In Alzheimer's disease (AD), memory impairment is the most prominent feature that afflicts patients and their families. Although reactive astrocytes have been observed around amyloid plaques since ...the disease was first described, their role in memory impairment has been poorly understood. Here, we show that reactive astrocytes aberrantly and abundantly produce the inhibitory gliotransmitter GABA by monoamine oxidase-B (Maob) and abnormally release GABA through the bestrophin 1 channel. In the dentate gyrus of mouse models of AD, the released GABA reduces spike probability of granule cells by acting on presynaptic GABA receptors. Suppressing GABA production or release from reactive astrocytes fully restores the impaired spike probability, synaptic plasticity, and learning and memory in the mice. In the postmortem brain of individuals with AD, astrocytic GABA and MAOB are significantly upregulated. We propose that selective inhibition of astrocytic GABA synthesis or release may serve as an effective therapeutic strategy for treating memory impairment in AD.
For the demonstration of remote‐controllable actuators, a dendronized polymer (denpol) is newly designed and successfully synthesized by ring‐opening metathesis polymerization of azobenzene‐based ...macromonomers. The incorporation of azobenzene mesogens into the denpols helps to construct finely tuned hierarchical superstructures with anisotropic physical properties and reversible photoisomerization. The polynorbornene backbones and azobenzene side chains in the uniaxially oriented films are aligned perpendicularly and parallel to the layer normal, respectively. Based on photoreversible actuation experiments combined with diffraction results, direct relationships between the chemical structures, hierarchical superstructures, and their corresponding photomechanical behaviors are proposed. Smart denpols possess great potential for practical applications in photoresponsive switches.
To demonstrate remote‐controllable actuators, a polynorbornene with dendronized azobenzene chromophores is synthesized by ring‐opening metathesis polymerization.
Defects of autophagy and endoplasmic reticulum (ER) stress are related to many diseases and tumors. However, only a few studies have examined hepatocellular carcinoma (HCC) as related to these ...processes. Therefore, in this study, we investigated the expression and extent of autophagy and ER stress-related markers in HCC and their influence on clinical characteristics and prognosis for each protein.
The expression of autophagy-related markers (LC3 and Beclin-1) and ER stress-related markers (GRP78 and CHOP) was analyzed by immunohistochemistry on tissues from completely resected specimens of 190 HCC patients. Their influence on clinicopathologic features and prognosis were evaluated using the chi-square test and Kaplan-Meier analysis. Correlations of each protein were determined by Spearman's correlation analysis.
LC3 expression was not correlated with TNM, BCLC stage, or Edmonson-Steiner grading, whereas it was correlated with longer overall survival (OS) (p = 0.039) and tended to be related with longer time to recurrence (TTR) (p=0.068) although it did not show statistical significance. Multivariate analysis indicated that LC3 expression was a significantly independent prognostic factor of OS (HR, 0.42; 95% CI, 0.22-0.80; p-value=0.009) and TTR (HR, 0.54; 95% CI, 0.33-0.90; p=0.017). Expression of LC3 in advanced stages of TNM (III) (p=0.045) and Edmonson-Steiner Grades (III and IV) (p=0.043) was correlated with longer survival, but not in the early stages. A positive correlation was not observed between the expression of autophagy-related markers and ER stress-related markers.
Our results suggest that the expression and extent of LC3 might be a strong prognostic factor of HCC, especially in patients with surgical resection.
To elucidate the effects of neoadjuvant chemotherapy (NAC), we conduct whole transcriptome profiling coupled with histopathology analyses of a longitudinal breast cancer cohort of 146 patients ...including 110 pairs of serial tumor biopsies collected before treatment, after the first cycle of treatment and at the time of surgery. Here, we show that cytotoxic chemotherapies induce dynamic changes in the tumor immune microenvironment that vary by subtype and pathologic response. Just one cycle of treatment induces an immune stimulatory microenvironment harboring more tumor infiltrating lymphocytes (TILs) and up-regulation of inflammatory signatures predictive of response to anti-PD1 therapies while residual tumors are immune suppressed at end-of-treatment compared to the baseline. Increases in TILs and CD8+ T cell proportions in response to NAC are independently associated with pathologic complete response. Further, on-treatment immune response is more predictive of treatment outcome than immune features in paired baseline samples although these are strongly correlated.
•Cognitive behavioral therapy for insomnia (CBT-I) was effective in schizophrenia.•The effect of CBT-I in schizophrenia patients lasted up to 8 weeks.•Depressive and anxiety symptoms were not reduced ...by CBT-I in schizophrenia.
This non–randomized, assessor blind study evaluated the effects of cognitive behavioral therapy for insomnia (CBT-I) delivered in a group format on insomnia symptoms as well as psychotic, depressive, and anxiety symptoms in schizophrenia patients (n = 63) recruited from residential or rehabilitative facilities in Seoul, South Korea. Thirty-one patients received four sessions of CBT-I in groups of 2–9 patients in addition to usual care, while the control group (n = 32) received no additional intervention. The Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI), Psychotic Symptoms Rating Scale (PSYRATS), Anxiety Sensitivity Index (ASI), and Beck Depression Inventory (BDI) were administered at baseline, week 4, and week 8. Both groups showed significant time-group interactions on the ISI and PSQI. Post hoc testing showed that, compared to the control group, the CBT-I group showed significant reductions in ISI and PSQI at both week 4 and week 8. For the PSYRATS, ASI, and BDI scores, the CBT-I and control groups showed significant time-group interactions, but post hoc testing revealed no significant group differences at either week 4 or week 8. Therefore, CBT-I was effective for reducing insomnia symptoms in patients with schizophrenia and the effect lasted for 4 weeks after the intervention.
The recent progress in ferroelectricity and antiferroelectricity in HfO2‐based thin films is reported. Most ferroelectric thin film research focuses on perovskite structure materials, such as ...Pb(Zr,Ti)O3, BaTiO3, and SrBi2Ta2O9, which are considered to be feasible candidate materials for non‐volatile semiconductor memory devices. However, these conventional ferroelectrics suffer from various problems including poor Si‐compatibility, environmental issues related to Pb, large physical thickness, low resistance to hydrogen, and small bandgap. In 2011, ferroelectricity in Si‐doped HfO2 thin films was first reported. Various dopants, such as Si, Zr, Al, Y, Gd, Sr, and La can induce ferroelectricity or antiferroelectricity in thin HfO2 films. They have large remanent polarization of up to 45 μC cm−2, and their coercive field (≈1–2 MV cm−1) is larger than conventional ferroelectric films by approximately one order of magnitude. Furthermore, they can be extremely thin (<10 nm) and have a large bandgap (>5 eV). These differences are believed to overcome the barriers of conventional ferroelectrics in memory applications, including ferroelectric field‐effect‐transistors and three‐dimensional capacitors. Moreover, the coupling of electric and thermal properties of the antiferroelectric thin films is expected to be useful for various applications, including energy harvesting/storage, solid‐state‐cooling, and infrared sensors.
Recent progress in ferroelectricity and antiferroelectricity in HfO2‐based thin films is comprehensively reviewed. The properties of ferroelectric HfO2‐based films, different from those of conventional ferroelectrics, are believed to solve the problems of conventional ferroelectrics in non‐volatile memory. Moreover, the pyroelectricity of antiferroelectric films is expected to be useful for various applications, including energy harvesting and storage, solid‐state cooling, and infrared sensors.
Lactobacillus plantarum DK119 (DK119) isolated from the fermented Korean cabbage food was used as a probiotic to determine its antiviral effects on influenza virus. DK119 intranasal or oral ...administration conferred 100% protection against subsequent lethal infection with influenza A viruses, prevented significant weight loss, and lowered lung viral loads in a mouse model. The antiviral protective efficacy was observed in a dose and route dependent manner of DK119 administration. Mice that were treated with DK119 showed high levels of cytokines IL-12 and IFN-γ in bronchoalveolar lavage fluids, and a low degree of inflammation upon infection with influenza virus. Depletion of alveolar macrophage cells in lungs and bronchoalveolar lavages completely abrogated the DK119-mediated protection. Modulating host innate immunity of dendritic and macrophage cells, and cytokine production pattern appeared to be possible mechanisms by which DK119 exhibited antiviral effects on influenza virus infection. These results indicate that DK119 can be developed as a beneficial antiviral probiotic microorganism.
The promising energy storage properties of new lead‐free antiferroelectric HfxZr1‐xO2 (x = 0.1–0.4) films with high energy storage density are reported. The energy storage density of the Hf0.3Zr0.7O2 ...capacitor does not decrease with the increase in temperature up to 175 °C, and it decreases by only ≈4.5% after field cycling 109 times.
Despite their advantageous attributes, such as a narrow bandgap and reduced toxicity, tin–lead halide perovskites (TLHPs) have received limited attention due to their lower power conversion ...efficiency (PCE) relative to lead‐only variants. In this study, a transformative approach is introduced that leverages perovskite quantum dots (PQDs) to optimize TLHP solar cells. While conventional oleyl‐capped PQDs enhance the open circuit voltage (VOC), the long‐chain ligands hinder charge transport. To overcome this limitation, a post‐treatment with isopropyl alcohol effectively dissociates these ligands and PQD crystals, resulting in reduced defect density, improved charge transfer, and elevated quasi‐Fermi level splitting in the TLHP device. Consequently, the PCE of the device is notably increased from 19.0% to 23.74% and elevated the VOC from 0.78 to 0.87 V, without compromising the photocurrent or fill factor. The findings highlight PQD modification as a compelling avenue for TLHP solar cell enhancement, particularly in boosting VOC.
A modification strategy for tin–lead halide perovskite (TLHP) assisted by quantum dots is introduced to enhance TLHP solar cell performance. This strategy optimizes energy levels and reduces trap densities at tin and lead defective sites, resulting in a 23.74% efficiency with minimal open‐circuit voltage loss. This innovation provides crucial insights for advancing TLHP solar cells and holds broader implications for optoelectronic device design.
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