Prussian blue analogues (PBAs, A2TM(CN)6, A = Li, K, Na; T = Fe, Co, Ni, Mn, Cu, etc.; M = Fe, Mn, Co, etc.) are a large family of materials with an open framework structure. In recent years, they ...have been intensively investigated as active materials in the field of energy conversion and storage, such as for alkaline‐ion batteries (lithium‐ion, LIBs; sodium‐ion, NIB; and potassium‐ion, KIBs), and as electrochemical catalysts. Nevertheless, few review papers have focused on the intrinsic chemical and structural properties of Prussian blue (PB) and its analogues. In this Review, a comprehensive insight into the PBAs in terms of their structural and chemical properties, and the effects of these properties on their materials synthesis and corresponding performance is provided.
This Review provides a comprehensive overview of the latest research progress on Prussian blue analogues (PBAs), including the synthesis methods, structural and chemical properties of PBAs, various applications for these PBAs, and the effects of their structural and chemical properties on material synthesis and applications. Finally, some personal viewpoints on the challenges and outlook for PBAs application are included.
To explore whether a cross-talk exists between PARP inhibition and PD-L1/PD-1 immune checkpoint axis, and determine whether blockade of PD-L1/PD-1 potentiates PARP inhibitor (PARPi) in tumor ...suppression.
Breast cancer cell lines, xenograft tumors, and syngeneic tumors treated with PARPi were assessed for PD-L1 expression by immunoblotting, IHC, and FACS analyses. The phospho-kinase antibody array screen was used to explore the underlying mechanism of PARPi-induced PD-L1 upregulation. The therapeutic efficacy of PARPi alone, PD-L1 blockade alone, or their combination was tested in a syngeneic tumor model. The tumor-infiltrating lymphocytes and tumor cells isolated from syngeneic tumors were analyzed by CyTOF and FACS to evaluate the activity of antitumor immunity in the tumor microenvironment.
PARPi upregulated PD-L1 expression in breast cancer cell lines and animal models. Mechanistically, PARPi inactivated GSK3β, which in turn enhanced PARPi-mediated PD-L1 upregulation. PARPi attenuated anticancer immunity via upregulation of PD-L1, and blockade of PD-L1 resensitized PARPi-treated cancer cells to T-cell killing. The combination of PARPi and anti-PD-L1 therapy compared with each agent alone significantly increased the therapeutic efficacy
Our study demonstrates a cross-talk between PARPi and tumor-associated immunosuppression and provides evidence to support the combination of PARPi and PD-L1 or PD-1 immune checkpoint blockade as a potential therapeutic approach to treat breast cancer.
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The epithelial‐mesenchymal transition (EMT) is critical for induction of invasiveness and metastasis of human cancers. In this study we investigated the expression profiles of the EMT markers, the ...relationship between EMT markers and patient/tumor/viral factors, and the interplay between major EMT regulators in human hepatocellular carcinoma (HCC). Reduced E‐cadherin and nonmembranous β‐catenin expression, the hallmarks of EMT, were shown in 60.2% and 51.5% of primary HCC samples, respectively. Overexpression of Snail, Twist, or Slug, the major regulators of EMT, was identified in 56.9%, 43.1%, and 51.4% of primary HCCs, respectively. Statistical analysis determined that Snail and Twist, but not Slug, are major EMT inducers in HCC: overexpression of Snail and/or Twist correlated with down‐regulation of E‐cadherin, nonmembranous expression of β‐catenin, and a worse prognosis. In contrast, there were no such significant differences in samples that overexpressed Slug. Coexpression of Snail and Twist correlated with the worst prognosis of HCC. Hepatitis C‐associated HCC was significantly correlated with Twist overexpression. HCC cell lines with increased Snail and Twist expression (e.g., Mahlavu) exhibited a greater capacity for invasiveness/metastasis than cells with low endogenous Twist/Snail expression (e.g., Huh‐7). Overexpression of Snail or/and Twist in Huh‐7 induced EMT and invasiveness/metastasis, whereas knockdown of Twist or Snail in Mahlavu reversed EMT and inhibited invasiveness/metastasis. Twist and Snail were independently regulated, but exerted an additive inhibitory effect to suppress E‐cadherin transcription. Conclusion: Our study provides a comprehensive profile of EMT markers in HCC, and the independent and collaborative effects of Snail and Twist on HCC metastasis were confirmed through different assays. (HEPATOLOGY 2009.)
With the development of science and technology, people are trying to use robots to assist in stroke rehabilitation training. This study aims to analyze the result of the formative test to provide the ...orientation of upper limb rehabilitation robot design optimization. We invited 21 physical therapists (PTs) and eight occupational therapists (OTs) who had no experience operating any upper limb rehabilitation robots before, and 4 PTs and 1 OT who had experience operating upper limb rehabilitation robots. Data statistics use the Likert scale. The general group scored 3.5 for safety-related topics, while the experience group scored 4.5. In applicability-related questions, the main function score was 2.3 in the general group and 2.4 in the experience group; and the training trajectory score was 3.5 in the general group and 5.0 in the experience group. The overall ease of use score was 3.1 in the general group and 3.6 in the experience group. There was no statistical difference between the two groups. The methods to retouch the trajectory can be designed through the feedback collected in the formative test and gathering further detail in the next test. Further details about the smooth trajectory must be confirmed in the next test. The optimization of the recording process is also important to prevent users from making additional effort to know it well.
Patients with knee osteoarthritis have a unique plantar-pressure pattern during walking, and lateral-wedge insoles are one of the treatment options. Participants were randomly assigned to either the ...lateral-wedge insole group or the ordinary insole group. The Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and plantar-pressure test scores were evaluated at the baseline and at 20 weeks. Plantar pressure data were collected using a pressure insole with 89 sensing locations. In the ordinary insole group, the function and total WOMAC scores decreased significantly (function score, 24.8 (baseline) to 16.5 (week 20); total score, 34.9 (baseline) to 24.6 (week 20)). During walking, the transverse width of the center of pressure as a percentage of foot width (%Trans) significantly increased in the ordinary insole group (baseline, 6.3%; week 20, 14.8%). In addition, the values of partial foot pressure as a percentage of body weight (%PFP) on the forefoot (baseline, 30.3%; week 20, 39.2%) and heel (baseline, 28.1%; week 20, 16.9%) also increased significantly in the ordinary insole group. Significant group-by-time interaction effects were observed for partial foot pressure per body weight in the forefoot (
= 0.031) and heel (
= 0.024). In the ordinary insole group, the plantar pressure on the heel significantly decreased (
= 0.011) and that on the forefoot significantly increased (
= 0.023). In contrast, plantar pressure remained stable in all regions in the lateral-wedge insole group. Thus, lateral-wedge insoles may protect against plantar pressure deterioration in patients with knee osteoarthritis.
Sodium‐ion batteries (SIBs) are considered as a low‐cost complementary or alternative system to prestigious lithium‐ion batteries (LIBs) because of their similar working principle to LIBs, ...cost‐effectiveness, and sustainable availability of sodium resources, especially in large‐scale energy storage systems (EESs). Among various cathode candidates for SIBs, Na‐based layered transition metal oxides have received extensive attention for their relatively large specific capacity, high operating potential, facile synthesis, and environmental benignity. However, there are a series of fatal issues in terms of poor air stability, unstable cathode/electrolyte interphase, and irreversible phase transition that lead to unsatisfactory battery performance from the perspective of preparation to application, outside to inside of layered oxide cathodes, which severely limit their practical application. This work is meant to review these critical problems associated with layered oxide cathodes to understand their fundamental roots and degradation mechanisms, and to provide a comprehensive summary of mainstream modification strategies including chemical substitution, surface modification, structure modulation, and so forth, concentrating on how to improve air stability, reduce interfacial side reaction, and suppress phase transition for realizing high structural reversibility, fast Na+ kinetics, and superior comprehensive electrochemical performance. The advantages and disadvantages of different strategies are discussed, and insights into future challenges and opportunities for layered oxide cathodes are also presented.
Recent progress in layered oxide cathodes for sodium‐ion batteries (SIBs) from air stability, interface chemistry, and phase transition are comprehensively summarized. The intrinsic degradation mechanisms behind electrochemical performance and mainstream modification strategies are systematically sorted out and analyzed. The remaining challenges, promising optimization strategies as well as endeavor directions to break current limitations are also presented for the future design of high‐performance layered oxide cathodes for SIBs.
Protein glycosylation provides proteomic diversity in regulating protein localization, stability, and activity; it remains largely unknown whether the sugar moiety contributes to immunosuppression. ...In the study of immune receptor glycosylation, we showed that EGF induces programmed death ligand 1 (PD-L1) and receptor programmed cell death protein 1 (PD-1) interaction, requiring β-1,3-N-acetylglucosaminyl transferase (B3GNT3) expression in triple-negative breast cancer. Downregulation of B3GNT3 enhances cytotoxic T cell-mediated anti-tumor immunity. A monoclonal antibody targeting glycosylated PD-L1 (gPD-L1) blocks PD-L1/PD-1 interaction and promotes PD-L1 internalization and degradation. In addition to immune reactivation, drug-conjugated gPD-L1 antibody induces a potent cell-killing effect as well as a bystander-killing effect on adjacent cancer cells lacking PD-L1 expression without any detectable toxicity. Our work suggests targeting protein glycosylation as a potential strategy to enhance immune checkpoint therapy.
•N-linked glycosylation is required for physical contact between PD-L1 and PD-1•EGF/EGFR stimulates PD-L1 glycosylation via B3GNT3 glycosyltransferase•Glycosylated-PD-L1 antibody induces PD-L1 internalization•Glycosylated-PD-L1-ADC possesses potent toxicity as well as bystander effects
Li et al. show that glycosylation of PD-L1 is essential for PD-L1/PD-1 interaction and immunosuppression in triple-negative breast cancer (TNBC). They generate a glycosylation-specific antibody that induces PD-L1 internalization and an antibody-drug conjugate with potent anti-tumor activities in TNBC models.
Although numerous epidemiological studies revealed an association between ambient fine particulate matter (PM
2.5
) exposure and Alzheimer’s disease (AD), the PM
2.5
-induced neuron toxicity and ...associated mechanisms were not fully elucidated. The present study assessed brain toxicity in 6-month-old female triple-transgenic AD (3xTg-AD) mice following subchronic exposure to PM
2.5
via an inhalation system. The treated mice were whole-bodily and continuously exposed to real-world PM
2.5
for 3 months, while the control mice inhaled filtered air. Changes in cognitive and motor functions were evaluated using the Morris Water Maze and rotarod tests. Magnetic resonance imaging analysis was used to record gross brain volume alterations, and tissue staining with hematoxylin and eosin, Nissl, and immunohistochemistry methods were used to monitor pathological changes in microstructures after PM
2.5
exposure. The levels of AD-related hallmarks and the oxidative stress biomarker malondialdehyde (MDA) were assessed using Western blot analysis and liquid chromatography-mass spectrometry, respectively. Our results showed that subchronic exposure to environmental levels of PM
2.5
induced obvious neuronal loss in the cortex of exposed mice, but without significant impairment of cognitive and motor function. Increased levels of phosphorylated-tau and MDA were also observed in olfactory bulb or hippocampus after PM
2.5
exposure, but no amyloid pathology was detected, as reported in previous studies. These results revealed that a relatively lower level of PM
2.5
subchronic exposure from the environmental atmosphere still induced certain neurodegenerative changes in the brains of AD mice, especially in the olfactory bulb, entorhinal cortex and hippocampus, which is consistent with the nasal entry and spreading route for PM exposure. Systemic factors may also contribute to the neuronal toxicity. The effects of PM
2.5
after a more prolonged exposure period are needed to establish a more comprehensive picture of the PM
2.5
-mediated development of AD.
•The state dependency of the neurovascular coupling was reflected by distinctive patterns of the EEG-fMRI spectra correspondence between task and resting conditions.•In the eye-open-eye-close (EOEC) ...task, a phase-amplitude coupling (PAC) was found between EEG alpha-band oscillations and the low-frequency fMRI signals in the visual area.•In the resting state, an amplitude-amplitude coupling (AAC) was demonstrated between gamma-band of EEG-Oz and the high-frequency fMRI signals (0.15–0.25 Hz) in the visual network.•Based on the hilbert-huang transform (HHT), the EEG-fMRI coupling was carried out for both PAC and AAC, exhibiting different sensitivity features between PAC/AAC spectral correspondence maps.
Neurovascular coupling serves as an essential neurophysiological mechanism in functional neuroimaging, which is generally presumed to be robust and invariant across different physiological states, encompassing both task engagement and resting state. Nevertheless, emerging evidence suggests that neurovascular coupling may exhibit state dependency, even in normal human participants. To investigate this premise, we analyzed the cross-frequency spectral correspondence between concurrently recorded electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data, utilizing them as proxies for neurovascular coupling during the two conditions: an eye-open-eye-close (EOEC) task and a resting state. We hypothesized that given the state dependency of neurovascular coupling, EEG-fMRI spectral correspondences would change between the two conditions in the visual system. During the EOEC task, we observed a negative phase-amplitude-coupling (PAC) between EEG alpha-band and fMRI visual activity. Conversely, in the resting state, a pronounced amplitude-amplitude-coupling (AAC) emerged between EEG and fMRI signals, as evidenced by the spectral correspondence between the EEG gamma-band of the midline occipital channel (Oz) and the high-frequency fMRI signals (0.15–0.25 Hz) in the visual network. This study reveals distinct scenarios of EEG-fMRI spectral correspondence in healthy participants, corroborating the state-dependent nature of neurovascular coupling.
We explored the macro-scale neurovascular coupling via the spectral correspondence of concurrent EEG-fMRI signals in a resting-state condition and a eye-open-eye-close (EOEC) task. By decomposing time-frequency maps for both signals, we revealed the EEG-fMRI spectral coupling through the temporal correlations at different frequency bands in the resting state, as compared with those in the EOEC task. Display omitted
A hierarchical microstructure strengthened high entropy superalloy (HESA) with superior cost specific yield strength from room temperature up to 1,023 K is presented. By phase transformation pathway ...through metastability, HESA possesses a hierarchical microstructure containing a dispersion of nano size disordered FCC particles inside ordered L1
precipitates that are within the FCC matrix. The average tensile yield strength of HESA from room temperature to 1,023 K could be 120 MPa higher than that of advanced single crystal superalloy, while HESA could still exhibit an elongation greater than 20%. Furthermore, the cost specific yield strength of HESA can be 8 times that of some superalloys. A template for lighter, stronger, cheaper, and more ductile high temperature alloy is proposed.