Selective Reduction of Triple Bond via Proton-Coupled Electron Transfer for the Synthesis of α,ß-Unsaturated γ-Lactams.

Described herein is the development of a visible-light-induced photoredox 1,6-enyne reductive cyclization via selective reduction of a triple bond instead of an activated double bond. The selective 1,6-enyne radical cyclization/carbon═carbon double bond cleavage provided a straightforward route to structurally valuable α,ß-unsaturated γ-lactams. TEMPO-trap experiments, control experiments, and DFT calculations have offered evidence supporting the possible catalytic cycle.

The mean Hounsfield unit range acquired from different slices produces superior predictive accuracy for pyonephrosis in obstructive uropathy.

PURPOSE: To determine the non-contrast computer tomography imaging features of pyonephrosis and evaluate the predictive value of Hounsfield units (HUs) in different hydronephrotic region slices. MATERIALS AND METHODS: We retrospectively reviewed data from patients with hydronephrosis who had renal-ureteral calculi. All patients were categorized into pyonephrosis and simple hydronephrosis groups. Baseline characteristics, the mean HU values in the maximal hydronephrotic region (uHU) slice, and the range of uHU in different slices (ΔuHU) were compared between the two groups. Univariate and multivariate analyses were performed to identify risk factors for pyonephrosis. RESULTS: Among the 181 patients enrolled in the current study, 71 patients (39.2%) were diagnosed with pyonephrosis. The mean dilated pelvis surface areas were comparable between patients with pyonephrosis and simple hydronephrosis (822.61 mm² vs. 877.23 mm², p=0.722). Collecting system debris (p=0.022), a higher uHU (p=0.038), and a higher ΔuHU (p<0.001) were identified as independent risk factors for pyonephrosis based on multivariate analysis. The ΔuHU sensitivity and specificity were 88.7% and 86.4%, respectively, at a cutoff value of 6.56 (p<0.001), whereas the sensitivity and specificity for detecting pyonephrosis at a uHU cutoff value of 7.96 was 50.7% and 70.9%, respectively (p=0.003). CONCLUSIONS: Non-contrast computer tomography was shown to accurately distinguish simple hydronephrosis from pyonephrosis in patients with obstructive uropathy. Evaluation of the ΔuHU in different slices may be more reliable than the uHU acquired from a single slice in predicting pyonephrosis.

Giant dielectric tunability in ferroelectric ceramics with ultralow loss by ion substitution design.

Due to their responsiveness to modulation by external direct current fields, dielectric tunable materials are extensively utilized in integrated components, such as ferroelectric phase shifters. Barium strontium titanate ceramics have been considered the most potential tunable materials for a long time. However, the significant dielectric loss and high voltage drive have limited their further applications. Recently, Bi6Ti5WO22 ceramic has regained attention for its high dielectric tunability with low loss. In this study, we judiciously introduce Nb5+ with a larger ionic radius, replacing Ti4+ and W6+. This successful substitution enables the modulation of the phase transition temperature of Bi6Ti5WO22 ceramics to room temperature, resulting in superior tunable properties. Specifically, the 0.7Bi6Ti5WO22-0.3Bi6Ti4Nb2O22 ceramics exhibit giant tunability (~75.6%) with ultralow loss (<0.002) under a low electric field (1.5 kV/mm). This tunability is twice that of barium strontium titanate ceramics with a similar dielectric constant and only one-tenth of the loss. Neutron powder diffraction and transmission-electron-microscopy illustrate the nanodomains and micro-strains influenced by ion substitution. Density functional theory simulation calculations reveal the contribution of ion substitution to polarization. The research provides an ideal substitute for tunable material and a general strategy for adjusting phase transition temperature to improve dielectric properties.

Targeting Non-Alcoholic Fatty Liver Disease with Hawthorn Ethanol Extract (HEE): A Comprehensive Examination of Hepatic Lipid Reduction and Gut Microbiota Modulation.

Recent studies have highlighted the lipid-lowering ability of hawthorn ethanol extract (HEE) and the role played by gut flora in the efficacy of HEE. Our study sought to explore the effects of HEE on non-alcoholic fatty liver disease (NAFLD) in normal flora and pseudo germ-free mice. The results showed that HEE effectively diminished hepatic lipid accumulation, ameliorated liver function, reduced inflammatory cytokine levels and blood lipid profiles, and regulated blood glucose levels. HEE facilitated triglyceride breakdown, suppressed fatty acid synthesis, and enhanced intestinal health by modulating the diversity of the gut microbiota and the production of short-chain fatty acids in the gut. In addition, HEE apparently helps to increase the presence of beneficial genera of bacteria, thereby influencing the composition of the gut microbiota, and the absence of gut flora affects the efficacy of HEE. These findings reveal the potential of hawthorn for the prevention and treatment of NAFLD and provide new perspectives on the study of functional plants to improve liver health.

The Effects of Tremella fuciformis Polysaccharide on the Physicochemical, Multiscale Structure and Digestive Properties of Cyperus esculentus Starch.

In this study, we have investigated the effects of Tremella fuciformis polysaccharide (TP) on the pasting, rheological, structural and in vitro digestive properties of Cyperus esculentus starch (CS). The results showed that the addition of TP significantly changed the pasting characteristics of CS, increased the pasting temperature and pasting viscosity, inhibited pasting, reduced the exudation of straight-chain starch and was positively correlated with the amount of TP added. The addition of the appropriate amount of TP could increase its apparent viscosity and enhance its viscoelasticity. The composite system of CS/TP exhibited higher short-range ordered structure and solid dense structure, which protected the crystal structure of CS, but was related to the amount of TP added. In addition, the introduction of TP not only decreased the in vitro digestion rate of CS and increased the content of slow-digestible starch (SDS) and resistant starch (RS), but also reduced the degree of digestion. Correlation studies established that TP could improve the viscoelasticity, relative crystallinity and short-range order of the CS/TP composite gel, maintain the integrity of the starch granule and crystalline structure, reduce the degree of starch pasting and strengthen the gel network structure of CS, which could help to lower the digestibility of CS.

NXPH4 can be used as a biomarker for pan-cancer and promotes colon cancer progression.

NXPH4 promotes cancer proliferation and invasion. However, its specific role and mechanism in cancer remain unclear. Transcriptome and clinical data for pan-cancer were derived from the TCGA database. K-M survival curve and univariate Cox were used for prognostic analysis. CIBERSORT and TIMER algorithms were employed to calculate immune cell infiltration. Gene set enrichment analysis (GSEA) was employed for investigating the function of NXPH4. Western blot verified differential expression of NXPH4 in colon cancer. Functional assays (CCK-8, plate clonogenicity assay, wound healing assay, and Transwell assay) confirmed the impact of NXPH4 on proliferation, invasion, and migration of colon cancer cells. Dysregulation of NXPH4 in pan-cancer suggests its potential as a diagnostic and prognostic marker for certain cancers, including colon and liver cancer. High expression of NXPH4 in pan-cancer might be associated with the increase in copy number and hypomethylation. NXPH4 expression in pan-cancer is substantially linked to immune cell infiltration in the immune microenvironment. NXPH4 expression is associated with the susceptibility to immunotherapy and chemotherapy. Western blot further confirmed the higher expression of NXPH4 in colon cancer. Knockdown of NXPH4 significantly suppresses proliferation, invasion, and migration of colon cancer cell lines HT-29 and HCT116, as validated by functional assays.

Aberrant dynamic functional network connectivity in progressive supranuclear palsy.

BACKGROUND: The clinical symptoms of progressive supranuclear palsy (PSP) may be mediated by aberrant dynamic functional network connectivity (dFNC). While earlier research has found altered functional network connections in PSP patients, the majority of those studies have concentrated on static functional connectivity. Nevertheless, in this study, we sought to evaluate the modifications in dynamic characteristics and establish the correlation between these disease-related changes and clinical variables. METHODS: In our study, we conducted a study on 53 PSP patients and 65 normal controls. Initially, we employed a group independent component analysis (ICA) to derive resting-state networks (RSNs), while employing a sliding window correlation approach to produce dFNC matrices. The K-means algorithm was used to cluster these matrices into distinct dynamic states, and then state analysis was subsequently employed to analyze the dFNC and temporal metrics between the two groups. Finally, we made a correlation analysis. RESULTS: PSP patients showed increased connectivity strength between medulla oblongata (MO) and visual network (VN) /cerebellum network (CBN) and decreased connections were found between default mode network (DMN) and VN/CBN, subcortical cortex network (SCN) and CBN. In addition, PSP patients spend less fraction time and shorter dwell time in a diffused state, especially the MO and SCN. Finally, the fraction time and mean dwell time in the distributed connectivity state (state 2) is negatively correlated with duration, bulbar and oculomotor symptoms. DISCUSSION: Our findings were that the altered connectivity was mostly concentrated in the CBN and MO. In addition, PSP patients had different temporal dynamics, which were associated with bulbar and oculomotor symptoms in PSPRS. It suggest that variations in dynamic functional network connectivity properties may represent an essential neurological mechanism in PSP.

Global, regional, and national burden of incidence, prevalence, and years lived with disability for facial fractures from 1990 to 2019: a systematic analysis for the Global Burden of Disease study 2019.

BACKGROUND: Facial fractures are common injuries causing cosmetic, functional, and psychological damage. The purpose of this study was to assess the incidence, prevalence, and years lived with disability (YLDs) of facial fractures from 1990 to 2019 using the Global Burden of Disease (GBD). METHODS: Detailed data for the disease burden of facial fractures were obtained from online available public data (Global Health Data Exchange) derived from the GBD study. The incidence, prevalence, and YLDs of facial fractures from 1990 to 2019 were analyzed by country, region, age, gender, sociodemographic index (SDI), and cause. The age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized YLDs rate (ASYR), and estimated annual percentage change (EAPC) were calculated to evaluate the disease burden and quantify the trends over time. The main causes of facial fractures in different years and ages were assessed. RESULTS: Globally, there were 8.9 million incident cases, 1.5 million cases prevalent cases, and 98.1 thousand years YLDs in 2019. Compared with 1990, the number of incident cases, prevalent cases, and YLDs increased, while ASIR (EAPC, - 0.47; 95% uncertainty interval [UI], - 0.57 to - 0.37), ASPR (EAPC, - 0.39; 95% UI, - 0.46 to - 0.31), ASYR (EAPC, - 0.39; 95% UI, - 0.47 to - 0.32) showed a downward trend. The high SDI region held the highest ASIR, ASPR, and ASYR both in 1990 and 2019, such as New Zealand, Slovenia, and Australia. The burden was higher in men than in women from 1990 to 2019, while the ASRs in women exceeded that of men in the elderly. The ASIR peaked in the young adult group, however, the ASPR and ASYR increased with age. Falls and road injuries were the leading causes of facial fractures. CONCLUSIONS: Facial fractures continue to cause a heavy burden on public health worldwide. More targeted strategies need to be established to control the burden of facial fractures.

Case report: Paralytic ileus resulted from nirmatrelvir/ritonavir-tacrolimus drug-drug interaction in a systemic lupus erythematosus patient with COVID-19.

Patients with systemic autoimmune rheumatic diseases are at a high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and effective antiviral treatments including nirmatrelvir/ritonavir can improve their outcomes. However, there might be potential drug-drug interactions when these patients take nirmatrelvir/ritonavir together with immunosuppressants with a narrow therapeutic window, such as tacrolimus and cyclosporine. We present a case of paralytic ileus resulting from tacrolimus toxicity mediated by the use of nirmatrelvir/ritonavir in a patient with systemic lupus erythematosus (SLE). A 37-year-old female SLE patient was prescribed nirmatrelvir/ritonavir without discontinuing tacrolimus. She presented to the emergency room with symptoms of paralytic ileus including persistent abdominal pain, nausea, and vomiting, which were verified to be associated with tacrolimus toxicity. The blood concentration of tacrolimus was measured >30 ng/mL. Urgent medical intervention was initiated, while tacrolimus was withheld. The residual concentration was brought within the appropriate range and tacrolimus was resumed 8 days later. Physicians must be aware of the potential DDIs when prescribing nirmatrelvir/ritonavir, especially to those taking immunosuppresants like tacrolimus.

Understanding the Effects of Ligand Configuration on Protoporphyrinogen IX Oxidase with Rationally Designed 3-(N-Phenyluracil)but-2-enoates.

Protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) is a promising target for green herbicide discovery. However, the ligand configuration effects on PPO activity were still poorly understood. Herein, we designed 3-(N-phenyluracil)but-2-enoates using our previously developed active fragments exchange and link (AFEL) approach and synthesized a series of novel compounds with nanomolar ranges of Nicotiana tabacum PPO (NtPPO) inhibitory potency and promising herbicidal potency. Our systematic structure-activity relationship investigations showed that the E isomers of 3-(N-phenyluracil)but-2-enoates displayed improved bioactivity than their corresponding Z isomers. Using molecular simulation studies, we found that the E isomers showed a relatively lower entropy change and could sample more stable binding conformation to the receptor than the Z isomers. Our density functional theory (DFT) calculations showed that the E isomers showed higher chemical reactivity and lower electronic chemical potential than their corresponding Z isomers. Compound E-Ic emerged as the optimal compound with a Ki value of 3.0 nM against NtPPO, exhibiting a broader spectrum of weed control than saflufenacil at 37.5-75 g ai/ha and also safe to maize at 75 g ai/ha, which could be considered as a promising lead herbicide for further development.

Preparation of Activated Carbon Nanostructured Al@CuO with Low Static Sensitivity and High Reactivity.

The porous skeleton structure of oxidizers can effectively enlarge the contact area with fuels and boost the reactivity of thermites, but the overly complex preparation processes tend to limit their use to some extent. To overcome this issue, water-soluble starch and copper nitrate were used as a template to form a carbon skeleton copper oxide (C-CuO) after spray drying and calcination. By adding nanoaluminum into the spray drying process, the n-Al@C-CuO was prepared and compared with the physically mixed n-Al/C-CuO in the context. Scanning electron microscopy and differential scanning calorimetry were used to observe the morphology and analyze the thermal process. The pressure-time test and the electrostatic sensitivity test were used to measure the energy release properties and the safety of the thermites. Results indicated that the n-Al@C-CuO had 60.97 °C earlier initial exothermic temperature and 1.74 times higher peak pressure than that of the physically mixed sample. The n-Al@C-CuO was not ignited under 25 kV in the electrostatic sensitivity test, showing the great electrostatic safety of the sample. These findings are expected to facilitate the development of spray drying and promote energy release of traditional thermites.

Tigroid Enhancement: A Characteristic Enhancement Pattern of the Cerebellar Hemisphere on MRI With Intracranial Dural Arteriovenous Fistulas.

PURPOSE: This study aims to investigate a characteristic cerebellar hemisphere enhancement pattern on magnetic resonance imaging (MRI) that could aid in early and specific diagnosis of intracranial dural arteriovenous fistulas (DAVFs). MATERIALS AND METHODS: Pretreatment MR images of 57 patients with intracranial DAVFs between January 1, 2017, and February 28, 2023, were retrospectively analyzed. A total of 128 patients with confirmed alternative cerebellar lesions during the same period were included as a control group. All patients underwent enhanced MRI with a 3.0T scanner. The presence or absence of parallel enhanced linear striations on the surface of the cerebellar lesions was documented. Statistically significant differences were determined by the Fisher exact test. RESULTS: Cerebellar lesions were identified in 4 intracranial DAVF patients (7.0%). All 4 patients were male, with an average age of 64 years (range: 58-76 years). The pretreatment MR images of all 4 DAVF patients with cerebellar lesions demonstrated the characteristic tigroid enhancement pattern. Tortuous flow voids were present in the MR images of 3 of the 4 patients. Tigroid enhancement pattern was not observed in the remaining 53 intracranial DAVF patients and all control patients. The differences in the incidence of the pattern were significant (p=0.01). CONCLUSION: A characteristic tigroid enhancement pattern of the cerebellar hemisphere on MRI may aid in the early and specific diagnosis of intracranial DAVFs, allowing timely treatment and improving outcomes. CLINICAL IMPACT: The identification of a characteristic tigroid enhancement pattern on MRI for cerebellar hemisphere lesions holds significant promise for clinical practice. This pattern serves as a distinctive marker aiding in the early and specific diagnosis of intracranial dural arteriovenous fistulas (DAVFs). Clinicians can now utilize this innovative finding to expedite diagnostic workflows, enabling timely intervention and management strategies. The incorporation of this novel imaging feature enhances diagnostic accuracy, potentially reducing misdiagnosis rates and preventing delays in treatment initiation. Ultimately, this advancement may lead to improved patient outcomes and quality of care in neurosurgical and neuroradiological practice.

Clinicopathological and Molecular Profile of Sellar Neurocytoma.

OBJECTIVE: To investigate the clinical features, imaging characteristics and molecular profile of Sellar neurocytoma (SN). METHODS: Clinical, imaging, and pathological features of eleven cases of sellar neurocytoma were retrospectively analyzed. Electron microscopy was performed in five cases. Molecular features were detected in tumor tissue by RNA sequencing, qPCR and IHC. RESULTS: The clinical features of SN patients showed high incidence of hyponatremia (73%,8/11) and the tumors tended to invaded lateral side of saddle area from preoperative imaging analysis. The tumors had positive NeuN, SYN, NF, SSTR2 immunohistochemistry staining. Tumor transcriptomic analysis suggested a new LMCD1-AS1:GRM7-AS1 fusion gene event and increased expression of 10 hypothalamus-secreted hormones in SN. 15 differentially expressed genes were verified for qPCR verification. SSTR2 has been verified by immunohistochemistry. CONCLUSIONS: Hyponatremia is the dominant clinical features of SN. Preoperative imaging suggests that growth toward the dorsal region is the imaging feature of SN. SSTR2 expression and LMCD1-AS1:GRM7-AS1 fusion gene event expected to become a new molecular marker for SN. Somatostatin receptor ligand therapy may be a potential therapy for SN.

Imagine before you leap: Episodic future thinking combined with transcranial direct current stimulation training for impulsive choice in repetitive negative thinking.

Background: Immediate reward preference in repetitive negative thinking (RNT) has a high clinical correlation with a variety of maladaptive behaviors, whereas episodic future thinking (EFT) may be conducive to dealing with non-adaptive thinking and decision-making. Objectives: This study aimed to evaluate the efficacy of EFT training combined with transcranial direct current stimulation (tDCS) stimulation over the ventromedial PFC (vmPFC) in inhibiting impulsive choice of RNT individuals. Method: Study 1 explored the effects of EFT on immediate reward preference of participants with high and low RNT (N = 48). Study 2 conducted a randomized controlled trial (RCT) to examine the treatment effect of the EFT-neural training on impulsive choice of high RNT individuals (N = 103). Results: In study 1, individuals with high RNT were more likely to choose smaller and sooner (SS) rewards, however, there were no significant differences between the high-RNT group and the low-RNT group under the positive EFT condition. In study 2, a significant decrease was shown in the proportion of choosing SS rewards under the 8-week EFT-neural training, and the effect was maintained at 1 month follow-up. Conclusion: RNT is a vulnerability factor for short-sighted behaviors, and EFT-neural training could be suitable for reducing RNT and improving immediate reward preference.

Polyoxomolybdate-Based Metal-Organic Framework-Derived Cu-Embedded Molybdenum Dioxide Hybrid Nanoparticles as Highly Efficient Electrocatalysts for Al-S Batteries.

High-performance rechargeable aluminum-sulfur batteries (RASB) have great potential for various applications owing to their high theoretical capacity, abundant sulfur resources, and good safety. Nevertheless, the practical application of RASB still faces several challenges, including the polysulfide shuttle phenomenon and low sulfur utilization efficiency. Here, we first developed a synergistic copper heterogeneous metal oxide MoO2 derived from polymolybdate-based metal-organic framework as an efficient catalyst for mitigating polysulfide diffusion. This composite enhances sulfur utilization and electrical conductivity of the cathode. DFT calculations and experimental results reveal the catalyst Cu/MoO2@C not only effectively anchors aluminum polysulfides (AlPSs) to mitigate the shuttle effect, but also significantly promotes the catalytic conversion of AlPSs on the sulfur cathode side during charging and discharging. The unique nanostructure contains abundant electrocatalytic active sites of oxide nanoparticles and Cu clusters, resulting in excellent electrochemical performance. Consequently, the established RASB exhibits an initial capacity of 875 mAh g-1 at 500 mA g-1 and maintains a capacity of 967 mAh g-1 even at a high temperature of 50 °C.

A Ternary Inverter Based on Hybrid Conduction Mechanism of Band-to-Band Tunneling and Drift-Diffusion Process.

In this paper, a novel transistor based on a hybrid conduction mechanism of band-to-band tunneling and drift-diffusion is proposed and investigated with the aid of TCAD tools. Besides the on and off states, the proposed device presents an additional intermediate state between the on and off states. Based on the tri-state behavior of the proposed TDFET (tunneling and drift-diffusion field-effect transistor), a ternary inverter is designed and its operation principle is studied in detail. It was found that this device achieves ternary logic with only two components, and its structure is simple. In addition, the influence of the supply voltage and the key device parameters are also investigated.

Assessment of using Google Trends for real-time monitoring of infectious disease outbreaks: a measles case study.

Measles remains a significant threat to children worldwide despite the availability of effective vaccines. The COVID-19 pandemic exacerbated the situation by leading to the postponement of supplementary measles immunization activities. Along with this postponement, measles surveillance also deteriorated, with the lowest number of submitted specimens in over a decade. In this study, we focus on measles as a challenging case study due to its high vaccination coverage, which leads to smaller outbreaks and potentially weaker signals on Google Trends. Our research aimed to explore the feasibility of using Google Trends for real-time monitoring of infectious disease outbreaks. We evaluated the correlation between Google Trends searches and clinical case data using the Pearson correlation coefficient and Spearman's rank correlation coefficient across 30 European countries and Japan. The results revealed that Google Trends was most suitable for monitoring acute disease outbreaks at the regional level in high-income countries, even when there are only a few weekly cases. For example, from 2017 to 2019, the Pearson correlation coefficient was 0.86 (p-value< 0.05) at the prefecture level for Okinawa, Japan, versus 0.33 (p-value< 0.05) at the national level for Japan. Furthermore, we found that the Pearson correlation coefficient may be more suitable than Spearman's rank correlation coefficient for evaluating the correlations between Google Trends search data and clinical case data. This study highlighted the potential of utilizing Google Trends as a valuable tool for timely public health interventions to respond to infectious disease outbreaks, even in the context of diseases with high vaccine coverage.

Anat-SFSeg: Anatomically-guided superficial fiber segmentation with point-cloud deep learning.

Diffusion magnetic resonance imaging (dMRI) tractography is a critical technique to map the brain's structural connectivity. Accurate segmentation of white matter, particularly the superficial white matter (SWM), is essential for neuroscience and clinical research. However, it is challenging to segment SWM due to the short adjacent gyri connection in a U-shaped pattern. In this work, we propose an Anatomically-guided Superficial Fiber Segmentation (Anat-SFSeg) framework to improve the performance on SWM segmentation. The framework consists of a unique fiber anatomical descriptor (named FiberAnatMap) and a deep learning network based on point-cloud data. The spatial coordinates of fibers represented as point clouds, as well as the anatomical features at both the individual and group levels, are fed into a neural network. The network is trained on Human Connectome Project (HCP) datasets and tested on the subjects with a range of cognitive impairment levels. One new metric named fiber anatomical region proportion (FARP), quantifies the ratio of fibers in the defined brain regions and enables the comparison with other methods. Another metric named anatomical region fiber count (ARFC), represents the average fiber number in each cluster for the assessment of inter-subject differences. The experimental results demonstrate that Anat-SFSeg achieves the highest accuracy on HCP datasets and exhibits great generalization on clinical datasets. Diffusion tensor metrics and ARFC show disorder severity associated alterations in patients with Alzheimer's disease (AD) and mild cognitive impairments (MCI). Correlations with cognitive grades show that these metrics are potential neuroimaging biomarkers for AD. Furthermore, Anat-SFSeg could be utilized to explore other neurodegenerative, neurodevelopmental or psychiatric disorders.

Ferrielectricity controlled widely-tunable magnetoelectric coupling in van der Waals multiferroics.

The discovery of various primary ferroic phases in atomically-thin van der Waals crystals have created a new two-dimensional wonderland for exploring and manipulating exotic quantum phases. It may also bring technical breakthroughs in device applications, as evident by prototypical functionalities of giant tunneling magnetoresistance, gate-tunable ferromagnetism and non-volatile ferroelectric memory etc. However, two-dimensional multiferroics with effective magnetoelectric coupling, which ultimately decides the future of multiferroic-based information technology, has not been realized yet. Here, we show that an unconventional magnetoelectric coupling mechanism interlocked with heterogeneous ferrielectric transitions emerges at the two-dimensional limit in van der Waals multiferroic CuCrP2S6 with inherent antiferromagnetism and antiferroelectricity. Distinct from the homogeneous antiferroelectric bulk, thin-layer CuCrP2S6 under external electric field makes layer-dependent heterogeneous ferrielectric transitions, minimizing the depolarization effect introduced by the rearrangements of Cu+ ions within the ferromagnetic van der Waals cages of CrS6 and P2S6 octahedrons. The resulting ferrielectric phases are characterized by substantially reduced interlayer magnetic coupling energy of nearly 50% with a moderate electric field of 0.3 V nm-1, producing widely-tunable magnetoelectric coupling which can be further engineered by asymmetrical electrode work functions.

Nobiletin alleviates cisplatin-induced ototoxicity via activating autophagy and inhibiting NRF2/GPX4-mediated ferroptosis.

Nobiletin, a citrus polymethoxy flavonoid with antiapoptotic and antioxidative properties, could safeguard against cisplatin-induced nephrotoxicity and neurotoxicity. Cisplatin, as the pioneer of anti-cancer drug, the severe ototoxicity limits its clinical applications, while the effect of nobiletin on cisplatin-induced ototoxicity has not been identified. The current study investigated the alleviating effect of nobiletin on cisplatin-induced ototoxicity and the underlying mechanisms. Apoptosis and ROS formation were evaluated using the CCK-8 assay, Western blotting, and immunofluorescence, indicating that nobiletin attenuated cisplatin-induced apoptosis and oxidative stress. LC3B and SQSTM1/p62 were determined by Western blotting, qPCR, and immunofluorescence, indicating that nobiletin significantly activated autophagy. Nobiletin promoted the nuclear translocation of NRF2 and the transcription of its target genes, including Hmox1, Nqo1, and ferroptosis markers (Gpx4, Slc7a11, Fth, and Ftl), thereby inhibiting ferroptosis. Furthermore, RNA sequencing analysis verified that autophagy, ferroptosis, and the NRF2 signaling pathway served as crucial points for the protection of nobiletin against ototoxicity caused by cisplatin. Collectively, these results indicated, for the first time, that nobiletin alleviated cisplatin-elicited ototoxicity through suppressing apoptosis and oxidative stress, which were attributed to the activation of autophagy and the inhibition of NRF2/GPX4-mediated ferroptosis. Our study suggested that nobiletin could be a prospective agent for preventing cisplatin-induced hearing loss.