Clinical application of sparse canonical correlation analysis to detect genetic associations with cortical thickness in Alzheimer's disease.

Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cerebral cortex atrophy. In this study, we used sparse canonical correlation analysis (SCCA) to identify associations between single nucleotide polymorphisms (SNPs) and cortical thickness in the Korean population. We also investigated the role of the SNPs in neurological outcomes, including neurodegeneration and cognitive dysfunction. Methods: We recruited 1125 Korean participants who underwent neuropsychological testing, brain magnetic resonance imaging, positron emission tomography, and microarray genotyping. We performed group-wise SCCA in Aß negative (-) and Aß positive (+) groups. In addition, we performed mediation, expression quantitative trait loci, and pathway analyses to determine the functional role of the SNPs. Results: We identified SNPs related to cortical thickness using SCCA in Aß negative and positive groups and identified SNPs that improve the prediction performance of cognitive impairments. Among them, rs9270580 was associated with cortical thickness by mediating Aß uptake, and three SNPs (rs2271920, rs6859, rs9270580) were associated with the regulation of CHRNA2, NECTIN2, and HLA genes. Conclusion: Our findings suggest that SNPs potentially contribute to cortical thickness in AD, which in turn leads to worse clinical outcomes. Our findings contribute to the understanding of the genetic architecture underlying cortical atrophy and its relationship with AD.

Diagnostic Decision Point for IgE-Mediated Wheat Allergy in Children.

The diagnostic decision point can help diagnose food allergies while reducing the need for oral food challenge (OFC) tests. We performed a multicenter survey of children aged 0-7 years from January 1, 2018 to March 31, 2022. A total of 231 children were recruited from 18 institutions. Wheat allergy (WA) or non-wheat allergy (NWA) was determined on the basis of OFC results and symptoms. There were no differences in age, sex, family history of allergy or allergic comorbidities between the WA and NWA groups. According to receiver operating characteristic analysis for wheat-specific immunoglobulin E (IgE), the optimal cutoff value, positive decision point, and negative decision point were 10.2, 33.5, and 0.41 kU/L, respectively. For the ω-5 gliadin-specific IgE, their values were 0.69, 3.88, and 0.01 kU/L, respectively. This new diagnostic decision point may be used to diagnose WA in Korean children.

Hf0.4Zr0.6O2 Thickness-Dependent Transfer Characteristics of InxZn1-xOy Channel Ferroelectric FETs.

We investigate how the threshold voltage (VT) is adjusted to create a memory window (MW) in ferroelectric field-effect transistors (FeFETs) composed of ferroelectric Hf0.4Zr0.6O2 and InZnO (In2O3:ZnO = 9:1 wt %). Temperature-dependent polarization measurements reveal a dipole switching in Hf0.4Zr0.6O2. The properties of the n-type InZnO channel are examined by fabricating an oxide transistor with an HfO2 gate dielectric. Upon replacement of HfO2 with Hf0.4Zr0.6O2 in the oxide transistor, a counterclockwise MW is observed. Specifically, as the Hf0.4Zr0.6O2 thickness increases from 16 to 24 nm, the VT of the FeFET after a + gate voltage (VG) sweep remains nearly constant, while the VT after a -VG sweep shifts significantly from -0.9 to 0.5 V. The enlarged MW of approximately 2 V, which is proportional to the Hf0.4Zr0.6O2 thickness in the FeFET, can be explained by considering the balance between VG controllability across the gate stack and the ferroelectric switching of Hf0.4Zr0.6O2.

Efficient multiplex non-viral engineering and expansion of polyclonal γδ CAR-T cells for immunotherapy.

Gamma delta (γδ) T cells are defined by their unique ability to recognize a limited repertoire of non-peptide, non-MHC-associated antigens on transformed and pathogen-infected cells. In addition to their lack of alloreactivity, γδ T cells exhibit properties distinct from other lymphocyte subsets, prompting significant interest in their development as an off-the-shelf cellular immunotherapeutic. However, their low abundance in circulation, heterogeneity, limited methods for ex vivo expansion, and under-developed methodologies for genetic modification have hindered basic study and clinical application of γδ T cells. Here, we implement a feeder-free, scalable approach for ex vivo manufacture of polyclonal, non-virally modified, gene edited chimeric antigen receptor (CAR)-γδ T cells in support of therapeutic application. Engineered CAR-γδ T cells demonstrate high function in vitro and and in vivo. Longitudinal in vivo pharmacokinetic profiling of adoptively transferred polyclonal CAR-γδ T cells uncover subset-specific responses to IL-15 cytokine armoring and multiplex base editing. Our results present a robust platform for genetic modification of polyclonal CAR-γδ T cells and present unique opportunities to further define synergy and the contribution of discrete, engineered CAR-γδ T cell subsets to therapeutic efficacy in vivo.

Real-Time Tracking of Vesicles in Living Cells Reveals That Tau-Hyperphosphorylation Suppresses Unidirectional Transport by Motor Proteins.

Synaptic vesicle transport by motor proteins along microtubules is a crucially active process underlying neuronal communication. It is known that microtubules are destabilized by tau-hyperphosphorylation, which causes tau proteins to detach from microtubules and form neurofibril tangles. However, how tau-phosphorylation affects the transport dynamics of motor proteins on the microtubule remains unknown. Here, we discover that the long-distance unidirectional motion of vesicle-motor protein multiplexes (VMPMs) in living cells is suppressed under tau-hyperphosphorylation, with the consequent loss of fast vesicle-transport along the microtubule. The VMPMs in hyperphosphorylated cells exhibit seemingly bidirectional random motion, with dynamic properties far different from those of VMPM motion in normal cells. We establish a parsimonious physicochemical model of VMPM's active motion that provides a unified, quantitative explanation and predictions for our experimental results. Our analysis reveals that, under hyperphosphorylation conditions, motor protein multiplexes have both static and dynamic motility fluctuations. The loss of fast vesicle-transport along the microtubule can be a mechanism of neurodegenerative disorders associated with tau-hyperphosphorylation.

Impact of liner treatment on the translucency of CAD/CAM multi-colored lithium disilicate and multi-layered zirconia implant-supported crowns, and evaluation of fracture strength of ceramic crowns.

This study aimed to evaluate the optical properties of liner-treated CAD/CAM Multi-colored lithium disilicate (Amber Mill Direct; AMD) and multi-layered zirconia (Omega multi; OM) implant-supported crowns, as well as their effect on the fracture strength of Ti or Zr abutments to which they were applied. After sintering AMD and OM ceramic blocks, they were classified into three groups: untreated, liner-treated, and liner-treated with added color. Optical properties were evaluated by analyzing color differences using background materials to assess translucency and the masking ability of liner-treated ceramics. Subsequently, the fracture strength of implant-supported crowns applied to Ti or Zr abutments was measured, and statistical analysis was conducted using Weibull statistics. Untreated AMD exhibited the highest translucency. Liner treatment reduced translucency in both ceramics, while color-added liner treatment increased translucency. Liner-treated AMD showed greater color difference compared to OM, whereas color-added liner treatment reduced the color difference. Fracture strength was highest in Ti abutment-OM crowns (548.03 N) and lowest in Zr abutment-AMD crowns (283.58 N). Additionally, the Weibull coefficient was over twice as high in Ti abutment-AMD crowns (m = 17.500). Color liners can adjust the high translucency of lithium disilicate ceramics to block discoloration, providing natural tooth-like color and enabling the creation of esthetic restorations. Furthermore, lithium disilicate ceramic crowns applied to Ti abutments exhibited high Weibull coefficients and fracture strengths.

Mesoporous structured MoS2 as an electron transport layer for efficient and stable perovskite solar cells.

Mesoporous structured electron transport layers (ETLs) in perovskite solar cells (PSCs) have an increased surface contact with the perovskite layer, enabling effective charge separation and extraction, and high-efficiency devices. However, the most widely used ETL material in PSCs, TiO2, requires a sintering temperature of more than 500 °C and undergoes photocatalytic reaction under incident illumination that limits operational stability. Recent efforts have focused on finding alternative ETL materials, such as SnO2. Here we propose mesoporous MoS2 as an efficient and stable ETL material. The MoS2 interlayer increases the surface contact area with the adjacent perovskite layer, improving charge transfer dynamics between the two layers. In addition, the matching between the MoS2 and the perovskite lattices facilitates preferential growth of perovskite crystals with low residual strain, compared with TiO2. Using mesoporous structured MoS2 as ETL, we obtain PSCs with 25.7% (0.08 cm2, certified 25.4%) and 22.4% (1.00 cm2) efficiencies. Under continuous illumination, our cell remains stable for more than 2,000 h, demonstrating improved photostability with respect to TiO2.

Rhizobacterial syntrophy between a helper and a beneficiary promotes tomato plant health.

None declared.Conflicts of interestMicrobial interactions impact the functioning of microbial communities. However, microbial interactions within host-associated communities remains poorly understood. Here, we report that the beneficiary rhizobacterium Niallia sp. RD1 requires the helper Pseudomonas putida H3 for bacterial growth and beneficial interactions with the plant host. In the absence of the helper H3 strain, the Niallia sp. RD1 strain exhibited weak respiration and elongated cell morphology without forming bacterial colonies. A transposon mutant of H3 in a gene encoding succinate-semialdehyde dehydrogenase displayed much attenuated support of RD1 colony formation. Through subsequent addition of succinate to the media, we found that succinate serves as a public good that supports RD1 growth. Comparative genome analysis highlighted that RD1 lacked the gene for sufficient succinate, suggesting its evolution as a beneficiary of succinate biosynthesis. The syntrophic interaction between RD1 and H3 efficiently protected tomato plants from bacterial wilt and promoted the tomato growth. The addition of succinate to the medium restored complex II-dependent respiration in RD1 and facilitated the cultivation of various bacterial isolates from the rhizosphere. Taken together, we delineate energy auxotrophic beneficiaries ubiquitous in the microbial community, and these beneficiaries could benefit host plants with the aid of helpers in the rhizosphere.

Exploring novel MYH7 gene variants using in silico analyses in Korean patients with cardiomyopathy.

BACKGROUND: Pathogenic variants of MYH7, which encodes the beta-myosin heavy chain protein, are major causes of dilated and hypertrophic cardiomyopathy. METHODS: In this study, we used whole-genome sequencing data to identify MYH7 variants in 397 patients with various cardiomyopathy subtypes who were participating in the National Project of Bio Big Data pilot study in Korea. We also performed in silico analyses to predict the pathogenicity of the novel variants, comparing them to known pathogenic missense variants. RESULTS: We identified 27 MYH7 variants in 41 unrelated patients with cardiomyopathy, consisting of 20 previously known pathogenic/likely pathogenic variants, 2 variants of uncertain significance, and 5 novel variants. Notably, the pathogenic variants predominantly clustered within the myosin motor domain of MYH7. We confirmed that the novel identified variants could be pathogenic, as indicated by high prediction scores in the in silico analyses, including SIFT, Mutation Assessor, PROVEAN, PolyPhen-2, CADD, REVEL, MetaLR, MetaRNN, and MetaSVM. Furthermore, we assessed their damaging effects on protein dynamics and stability using DynaMut2 and Missense3D tools. CONCLUSIONS: Overall, our study identified the distribution of MYH7 variants among patients with cardiomyopathy in Korea, offering new insights for improved diagnosis by enriching the data on the pathogenicity of novel variants using in silico tools and evaluating the function and structural stability of the MYH7 protein.

Highly Durable Chemoresistive Micropatterned PdAu Hydrogen Sensors: Performance and Mechanism.

Hydrogen (H2) is a promising alternative energy source for Net-zero, but the risk of explosion requires accurate and rapid detection systems. As the use of H2 energy expands, sensors require high performance in a variety of properties. Palladium (Pd) is an attractive material for H2 detection due to its high H2 affinity and catalytic properties. However, poor stability caused by volume changes and reliability due to environmental sensitivity remain obstacles. This study proposes a micropatterned thin film of PdAu with optimized composition (Pd0.62Au0.38) as a chemoresistive sensor to overcome these issues. At room temperature, the sensor has a wide detection range of 0.0002% to 5% and a fast response time of 9.5 s. Significantly, the sensor exhibits excellent durability for repeated operation (>35 h) in 5% H2 and resistance to humidity and carbon monoxide. We also report a negative resistivity change in PdAu, which is opposite to that of Pd. Density functional theory (DFT) calculations were performed to investigate the resistance change. DFT analysis revealed that H2 penetrates specific interstitial sites, causing partial lattice compression. The lattice compression causes a decrease in electrical resistance. This work is expected to contribute to the development of high-performance H2 sensors using Pd-based alloys.

Strategies to Overcome Hurdles in Cancer Immunotherapy.

Despite marked advancements in cancer immunotherapy over the past few decades, there remains an urgent need to develop more effective treatments in humans. This review explores strategies to overcome hurdles in cancer immunotherapy, leveraging innovative technologies including multi-specific antibodies, chimeric antigen receptor (CAR) T cells, myeloid cells, cancer-associated fibroblasts, artificial intelligence (AI)-predicted neoantigens, autologous vaccines, and mRNA vaccines. These approaches aim to address the diverse facets and interactions of tumors' immune evasion mechanisms. Specifically, multi-specific antibodies and CAR T cells enhance interactions with tumor cells, bolstering immune responses to facilitate tumor infiltration and destruction. Modulation of myeloid cells and cancer-associated fibroblasts targets the tumor's immunosuppressive microenvironment, enhancing immunotherapy efficacy. AI-predicted neoantigens swiftly and accurately identify antigen targets, which can facilitate the development of personalized anticancer vaccines. Additionally, autologous and mRNA vaccines activate individuals' immune systems, fostering sustained immune responses against cancer neoantigens as therapeutic vaccines. Collectively, these strategies are expected to enhance efficacy of cancer immunotherapy, opening new horizons in anticancer treatment.

Clinical assessment and striatal dopaminergic activity in healthy controls and patients with Parkinson's disease: a Bayesian approach.

OBJECTIVES: We aimed to evaluate correlations between striatal dopamine transporter (DAT) uptake and clinical assessments in both patients with Parkinson's disease (PD) and healthy controls. METHODS: This study enrolled 193 healthy controls, and 581 patients with PD. They underwent various clinical assessments and 123I-FP-CIT SPECT scans. After reconstruction, attenuation correction, and normalization of SPECT images, counts were measured from the bilateral caudate and putamen, and the occipital cortex for reference. Count densities for each region were extracted and used to calculate striatal binding ratios (SBRs) for each striatal region. SBR is calculated as (target region/reference region)-1. After logarithmic transformation of striatal SBRs, we analyzed the effects of clinical assessments on striatal SBRs using Bayesian hierarchical modeling. RESULTS: MDS-UPDRS total score, part I, part II, part III, Epworth Sleepiness Scale, REM sleep behavior disorder screening questionnaire, SCOPA-AUT total score were negatively associated with striatal SBR in patients with PD. Also, HVLT recognition discrimination was positively associated with striatal SBR in both healthy controls and patients with PD. In healthy control, MDS-UPDRS part II, MOCA, SCOPA-AUT total score were positively associated with striatal SBR. CONCLUSION: We demonstrated that motor symptom, sleep disturbance, autonomic symptom, and cognition of patients with PD were associated with striatal dopaminergic activity. In healthy controls, motor symptoms, autonomic symptom, and cognition were associated with striatal dopaminergic activity, some of which showing the opposite direction with patients with PD. This result might provide new insight to underlying mechanism of dopamine system with motor and non-motor assessments.

Non-invasive strategy: Developing a topical IL-4Rα-specific nanobody for the treatment of allergic airway diseases.

Inhibiting IL-4 and IL-13 are critical cytokines that induce the pathogenic responses of allergic airway diseases. Currently, monoclonal antibodies targeting IL-4Rα are administered subcutaneously to treat eosinophilic rhinosinusitis and allergic asthma. However, these treatments have several drawbacks. To address these issues, we have developed a novel IL-4Rα-targeting nanobody designed for non-invasive delivery to local inflammatory sites in allergic airway diseases. H5, selected via the ribosomal display applied screening from synthetic nanobody library, underwent dimerization and in-silico affinity maturation using AlphaFold2 and GROMACS resulting in a substantial/dramatic enhancement of its binding affinity. H5 effectively controlled inflammatory markers such as MUC5AC, CCL26, and FOXJ1 in human nasal epithelial cells (HNECs) by inhibiting IL-4 and IL-13 signaling. The bivalent form of H5 showed efficacy in easily accessible cells, such as multi-ciliated cells, while the monovalent variant targeted hard-to-reach cells, such as basal cells of HNECs. In summary, we developed a nanobody that could effectively inhibit inflammatory signaling in HNECs via intranasal administration, showing promise as a non-invasive rhinitis treatment.

Protective effect of Phyllostachys edulis (Carrière) J. Houz against chronic ethanol-induced cognitive impairment in vivo.

BACKGROUND/OBJECTIVES: Chronic alcohol consumption causes oxidative stress in the body, which may accumulate excessively and cause a decline in memory; problem-solving, learning, and exercise abilities; and permanent damage to brain structure and function. Consequently, chronic alcohol consumption can cause alcohol-related diseases. MATERIALS/METHODS: In this study, the protective effects of Phyllostachys edulis (Carrière) J. Houz (PE) against alcohol-induced neuroinflammation and cognitive impairment were evaluated using a mouse model. Alcohol (16%, 5 g/kg/day for 6 weeks) and PE (100, 250, and 500 mg/kg/day for 21 days) were administered intragastrically to mice. RESULTS: PE showed a protective effect against memory deficits and cognitive dysfunction caused by alcohol consumption, confirmed through behavioral tests such as the T-maze, object recognition, and Morris water maze tests. Additionally, PE attenuated oxidative stress by reducing lipid oxidation, nitric oxide, and reactive oxygen species levels in the mice's brains, livers, and kidneys. Improvement of neurotrophic factors and downregulation of apoptosis-related proteins were confirmed in the brains of mice fed low and medium concentrations of PE. Additionally, expression of antioxidant enzyme-related proteins GPx-1 and SOD-1 was enhanced in the liver of PE-treated mice, related to their inhibitory effect on oxidative stress. CONCLUSION: This suggests that PE has both neuroregenerative and antioxidant effects. Collectively, these behavioral and histological results confirmed that PE could improve alcohol-induced cognitive deficits through brain neurotrophic and apoptosis protection and modulation of oxidative stress.

Fully autonomous water monitoring by plant-inspired robots.

Developing countries struggle with water quality management owing to poor infrastructure, limited expertise, and financial constraints. Traditional water testing, relying on periodic site visits and manual sampling, is impractical for continuous wide-area monitoring and fails to detect sudden heavy metal contamination. To address this, plant-inspired robots capable of fully autonomous water quality monitoring are proposed. Constructed from paper, the robot absorbs surrounding water through its roots. This paper robot is controlled by paper-based microfluidic logic that sends absorbed water to petal-shaped actuators only when the water is polluted by heavy metals. This triggers the actuators to swell and bend like a blooming flower, visually signaling contamination to local residents. In tests with copper-contaminated water, the robotic flower's diameter increased from 4.69 cm to 14.89 cm, a more than threefold expansion (217.25 %). This significant blooming movement serves as a highly visible and easily recognizable indicator of water pollution, even for the public. Furthermore, the paper robot can be mass-produced at a low cost (∼$0.2 per unit) and deployed over large areas. Once installed, the paper robot operates autonomously using surrounding water as a power source, eliminating the need for external electrical infrastructure and expert intervention. Therefore, this autonomous robot offers a new approach to water quality monitoring suitable for resource-limited environments, such as Sub-Saharan Africa.

Self-Aligned Edge Contact Process for Fabricating High-Performance Transition-Metal Dichalcogenide Field-Effect Transistors.

The persistent challenges encountered in metal-transition-metal dichalcogenide (TMD) junctions, including tunneling barriers and Fermi-level pinning, pose significant impediments to achieving optimal charge transport and reducing contact resistance. To address these challenges, a pioneering self-aligned edge contact (SAEC) process tailored for TMD-based field-effect transistors (FETs) is developed by integrating a WS2 semiconductor with a hexagonal boron nitride dielectric via reactive ion etching. This approach streamlines semiconductor fabrication by enabling edge contact formation without the need for additional lithography steps. Notably, SAEC TMD-based FETs exhibit exceptional device performance, featuring a high on/off current ratio of ∼108, field-effect mobility of up to 120 cm2/V·s, and controllable polarity─essential attributes for advanced TMD-based logic circuits. Furthermore, the SAEC process enables precise electrode positioning and effective minimization of parasitic capacitance, which are pivotal for attaining high-speed characteristics in TMD-based electronics. The compatibility of the SAEC technique with existing Si self-aligned processes underscores its feasibility for integration into post-CMOS applications, heralding an upcoming era of integration of TMDs into Si semiconductor electronics. The introduction of the SAEC process represents a significant advancement in TMD-based microelectronics and is poised to unlock the full potential of TMDs for future electronic technologies.

Poor sleep quality is associated with decreased regional brain glucose metabolism in healthy middle-aged adults.

Sleep disturbance is associated with the development of neurodegenerative disease. We aimed to address the effects of sleep quality on brain glucose metabolism measured by 18F-Fl uorodeoxyglucose (18F-FDG) positron emission tomography (PET) in healthy middle-aged adults. A total of 378 healthy men (mean age: 42.8±3.6 years) were included in this study. Participants underwent brain 18F-FDG PET and completed the Korean version of the Pittsburgh Sleep Quality Index (PSQI-K). Additionally, anthropometric measurements were obtained. PETs were spatially normalized to MNI space using PET templates from SPM5 with PMOD. The Automated Anatomical Labeling 2 atlas was used to define regions of interest (ROIs). The mean uptake of each ROI was scaled to the mean of the global cortical uptake of each individual and defined as the standardized uptake value ratio (SUVR). After the logarithmic transformation of the regional SUVR, the effects of the PSQI-K on the regional SUVR were investigated using Bayesian hierarchical modeling. Brain glucose metabolism of the posterior cingulate, precuneus, and thalamus showed a negative association with total PSQI-K scores in the Bayesian model ROI-based analysis. Voxel-based analysis using statistical parametric mapping revealed a negative association between the total PSQI-K scores and brain glucose metabolism of the precuneus, postcentral gyrus, posterior cingulate, and thalamus. Poor sleep quality is negatively associated with brain glucose metabolism in the precuneus, posterior cingulate, and thalamus. Therefore, the importance of sleep should not be overlooked, even in healthy middle-aged adults.

From Wide-Bandgap to Narrow-Bandgap Perovskite: Applications from Single-Junction to Tandem Optoelectronics.

As perovskite solar device is burgeoning photoelectronic device, numerous studies to optimize perovskite solar device have been demonstrated. Amongst various advantages from perovskite light absorbing layer, attractive property of tunable bandgap allowed perovskite to be adopted in many different fields. Easily tunable bandgap property of perovskite opened the wide application and to get the most out of its potential, many researchers contributed as well. By precursor composition engineering, narrow bandgap with bandgap of less than 1.4 eV and wide bandgap with bandgap of more than 1.7 eV were achieved. Optimization of both narrow and wide bandgap perovskite solar cell could pave the way to all-perovskite tandem solar cell which is combination of top cell with wide bandgap and bottom cell with narrow bandgap. This review highlights numerous efforts to advance device performance of both narrow and wide bandgap perovskite solar cell and how they challenged the issues. And finally, efforts to operate and utilize all-tandem perovskite device in real world will be discussed.