely associated conditions of other organs, especially lungs as well as degree of brain injury. Even if there is no direct lung damage, severe brain injury can enhance sympathetic tones on blood vessels and vascular resistance, resulting in neurogenic pulmonary edema. Conversely, lung damage can worsen brain damage by dysregulating immunity. These findings suggest the importance of brain-lung axis interactions in TBI. However, little research has been conducted on the topic. An advanced disease model using stem cell technology may be an alternative for investigating the brain and lungs simultaneously but separately, as they can be potential candidates for improving the clinical outcomes of TBI. In this review, we describe the importance of brain-lung axis interactions in TBI by focusing on the concepts and reproducibility of brain and lung organoids in vitro. We also summarize recent research using pluripotent stem cell-derived brain organoids and their preclinical applications in various brain disease conditions and explore how they mimic the brain-lung axis. Reviewing the current status and discussing the limitations and potential perspectives in organoid research may offer a better understanding of pathophysiological interactions between the brain and lung after TBI.

Peptide-based therapeutics have traditionally faced challenges, including instability in the bloodstream and limited cell membrane permeability. However, recent advancements in α-helix stapled peptide modification techniques have rekindled interest in their efficacy. Notably, these developments ensure a highly effective method for improving peptide stability and enhancing cell membrane penetration. Particularly in the realm of antimicrobial peptides (AMPs), the application of stapled peptide techniques has significantly increased peptide stability and has been successfully applied to many peptides. Furthermore, constraining the secondary structure of peptides has also been proven to enhance their biological activity. In this review, the entire process through which hydrocarbon-stapled antimicrobial peptides attain improved drug-like properties is examined. First, the essential secondary structural elements required for their activity as drugs are validated, specific residues are identified using alanine scanning, and stapling techniques are strategically incorporated at precise locations. Additionally, the mechanisms by which these structure-based stapled peptides function as AMPs are explored, providing a comprehensive and engaging discussion.

Iron is crucial for the metabolism and growth of most prokaryotic cells. The ferric uptake regulator (Fur) protein plays a central role in regulating iron homeostasis and metabolic processes in bacteria. It ensures the proper utilization of iron and the maintenance of cellular functions in response to environmental cues. Fur proteins are composed of an N-terminal DNA-binding domain (DBD) and a C-terminal dimerization domain (DD), typically existing as dimers in solution. Fur proteins have conserved metal-binding sites named S1, S2, and S3. Among them, site S2 serves as a regulatory site, and metal binding at S2 results in conformational changes. Additionally, as a transcriptional regulator, Fur specifically binds to a consensus DNA sequence called the Fur box. To elucidate the structural and functional properties of Fur proteins, various structures of metal- or DNA-bound Fur proteins or apo-Fur proteins have been determined. In this review, we focus on the structural properties of Fur proteins according to their ligand-bound state and the drug development strategies targeting Fur proteins. This information provides valuable insights for drug discovery.

Klebsiella pneumoniae causes severe human diseases, but its resistance to current antibiotics is increasing. Therefore, new antibiotics to eradicate K. pneumoniae are urgently needed. Bacterial toxin–antitoxin (TA) systems are strongly correlated with physiological processes in pathogenic bacteria, such as growth arrest, survival, and apoptosis. By using structural information, we could design the peptides and small-molecule compounds that can disrupt the binding between K. pneumoniae MazE and MazF, which release free MazF toxin. Because the MazEF system is closely implicated in programmed cell death, artificial activation of MazF can promote cell death of K. pneumoniae. The effectiveness of a discovered small-molecule compound in bacterial cell killing was confirmed through flow cytometry analysis. Our findings can contribute to understanding the bacterial MazEF TA system and developing antimicrobial agents for treating drug-resistant K. pneumoniae.

Microfluidic paper-based analytical devices (μPADs) have been developed for use in a variety of diagnosis and analysis fields. However, conventional μPADs with an open-channel system have limitations for application as analytical platforms mainly because of the evaporation and contamination of the sample solution. This study demonstrates the design and fabrication of an enclosed three-dimensional(3D)-μPAD and its application as a primary early analysis platform for ionic contaminants. To generate the hydrophobic PDMS barrier, double-sided patterning is carried out using a PDMS blade-coated stamp mold that is fabricated using 3D printing. The selective PDMS patterning can be achieved with controlled PDMS permeation of the cellulose substrate using 3D-designed stamp molds. We find the optimal conditions enabling the formation of enclosed channels, including round shape pattern and inter-pattern distance of 10 mm of stamp design, contact time of 0.5 min, and spacer height of 300 µm of double-sided patterning procedure. As a proof of concept, this enclosed 3D-μPAD is used for the simultaneous colorimetric detection of heavy metal ions in a concentration range of 0.1–2000 ppm, including nickel (Ni2+), copper (Cu2+), mercury (Hg2+), and radioactive isotope cesium-137 ions (Cs+). We confirm that qualitative analysis and image-based quantitative analysis with high reliability are possible through rapid color changes within 3 min. The limits of detection (LOD) for 0.55 ppm of Ni2+, 5.05 ppm of Cu2+, 0.188 ppm of Hg2+, and 0.016 ppm of Cs+ are observed, respectively. In addition, we confirm that the analysis is highly reliable in a wide range of ion concentrations with CV values below 3% for Ni2+ (0.56%), Cu2+ (0.45%), Hg2+ (1.35%), and Cs+ (2.18%). This method could be a promising technique to develop a 3D-μPAD with various applications as a primary early analysis device in the environmental and biological industries.

Tuberculosis, caused by Mycobacterium tuberculosis, is a lethal infectious disease of significant public health concern. The rise of multidrug-resistant and drug-tolerant strains has necessitated novel approaches to combat the disease. Toxin–antitoxin (TA) systems, key players in bacterial adaptive responses, are prevalent in prokaryotic genomes and have been linked to tuberculosis. The genome of M. tuberculosis strains harbors an unusually high number of TA systems, prompting questions about their biological roles. The VapBC family, a representative type II TA system, is characterized by the VapC toxin, featuring a PilT N-terminal domain with nuclease activity. Its counterpart, VapB, functions as an antitoxin, inhibiting VapC’s activity. Additionally, we explore peptide mimics designed to replicate protein helical structures in this review. Investigating these synthetic peptides offers fresh insights into molecular interactions, potentially leading to therapeutic applications. These synthetic peptides show promise as versatile tools for modulating cellular processes and protein–protein interactions. We examine the rational design strategies employed to mimic helical motifs, their biophysical properties, and potential applications in drug development and bioengineering. This review aims to provide an in-depth understanding of TA systems by introducing known complex structures, with a focus on both structural aspects and functional and molecular details associated with each system.

Bacterial toxin–antitoxin (TA) systems correlate strongly with physiological processes in bacteria, such as growth arrest, survival and apoptosis. Here, the first crystal structure of a type II TA complex structure of Klebsiella pneumoniae at 2.3 Å resolution is presented. The K. pneumoniae MazEF complex consists of two MazEs and four MazFs in a heterohexameric assembly. It was estimated that MazEF forms a dodecamer with two heterohexameric MazEF complexes in solution, and a truncated complex exists in heterohexameric form. The MazE antitoxin interacts with the MazF toxin via two binding modes, namely, hydrophobic and hydrophilic interactions. Compared with structural homologs, K. pneumoniae MazF shows distinct features in loops β1–β2, β3–β4 and β4–β5. It can be inferred that these three loops have the potential to represent the unique characteristics of MazF, especially various substrate recognition sites. In addition, K. pneumoniae MazF shows ribonuclease activity and the catalytic core of MazF lies in an RNA-binding pocket. Mutation experiments and cell-growth assays confirm Arg28 and Thr51 as critical residues for MazF ribonuclease activity. The findings shown here may contribute to the understanding of the bacterial MazEF TA system and the exploration of antimicrobial candidates to treat drug-resistant K. pneumoniae.

Abstract In the present study, we successfully synthesized a porous three-dimensional Prussian blue-cellulose aerogel (PB-CA) composite and used it as a decorporation agent for the selective removal of ingested cesium ions (Cs+) from the gastrointestinal (GI) tract. The safety of the PB-CA composite was evaluated through an in vitro cytotoxicity study using macrophage-like THP-1 cells and Caco-2 intestinal epithelial cells. The results revealed that the PB-CA composite was not cytotoxic. An adsorption study to examine the efficiency of the decorporation agent was conducted using a simulated intestinal fluid (SIF). The adsorption isotherm was fitted to the Langmuir model with a maximum Cs+ adsorption capacity of 13.70 mg/g in SIF that followed pseudo-second-order kinetics. The PB-CA composite showed excellent stability in SIF with a maximum Cs+ removal efficiency of 99.43%. The promising safety toxicology profile, remarkable Cs+ adsorption efficacy, and excellent stability of the composite demonstrated its great potential for use as an orally administered drug for the decorporation of Cs+ from the GI tract.

Autophagy is a lysosome-dependent intracellular degradation machinery that plays an essential role in the regulation of cellular homeostasis. As many studies have revealed that autophagy is related to cancer, neurodegenerative diseases, metabolic diseases, and so on, and it is considered as a promising drug target. Recent advances in structural determination and computational technologies provide important structural information on essential autophagy-related proteins. Combined with high-throughput screening methods, structure-activity relationship studies have led to the discovery of molecules that modulate autophagy. In this review, we summarize the recent structural studies on autophagy-related proteins and the discovery of modulators, indicating that targeting autophagy can be utilized as an effective strategy for novel drug development.

The structure-function relationships of toxin-antitoxin (TA) systems from Mycobacterium tuberculosis have prompted the development of novel and effective antimicrobial agents that selectively target this organism. The artificial activation of toxins by peptide inhibitors can lead to the growth arrest and eventual death of bacterial cells. Optimizing candidate peptides by hydrocarbon α-helix stapling based on structural information from the VapBC TA system and in vitro systematic validation led to V26-SP-8, a VapC26 activator of M. tuberculosis. This compound exhibited highly enhanced activity and cell permeability owing to the stabilizing helical propensity of the peptide. These characteristics will increase its efficacy against multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. Similar approaches utilizing structural and biochemical information for new antibiotic targets opens a new era for developing TB therapies.

Toxin–antitoxin (TA) systems are prevalent in bacteria and are known to regulate cellular growth in response to stress. As various functions related to TA systems have been revealed, the importance of TA systems are rapidly emerging. Here, we present the crystal structure of putative mRNA interferase BC0266 and report it as a type II toxin MazF. The MazF toxin is a ribonuclease activated upon and during stressful conditions, in which it cleaves mRNA in a sequence-specific, ribosome-independent manner. Its prolonged activity causes toxic consequences to the bacteria which, in turn, may lead to bacterial death. In this study, we conducted structural and functional investigations of Bacillus cereus MazF and present the first toxin structure in the TA system of B. cereus. Specifically, B. cereus MazF adopts a PemK-like fold and also has an RNA substrate-recognizing loop, which is clearly observed in the high-resolution structure. Key residues of B. cereus MazF involved in the catalytic activity are also proposed, and in vitro assay together with mutational studies affirm the ribonucleic activity and the active sites essential for its cellular toxicity.

The increasing prevalence of Alzheimer’s disease (AD) has become a global phenomenon presenting serious social and health challenges. For detecting early molecular changes in the disease, several techniques to measure varied species of amyloid beta in the peripheral blood have been recently developed, but the efforts to associate them with cognitive assessments have yet to produce sufficient data. We prospectively collected participants from the consecutive population who visited our center for brain health screening. In total, 97 participants (F:M = 58:39) aged 69.4 ± 7.52 were assessed. Participants performed the Korean version of the Consortium to Establish a Registry for Alzheimer’s disease (CERAD-K), the clinical dementia rating (CDR), plasma oligomeric amyloid-β (OAβ) level tests, routine blood tests, ApoE genotype, and brain MRI. Among total population, 55.7% had a CDR of 0, and 40.2% had a CDR of 0.5. The results showed that word memory and word recall, and the total scores of the CERAD-K were negatively correlated with the plasma OAβ level. With a cut-off value of 0.78 ng/mL for the OAβ level and a −1.5 standard deviation of age/sex/education adjusted norms for the CERAD-K; naming, word memory, word recall, word recognition, and total score were significantly correlated with the OAβ level. No correlation between the OAβ level and mini-mental status examination was found. Our results demonstrate that the level of plasma OAβ was well correlated with the measure of cognitive function through the CERAD-K in the field data collected from consecutive populations. Studies on longitudinal comparisons with large cohorts will further validate the diagnostic value of plasma OAβ as a useful biomarker for screening AD and predicting progression.

FolC plays important roles in the folate metabolism of cells by attaching l-Glu to dihydropteroate (DHP) and folate, which are known activities of dihydrofolate synthetase (DHFS) and folylpolyglutamate synthetase (FPGS), respectively. Here, we determined the crystal structure of Helicobacter pylori FolC (HpFolC) at 1.95 Å resolution using the single-wavelength anomalous diffraction method. HpFolC has globular N- and C-terminal domains connected by a single loop, and a binding site for ATP is located between the two domains. Apo-HpFolC was crystallized in the presence of citrate in a crystallization solution, which was held in the ATP-binding site. Structural motifs such as the P-loop and Ω-loop of HpFolC for binding of ATP and two magnesium ions are well conserved in spite of the low overall sequence similarity to other FolC/FPGSs. The Ω-loop would also recognize a folate molecule, and the DHP-binding loop of HpFolC is expected to exhibit a unique recognition mode on DHP, compared with other FolCs. Because human FolC is known to only exhibit FPGS activity, the DHFS activity of bacterial FolC is an attractive target for the eradication of pathogenic bacteria. Consequently, our structural analyses of HpFolC provide a valuable foundation for a universal antibacterial strategy against H. pylori as well as other pathogenic bacteria.

Toxin-antitoxin (TA) systems are known to play various roles in physiological processes, such as gene regulation, growth arrest and survival, in bacteria exposed to environmental stress. Type II TA systems comprise natural complexes consisting of protein toxins and antitoxins. Each toxin and antitoxin participates in distinct regulatory mechanisms depending on the type of TA system. Recently, peptides designed by mimicking the interfaces between TA complexes showed its potential to activate the activity of toxin by competing its binding counterparts. Type II TA systems occur more often in pathogenic bacteria than in their nonpathogenic kin. Therefore, they can be possible drug targets, because of their high abundance in some pathogenic bacteria, such as Mycobacterium tuberculosis. In addition, recent bioinformatic analyses have shown that type III TA systems are highly abundant in the intestinal microbiota, and recent clinical studies have shown that the intestinal microbiota is linked to inflammatory diseases, obesity and even several types of cancer. We therefore focused on exploring the putative relationship between intestinal microbiota-related human diseases and type III TA systems. In this paper, we review and discuss the development of possible druggable materials based on the mechanism of type II and type III TA system.

Current trends in the application of nanomaterials are emerging in the nano-biotechnological sector for development of medicines. Cyanobacteria (blue-green algae) are photosynthetic prokaryotes that have applications to human health and numerous biological activities as dietary supplements. Cyanobacteria produce biologically active and chemically diverse compounds such as cyclic peptides, lipopeptides, fatty acid amides, alkaloids, and saccharides. More than 50% of marine cyanobacteria are potentially exploitable for the extraction of bioactive substances, which are effective in killing cancer cells by inducing apoptotic death. The current review emphasizes that not even 10% of microalgal bioactive components have reached commercialized platforms due to difficulties related to solubility. Considering these factors, they should be considered as a potential source of natural products for drug discovery and drug delivery approaches. Nanoformulations employing a wide variety of nanoparticles and their polymerized forms could be an emerging approach to the development of new cancer drugs. This review highlights recent research on microalgae-based medicines or compounds as well as their biomedical applications. This review further discusses the facts, limitations, and commercial market trends related to the use of microalgae for industrial and medicinal purposes.