Ferroelectric tungsten bronze-based ceramics with high-energy storage performance via weakly coupled relaxor design and grain boundary optimization.

A multiscale regulation strategy has been demonstrated for synthetic energy storage enhancement in a tetragonal tungsten bronze structure ferroelectric. Grain refining and second-phase precipitation (perovskite phase) are introduced in the BaSrTiNb2-xTaxO9 ceramics by regulating the composition and sintering process. Disordered polarization and distribution, chemical inhomogeneity, and insulating boundary layers are achieved to provide the fundamental structural origin of the relaxation characteristic, high breakdown strength, and superior energy storage performance. Thus, an ultrahigh energy storage density of 12.2 J cm-3 with an low energy consumption was achieved at an electric field of 950 kV cm-1. This is the highest known energy storage performance in tetragonal tungsten bronze-based ferroelectric. Notably, this ceramic shows remarkable stability over frequency, temperature, and cycling electric fields. This work brings new material candidates and structure design for developing of energy storage capacitors apart from the predominant perovskite ferroelectric ceramics.

Wireless neuromodulation at submillimeter precision via a microwave split-ring resonator.

A broad spectrum of electromagnetic waves has been explored for wireless neuromodulation. Transcranial magnetic stimulation, with long wavelengths, cannot provide submillimeter spatial resolution. Visible light, with its short wavelengths, suffers from strong scattering in the deep tissue. Microwaves have centimeter-scale penetration depth and have been shown to reversibly inhibit neuronal activity. Yet, microwaves alone do not provide sufficient spatial precision to modulate target neurons without affecting surrounding tissues. Here, we report a split-ring resonator (SRR) that generates an enhanced microwave field at its gap with submillimeter spatial precision. With the SRR, microwaves at dosages below the safe exposure limit are shown to inhibit the firing of neurons within 1 mm of the SRR gap site. The microwave SRR reduced seizure activity at a low dose in both in vitro and in vivo models of epilepsy. This microwave dosage is confirmed to be biosafe via histological and biochemical assessment of brain tissue.

Mining and evaluation of adverse event signals for capmatinib based on the FAERS database.

Objective: To conduct a comprehensive data analysis based on the FDA's Adverse Event Reporting System (FAERS) to mine possible adverse event (AE) signals of Capmatinib, providing valuable references for its clinical application. Methods: Capmatinib was the primary suspected drug in the search of FAERS database from the second quarter of 2020 to the fourth quarter of 2023. Data processing, screening, and classification were performed using methods such as the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Results: A total of 1,991 AE reports directly related to Capmatinib were screened, identifying 269 Preferred Terms (PTs) involving 26 System Organ Classes (SOCs). Besides the AEs recorded in the drug label (such as edema, nausea, fatigue, and dyspnea), the study unearthed other high-risk AEs not listed in the label, including Renal and urinary disorders, Vocal cord paralysis, and Ear and labyrinth disorders. Among these, renal and urinary disorders, and ear and labyrinth disorders had a higher frequency and intensity of signals, suggesting that their mechanisms of occurrence could be a future research direction. Conclusion: This study uncovered new potential AEs of Capmatinib based on the FAERS database, providing reference for its safe clinical use. Special attention should be given to the occurrence of ear and labyrinth disorders and renal and urinary disorders, primarily presenting as pseudo-acute kidney injury, during treatment.

Determinant of 30-Day Mortality of Pulmonary Legionellosis: Do Coinfections Matter?

We retrospectively reviewed 64 cases of cancer with pulmonary legionellosis (Legionella pneumophila in 73%). Nearly all patients received Legionella-active antibiotics, yet 30-day mortality was 23%. Independent predictors of 30-day mortality were hyponatremia, bilateral lung involvement, and Sequential Organ Failure Assessment score ≥5. Lung coinfections were common (31%) but did not significantly increase mortality.

Aspirin may be more suitable for patients with major depression: Evidence from two-sample Mendelian randomization analysis.

OBJECTIVE: Utilizing two-sample Mendelian randomization (TSMR) analysis, this study aims to explore the potential bidirectional causal relationship between common nonsteroidal anti-inflammatory drugs (paracetamol, ibuprofen, aspirin) and major depression (MD) from a genetic standpoint. METHODS: We employed summarized data from a Genome-Wide Association Study (GWAS) of European populations. The inverse variance weighted (IVW) method was used for TSMR analysis; outcomes were evaluated based on p-value, OR (Odds Ratio), and 95% confidence interval (95% CI). RESULTS: From a genetic perspective, the study found that the use of paracetamol and ibuprofen increased the risk of MD (IVW (MRE): OR = 2.314, 95% CI: 1.609-3.327; p = 6.07E-06) and (IVW (MRE): OR = 2.308, 95% CI: 1.780-3.653; p = 0.002), respectively. No significant causal relationship was found between aspirin and MD (p > 0.05). Reverse TSMR analysis found that MD increased the genetic predisposition to use paracetamol, ibuprofen, and aspirin (IVW (MRE): OR = 1.042, 95% CI: 1.030-1.054, p = 3.07E-12), (IVW (FE): OR = 1.015, 95% CI: 1.007-1.023, p = 1.13E-04), (IVW (MRE): OR = 1.019, 95% CI: 1.009-1.030, p = 4.22E-04), respectively. Other analytical methods and sensitivity analyses further supported the robustness and reliability of these findings. CONCLUSION: This study provides preliminary genetic evidence through bidirectional TSMR analysis that MD increases the genetic predisposition to use paracetamol, ibuprofen, and aspirin, aiding clinicians in devising preventive strategies against the misuse of non-steroidal anti-inflammatory drugs. Moreover, we found that the use of paracetamol and ibuprofen increases the risk of MD, whereas aspirin did not. This suggests a crucial clinical implication: clinicians treating MD patients could opt for the relatively safer aspirin over paracetamol and ibuprofen.

Analysis of the health status and its influencing factors of the low-income populations in Wuxi, China.

Objective: To understand the physical health condition and its influencing factors among the low-income population. Method: Low-income residents who visited or consulted at our Hospital during 2022 were selected for this study. Through telephone or face-to-face interviews, a self-made basic information questionnaire was used for data collection. The physical health level of the low-income population was analyzed, and a logistic regression model was applied to study its influencing factors. Results: A total of 2,307 people were included in this study, of which 2,069 had various types of diseases, indicating a disease rate of 89.68%. Multivariate logistic regression analysis showed that age ≥ 60 years old (OR = 1.567, 95%CI: 1.122-2.188), poor mental health status (OR = 2.450, 95%CI: 1.203-3.678), smoking (OR = 1.752, 95%CI: 1.269-2.206), pulse pressure difference ≥ 60 (OR = 1.485, 95%CI: 1.164-1.787), and poor hearing (OR = 1.268, 95%CI: 1.026-1.324) were risk factors for disease, whereas being female (OR = 0.729, 95%CI: 0.540-0.984) was a protective factor for physical health. Conclusion: As a developing country with a large population, we should particularly focus on the physical health issues of the low-income population, take targeted measures for disease situations, and improve the quality of life of the low-income population.

Effect of Tryptophan Restriction in the Therapy of Irritable Bowel Syndrome: a Systematic Review.

Background & Aims: The metabolic pathways of tryptophan (TRP) have been implicated in the pathophysiology of irritable bowel syndrome (IBS), positing that the strategic modulation of TRP consumption may exert regulatory effects on serotonin levels, consequently altering the clinical manifestation of IBS. This systematic review was meticulously orchestrated to evaluate the effect of TRP restriction on IBS. Methods: A comprehensive search of the MEDLINE/PubMed, Cochrane Library, and Embase databases was conducted. Controlled trials that compared the efficacy of TRP restriction in IBS patients were scrutinized. The primary outcomes were gastrointestinal symptoms, quality of life, and pain, whereas the secondary outcomes included anxiety, mood, and safety. The risk of bias was meticulously assessed according to the guidelines recommended by the Cochrane Collaboration. Results: A total of five trials, enrolling 135 participants, were incorporated into the qualitative synthesis. Low-TRP intake attenuated gastrointestinal discomfort and enhanced psychological well-being in IBS patients, while the effects of acute TRP depletion were controversial. Safety data from one randomized controlled trial reported no occurrence of adverse events. Conclusion: This systematic review suggests that moderating, rather than depleting, TRP intake may potentially be a feasible and safe adjunctive treatment for patients with IBS. Future research incorporating a high-quality study design and consensus on clinical outcome measurements for IBS is warranted.

Dynamic bTMB combined with residual ctDNA improves survival prediction in locally advanced NSCLC patients with chemoradiotherapy and consolidation immunotherapy.

Background: Liquid biopsy-based biomarkers, including circulating tumor DNA (ctDNA) and blood tumor mutational burden (bTMB), are recognized as promising predictors of prognoses and responses to immune checkpoint inhibitors (ICIs), despite insufficient sensitivity of single biomarker detection. This research aims to determine whether the combinatorial utility of longitudinal ctDNA with bTMB analysis could improve the prognostic and predictive effects. Methods: This prospective two-center cohort trial, consisting of discovery and validation datasets, enrolled unresectable locally advanced non-small-cell lung cancer (LA-NSCLC) patients and assigned them to chemoradiotherapy (CRT) or CRT + consolidation ICI cohorts from 2018 to 2022. Blood specimens were collected pretreatment, 4 weeks post-CRT, and at progression to assess bTMB and ctDNA using 486-gene next-generation sequencing. Dynamic ∆bTMB was calculated as post-CRT bTMB minus baseline bTMB levels. Decision curve analyses were performed to calculate Concordance index (C-index). Results: One hundred twenty-eight patients were enrolled. In the discovery dataset (n = 73), patients treated with CRT and consolidation ICI had significantly longer overall survival (OS; median not reached [NR] vs 20.2 months; P < 0.001) and progression-free survival (PFS; median 25.2 vs 11.4 months; P = 0.011) than those without ICI. Longitudinal analysis demonstrated a significant decrease in ctDNA abundance post-CRT (P < 0.001) but a relative increase with disease progression. Post-CRT detectable residual ctDNA correlated with significantly shorter OS (median 18.3 months vs NR; P = 0.001) and PFS (median 7.3 vs 25.2 months; P < 0.001). For patients with residual ctDNA, consolidation ICI brought significantly greater OS (median NR vs 14.8 months; P = 0.005) and PFS (median 13.8 vs 6.2 months; P = 0.028) benefit, but no significant difference for patients with ctDNA clearance. Dynamic ∆bTMB was predictive of prognosis. Patients with residual ctDNA and increased ∆bTMB (∆bTMB > 0) had significantly worse OS (median 9.0 vs 23.0 months vs NR; P < 0.001) and PFS (median 3.4 vs 7.3 vs 25.2 months; P < 0.001). The combinatorial model integrating post-CRT ctDNA with ∆bTMB had optimal predictive effects on OS (C-index = 0.723) and PFS (C-index = 0.693), outperforming individual features. In the independent validation set, we confirmed residual ctDNA predicted poorer PFS (median 50.8 vs 14.3 months; P = 0.026) but identified more consolidation ICI benefit (median NR vs 8.3 months; P = 0.039). The combined model exhibited a stable predictive advantage (C-index = 0.742 for PFS). Conclusions: The multiparameter assay integrating qualitative residual ctDNA testing with quantitative ∆bTMB dynamics improves patient prognostic risk stratification and efficacy predictions, allowing for personalized consolidation therapy for LA-NSCLC.

Clinical characteristics, in-hospital management, and outcomes among patients hospitalized for acute ischemic stroke in rural versus urban hospitals in China: A nationwide hospital-based study.

BACKGROUND: Efforts to improve rural stroke care have intensified in China. However, high-quality comprehensive data on the differences in care and outcomes between rural and urban hospitals are limited. METHODS: We analyzed data on patients with acute ischemic stroke hospitalized in the China Stroke Center Alliance hospitals from 2015 to 2022. The in-hospital management measures assessed included nine acute and five discharge management measures. Outcomes evaluated included death or discharge against medical advice (DAMA), major adverse cardiovascular events (MACE), disability at discharge, and in-hospital complications. RESULTS: We enrolled 1,583,271 patients with acute ischemic stroke from 1930 hospitals, comprising 1086 (56.3%) rural sites with 735,452 patients and 844 (43.7%) urban sites with 847,891 patients. Patients in rural hospitals demonstrate suboptimal management measures compared to those in urban hospitals, including lower rates of intravenous recombinant tissue plasminogen activator within 4.5 h (26.0% vs 28.3%; difference: -2.3% (-2.5% to -2.0%)), endovascular treatment (0.6% vs 1.9%; difference: -1.3% (-1.3% to -1.2%)), vessel assessment (88.5% vs 92.0%; difference: -3.5% (95% confidence interval (CI): -3.6% to -3.4%)), and anticoagulants for atrial fibrillation at discharge (42.9% vs 47.7%; difference: -4.8% (95% CI: -5.4% to -4.2%)). Overall, the rural-urban disparity in in-hospital outcomes was small. Rural patients had a slightly higher rate of in-hospital death/DAMA (9.0% vs 8.0%; adjusted odds ratio (OR): 1.22 (95% CI: 1.20-1.23); adjusted risk difference (aRD): 1.3% (95% CI: 1.2%-1.4%)) and a slightly lower rate of complications (10.9% vs 13.0%; aOR: 0.83 (95% CI: 0.82-0.84); aRD: -1.3% (95% CI: -1.3% to -1.3%)). No notable rural-urban differences were observed in MACE and disability at discharge. CONCLUSION: Patients in rural hospitals demonstrated suboptimal management measures and had higher rates of in-hospital death/DAMA compared to those in urban hospitals. Prioritizing the allocation of health resources to rural hospitals is essential to improve healthcare quality and outcomes. DATA ACCESS STATEMENT: The data supporting the findings of this study are available from the corresponding author upon reasonable request.

Humoral Immunity and Antibody Responses against Diphtheria, Tetanus, and Pneumococcus after Immune Effector Cell Therapies: A Prospective Study.

Patients undergoing immune effector cell therapy (IECT) are at high risk for infections. We assessed seropositivity against pneumococcus, tetanus, and diphtheria in patients before and after IECT and the patients' response to vaccination. We enrolled patients who underwent IECT from January 2020 to March 2022. Antibody levels for diphtheria, tetanus, and pneumococcus were measured before IECT, at 1 month, and 3-6 months after. Eligible patients were vaccinated after IECT. In non-seroprotected patients, we discontinued testing. Before IECT, most patients had seroprotective antibody levels against tetanus (68/69, 99%) and diphtheria (65/69, 94%), but fewer did against pneumococcus (24/67, 36%). After IECT, all patients had seroprotective antibody levels for tetanus at 1 month (68/68) and 3-6 months (56/56). For diphtheria, 65/65 patients (100%) had seroprotective antibody levels at 1 month, and 48/53 (91%) did at 3-6 months. For pneumococcus, seroprotective antibody levels were identified in 91% (21/23) of patients at 1 month and 79% (15/19) at 3-6 months following IECT. Fifteen patients received a pneumococcal vaccine after IECT, but none achieved seroprotective response. One patient received the tetanus-diphtheria vaccine and had a seroprotective antibody response. Because some patients experience loss of immunity after IECT, studies evaluating vaccination strategies post-IECT are needed.

Effect of light conditions on phycoerythrin accumulation by thermophilic cyanobacterium Leptothermofonsia sichuanensis and characterization of pigment stability.

Phycoerythrin (C-PE) is a cyanobacterial phycobiliprotein with extensive applications. This work sought to investigate the effects of various light conditions on C-PE accumulation by thermophilic Leptothermofonsia sichuanensis and characterize its C-PE stability and purity. Accumulation of C-PE as the predominant phycobiliprotein was significantly affected by light regime and light colours, reaching the highest C-PE accumulation (21.92 mg/gDCW) under blue light. Importantly, the results suggested the superior C-PE thermostability of Leptothermofonsia than the mesophilic counterparts and good pH stability at a range of 4 to 7. Additionally, C-PE indicated advantageous potential for preservation as revealed by photostability experiments. Moreover, sorbitol, sucrose, and NaCl can further stabilise C-PE at 60 °C, of which 10 % sorbitol is the most effective. The extraction process herein resulted in a C-PE purity of 2.68, much higher than the food grade. Collectively, this work demonstrates the Leptothermofonsia strain as a promising bioresource for thermostable C-PE production.

Correction: Huang et al. Endogenous Propionibacterium acnes Promotes Ovarian Cancer Progression via Regulating Hedgehog Signalling Pathway. Cancers 2022, 14, 5178.

In the original publication [...].

Increased neuronal expression of the early endosomal adaptor APPL1 leads to endosomal and synaptic dysfunction with cholinergic neurodegeneration.

Dysfunction of the endolysosomal system within neurons is a prominent feature of Alzheimer's disease (AD) pathology. Multiple AD-risk factors are known to cause hyper-activity of the early-endosome small GTPase rab5, resulting in neuronal endosomal pathway disruption. APPL1, an important rab5 effector protein, is an interface between endosomal and neuronal function through a rab5-activating interaction with the BACE1-generated C-terminal fragment (ßCTF or C99) of the amyloid precursor protein (APP), a pathogenic APP fragment generated within endolysosomal compartments. To better understand the role of APPL1 in the AD endosomal phenotype, we generated a transgenic mouse model over-expressing human APPL1 within neurons (Thy1-APPL1 mice). Consistent with the important endosomal regulatory role of APPL1, Thy1-APPL1 mice have enlarged neuronal early endosomes and increased synaptic endocytosis due to increased rab5 activation. We additionally demonstrate pathological consequences of APPL1 overexpression, including functional changes in hippocampal long-term potentiation (LTP) and long-term depression (LTD), as well as degeneration of the large projection cholinergic neurons of the basal forebrain and impairment of hippocampal-dependent memory. Our findings show that increased neuronal APPL1 levels lead to a cascade of pathological effects within neurons, including early endosomal alterations, synaptic dysfunction, and neurodegeneration. Multiple risk factors and molecular regulators, including APPL1 activity, are known to contribute to the endosomal dysregulation seen in the early stages of AD, and these findings further highlight the shared pathobiology and consequences to a neuron of early endosomal pathway disruption. Significance Statement: Dysfunction in the endolysosomal system within neurons is a key feature of Alzheimer's disease (AD). Multiple AD risk factors lead to hyperactivity of the early-endosome GTPase rab5, disrupting neuronal pathways including the cholinergic circuits involved early in memory decline. APPL1, a crucial rab5 effector, connects endosomal and neuronal functions through its interaction with a specific amyloid precursor protein (APP) fragment generated within endosomes. To understand APPL1's role, a transgenic mouse model over-expressing human APPL1 in neurons (Thy1-APPL1 mice) was developed. These mice show enlarged early endosomes and increased synaptic endocytosis due to rab5 activation, resulting in impaired hippocampal long-term potentiation and depression, the degeneration of basal forebrain cholinergic neurons, and memory deficits, highlighting a pathological cascade mediated through APPL1 at the early endosome.

Antibacterial effect of Cu2O/TiO2 visible-light photocatalytic composite on Xanthomonas campestris.

In this study, a Cu2O/TiO2 (CuTi) visible-light photocatalytic composite was employed for the treatment of Xanthomonas campestris and X. campestris-infected Brassica napus seedlings. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values against X. campestris were determined to be 8 and 32 µg ml-1, respectively. Transmission electron microscopy analysis demonstrated a direct correlation between the extent of bacterial cell damage and the concentration of CuTi. Noteworthily, a bactericidal rate of 100% was achieved at a concentration of 150 µg ml-1 over a treatment duration of 120 min. Moreover, alterations in active oxidants and antioxidants, including reactive oxygen species, glutathione reductase, superoxide dismutase, peroxidase, and catalase within the bacterial cells, were examined to elucidate the underlying mechanism of inhibition by the CuTi. The B. napus infected by X. campestris was treated with CuTi, and the efficacy was validated through determination of plant resistance indexes. The combined data confirmed that the CuTi is characterized by a low dose, fast onset, good effect, and higher safety for killing X. campestris, and it is expected to be developed as an antimicrobial agent for vegetables.

Fungibility, accessibility and clinical utility of remote electronic fetal monitoring in improving maternal emotional status compared with traditional method: A multicenter prospective cohort analysis.

OBJECTIVE: Supported by remote signal processing techniques and wireless communication technology, remote electronic fetal monitoring (REFM) has emerged as a promising alternative to traditional electronic fetal monitoring (TEFM) in clinical practice. The aim of this study was to evaluate the comparability, accessibility, and clinical utility of REFM in contrast to TEFM. METHODS: This was a multicenter prospective cohort study. A cohort of 2900 pregnant women were enrolled from three medical centers between June 1, 2021 and June 31, 2022. Among them, 800 utilized REFM, with 760 of them completing the self-rating anxiety scale (SAS) and self-rating depression scale (SDS) assessments using the devices for 1 month. The control group comprised 2100 pregnant women who did not use REFM. Additionally, 80 pregnant women concurrently employed both REFM and TEFM, and their respective curve coincidence rates were determined through curve fitting. Primary outcomes encompassed pregnancy outcomes in both groups, average curve coincidence rates between REFM and TEFM, as well as SDS and SAS scores. RESULTS: Among the 760 pregnant women who completed SAS and SDS assessments, their average SAS scores before and after 1 month of REFM usage were 43.09 ± 8.04 and 41.58 ± 6.59, respectively. Concurrently, the average SDS scores before and after 1 month of REFM usage were 45.45 ± 9.60 and 44.80 ± 9.17, respectively. A statistically significant decrease was observed in SAS scores (P = 0.005), whereas no significant difference was noted in SDS scores (P = 0.340). Furthermore, a statistically significant difference in the rate of adverse pregnancy outcomes (neonatal asphyxia) emerged between the two groups, those who employed REFM and those who did not (P = 0.021). In the subset of 80 pregnant women employing both REFM and TEFM, all 80 results showed precise congruence between the two methods. The average coincidence rate was determined to be 79.45% ± 12.64%. CONCLUSION: REFM contributes to improved pregnancy outcomes and exhibits a high level of concordance with TEFM, thereby accurately reflecting the quality of fetal heart monitoring. Additionally, REFM effectively mitigates pregnant women's anxiety. Thus, REFM demonstrates comparability, accessibility, and clinical utility.

Multivariate analysis of metabolic state vulnerabilities across diverse cancer contexts reveals synthetically lethal associations.

Targeting the distinct metabolic needs of tumor cells has recently emerged as a promising strategy for cancer therapy. The heterogeneous, context-dependent nature of cancer cell metabolism, however, poses challenges to identifying effective therapeutic interventions. Here, we utilize various unsupervised and supervised multivariate modeling approaches to systematically pinpoint recurrent metabolic states within hundreds of cancer cell lines, elucidate their association with tumor lineage and growth environments, and uncover vulnerabilities linked to their metabolic states across diverse genetic and tissue contexts. We validate key findings via analysis of data from patient-derived tumors and pharmacological screens and by performing genetic and pharmacological experiments. Our analysis uncovers synthetically lethal associations between the tumor metabolic state (e.g., oxidative phosphorylation), driver mutations (e.g., loss of tumor suppressor PTEN), and actionable biological targets (e.g., mitochondrial electron transport chain). Investigating the mechanisms underlying these relationships can inform the development of more precise and context-specific, metabolism-targeted cancer therapies.

Dysregulation and impaired anti-bacterial potential of mucosal-associated invariant T cells in autoimmune liver diseases.

Autoimmune liver diseases (AILD) encompass a group of conditions in which the immune system mistakenly attacks the liver tissue. Mucosal-associated invariant T (MAIT) cells are enriched in the liver, where they play crucial roles in antibacterial defense and inflammation regulation. Compared to other autoimmune conditions affecting the synovium of the joints, MAIT cells from AILD exhibited a greater deficiency in ratio, elevated activation markers, increased apoptosis, and higher pro-inflammatory cytokines production. However, the frequency of MAIT cells in AILD was negatively correlated with anti-bacterial indexes, and their impaired responsiveness and weakened anti-bacterial potential were evidenced by reduced expansion ability, lower maximal IFN-γ production, and diminished E. coli-induced cytotoxic mediators release. Similar shifts in MAIT cell ratios and phenotypes were observed in both primary biliary cirrhosis and autoimmune hepatitis, linked to upregulation of bile acid components in the affected tissue. Specifically, ursodeoxycholic acid, a metabolic intermediate and traditional anti-primary biliary cirrhosis drug, inhibited TCR-mediated expansion and downregulated pro-inflammatory cytokines and anti-bacterial-related mediators in MAIT cells. These findings underscore the intricate interplay between hepatic pathology and MAIT cells, and highlight the importance of antibacterial monitoring during ursodeoxycholic acid treatment in AILD.

A self-healing composite solid electrolyte with dynamic three-dimensional inorganic/organic hybrid network for flexible all-solid-state lithium metal batteries.

Composite solid electrolytes (CSEs), which combine the advantages of solid polymer electrolytes and inorganic solid electrolytes, are considered to be promising electrolytes for all-solid-state lithium metal batteries. However, the current CSEs suffer from defects such as poor inorganic/organic interface compatibility, lithium dendrite growth, and easy damage of electrolyte membrane, which hinder the practical application of CSEs. Herein, a CSE (PBHL@LLZTO@DDB) with polyurethane (PBHL) as the polymer matrix and Li6.4La3Zr1.4Ta0.6O12 (LLZTO) modified by silane coupling agent (DDB) as inorganic fillers (LLZTO@DDB) has been prepared. Disulfide bond exchange reactions between PBHL and LLZTO@DDB enable PBHL@LLZTO@DDB to form a dynamic three-dimensional (3D) inorganic/organic hybrid network, which promotes the uniform dispersion of LLZTO in PBHL@LLZTO@DDB, improves the Li+ conductivity (1.24 ± 0.08 × 10-4 S cm-1 at 30 â„ƒ), and broadens the electrochemical stability window (5.16 V vs. Li+/Li). Moreover, a combination of hydrogen bonds and disulfide bonds endows PBHL@LLZTO@DDB with excellent self-healing properties. As such, both all-solid-state symmetric and full cells exhibit excellent cycle performance at ambient temperature. More importantly, the healed PBHL@LLZTO@DDB can almost completely restore its original electrochemical properties, indicating its application potential in flexible electronic products.

ZIKV induces P62-mediated autophagic degradation of TRAF6 through TRAF6-NS1 interaction.

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is crucial in flavivirus infections, modulating the host immune response through interactions with viral proteins. Despite its importance, the relationship between TRAF6 and Zika virus (ZIKV) remains poorly understood. Our prior proteomics analysis revealed reduced TRAF6 protein levels in ZIKV-infected human trophoblast cells compared to non-infected controls. Subsequent studies in cell models and murine tissues confirmed a significant reduction in both TRAF6 mRNA and protein levels post-ZIKV infection. Further investigations unveiled that ZIKV induces P62-mediated degradation of TRAF6, with NS1 identified as the primary contributor. Co-localization and interaction studies demonstrated that NS1 promotes the association of P62, a key autophagy mediator, with TRAF6. Notably, our findings revealed TRAF6 enhances ZIKV infection, NS1 ubiquitination, NS1 expression, and the production of inflammatory cytokines and chemokines. These insights highlight the intricate TRAF6-ZIKV relationship, offering potential for drug targeting NS1-TRAF6 interactions to manage ZIKV infections effectively.

AgI Precipitation Induced Polarity Reversal with Formation of Z-Type Heterojunction for Photoelectrochemical Sensing.

Regulating photocurrent polarity is highly attractive for fabricating photoelectrochemical (PEC) biosensors with improved sensitivity and accuracy in practical samples. Here, a new approach that adopts the in situ generated AgI precipitate and AgNCs to reversal Bi2WO6 polarity with formation of Z-type heterojunction was proposed for the first time, which coupled with a high-efficient target conversion strategy of exonuclease III (Exo III)-assisted triple recycling amplification for sensing miRNA-21. The target-related DNA nanospheres in situ generated on electrode with loading of plentiful AgI and AgNCs not only endowed the photocurrent of Bi2WO6 switching from the anodic to cathodic one due to the changes in the electron transfer pathway but also formed AgI/AgNCs/Au/Bi2WO6 Z-type heterojunction to improve the photoelectric conversion efficiency for acquiring extremely enhanced PEC signal, thereby significantly avoiding the problem of high background signal derived from traditional unidirectional increasing/decreasing response and false-positive/false-negative. Experimental data showed that the PEC biosensor had a low detection limit down to 0.085 fM, providing a new polarity-reversal mechanism and expected application in diverse fields, including biomedical research and clinical diagnosis.