Design and Synthesis of Potent Ridaifen Analogues: Evaluation as Anticancer, 20S Proteasomal Inhibitors, and Antiebola Virus Agents through In vitro and In Silico Studies.

Ridaifen (RID) analogues are identified as nonpeptide, noncovalent inhibitors of the catalytic subunits of the human 20S proteasome. They demonstrated effectiveness against both multiple myeloma and solid tumors. Herein, the synthesis and biological evaluation of 20 novel RID analogs that exhibit inhibitory effects on the three catalytic subunits of the 20S proteasome are reported.

IDRdecoder: a machine learning approach for rational drug discovery toward intrinsically disordered regions.

Introduction: Intrinsically disordered regions (IDRs) of proteins have traditionally been overlooked as drug targets. However, with growing recognition of their crucial role in biological activity and their involvement in various diseases, IDRs have emerged as promising targets for drug discovery. Despite this potential, rational methodologies for IDR-targeted drug discovery remain underdeveloped, primarily due to a lack of reference experimental data.

Molecular Structure and Biosynthesis of Pyoverdines Produced by .

This study explored the biosynthetic mechanisms and structural diversity of pyoverdines (PVDs) produced by . Genomic analysis using antiSMASH identified the PVD biosynthetic gene cluster, although the C-terminal peptide sequence could not be predicted. Subsequent liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis revealed the full peptide structure, including modified residues, such as N-acetylhydroxyornithine and cyclohydroxyornithine, and confirmed the presence of several PVD isoforms with different chromophore side chains.

Alternative Splicing in TRPA1 Drives Sensory Adaptation to Electrophiles in Drosophilids.

Behaviors are among the first traits to evolve as animals enter new niches, but their molecular bases are poorly understood. To address this gap, we used the mustard-feeding drosophilid fly , which feeds on toxic Brassicales plants like wasabi that produce noxious, electrophilic isothiocyanates (ITCs or mustard oils). We found that exhibits dramatically reduced behavioral sensitivity to allyl isothiocyanate (AITC) compared to its microbe-feeding relatives and .

Photodetectors based on chlorophyll for visible image sensing and near-infrared moving detection with bidirectional current response.

Photodetectors, with high sensitivity and broad spectral response, drive the advancements in optical imaging technology. In this work, utilizing the absorption differences of chlorophyll-a derivative (Chl) and [6,6]-phenyl-C-butyric acid methyl ester, two distinct structures of multifunctional organic photodetectors (OPDs) are fabricated, namely, bulk heterojunction (BHJ) and quasiplanar heterojunction (Q-PHJ). Chl, by modulating its doping concentration, served as both an active layer and an electron trap, enabling the BHJ OPD to exhibit a photomultiplication effect, and allowing the Q-PHJ OPD to achieve improved response speed (0.

Quantum-like Qualia hypothesis: from quantum cognition to quantum perception.

To arbitrate theories of consciousness, scientists need to understand mathematical structures of quality of consciousness, or qualia. The dominant view regards qualia as points in a dimensional space. This view implicitly assumes that qualia can be measured without any effect on them.

Fragmented QRS in Lateral Leads on Electrocardiography Is Associated with Cardiac Dysfunction and Left Ventricular Dilation in Duchenne Muscular Dystrophy.

: Duchenne muscular dystrophy (DMD) is an X-linked inherited muscle disease. Patients with DMD demonstrate improved prognosis with angiotensin-converting enzyme inhibitors and beta-blockers at the time of cardiac dysfunction. However, most deaths due to DMD are due to cardiac dysfunction.

Tribe Paniceae Cereals with Different Ploidy Levels: , , and .

Plants have repeatedly undergone whole-genome duplication during their evolutionary history. Even in modern plants, there is diversity in ploidy within and between species, providing a snapshot of the evolutionary turnover of ploidy. Here, I will review the diversity of ploidy and the evolution of the genome constitution, focusing on the millet species , , and .

Nickel Chlorophyll-Derived Hole Transport Materials for Stable and Efficient Inverted Perovskite Solar Cells.

Hole-selective layers (HSLs) are critical for efficient and stable perovskite solar cells (PSCs). Chlorophylls (Chls) and their analogs exhibit unique optoelectronic properties, making them attractive for photovoltaics. However, dopant-free Chl-based materials remain underexplored, with reported power conversion efficiencies (PCEs) below 19%.

Achieving Buried Interface/Bulk Synergistic Passivation via Chlorophyll Derivative for Efficient Inverted Perovskite Solar Cells.

Buried interfacial engineering is crucial for NiO-based inverted perovskite solar cells (PSCs), while most passivation measures focus only on the interface and neglect the perovskite bulk. In this work, a stable free-base chlorin possessing an amino acid terminal (serinyl pyropheophorbide-a, SPPa) was synthesized as a functional chlorophyll derivative, and its trifluoroacetic acid and hydrogen chloride salts (SPPaX; X = TFA, HCl) were introduced into the NiO/perovskite interface. Thanks to the high solubility in N,N-dimethylformamide and dimethyl sulfoxide, SPPaX can diffuse into the perovskite through the precursor.

IgG4 and IgG1 undergo common acid-induced compaction into an alternatively folded state.

Immunoglobulin G1 (IgG1) antibodies undergo denaturation in acidic conditions, resulting in an alternatively folded state (AFS). The AFS structure is more compact than the native state. However, the prevalence of AFS in other subclasses remains largely unexplored.

Chromosomal domain formation by archaeal SMC, a roadblock protein, and DNA structure.

In eukaryotes, structural maintenance of chromosomes (SMC) complexes form topologically associating domains (TADs) by extruding DNA loops and being stalled by roadblock proteins. It remains unclear whether a similar mechanism of domain formation exists in prokaryotes. Using high-resolution chromosome conformation capture sequencing, we show that an archaeal homolog of the bacterial Smc-ScpAB complex organizes the genome of Thermococcus kodakarensis into TAD-like domains.

Visualization of Small Vessels by Micro-Computed Tomography Using Titanium Dioxide Nanoparticles as a Novel Contrast Agent.

Angiography by means of micro-computed tomography (m-CT) is extensively used for the diagnosis of vasculature disorders. To establish a connection between m-CT images and genuine histopathology findings, we developed two novel titanium dioxide nanoparticle (TiO-NP)-based perfusion contrast agents: TiNpCA-1 and TiNpCA-2. Three-dimensionally reconstructed m-CT images in mice perfused with these contrast agents showed high resolution and accuracy in various organs without deformation or dilation of vessels.

Evolution of Temperature Receptors and Their Roles in Sensory Diversification and Adaptation.

Among various environmental factors, temperature is one of the critical factors for organisms since it can affect most, if not all, biological processes. Therefore, animals precisely sense ambient and body temperatures and physiologically and behaviorally respond to temperature changes. Taking such nature into consideration, alteration of thermal perception should have played a pivotal role in adaptation to diverse thermal niches.

Functional characterization of thermosensitive TRPV channels from holocephalan elephant shark (Callorhinchus milii) illuminate the ancestral thermosensory system in vertebrates.

Homeostasis and survival of various animal species have been affected by changes in environmental temperature, causing animals to evolve physiological systems for sensing ambient and body temperature. Temperature-sensitive transient receptor potential (TRP) channels have multimodal properties that are activated by physical stimuli such as temperature, as well as by various chemical substances. Our goal is to understand the diversity of the vertebrate thermosensory system by characterizing the temperature-sensitive TRPV channels of the elephant shark, which belongs to the Holocephali of the cartilaginous fishes.

Mechanism of polymer molecular weight-dependent suppression and promotion of liquid-liquid phase separation of a protein solution by the addition of polymer.

Polyethylene glycol (PEG) is a widely used precipitant to concentrate proteins. The effect of PEG is generally understood to be an entropic attraction between proteins due to the depletion effect of PEG around proteins. However, measurements by Bloustine et al.

Engineering Cascade Bio-Solar Cells Inspired by the Z-Scheme of Oxygenic Photosynthesis: Layered Chlorophyll and Bacterio-Chlorophyll Derivatives.

The natural Z-scheme of oxygenic photosynthesis efficiently drives electron transfer from photosystem II (PSII) to photosystem I (PSI) via an electron transport chain, despite the lower energy levels of PSII. Inspired by this sophisticated mechanism, we present a layered cascade bio-solar cell (CBSC) that emulates the Z-scheme. In this design, chlorophyll derivatives (Chl) act as PSI analogs, while bacteriochlorophyll derivatives (BChl) serve as PSII analogs in the active layer.

Salivary chromogranin A levels relate to fatigability after waking up.

This study aimed to assess fatigue using a noninvasive, quantitative, and simple method using salivary chromogranin A (CgA). In total, 171 adults participated in this study. We used the Cornell Medical Index (CMI) as a questionnaire that included a fatigability section.

Exploring the Allelic Diversity of the Self-Incompatibility Gene Across Natural Populations in Petunia (Solanaceae).

Self-incompatibility (SI) is a genetic mechanism to prevent self-fertilization and thereby promote outcrossing in hermaphroditic plant species through discrimination of self and nonself-pollen by pistils. In many SI systems, recognition between pollen and pistils is controlled by a single multiallelic locus (called the S-locus), in which multiple alleles (called S-alleles) are segregating. Because of the extreme level of polymorphism of the S-locus, identification of S-alleles has been a major issue in many SI studies for decades.

cDNA Display Selection of Interacting Peptide Ligands of the Guanylate Cyclase C Receptor.

Guanylate cyclase C (GC-C), a receptor expressed on the apical membrane of intestinal mucosal cells, is activated by heat-stable enterotoxin (STa) produced by enterotoxigenic Escherichia coli, as well as the endogenous ligands guanylin and uroguanylin. In this study, novel peptides that interact with GC-C were generated using the cDNA display method, and their binding affinity and biological activity were evaluated. While the linear peptide library did not yield peptides with sufficient affinity for GC-C, three cyclic peptides (GCC-P1, GCC-P2, and GCC-P3), each containing two cysteine residues within a 15-residue sequence, were obtained from a cyclic peptide library containing nine-residue random sequences.

Choline chloride and N-allylglycine promote plant growth by increasing the efficiency of photosynthesis.

We previously reported that choline chloride and N-allylglycine stimulate photosynthesis in wheat protoplasts. Treatment of Arabidopsis thaliana and Brassica rapa plants with both compounds promoted growth and photosynthesis. To clarify the relationship between the enhancement of photosynthesis and increased growth, A.

Clinical Utility of Synthesized 18-Lead Electrocardiography.

Eighteen-lead electrocardiography (18-ECG) includes, in addition to those in standard 12-lead ECG (12-ECG), six additional chest leads: V7-V9 and V3RV5R. Leads V7-V9 require the patient to be in a lateral decubitus position for the electrodes to be attached to the back. Synthesized 18-ECG (syn18-ECG) is a method that only records 12-ECG and uses computational logic to record the posterior wall (V7-V9) and right-sided (V3R-V5R) leads.