Unveiling the Nanocluster Conversion Pathway for Highly Monodisperse InAs Colloidal Quantum Dots.

Colloidal quantum dots (CQDs) have garnered significant attention in nanoscience and technology, with a particular emphasis on achieving high monodispersity in their synthesis. Recent advances in understanding the chemistry of reaction intermediates such as magic-sized nanoclusters (MSC) have paved the way for innovative synthetic strategies. Notably, monodisperse CQDs of various compositions, including indium phosphide, indium arsenide, and cadmium chalcogenide, have been successfully prepared using nanocluster intermediates as single-source precursors. Still, the early stage conversion chemistry of these nanoclusters preceding CQD formation has not been fully unveiled yet. Herein, we report the first-order conversion of amorphous nanoclusters (AMCs) to InAs MSCs prior to the formation of CQDs. We find that MSC, isolated via gel-permeation chromatography, is more stable than purified AMCs, as demonstrated in various chemical and thermolytic reactions. While the surface of InAs AMCs and MSC is similarly bound with carboxylate ligands, detailed structural analyses employing synchrotron X-ray scattering and X-ray absorption spectroscopy unveil subtle distinctions arising from the distinct surface properties and structural disorder characteristics of InAs nanoclusters. We propose that InAs AMCs undergo a surface reduction and structural ordering process, resulting in the formation of an InAs MSC in a thermodynamically local minimum state. Furthermore, we demonstrate that both types of nanoclusters serve as viable precursors, providing a similar monomer supply rate at elevated temperatures of around 300 °C. This study offers invaluable insights into the interplay of structure and chemical stability in binary nanoclusters, enhancing our ability to design these nanoclusters as precursors for highly monodisperse CQDs.

Enhancement of acousto-optic interaction using a phoxonic cavity with structural hierarchy.

We propose a phoxonic cavity with structural hierarchy to enhance acousto-optic interaction in acoustically dissipative media. In a conventional phoxonic cavity, interaction between infrared light and hypersound with the same wavelength scale became weak due to large acoustic attenuation whose coefficient is proportional to the square of the frequency. To alleviate the acoustic attenuation, it is necessary to use low-frequency sound with much longer wavelength than the infrared light, but the conventional phoxonic cavity is not suitable for confining such hypersound and infrared light simultaneously. In this study, we employ the concept of structural hierarchy into the phoxonic cavity to control infrared light and hypersound with different wavelength scales. A phoxonic cavity with two different scales achieves the acousto-optic interaction approximately 1.6 times that in the conventional one. To further enhance the interaction, we adjust geometrical constitution and material properties of the two-scale phoxonic cavity using quasi-static homogenization theory, leading to the interaction about 2.1 times that in the conventional cavity.

Surface-Originated Weak Confinement in Tetrahedral Indium Arsenide Quantum Dots.

While the shape-dependent quantum confinement (QC) effect in anisotropic semiconductor nanocrystals has been extensively studied, the QC in facet-specified polyhedral quantum dots (QDs) remains underexplored. Recently, tetrahedral nanocrystals have gained prominence in III-V nanocrystal synthesis. In our study, we successfully synthesized well-faceted tetrahedral InAs QDs with a first excitonic absorption extending up to 1700 nm. We observed an unconventional sizing curve, indicating weaker confinement than for equivalently volumed spherical QDs. The (111) surface states of InAs QDs persist at the conduction band minimum state even after ligand passivation with a significantly reduced band gap, which places tetrahedral QDs at lower energies in the sizing curve. Consequently, films composed of tetrahedral QDs demonstrate an extended photoresponse into the short-wave infrared region, compared to isovolume spherical QD films.

Targeting cell surface glucose-regulated protein 94 in gastric cancer with an anti-GRP94 human monoclonal antibody.

Gastric cancer (GC), a leading cause of cancer-related mortality, remains a significant challenge despite recent therapeutic advancements. In this study, we explore the potential of targeting cell surface glucose-regulated protein 94 (GRP94) with antibodies as a novel therapeutic approach for GC. Our comprehensive analysis of GRP94 expression across various cancer types, with a specific focus on GC, revealed a substantial overexpression of GRP94, highlighting its potential as a promising target. Through in vitro and in vivo efficacy assessments, as well as toxicological analyses, we found that K101.1, a fully human monoclonal antibody designed to specifically target cell surface GRP94, effectively inhibits GC growth and angiogenesis without causing in vivo toxicity. Furthermore, our findings indicate that K101.1 promotes the internalization and concurrent downregulation of cell surface GRP94 on GC cells. In conclusion, our study suggests that cell surface GRP94 may be a potential therapeutic target in GC, and that antibody-based targeting of cell surface GRP94 may be an effective strategy for inhibiting GRP94-mediated GC growth and angiogenesis. [BMB Reports 2024; 57(4): 188-193].

Decoding the Parkinson's Symphony: PARIS, Maestro of Transcriptional Regulation and Metal Coordination for Dopamine Release.

Parkin interacting substrate (PARIS) is a pivotal transcriptional regulator in the brain that orchestrates the activity of various enzymes through its intricate interactions with biomolecules, including nucleic acids. Notably, the binding of PARIS to insulin response sequences (IRSs) triggers a cascade of events that results in the functional loss in the substantia nigra, which impairs dopamine release and, subsequently, exacerbates the relentless neurodegeneration. Here, we report the details of the interactions of PARIS with IRSs via classical zinc finger (ZF) domains in PARIS, namely, PARIS(ZF2-4). Our biophysical studies with purified PARIS(ZF2-4) elucidated the binding partner of PARIS, which generates specific interactions with the IRS1 (5'-TATTTTT, Kd = 38.9 ± 2.4 nM) that is positioned in the promoter region of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α). Mutational and metal-substitution studies demonstrated that Zn(II)-PARIS(ZF2-4) could recognize its binding partner selectively. Overall, our work provides submolecular details regarding PARIS and shows that it is a transcriptional factor that regulates dopamine release. Thus, PARIS could be a crucial target for therapeutic applications.

P- and N-type InAs nanocrystals with innately controlled semiconductor polarity.

InAs semiconductor nanocrystals (NCs) exhibit intriguing electrical/optoelectronic properties suitable for next-generation electronic devices. Although there is a need for both n- and p-type semiconductors in such devices, InAs NCs typically exhibit only n-type characteristics. Here, we report InAs NCs with controlled semiconductor polarity. Both p- and n-type InAs NCs can be achieved from the same indium chloride and aminoarsine precursors but by using two different reducing agents, diethylzinc for p-type and diisobutylaluminum hydride for n-type NCs, respectively. This is the first instance of semiconductor polarity control achieved at the synthesis level for InAs NCs and the entire semiconductor nanocrystal systems. Comparable field-effective mobilities for holes (3.3 × 10-3 cm2/V·s) and electrons (3.9 × 10-3 cm2/V·s) are achieved from the respective NC films. The mobility values allow the successful fabrication of complementary logic circuits, including NOT, NOR, and NAND comprising photopatterned p- and n-channels based on InAs NCs.

Designing multi-target-directed flavonoids: a strategic approach to Alzheimer's disease.

The underlying causes of Alzheimer's disease (AD) remain a mystery, with multiple pathological components, including oxidative stress, acetylcholinesterase, amyloid-ß, and metal ions, all playing a role. Here we report a strategic approach to designing flavonoids that can effectively tackle multiple pathological elements involved in AD. Our systematic investigations revealed key structural features for flavonoids to simultaneously target and regulate pathogenic targets. Our findings led to the development of a highly promising flavonoid that exhibits a range of functions, based on a complete structure-activity relationship analysis. Furthermore, our mechanistic studies confirmed that this flavonoid's versatile reactivities are driven by its redox potential and direct interactions with pathogenic factors. This work highlights the potential of multi-target-directed flavonoids as a novel solution in the fight against AD.

Asymptomatic Type 2 Perioperative Myocardial Infarction Detected before Anesthetic Induction in a Patient Undergoing Non-Cardiac Surgery-A Case Report.

Background: Perioperative myocardial infarction (PMI) is a life-threatening complication in major non-cardiac surgeries (NCS) and constitutes the most common cause of postoperative morbidity and mortality. A PMI that is associated with prolonged oxygen supply-demand imbalance and its etiology is defined as a type 2 MI. Asymptomatic myocardial ischemia can occur in patients with stable coronary artery disease (CAD), especially those with comorbidities such as diabetes mellitus (DM), hypertension, or, in some cases, without any risk factors. Case: We report a case of asymptomatic PMI in a 76-year-old patient with underlying hypertension and DM without a previous history of CAD. During the induction of anesthesia, abnormal electrocardiography was discovered, and the surgery was postponed after further studies revealed almost completely occluded three-vessel CAD and type 2 PMI. Conclusions: Anesthesiologists should closely monitor and evaluate the associated cardiovascular risk, including cardiac biomarkers of each patient before surgery, to minimize the possibility of PMI.

Management of unanticipated difficult airway in a patient with well-visualized vocal cords using video laryngoscopy - A case report.

BACKGROUND: Difficult airway occurs due to anatomical abnormalities of the airway that can be predicted through airway assessments; however, abnormalities beyond the vocal cord can be clinically asymptomatic and undetected until intubation failure to advance the endotracheal tube. CASE: We present a case of an unanticipated difficult airway in a stuporous 80-year-old female with a recent history of intracerebral hemorrhage and prolonged intubation. She required emergency ventriculo-peritoneal shunt surgery due to the progression of her hydrocephalus. Under anesthesia, facemask ventilation was easy and video laryngoscopy provided a full view of the glottis; however, endotracheal tube (ETT) entry failed. We suspected stenosis beyond the vocal cord, and a smaller diameter ETT was inserted and maintained for airway management during emergency surgery. Postoperative neck computed tomography findings revealed laryngotracheal stenosis (LTS). CONCLUSIONS: Anesthesiologists should be aware that LTS may be asymptomatic and consider difficult airway guidelines in patients with history of prolonged endotracheal intubation.

Goal-oriented representations in the human hippocampus during planning and navigation.

Recent work in cognitive and systems neuroscience has suggested that the hippocampus might support planning, imagination, and navigation by forming cognitive maps that capture the abstract structure of physical spaces, tasks, and situations. Navigation involves disambiguating similar contexts, and the planning and execution of a sequence of decisions to reach a goal. Here, we examine hippocampal activity patterns in humans during a goal-directed navigation task to investigate how contextual and goal information are incorporated in the construction and execution of navigational plans. During planning, hippocampal pattern similarity is enhanced across routes that share a context and a goal. During navigation, we observe prospective activation in the hippocampus that reflects the retrieval of pattern information related to a key-decision point. These results suggest that, rather than simply representing overlapping associations or state transitions, hippocampal activity patterns are shaped by context and goals.

IGFBP5 is an ROR1 ligand promoting glioblastoma invasion via ROR1/HER2-CREB signaling axis.

Diffuse infiltration is the main reason for therapeutic resistance and recurrence in glioblastoma (GBM). However, potential targeted therapies for GBM stem-like cell (GSC) which is responsible for GBM invasion are limited. Herein, we report Insulin-like Growth Factor-Binding Protein 5 (IGFBP5) is a ligand for Receptor tyrosine kinase like Orphan Receptor 1 (ROR1), as a promising target for GSC invasion. Using a GSC-derived brain tumor model, GSCs were characterized into invasive or non-invasive subtypes, and RNA sequencing analysis revealed that IGFBP5 was differentially expressed between these two subtypes. GSC invasion capacity was inhibited by IGFBP5 knockdown and enhanced by IGFBP5 overexpression both in vitro and in vivo, particularly in a patient-derived xenograft model. IGFBP5 binds to ROR1 and facilitates ROR1/HER2 heterodimer formation, followed by inducing CREB-mediated ETV5 and FBXW9 expression, thereby promoting GSC invasion and tumorigenesis. Importantly, using a tumor-specific targeting and penetrating nanocapsule-mediated delivery of CRISPR/Cas9-based IGFBP5 gene editing significantly suppressed GSC invasion and downstream gene expression, and prolonged the survival of orthotopic tumor-bearing mice. Collectively, our data reveal that IGFBP5-ROR1/HER2-CREB signaling axis as a potential GBM therapeutic target.

Methods for analyzing the coordination and aggregation of metal-amyloid-ß.

The misfolding and aggregation of amyloid-ß (Aß) peptides are histopathological features found in the brains of Alzheimer's disease (AD). To discover effective therapeutics for AD, numerous efforts have been made to control the aggregation of Aß species and their interactions with other pathological factors, including metal ions. Metal ions, such as Cu(II) and Zn(II), can bind to Aß peptides forming metal-bound Aß (metal-Aß) complexes and, subsequently, alter their aggregation pathways. In particular, redox-active metal ions bound to Aß species can produce reactive oxygen species leading to oxidative stress. In this review, we briefly illustrate some experimental approaches for characterizing the coordination and aggregation properties of metal-Aß complexes.

Rational design of photoactivatable metal complexes to target and modulate amyloid-ß peptides.

The accumulation of amyloid-ß (Aß) aggregates is found in the brains of Alzheimer's disease patients. Thus, numerous efforts have been made to develop chemical reagents capable of targeting Aß peptides and controlling their aggregation. In particular, tunable coordination and photophysical properties of transition metal complexes, with variable oxidation and spin states on the metal centers, can be utilized to probe Aß aggregates and alter their aggregation profiles. In this review, we illustrate some rational strategies for designing photoactivatable metal complexes as chemical sensors for Aß peptides or modulators against their aggregation pathways, with some examples.

Universal Ligands for Dispersion of Two-Dimensional MXene in Organic Solvents.

Ligands can control the surface chemistry, physicochemical properties, processing, and applications of nanomaterials. MXenes are the fastest growing family of two-dimensional (2D) nanomaterials, showing promise for energy, electronic, and environmental applications. However, complex oxidation states, surface terminal groups, and interaction with the environment have hindered the development of organic ligands suitable for MXenes. Here, we demonstrate a simple, fast, scalable, and universally applicable ligand chemistry for MXenes using alkylated 3,4-dihydroxy-l-phenylalanine (ADOPA). Due to the strong hydrogen-bonding and π-electron interactions between the catechol head and surface terminal groups of MXenes and the presence of a hydrophobic fluorinated alkyl tail compatible with organic solvents, the ADOPA ligands functionalize MXene surfaces under mild reaction conditions without sacrificing their properties. Stable colloidal solutions and highly concentrated liquid crystals of various MXenes, including Ti2CTx, Nb2CTx, V2CTx, Mo2CTx, Ti3C2Tx, Ti3CNTx, Mo2TiC2Tx, Mo2Ti2C3Tx, and Ti4N3Tx, have been produced in various organic solvents. Such products offer excellent electrical conductivity, improved oxidation stability, and excellent processability, enabling applications in flexible electrodes and electromagnetic interference shielding.

Development of a fuzzy logic-controlled system for home cultivation of sweet basil.

As environmental pollution and the global population increase, and the COVID-19 pandemic becomes more severe, demands for indoor farming, especially home food gardening, have also increased. However, most research thus far has focused on large-scale food production, with very few studies having been conducted at the household scale. Also, the devices cultivating household crops with control systems in a continuous way, which minimize fluctuations of environmental conditions, have been rarely developed. Therefore, this study aimed to design a household cultivation system for sweet basil that is automatically and continuously controlled by fuzzy logic with a Raspberry Pi4. Three inputs (temperature, humidity, and growth stage) and seven outputs (fan, humidifier, heater 1, heater 2, LED red, green, and blue) were used with six rules, ensuring that three lights operated independently upon three growth stages. Simulation and actual operation were carried out, resulting in an appropriately controlled system that operated with few defects. In the case of an operation of the input variable, temperature and humidity were maintained at an average of 21.24 °C and 75.58%, respectively, and the LED operation for the growth stage was confirmed to be flawless. For verification of the designed fuzzy system, a comparison between the simulation and actual operation was performed to examine differences and identify problems. To this end, Pearson's correlation coefficients were used, and the direction of correction of the fuzzy logic system was proposed. Through these results, the feasibility of a home cultivation system using fuzzy logic was demonstrated, and it is expected that further studies applying it will be conducted in the future.

Neural mechanisms of credit assignment for inferred relationships in a structured world.

Animals abstract compact representations of a task's structure, which supports accelerated learning and flexible behavior. Whether and how such abstracted representations may be used to assign credit for inferred, but unobserved, relationships in structured environments are unknown. We develop a hierarchical reversal-learning task and Bayesian learning model to assess the computational and neural mechanisms underlying how humans infer specific choice-outcome associations via structured knowledge. We find that the medial prefrontal cortex (mPFC) efficiently represents hierarchically related choice-outcome associations governed by the same latent cause, using a generalized code to assign credit for both experienced and inferred outcomes. Furthermore, the mPFC and lateral orbitofrontal cortex track the current "position" within a latent association space that generalizes over stimuli. Collectively, these findings demonstrate the importance of both tracking the current position in an abstracted task space and efficient, generalizable representations in the prefrontal cortex for supporting flexible learning and inference in structured environments.

Shape-Tuned Multiphoton-Emitting InP Nanotetrapods.

As the properties of a semiconductor material depend on the fate of the excitons, manipulating exciton behavior is the primary objective of nanomaterials. Although nanocrystals exhibit unusual excitonic characteristics owing to strong spatial confinement, studying the interactions between excitons in a single nanoparticle remains challenging due to the rapidly vanishing multiexciton species. Here, a platform for exciton tailoring using a straightforward strategy of shape-tuning of single-crystalline nanocrystals is presented. Spectroscopic and theoretical studies reveal a systematic transition of exciton confinement orientation from 3D to 2D, which is solely tuned by the geometric shape of material. Such a precise shape-effect triggers a multiphoton emission in single nanotetrapods with arms longer than the exciton Bohr radius of material. In consequence, the unique interplay between the multiple quantum states allows a geometric modulation of the quantum-confined Stark effect and nanocrystal memory effect in single nanotetrapods. These results provide a useful metric in designing nanomaterials for future photonic applications.

Understanding the Effects of Perpetrators' Aggressiveness and Victim-Related Factors on Sexual Revictimization: Stepwise GLM Analysis of the 2010 NISVS.

Studies on sexual revictimization have employed two distinct approaches: perpetrator-oriented and victim-oriented approaches. Although the former posits that sexual revictimization is associated with perpetrators' aggressiveness and victim-offender proximity, the latter focuses on the effects of victims' situational and behavioral factors. In addition to these conflicting approaches, studies have grappled with the fact that a large number of respondents have not experienced victimization, thereby impacting the analytical strategies that should be used. This study uses the data from the National Intimate Partner and Sexual Violence Survey and employs stepwise zero-inflated and non-zero-inflated methods to examine the impact of perpetrator-oriented and victim-oriented approaches on sexual victimizations that occur by force and those that occur due to incapacitation while taking into consideration that the majority of respondents have not experienced the victimizations under study. Findings show that both perpetrator-oriented (particularly aggressiveness) and victim-oriented factors impact sexual revictimization. The implications of the findings and the limitations of this study are discussed.

A Neural Network Model of Continual Learning with Cognitive Control.

Neural networks struggle in continual learning settings from catastrophic forgetting: when trials are blocked, new learning can overwrite the learning from previous blocks. Humans learn effectively in these settings, in some cases even showing an advantage of blocking, suggesting the brain contains mechanisms to overcome this problem. Here, we build on previous work and show that neural networks equipped with a mechanism for cognitive control do not exhibit catastrophic forgetting when trials are blocked. We further show an advantage of blocking over interleaving when there is a bias for active maintenance in the control signal, implying a tradeoff between maintenance and the strength of control. Analyses of map-like representations learned by the networks provided additional insights into these mechanisms. Our work highlights the potential of cognitive control to aid continual learning in neural networks, and offers an explanation for the advantage of blocking that has been observed in humans.

A Wearable System for Heart Rate Recovery Evaluation with Real-Time Classification on Exercise Condition.

Heart rate recovery (HRR) is a convenient index to assess a cardiovascular autonomic function response to physical exercise. HRR monitoring during daily exercise can be an effective way to verify cardiorespiratory performance. Because HRR varies depending on exercise intensity and resting condition, an exercise condition needs to be acquired for a reliable HRR analysis. This study presents a wearable system for HRR evaluation with automatic labeling of exercise conditions using real-time activity classification. We developed an activity classification algorithm using two features from accelerometer sensor: an acceleration peak and an angle tilt peak. The classification algorithm was applied to a chest-attached wearable device with an embedded electrocardiogram sensor and accelerometer sensors. We classified daily activities such as running, walking, and postural transitions performed under supervised conditions. The wearable device system accurately detected activities with a sensitivity of 99.2 % and posture transitions with a sensitivity of 92 % and specificity of 93.3 % for seven healthy subjects. The proposed wearable system can help monitor HRR during exercise training by labeling the exercise condition simultaneously.