Low-intensity transcranial ultrasound stimulation modulates neurovascular coupling in mouse models of Alzheimer's disease.

Neurovascular coupling plays an important role in the progression of Alzheimer's disease. However, it is unclear how ultrasound stimulation modulates neurovascular coupling in Alzheimer's disease. Here, we found that (i) transcranial ultrasound stimulation modulates the time domain and frequency domain characteristics of cerebral blood oxygen metabolism in Alzheimer's disease mice; (ii) transcranial ultrasound stimulation can significantly modulate the relative power of theta and gamma frequency of local field potential in Alzheimer's disease mice; and (iii) transcranial ultrasound stimulation can significantly modulate the neurovascular coupling in time domain and frequency domain induced by forepaw electrical stimulation in Alzheimer's disease mice. It provides a research basis for the clinical application of transcranial ultrasound stimulation in Alzheimer's disease patients.

Low-intensity transcranial ultrasound stimulation improves memory behavior in an ADHD rat model by modulating cortical functional network connectivity.

Working memory in attention deficit hyperactivity disorder (ADHD) is closely related to cortical functional network connectivity (CFNC), such as abnormal connections between the frontal, temporal, occipital cortices and with other brain regions. Low-intensity transcranial ultrasound stimulation (TUS) has the advantages of non-invasiveness, high spatial resolution, and high penetration depth and can improve ADHD memory behavior. However, how it modulates CFNC in ADHD and the CFNC mechanism that improves working memory behavior in ADHD remain unclear. In this study, we observed working memory impairment in ADHD rats, establishing a corresponding relationship between changes in CFNCs and the behavioral state during the working memory task. Specifically, we noted abnormalities in the information transmission and processing capabilities of CFNC in ADHD rats while performing working memory tasks. These abnormalities manifested in the network integration ability of specific areas, as well as the information flow and functional differentiation of CFNC. Furthermore, our findings indicate that TUS effectively enhances the working memory ability of ADHD rats by modulating information transmission, processing, and integration capabilities, along with adjusting the information flow and functional differentiation of CFNC. Additionally, we explain the CFNC mechanism through which TUS improves working memory in ADHD. In summary, these findings suggest that CFNCs are important in working memory behaviors in ADHD.

Recent Progress on Stability of Layered Double Hydroxide-Based Catalysts for Oxygen Evolution Reaction.

Water electrolysis is regarded as one of the most viable technologies for the generation of green hydrogen. Nevertheless, the anodic oxygen evolution reaction (OER) constitutes a substantial obstacle to the large-scale deployment of this technology, due to the considerable overpotential resulting from the retardation kinetics associated with the OER. The development of low-cost, high-activity, and long-lasting OER catalysts has emerged as a pivotal research area. Layered double hydroxides (LDHs) have garnered significant attention due to their suitability for use with base metals, which are cost-effective and exhibit enhanced activity. However, the current performance of LDHs OER catalysts is still far from meeting the demands of industrial applications, particularly in terms of their long-term stability. In this review, we provide an overview of the causes for the deactivation of LDHs OER catalysts and present an analysis of the various mechanisms employed to improve the stability of these catalysts, including the synthesis of LDH ultrathin nanosheets, adjustment of components and doping, dissolution and redeposition, defect creation and corrosion, and utilization of advanced carbon materials.

Copper exposure promotes ferroptosis of chicken (Gallus gallus) kidney cells and causes kidney injury.

PURPOSE: While copper (Cu) is essential for biological organisms, excessive Cu can be harmful. Ferroptosis is a programmed cell death pathway, but the role of ferroptosis in renal injury induced by Cu is limited. The aim of this study was to investigate the role of ferroptosis in kidney injury in chickens and the molecular mechanism by which Cu promotes renal ferroptosis. MATERIALS AND METHODS: Chicken were subjected to Cu treatment by artificially adding excess Cu to the basal diet (the Cu concentration in the diet was supplemented to 110-330 mg/kg), and the impact on kidney fibrosis, tissue structure, and ferroptosis-related molecular markers was studied. Then, the expression levels of genes and proteins related to ferroptosis, iron metabolism and ferroautophagy were detected to explore the promoting effect of Cu on ferroptosis in chicken kidney. MAIN FINDINGS: Cu treatment resulted in significant fibrosis and tissue structure damage in chicken kidneys. Molecular analysis revealed a significant upregulation of LC3Ⅱ, P62, ATG5, and NCOA4, along with a decrease in FTH1 and FTL protein levels. Additionally, crucial markers of ferroptosis, including the loss of GPX4, SLC7A11, and FSP1, and an increase in PTGS2 and ACSL4 protein levels, were observed in chicken kidneys after Cu exposure. CONCLUSION: Our study showed that dietary Cu excess caused kidney injury in brochickens and exhibited ferroptosis-related features, including lipid peroxidation, reduction of ferritin, and downregulation of FSP1 and GPX4. These results indicate that excess Cu can induce renal ferroptosis and lead to kidney injury in chickens. This study highlights the complex interplay between Cu ions and ferroptosis in the context of renal injury and provides a new perspective for understanding the mechanism of Cu-induced renal injury.

Mitochondrial miR-12294-5p-Regulated Copper Exposure-Caused Mitochondrial-Dependent Ferroptosis by Targeted Inhibition of CISD1 in Chicken Hepatocytes.

Copper (Cu) is a common trace element additive in animal and human foods, and excessive intake of Cu has been shown to cause hepatotoxicity, but the underlying mechanism remains unclear. Our previous research found that Cu exposure dramatically upregulated mitochondrial miR-12294-5p expression and confirmed its targeted inhibition of CISD1 expression in chicken hepatocytes. Thus, we aimed to explore the potential role of mitomiR-12294-5p/CISD1 axis in Cu exposure-resulted hepatotoxicity. Here, we observed that Cu exposure resulted in Cu accumulation and pathological injury in chicken livers. Moreover, we found that Cu exposure caused mitochondrial-dependent ferroptosis in chicken hepatocytes, which were prominent on the increased mitochondrial Fe2+ and mitochondrial lipid peroxidation, inhibited levels of CISD1, GPX4, DHODH, and IDH2, and also enhanced level of PTGS2. Notably, we identified that inhibition of mitomiR-2954 level effectively mitigated Cu-exposure-resulted mitochondrial Fe2+ accumulation and mitochondrial lipid peroxidation and prevented the development of mitochondrial-dependent ferroptosis. However, increasing the mitomiR-12294-5p expression considerably aggravated the influence of Cu on these indicators. Meanwhile, the overexpression of CISD1 effectively alleviated Cu-caused mitochondrial-dependent ferroptosis, while silent CISD1 eliminated the therapeutic role of mitomiR-12294-5p inhibitor. Overall, our findings indicated that mitomiR-12294-5p/CISD1 axis played a critical function in Cu-caused hepatotoxicity in chickens by regulating mitochondrial-dependent ferroptosis.

Highly efficient ion-transport "polymer-in-ceramic" electrolytes boost stable all-solid-state Li metal batteries.

"Polymer-in-ceramic" (PIC) electrolytes are widely investigated for all-solid-state batteries (ASSBs) due to their good thermal stability and mechanical performance. However, achieving fast and diversified lithium-ion transport inside the PIC electrolyte and uniform Li+ deposition at the electrolyte/Li anode interface simultaneously remains a challenge. Besides, the effect of ceramic particle size on Li+ transport and Li anodic compatibility is still unclear, which is essential for revealing the enhanced mechanism of the performance for PIC electrolytes. Herein, PIC with moderate ceramic size and contents are prepared and studied to strike a balance between ionic conductivity and anodic compatibility. Through moderate filler-filler interfacial impedance and appropriate surface roughness, a particle size of 17 µm is optimized to facilitate homogeneous Li+ flux on anode and enhance Li+ conductivity of the electrolyte. The PIC electrolyte with ceramic particle size of 17 µm achieves a high lithium ion transference number (0.74) and an ionic conductivity of 4.11 × 10-4 S cm-1 at 60 °C. The Li/PIC/Li symmetric cell can stably cycle for 2800 h at 0.2 mA cm-2 with 0.2 mAh cm-2. Additionally, the Li/PIC/LiFePO4 cell also delivers a superior cycling performance at 0.5C, a high capacity retention of 93.28% after 100 cycles and 83.17% after 200 cycles, respectively.

Verification of AKT and CDK5 Gene and RNA Interference Combined with Irradiation to Mediate Fertility Changes in Plutella xylostella (Linnaeus).

Plutella xylostella (Linnaeus) mainly damages cruciferous crops and causes huge economic losses. Presently, chemical pesticides dominate its control, but prolonged use has led to the development of high resistance. In contrast, the sterile insect technique provides a preventive and control method to avoid the development of resistance. We discovered two genes related to the reproduction of Plutella xylostella and investigated the efficacy of combining irradiation with RNA interference for pest management. The results demonstrate that after injecting PxAKT and PxCDK5, there was a significant decrease of 28.06% and 25.64% in egg production, and a decrease of 19.09% and 15.35% in the hatching rate compared to the control. The ratio of eupyrene sperm bundles to apyrene sperm bundles also decreased. PxAKT and PxCDK5 were identified as pivotal genes influencing male reproductive processes. We established a dose-response relationship for irradiation (0-200 Gy and 200-400 Gy) and derived the irradiation dose equivalent to RNA interference targeting PxAKT and PxCDK5. Combining RNA interference with low-dose irradiation achieved a sub-sterile effect on Plutella xylostella, surpassing either irradiation or RNA interference alone. This study enhances our understanding of the genes associated with the reproduction of Plutella xylostella and proposes a novel approach for pest management by combining irradiation and RNA interference.

Modulatory effects of low-intensity retinal ultrasound stimulation on rapid and non-rapid eye movement sleep.

Prior investigations have established that the manipulation of neural activity has the potential to influence both rapid eye movement and non-rapid eye movement sleep. Low-intensity retinal ultrasound stimulation has shown effectiveness in the modulation of neural activity. Nevertheless, the specific effects of retinal ultrasound stimulation on rapid eye movement and non-rapid eye movement sleep, as well as its potential to enhance overall sleep quality, remain to be elucidated. Here, we found that: In healthy mice, retinal ultrasound stimulation: (i) reduced total sleep time and non-rapid eye movement sleep ratio; (ii) changed relative power and sample entropy of the delta (0.5-4 Hz) in non-rapid eye movement sleep; and (iii) enhanced relative power of the theta (4-8 Hz) and reduced theta-gamma coupling strength in rapid eye movement sleep. In Alzheimer's disease mice with sleep disturbances, retinal ultrasound stimulation: (i) reduced the total sleep time; (ii) altered the relative power of the gamma band during rapid eye movement sleep; and (iii) enhanced the coupling strength of delta-gamma in non-rapid eye movement sleep and weakened the coupling strength of theta-fast gamma. The results indicate that retinal ultrasound stimulation can modulate rapid eye movement and non-rapid eye movement-related neural activity; however, it is not beneficial to the sleep quality of healthy and Alzheimer's disease mice.

Site-Selective Polyfluoroaryl Modification and Unsymmetric Stapling of Unprotected Peptides.

Peptide stapling is recognized as an effective strategy for improving the proteolytic stability and cell permeability of peptides. In this study, we present a novel approach for the site-selective unsymmetric perfluoroaryl stapling of Ser and Cys residues in unprotected peptides. The stapling reaction proceeds smoothly under very mild conditions, exhibiting a remarkably rapid reaction rate. It can furnish stapled products in both liquid and solid phases, and the presence of nucleophilic groups other than Cys thiol within the peptide does not impede the reaction, resulting in uniformly high yields. Importantly, the chemoselective activation of Ser ß-C(sp3)-H enables the unreacted -OH to serve as a reactive handle for subsequent divergent modification of the staple moiety with various therapeutic functionalities, including a clickable azido group, a polar moiety, a lipid tag, and a fluorescent dye. In our study, we have also developed a visible-light-induced chemoselective C(sp3)-H polyfluoroarylation of the Ser ß-position. This reaction avoids interference with the competitive reaction of Ser -OH, enabling the precise late-stage polyfluoroarylative modification of Ser residues in various unprotected peptides containing other highly reactive amino acid residues. The biological assay suggested that our peptide stapling strategy would potentially enhance the proteolytic stability and cellular permeability of peptides.

Band Structure Engineering Promotes Anionic Redox Reversibility of Cobalt-Free Li-Rich Layered Oxides Cathodes.

Li-rich layered oxides cathodes (LLOs) have prevailed as the promising high-energy-density cathode materials due to their distinctive anionic redox chemistry. However, uncontrollable anionic redox process usually leads to structural deterioration and electrochemical degradation. Herein, a Mo/Cl co-doping strategy is proposed to regulate the relative position of energy band for modulating the anionic redox chemistry and strengthening the structural stability of Co-free Li1.16Mn0.56Ni0.28O2 cathodes. The incorporation of Mo with high d state orbit and Cl with low electronegativity can narrow the band energy gap between bonding and antibonding bands via increasing the filled lower-Hubbard band (LHB) and decreasing the non-bonding O 2p energy bands, promoting the anionic redox reversibility. In addition, strong covalent Mo─O and Mn─Cl bonding further increases the covalency of Mn─O band to further stabilize the O2 n- species and enhance the reversible distortion of MnO6 octahedron. The strengthening electronic conductivity, together with the epitaxial structure Li2MoO4 facilitates the fast Li+ kinetics. As a result, the dual doping material exhibits enhanced anionic redox reversibility and suppressed oxygen release with increased cyclic stability and excellent rate performance. This strategy provides some guidance to design high-energy-density LLOs with desirable anionic redox reversibility and stable crystal structure via band structure engineering.

Recruitment of ubiquitin E2 enzymes is determined jointly by the U-box domains and substrates of E3 ligases.

Ubiquitination is a cascade reaction involving E1, E2, and E3 enzymes. The orthogonal ubiquitin transfer (OUT) method has been previously established to identify potential substrates of E3 ligases. In this study, we verified the ubiquitination of five substrates mediated by the E3 ligases CHIP and E4B. To further explore the activity of U-box domains of E3 ligases, two mutants with the U-box domains interchanged between CHIP and E4B were generated. They exhibited a significantly reduced ubiquitination ability. Additionally, different E3s recruited similar E2 ubiquitin-conjugating enzymes when ubiquitinating the same substrates, highlighting that U-box domains determined the E2 recruitment, while the substrate determined the E2 selectivity. This study reveals the influence of substrates and U-box domains on E2 recruitment, providing a novel perspective on the function of U-box domains of E3 ligases.

A quantitative analysis method of complex sulfide components for understanding initial capacity degradation mechanism in lithium-sulfur batteries.

Lithium-sulfur (Li-S) batteries are a strong contender for the new-generation battery system to meet the growing energy demand due to their significantly high energy density (2600 Wh/kg) and cost-effectiveness. However, the practical operating conditions yield an initial capacity of less than 80 % of the theoretical capacity, resulting in a limited lifespan and hindering broader application. What's worse, current mechanism, especially the evolution process of sulfides for the initial capacity degradation is not clear due to the practical difficulties of effective separation and detection of sulfur-containing components. Herein, we have developed an instrumental analysis method enabling graded leaching and quantitative determination of sulfur-containing components. This technology achieves a detection precision surpassing 99.11 %, addressing the inherent deficiency in calculating sulfur-containing components using the decrement method. Applying this method reveals that the presence of lithium polysulfides in the electrolyte (26.34 wt%) after discharging is the primary factor causing insufficient capacity utilization in Li-S batteries. This work not only demonstrates the unique behavior of Li-S batteries at high sulfur loading but also provides a systematic evaluation method to guide further research on high-energy-density batteries, and provides theoretical and technical support to promote the development of high-energy, long-life Li-S batteries.

Modulatory Effect of Low-Intensity Transcranial Ultrasound Stimulation on Behaviour and Neural Oscillation in Mouse Models of Alzheimer's Disease.

Transcranial ultrasound stimulation (TUS) is a noninvasive brain neuromodulation technique. The application of TUS for Alzheimer's disease (AD) therapy has not been widely studied. In this study, a long-term course (28 days) of TUS was used to stimulate the hippocampus of APP/PS1 mice. We examined the modulatory effect of TUS on behavior and neural oscillation in AD mice. We found that TUS can 1) improve the learning and memory abilities of AD mice; 2) reduce the phase-amplitude coupling of delta-epsilon, delta-gamma and theta-gamma frequency bands of local field potential, and increase the relative power of epsilon frequency bands in AD mice; 3) reduce the spike firing rate of interneurons and inhibit the phase-locked angle deflection between the theta frequency bands and the spikes of the two types of neurons that develops with the progression of the disease in AD mice. In summary, we demonstrate that TUS could effectively improve cognitive behavior and modulate neural oscillation with AD.

Protective effect of FXN overexpression on ferroptosis in L-Glu-induced SH-SY5Y cells.

BACKGROUND: Alzheimer's disease (AD) is a complex, multifactorial neurodegenerative disease. However, the pathogenesis remains unclear. Recently, an increasing number of studies have demonstrated that ferroptosis is a new type of iron-dependent programmed cell death, contributes to the death of nerve cells in AD. By controlling iron homeostasis and mitochondrial function, the particular protein called frataxin (FXN), which is situated in the mitochondrial matrix, is a critical regulator of ferroptosis disease. It is encoded by the nuclear gene FXN. Here, we identified a novel underlying mechanism through which ferroptosis mediated by FXN contributes to AD. METHODS: Human neuroblastoma cells (SH-SY5Y) were injured by L-glutamate (L-Glu). Overexpression of FXN by lentiviral transfection. In each experimental group, we assessed the ultrastructure of the mitochondria, the presence of iron and intracellular Fe2 + , the levels of reactive oxygen species, the mitochondrial membrane potential (MMP), and lipid peroxidation. Quantification was done for malondialdehyde (MDA) and reduced glutathione (GSH), as well as reactive oxygen species (ROS). Western blot and cellular immunofluorescence assays were used to detect the expression of xCT and GPX4 proteins which in System Xc-/GPX4 pathway, and the protein expressions of ACSL4 and TfR1 were investigated by Western blot. RESULTS: The present work showed: (1) The expression of FXN was reduced in the L-Glu group; (2) Compared with the Control group, MMP was reduced in the L-Glu group, and mitochondria were observed to shrink and cristae were deformed, reduced or disappeared by transmission electron microscopy, and after FXN overexpression and ferrostatin-1 (Fer-1) (10 µmol/L) intervened, MMP was increased and mitochondrial morphology was significantly improved, suggesting that mitochondrial function was impaired in the L-Glu group, and overexpression of FXN could improve the manifestation of mitochondrial function impairment. (3) In the L-Glu group, ROS, MDA, iron ion concentration and Fe2+ levels were increased, GSH was decreased. Elevated expression of ACSL4 and TfR1, important regulatory proteins of ferroptosis, was detected by Western blot, and the expression of xCT and GPX4 in the System Xc-/GPX4 pathway was reduced by Western blot and cellular immunofluorescence. However, the above results were reversed when FXN overexpression and Fer-1 intervened. CONCLUSION: To conclude, our research demonstrates that an elevated expression of FXN effectively demonstrates a robust neuroprotective effect against oxidative damage induced by L-Glu. Moreover, it mitigates mitochondrial dysfunction and lipid metabolic dysregulation associated with ferroptosis. FXN overexpression holds promise in potential therapeutic strategies for AD by inhibiting ferroptosis in nerve cells and fostering their protection.

CHIP suppresses the proliferation and migration of A549 cells by mediating the ubiquitination of eIF2α and upregulation of tumor suppressor RBM5.

The protein kinase RNA-like endoplasmic reticulum kinase (PERK)-eukaryotic translation initiation factor 2 subunit α (eIF2α) pathway plays an essential role in endoplasmic reticulum (ER) stress. When the PERK-eIF2α pathway is activated, PERK phosphorylates eIF2α (p-eIF2α) at Ser51 and quenches global protein synthesis. In this study, we verified eIF2α as a bona fide substrate of the E3 ubiquitin ligase carboxyl terminus of the HSC70-interaction protein (CHIP) both in vitro and in cells. CHIP mediated the ubiquitination and degradation of nonphosphorylated eIF2α in a chaperone-independent manner and promoted the upregulation of the cyclic AMP-dependent transcription factor under endoplasmic reticulum stress conditions. Cyclic AMP-dependent transcription factor induced the transcriptional enhancement of the tumor suppressor genes PTEN and RBM5. Although transcription was enhanced, the PTEN protein was subsequently degraded by CHIP, but the expression of the RBM5 protein was upregulated, thereby suppressing the proliferation and migration of A549 cells. Overall, our study established a new mechanism that deepened the understanding of the PERK-eIF2α pathway through the ubiquitination and degradation of eIF2α. The crosstalk between the phosphorylation and ubiquitination of eIF2α shed light on a new perspective for tumor progression.

Pooled CRISPR Screening Identifies P-Bodies as Repressors of Cancer Epithelial-Mesenchymal Transition.

Epithelial-mesenchymal transition (EMT) is a fundamental cellular process frequently hijacked by cancer cells to promote tumor progression, especially metastasis. EMT is orchestrated by a complex molecular network acting at different layers of gene regulation. In addition to transcriptional regulation, posttranscriptional mechanisms may also play a role in EMT. Here, we performed a pooled CRISPR screen analyzing the influence of 1,547 RNA-binding proteins on cell motility in colon cancer cells and identified multiple core components of P-bodies (PB) as negative modulators of cancer cell migration. Further experiments demonstrated that PB depletion by silencing DDX6 or EDC4 could activate hallmarks of EMT thereby enhancing cell migration in vitro as well as metastasis formation in vivo. Integrative multiomics analysis revealed that PBs could repress the translation of the EMT driver gene HMGA2, which contributed to PB-meditated regulation of EMT. This mechanism is conserved in other cancer types. Furthermore, endoplasmic reticulum stress was an intrinsic signal that induced PB disassembly and translational derepression of HMGA2. Taken together, this study has identified a function of PBs in the regulation of EMT in cancer. SIGNIFICANCE: Systematic investigation of the influence of posttranscriptional regulation on cancer cell motility established a connection between P-body-mediated translational control and EMT, which could be therapeutically exploited to attenuate metastasis formation.

Selective Photoelectrochemical Oxidation of Glycerol to Glyceric Acid on (002) Facets Exposed WO3 Nanosheets.

Glycerol is a byproduct of biodiesel production. Selective photoelectrochemical oxidation of glycerol to high value-added chemicals offers an economical and sustainable approach to transform renewable feedstock as well as store green energy at the same time. In this work, we synthesized monoclinic WO3 nanosheets with exposed (002) facets, which could selectively oxidize glycerol to glyceric acid (GLYA) with a photocurrent density of 1.7 mA cm-2 , a 73 % GLYA selectivity and a 39 % GLYA Faradaic efficiency at 0.9 V vs. reversible hydrogen electrode (RHE) under AM 1.5G illumination (100 mW cm-2 ). Compared to (200) facets exposed WO3 , a combination of experiments and theoretical calculations indicates that the superior performance of selective glycerol oxidation mainly originates from the better charge separation and prolonged carrier lifetime resulted from the plenty of surface trapping states, lower energy barrier of the glycerol-to-GLYA reaction pathway, more abundant active sites and stronger oxidative ability of photogenerated holes on the (002) facets exposed WO3 . Our findings show great potential to significantly contribute to the sustainable and environmentally friendly chemical processes via designing high performance photoelectrochemical cell via facet engineering for renewable feedstock transformation.

Photomodulation of Proton Conductivity by Nitro-Nitroso Transformation in a Metal-Organic Framework.

The design of a highly and photomodulated proton conductor is important for advanced potential applications in chemical sensors and bioionic functions. In this work, a metal-organic framework (MOF; Gd-NO2) with high proton conductivity is synthesized with a photosensitive ligand of 5-nitroisophthalic acid (BDC-NO2), and it provides remote-control photomodulated proton-conducting behavior. The proton conduction of Gd-NO2 reaches 3.66 × 10-2 S cm-1 at 98% relative humidity (RH) and 25 °C, while it decreases by ∼400 times after irradiation with a 355 nm laser. The newly generated and disappearing FT-IR characteristic peaks reveal that this photomodulated process is realized by the photoinduced transformation from BDC-NO2 to 5-nitroso-isophthalic acid (BDC-NO). According to density functional theory, the smaller electronegativity of the -NO group, the longer distance of the hydrogen bond between BDC-NO and H2O molecules, and the lower water adsorption energy of BDC-NO indicate that the irradiated sample possesses a poorer hydrophilicity and has difficulty forming rich hydrogen-bonded networks, which results in the remarkable decrease of proton conductivity.