In vitro and in vivo validation of the antiviral effect of hCypA against SARS-CoV-2 via binding to the RBD of spike protein.

The novel coronavirus disease 2019 has stimulated the rapid development of new biological therapeutics to inhibit SARS-CoV-2 infection; however, this remains a challenging task. In a previous study using structural analysis, we revealed that human cyclophilin A inhibits the entry of SARS-CoV-2 into host cells by interfering with the interaction of the receptor-binding domain of the spike protein with angiotensin-converting enzyme 2 on the host cell surface, highlighting its potential for antiviral therapy. For a comprehensive experimental validation, in this study, we verified the antiviral effects of human cyclophilin A against SARS-CoV-2, including its variants, using in vitro assays and experiments on an in vivo mouse model. Human cyclophilin A demonstrated a highly effective antiviral effect, with an 85% survival rate upon SARS-CoV-2 infection. It also reduced viral titers, inflammation in the lungs and brain, and cytokine release in the serum, suggesting a controlled immune response and potentially faster recovery. Overall, our study provides insights into the potential of human cyclophilin A as a therapeutic agent against SARS-CoV-2, which should guide future clinical trials that might provide an additional therapeutic option for patients.

Reassembled Vacuoles for Drug Delivery Carriers Using Yeast Vacuoles for Enhanced Antibacterial Activity.

In this study, we aimed to develop an efficient drug delivery system by reassembling vacuoles isolated from Saccharomyces cerevisiae. Initially, we assessed the impact of vacuolar enzymes on the efficacy of the loaded antibiotic polymyxin B (PMB), by conducting antibacterial activity tests using Shigella flexneri and Salmonella enteritidis. The results showed that vacuolar enzymes inhibited the effectiveness of PMB, highlighting the limitations of using natural vacuoles as drug carriers. To overcome this, we proposed a new drug delivery system called reassembled vacuoles (ReV). ReV particles were created by removing vacuolar enzymes and reassembling the vacuolar membrane through extrusion. ReV demonstrated improved structural stability, a more uniform size, and enhanced PMB release compared to natural vacuoles. Encapsulation efficiency tests revealed high loading efficiency for both normal vacuoles (NorV) and ReV, with over 80% efficiency at concentrations up to 600 µg/mL. The antibacterial activity of PMB-loaded ReV showed comparable results to PMB alone, indicating the potential of ReV as a drug delivery system. In conclusion, reassembled vacuoles offer a promising approach for drug delivery, addressing the limitations of natural vacuoles and providing opportunities for targeted and efficient drug release.

Structure based innovative approach to analyze aptaprobe-GPC3 complexes in hepatocellular carcinoma.

BACKGROUND: Glypican-3 (GPC3), a membrane-bound heparan sulfate proteoglycan, is a biomarker of hepatocellular carcinoma (HCC) progression. Aptamers specifically binding to target biomolecules have recently emerged as clinical disease diagnosis targets. Here, we describe 3D structure-based aptaprobe platforms for detecting GPC3, such as aptablotting, aptaprobe-based sandwich assay (ALISA), and aptaprobe-based imaging analysis. RESULTS: For preparing the aptaprobe-GPC3 platforms, we obtained 12 high affinity aptamer candidates (GPC3_1 to GPC3_12) that specifically bind to target GPC3 molecules. Structure-based molecular interactions identified distinct aptatopic residues responsible for binding to the paratopic nucleotide sequences (nt-paratope) of GPC3 aptaprobes. Sandwichable and overlapped aptaprobes were selected through structural analysis. The aptaprobe specificity for using in HCC diagnostics were verified through Aptablotting and ALISA. Moreover, aptaprobe-based imaging showed that the binding property of GPC3_3 and their GPC3 specificity were maintained in HCC xenograft models, which may indicate a new HCC imaging diagnosis. CONCLUSION: Aptaprobe has the potential to be used as an affinity reagent to detect the target in vivo and in vitro diagnosing system.

Role of the A-Site Cation in Low-Temperature Optical Behaviors of APbBr3 (A = Cs, CH3NH3).

APbBr3 (A = Cs, CH3NH3) are prototype halide perovskites having bandgaps of 2.30-2.35 eV at room temperature, rendering their apparent color nearly identical (bright orange but opaque). Upon optical excitation, they emit bright photoluminescence (PL) arising from carrier recombination whose spectral features are also similar. At 10 K, however, the apparent color of CsPbBr3 becomes transparent yellow, whereas that of CH3NH3PbBr3 does not change significantly due to the presence of an indirect Rashba gap. With increasing the excitation level, evolution of the PL spectra, which are excitonic at 10 K, reveals the emergence of P-band emission arising from inelastic exciton-exciton scattering. Based on the spectral location of the P-band, exciton binding energies are determined to be 21.6 ± 2.0 and 38.3 ± 3.0 meV for CsPbBr3 and CH3NH3PbBr3, respectively. Intriguingly, upon further increase in the exciton density, electron-hole plasma appears in CsPbBr3 as evidenced by both red-shift and broadening of the PL. This phase, however, does not occur in CH3NH3PbBr3 presumably due to polaronic effects. Although the A-site cation is believed not to directly impact optical properties of APbBr3, our results underscore its critical role, which destines different high-density phases and apparent color at low temperatures.

Static Rashba Effect by Surface Reconstruction and Photon Recycling in the Dynamic Indirect Gap of APbBr3 (A = Cs, CH3NH3) Single Crystals.

Recently, halide perovskites have gained significant attention from the perspective of efficient spintronics owing to the Rashba effect. This effect occurs as a consequence of strong spin-orbit coupling under a noncentrosymmetric environment, which can be dynamic and/or static. However, there exist intense debates on the origin of broken inversion symmetry since the halide perovskites typically crystallize into a centrosymmetric structure. In order to clarify the issue, we examine both dynamic and static effects in the all-inorganic CsPbBr3 and organic-inorganic CH3NH3PbBr3 (MAPbBr3) perovskite single crystals by employing temperature- and polarization-dependent photoluminescence excitation spectroscopy. The perovskite single crystals manifest the dynamic effect by photon recycling in the indirect Rashba gap, causing dual peaks in the photoluminescence. However, the effect vanishes in CsPbBr3 at low temperatures (<50 K) accompanied by a striking color change of the crystal, arising presumably from lower degrees of freedom for inversion symmetry breaking associated with the thermal motion of the spherical Cs cation compared with the polar MA cation in MAPbBr3. We also show that the static Rashba effect occurs only in MAPbBr3 below 90 K, presumably due to surface reconstruction via MA-cation ordering, which likely extends across a few layers from the crystal surface to the interior. We further demonstrate that this static Rashba effect can be completely suppressed upon surface treatment with polymethyl methacrylate (PMMA) coating. We believe that our results provide a rationale for the Rashba effects in halide perovskites.

Refractive corneal inlay for presbyopia in emmetropic patients in Asia: 6-month clinical outcomes.

BACKGROUND: To evaluate the 6-month clinical outcomes of Flexivue Microlens refractive corneal inlay in emmetropic patients in Asia for the surgical compensation of presbyopia. METHODS: In this retrospective study, corneal inlay implantation was done using a femtosecond laser. The follow-up period was 6 months. Near/intermediate/distant visual acuities, refraction, keratometry, defocus curve, wavefront aberrations, contrast sensitivity, Scheimpflug corneal scanning, endothelial cell density, dry eye test, confocal microscopy scanning, and patient questionnaires were evaluated. RESULTS: The inlay implantation was performed in 21 eyes from June 2015 to April 2017. 6 months after surgery, the uncorrected near visual acuity of the operated eyes increased significantly from 0.55 ± 0.22 logMAR preoperatively to 0.25 ± 0.15 logMAR (p < 0.05) but mean bilateral uncorrected distant visual acuity did not change significantly (p = 0.90). Total higher-order aberration and spherical aberration increased, and the contrast sensitivity of the operated eyes decreased. Endothelial cell density and central corneal thickness did not change from preoperative values. Patient satisfaction for near vision was increased 6 months after implantation, and 50.0% of patients were independent of near spectacles. Explantation was done in 2 cases. CONCLUSION: The Flexivue Microlens refractive corneal inlay was effective for improving near visual acuity at 6 months follow-up But proportion of spectacle independency and patient satisfaction were lower in this Korean population than in previous reports. Further study with a longer follow-up period is needed.

Perilipin+ embryonic preadipocytes actively proliferate along growing vasculatures for adipose expansion.

Despite the growing interest in adipose tissue as a therapeutic target of metabolic diseases, the identity of adipocyte precursor cells (preadipocytes) and the formation of adipose tissue during embryonic development are still poorly understood. Here, we clarified the identity and dynamic processes of preadipocytes in mouse white adipose tissue during embryogenesis through direct examination, lineage tracing and culture systems. Surprisingly, we found that lipid-lacking but perilipin(+) or adiponectin(+) proliferating preadipocytes started to emerge at embryonic day 16.5, and these cells underwent active proliferation until birth. Moreover, these preadipocytes resided as clusters and were distributed along growing adipose vasculatures. Importantly, the embryonic preadipocytes exhibited considerable coexpression of stem cell markers, such as CD24, CD29 and PDGFRα, and a small portion of preadipocytes were derived from PDGFRß(+) mural cells, in contrast to the adult preadipocytes present in the stromal vascular fraction. Further analyses with in vitro and ex vivo culture systems revealed a stepwise but dynamic regulation of preadipocyte formation and differentiation during prenatal adipogenesis. To conclude, we unraveled the identity and characteristics of embryonic preadipocytes, which are crucial for the formation and expansion of adipose tissue during embryogenesis.

Comparison of astigmatism prediction error taken with the Pentacam measurements, Baylor nomogram, and Barrett formula for toric intraocular lens implantation.

BACKGROUND: To evaluate and compare the astigmatism prediction errors taken with the Pentacam measurements, Baylor nomogram, and Barrett formula for toric intraocular lens (IOL) implantation. METHODS: Phacoemulsification with toric Precizon IOL implantation was performed in 41 eyes with corneal astigmatism (range, 1 to 5 diopters (D)) determined by IOLMaster and SimK on Pentacam. Preoperative corneal astigmatism measurements were obtained from IOLMaster readings (IOLMaster, Baylor-IOLMaster, and Barrett-IOLMaster) and Pentacam readings (SimK, Baylor-SimK, Barrett-SimK, wavefront, true net power, total corneal refractive power, and vector derived by manual vector summation using corneal front and back astigmatism). Prediction error and intraclass correlation coefficient (ICC) between the measured (or calculated) astigmatism by IOLMaster and Pentacam and the estimated corneal astigmatism estimated by IOL toricity power and residual astigmatism were determined. RESULTS: The centroid errors in prediction error with IOLMaster, SimK, Baylor-IOLMaster, Baylor-SimK, Barrett-IOLMaster, Barrett-SimK, wavefront, true net power, total corneal refractive power, and vector were 0.59@103, 0.61 @103, 0.37@161, 0.41@162, 0.24@171, 0.36@162, 0.42@106, 0.04@8, 0.07@82, and 0.03@82, respectively, in with-the-rule (WTR) astigmatism eyes at postoperative 3-month. They were 0.22@87, 0.20@74, 0.16@21, 0.54@10, 0.43@3, 0.33@19, 0.51@25, 0.31@58, 0.29@50, and 0.14@50 in against-the-rule (ATR) astigmatism eyes. Of the ten modalities, vector showed the lowest WTR astigmatism prediction error and the highest ICC between the predicted and the estimated corneal astigmatism for both WTR and ATR eyes. CONCLUSION: Vector summation using anterior and posterior corneal surface power taken with the Pentacam yields the least astigmatism prediction error and is a promising tool for determining toric IOL cylinder power.

miRNA profiling of B16F10 melanoma cell exosomes reveals melanin synthesis-related genes.

This study investigates the communication between skin cells, specifically melanocytes, keratinocytes, and fibroblasts, which is crucial for the process of melanin production known as melanogenesis. We aimed to understand the role of melanocyte exosomes in regulating melanogenesis and to uncover the microRNAs influencing this process. We isolated exosomes and characterized them using advanced microscopy and protein analysis to achieve this. We conducted experiments on melanoma cells to study melanin production regulation and examined how exosomes influenced gene expression related to melanogenesis. The results revealed that melanocyte exosomes increased certain types of tyrosinases, thereby enhancing melanin production. Furthermore, we acquired the miRNA profile of exosomes and hypothesized that specific siRNAs, such as miR-21a-5p, could potentially facilitate melanin synthesis. Our findings shed light on the importance of exosomes in skin health and provide valuable insights into intercellular communication mechanisms. Understanding these processes can pave the way for innovative therapies to treat melanin-related disorders and maintain healthy skin.

Mitigating substrate effects of van der Waals semiconductors using perfluoropolyether self-assembled monolayers.

The properties of transition metal dichalcogenides (TMDCs) are critically dependent on the dielectric constant of substrates, which significantly limits their application. To address this issue, we used a perfluorinated polyether (PFPE) self-assembled monolayer (SAM) with low surface energy to increase the van der Waals (vdW) gap between TMDCs and the substrate, thereby reducing the interaction between them. This resulted in a reduction in the subthreshold swing value, an increase in the photoluminescence intensity of excitons, and a decrease in the doping effect by the substrate. This work will provide a new way to control the TMDC/dielectric interface and contribute to expanding the applicability of TMDCs.

Pathogenic Factors and Recent Study on the Rapid Detection of Shiga Toxin-Producing Escherichia coli (STEC).

This comprehensive review delves into the pathogenicity and detection of Shiga Toxin-Producing Escherichia coli (STEC), shedding light on its various genetic and clinical manifestations. STEC originating from E. coli acquires pathogenicity through mobility and genetic elements. The pathogenicity of STEC is explored in terms of clinical progression, complications, and key toxins such as Shiga toxin (Stx). Stx1 and Stx2 are two distinct Stx types exhibiting different toxicities, with Stx2 often associated with severe diseases. This review also delves into Subtilase cytotoxin, an additional cytotoxin produced by some STEC strains. Pathogenic mechanisms of STEC, such as attaching and effacing intestinal lesions, are discussed, with a focus on roles of genetic factors. Plasmids in STEC can confer unique pathogenicity. Hybridization with other pathogenic E. coli can create more lethal pathogens. This review covers a range of detection methods, ranging from DNA amplification to antigen detection techniques, emphasizing the need for innovative approaches to improve the sensitivity and speed of STEC diagnosis. In conclusion, understanding diverse aspects of STEC pathogenicity and exploring enhanced diagnostic methods are critical to addressing this foodborne pathogen effectively. Pathology of Shiga toxin toxicity. STEC-derived Shiga toxin consists of one A subunit and five B subunits. Pathological symptoms of the disease can progress to HUS within two weeks after the onset of diarrhea. Shiga toxin intoxication is also associated with many complications, such as neurological and cardiac complications. This figure was reconstructed based on data from Bruyand et al.

Nano-Thermal Analysis of Defect-Induced Surface Pre-Melting in 2D Tellurium.

Thermal properties, such as thermal conductivity, heat capacity, and melting temperature, influence the efficiency and stability of two-dimensional (2D) material applications. However, existing studies on thermal characteristics-except for thermal conductivity-are insufficient for 2D materials. Here, we investigated the melting temperature of 2D Tellurium (2D Te) using the nano-thermal analysis technique and found anomalous behavior that occurs before the melting temperature is reached. The theoretical calculations present surface pre-melting in 2D Te and Raman scattering measurements suggest that defects in 2D Te accelerate surface pre-melting. Understanding the pre-melting surface characteristics of 2D Te will provide valuable information for practical applications.

Large-Area MoS2 via Colloidal Nanosheet Ink for Integrated Memtransistor.

2D transition metal dichalcogenides (TMDs) exhibit intriguing properties for applications in optoelectronics and electronics, among which memtransistors received extensive attention as multifunctional devices. For practical applications of 2D TMDs, large-area fabrication of the materials via reliable processes, which is in trade-off with their quality, has been a long-standing issue. Here, a simple and effective way is proposed to fabricate large-area and high-quality molybdenum disulfide thin films using MoS2 colloidal ink through a spray coating, followed by a postsulfurization process. High-quality MoS2 thin films exhibit excellent optical and electrical properties that can be utilized in field-effect transistors (FETs) and memtransistor arrays. The MoS2 FETs show an average on/off ratio of 5 × 106 and a high electron mobility of 10.34 cm2  V-1  s-1 , which can be understood by the healing of sulfur vacancies, recrystallization, and the removal of the carbon contamination of the MoS2 . These MoS2 -based memtransistors present stable operations with a high switching ratio tuned by back gate and light illumination, which is promising for multiple-levels memory and complex neuromorphic computing. This study demonstrates a new strategy to fabricate 2D TMDs with large-area and high quality for integrated optoelectronic and memory device applications.

Investigation of Cation Exchange Behaviors of FAxMA1-xPbI3 Films Using Dynamic Spin-Coating.

In this study, we fabricated and characterized uniform multi-cation perovskite FAxMA1-xPbI3 films. We used the dynamic spin-coating method to control the cation ratio of the film by gradually increasing the FA+, which replaced the MA+ in the films. When the FA+ concentration was lower than xFA ~0.415 in the films, the stability of the multi-cation perovskite improved. Above this concentration, the film exhibited δ-phase FAPbI3 in the FAxMA1-xPbI3 films. The formation of δ-phase FAPbI3 disturbed the homogeneity of the photoluminescence spatial distribution and suppressed the absorption spectral bandwidth with the increasing bandgap. The precise control of the cation ratio of multi-cation perovskite films is necessary to optimize the energy-harvesting performance.

Interface Trap Suppression and Electron Doping in Van der Waals Materials Using Cross-Linked Poly(vinylpyrrolidone).

The instability of van der Waals (vdW) materials leads to spontaneous morphological and chemical transformations in the air. Although the passivation of vdW materials with other resistive materials is often used to solve stability issues, this passivation layer can block carrier injection and thus interfere with charge transfer doping. In this study, a facile method is proposed for n-doping and mediation of Se vacancies in tungsten diselenide (WSe2) by poly(vinylpyrrolidone) (PVP) coating. The major carrier type of the PVP-coated WSe2-based field-effect transistor (FET) was converted from hole (p-type) to electron (n-type). Furthermore, the vacancy-induced interface trap density was reduced by approximately 500 times. This study provides a practical doping and passivation method for the van der Waals materials, as well as a comprehensive understanding of the chemical reaction and electronic transport in these materials.

Tip-Induced Strain Engineering of a Single Metal Halide Perovskite Quantum Dot.

Strain engineering of perovskite quantum dots (pQDs) enables widely tunable photonic device applications. However, manipulation at the single-emitter level has never been attempted. Here, we present a tip-induced control approach combined with tip-enhanced photoluminescence (TEPL) spectroscopy to engineer strain, bandgap, and the emission quantum yield of a single pQD. Single CsPbBrxI3-x pQDs are clearly resolved through hyperspectral TEPL imaging with ∼10 nm spatial resolution. The plasmonic tip then directly applies pressure to a single pQD to facilitate a bandgap shift up to ∼62 meV with Purcell-enhanced PL increase as high as ∼105 for the strain-induced pQD. Furthermore, by systematically modulating the tip-induced compressive strain of a single pQD, we achieve dynamical bandgap engineering in a reversible manner. In addition, we facilitate the quantum dot coupling for a pQD ensemble with ∼0.8 GPa tip pressure at the nanoscale estimated theoretically. Our approach presents a strategy to tune the nano-opto-electro-mechanical properties of pQDs at the single-crystal level.

A TRPV family ion channel required for hearing in Drosophila.

The many types of insect ear share a common sensory element, the chordotonal organ, in which sound-induced antennal or tympanal vibrations are transmitted to ciliated sensory neurons and transduced to receptor potentials. However, the molecular identity of the transducing ion channels in chordotonal neurons, or in any auditory system, is still unknown. Drosophila that are mutant for NOMPC, a transient receptor potential (TRP) superfamily ion channel, lack receptor potentials and currents in tactile bristles but retain most of the antennal sound-evoked response, suggesting that a different channel is the primary transducer in chordotonal organs. Here we describe the Drosophila Nanchung (Nan) protein, an ion channel subunit similar to vanilloid-receptor-related (TRPV) channels of the TRP superfamily. Nan mediates hypo-osmotically activated calcium influx and cation currents in cultured cells. It is expressed in vivo exclusively in chordotonal neurons and is localized to their sensory cilia. Antennal sound-evoked potentials are completely absent in mutants lacking Nan, showing that it is an essential component of the chordotonal mechanotransducer.

Colloidal MoS2 van der Waals Template for Growing Highly Uniform Nanomaterials.

The van der Waals (vdW) structures of transition metal dichalcogenides (TMDCs) have been studied extensively owing to the excellent electronic, optoelectronic, and catalytic performance with the atomic-scale sharpness of the interfaces. In addition, the presence of substitution and redox reactions in the vdW gaps also provides huge potential to be employed as a nanoscale reactor. Herein, the vdW gap of colloidal MoS2 is reported as a natural template for the formation of CoMo bimetallic oxide nanoparticles (BMONPs) with highly uniform size (∼4 nm), which resulted in further synthesis of the thin multiwalled carbon nanotubes with extremely narrow diameter distribution. This study not only pioneers a new application of TMDCs but also provides an efficient means to control the size of nanomaterials, which directly affect material properties.

Fabrication of pyramidal (111) MAPbBr3 film with low surface defect density using homogeneous quantum-dot seeds.

Nucleation and seeding of organometal halide perovskite (OHP) films have been extensively investigated for forming high-density, large-crystalline, and low-defect films. In this study, CH3NH3PbBr3 (MAPbBr3) films with a low defect density are synthesized via a molecular exchange mechanism using MAPbBr3 quantum dots as seeds. The synthesized films exhibit a pyramidal morphology with a (111) crystal plane. The distribution of the (111) plane is controlled by adjusting the seed concentration. The pyramidal MAPbBr3 films exhibit improved photoluminescence intensity and uniformity compared with films produced using seedless toluene. When the seeds are employed, the surface trap density is reduced by a factor of 3.5, suppressing the photocurrent hysteresis and nonsaturated response of photodetectors. Additionally, the films formed using the seeds have improved stability owing to the chain decomposition reaction induced by electron beam heating.

Docking Simulation and Sandwich Assay for Aptamer-Based Botulinum Neurotoxin Type C Detection.

Aptamers are biomaterials that bind to a target molecule through a unique structure, and have high applicability in the diagnostic and medical fields. To effectively utilize aptamers, it is important to analyze the structure of the aptamer binding to the target molecule; however, there are difficulties in experimentally identifying this structure. In the modern pharmaceutical industry, computer-driven docking simulations that predict intermolecular binding models are used to select candidates that effectively bind target molecules. Botulinum toxin (BoNT) is the most poisonous neurotoxin produced from the Clostridium botulinum bacteria, and BoNT/C, one of the eight serotypes, causes paralysis in livestock. In this study, the aptamers that bound to BoNT/C were screened via the systematic evolution of ligands by exponential enrichment, and the binding affinity analysis and binding model were evaluated to select optimal aptamers. Based on surface plasmon resonance analysis and molecular operating environment docking simulation, a pair of aptamers that had high binding affinity to BoNT/C and were bound to different BoNT/C sites were selected. A sandwich assay based on this aptamer pair detected the BoNT/C protein to a concentration as low as ~0.2 ng Ml-1. These results show that docking simulations are a useful strategy for screening aptamers that bind to specific targets.