Abrogating K458 acetylation enhances hepatocyte nuclear factor 4α (HNF4α)-induced differentiation therapy for hepatocellular carcinoma.

OBJECTIVES: In this study we aimed to assess the impact of acetylation of hepatocyte nuclear factor 4α (HNF4α) on lysine 458 on the differentiation therapy of hepatocellular carcinoma (HCC). METHODS: Periodic acid-Schiff (PAS) staining, Dil-acetylated low-density lipoprotein (Dil-Ac-LDL) uptake, and senescence-associated ß-galactosidase (SA-ß-gal) activity analysis were performed to assess the differentiation of HCC cells. HNF4α protein was detected by western blot and immunohistochemistry (IHC). The effects of HNF4α-K458 acetylation on HCC malignancy were evaluated in HCC cell lines, a Huh-7 xenograft mouse model, and an orthotopic model. The differential expression genes in Huh-7 xenograft tumors were screened by RNA-sequencing analysis. RESULTS: K458R significantly enhanced the inhibitory effect of HNF4α on the malignancy of HCC cells, whereas K458Q reduced the inhibitory effects of HNF4α. Moreover, K458R promoted, while K458Q decreased, HNF4α-induced HCC cell differentiation. K458R stabilized HNF4α, while K458Q accelerated the degradation of HNF4α via the ubiquitin proteasome system. K458R also enhanced the ability of HNF4α to inhibit cell growth of HCC in the Huh-7 xenograft mouse model and the orthotopic model. RNA-sequencing analysis revealed that inhibiting K458 acetylation enhanced the transcriptional activity of HNF4α without altering the transcriptome induced by HNF4α in HCC. CONCLUSION: Our data revealed that inhibiting K458 acetylation of HNF4α might provide a more promising candidate for differential therapy of HCC.

Digital versus non-digital health interventions to improve iron supplementation in pregnant women: a systematic review and meta-analysis.

Objective: To investigate the effects of digital health interventions for improving adherence to oral iron supplementation in pregnant women. Literature search: Five databases were searched from their inception to October 2023 with no date restrictions. Study selection: Randomized controlled trials (RCTs) that assessed the effects of digital health interventions on adherence to oral iron supplementation (e.g., tablets and capsules) compared to non-digital health interventions for pregnant women were eligible. Data synthesis: We calculated standardized mean differences (SMDs) and mean differences (MDs) with 95% confidence intervals (CIs) for continuous variables using the inverse variance method. We calculated odds ratios (OR) with 95%CI for categorical variables using the Mantel-Haenszel model. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The risk of bias of the included RCTs was assessed using the Cochrane risk of bias tool 2.0. Results: Ten trials with 1,633 participants were included. Based on 7 trials, digital health interventions can improve objective adherence rate comparing with non-digital health interventions (1,289 participants, OR = 4.07 [2.19, 7.57], p < 0.001, I2 = 69%) in pregnant women. Digital health interventions can improve subjective adherence behavior comparing with non-digital health interventions (3 trials, 434 participants, SMD = 0.82 [0.62, 1.01], p < 0.001, I2 = 0%) in pregnant women. Based on 3 trials, digital health interventions can improve tablets consumption comparing with non-digital health interventions (333 participants, SMD = 1.00 [0.57, 1.42], p < 0.001, I2 = 66%) in pregnant women. Digital health interventions can improve hemoglobin level comparing with non-digital health interventions (7 trials, 1,216 participants, MD = 0.59 [0.31, 0.88], p < 0.001, I2 = 93%) in pregnant women. Conclusion: Digital health interventions were effective at improving adherence to oral iron supplementation and hemoglobin levels in pregnant women.

Control of Multi-Fluorination Number and Position in D-π-A Type Polymers and Their Impact on High-Voltage Organic Photovoltaics.

Exploring the structure-performance relationship of high-voltage organic solar cells (OSCs) is significant for pushing material design and promoting photovoltaic performance. Herein, we chose a D-π-A type polymer composed of 4,8-bis(thiophene-2-yl)-benzo[1,2-b:4,5-b']dithiophene (BDT-T) and benzotriazole (BTA) units as the benchmark to investigate the effect of the fluorination number and position of the polymers on the device performance of the high-voltage OSCs, with a benzotriazole-based small molecule (BTA3) as the acceptor. F00, F20, and F40 are the polymers with progressively increasing F atoms on the D units, while F02, F22, and F42 are the polymers with further attachment of F atoms to the BTA units based on the above three polymers. Fluorination positively affects the molecular planarity, dipole moment, and molecular aggregations. Our results show that VOC increases with the number of fluorine atoms, and fluorination on the D units has a greater effect on VOC than on the A unit. F42 with six fluorine atom substitutions achieves the highest VOC (1.23 V). When four F atoms are located on the D units, the short-circuit current (JSC) and fill factor (FF) plummet, and before that, they remain almost constant. The drop in JSC and FF in F40- and F42-based devices may be attributed to inefficient charge transfer and severe charge recombination. The F22:BTA3 system achieves the highest power conversion efficiency of 9.5% with a VOC of 1.20 V due to the excellent balance between the photovoltaic parameters. Our study provides insights for the future application of fluorination strategies in molecular design for high-voltage organic photovoltaics.

AMPK induces PIAS3 mediated SUMOylation of E3 ubiquitin ligase Smurf1 impairing osteogenic differentiation and traumatic heterotopic ossification.

AMP-activated protein kinase (AMPK) is a typical sensor of intracellular energy metabolism. Our previous study revealed the role of activated AMPK in the suppression of osteogenic differentiation and traumatic heterotopic ossification, but the underlying mechanism remains poorly understood. The E3 ubiquitin ligase Smurf1 is a crucial regulator of osteogenic differentiation and bone formation. We report here that Smurf1 is primarily SUMOylated at a C-terminal lysine residue (K324), which enhances its activity, facilitating ALK2 proteolysis and subsequent bone morphogenetic protein (BMP) signaling pathway inhibition. Furthermore, SUMOylation of the SUMO E3 ligase PIAS3 and Smurf1 SUMOylation was suppressed during the osteogenic differentiation and traumatic heterotopic ossification. More importantly, we found that AMPK activation enhances the SUMOylation of Smurf1, which is mediated by PIAS3 and increases the association between PIAS3 and AMPK. Overall, our study revealed that Smurf1 can be SUMOylated by PIAS3, Furthermore, Smurf1 SUMOylation mediates osteogenic differentiation and traumatic heterotopic ossification through suppression of the BMP signaling pathway. This study revealed that promotion of Smurf1 SUMOylation by AMPK activation may be implicated in traumatic heterotopic ossification treatment.

Angiogenesis in heterotopic ossification: From mechanisms to clinical significance.

Heterotopic ossification (HO) refers to the formation of pathologic bone in nonskeletal tissues (including muscles, tendons or other soft tissues). HO typically occurs after a severe injury and can occur in any part of the body. HO lesions are highly vascularized. Angiogenesis, which is the formation of new blood vessels, plays an important role in the pathophysiology of HO. Surgical resection is considered an effective treatment for HO. However, it is difficult to completely remove new vessels, which can lead to the recurrence of HO and is often accompanied by significant problems such as intraoperative hemorrhage, demonstrating the important role of angiogenesis in HO. Here, we broadly summarize the current understanding of how angiogenesis contributes to HO; in particular, we focus on new insights into the cellular and signaling mechanisms underlying HO angiogenesis. We also review the development and current challenges associated with antiangiogenic therapy for HO.

Tripartite motif 8 promotes the progression of hepatocellular carcinoma via mediating ubiquitination of HNF1α.

Tripartite motif 8 (TRIM8) is an E3 ligase that plays dual roles in various tumor types. The biological effects and underlying mechanism of TRIM8 in hepatocellular carcinoma (HCC) remain unknown. Hepatocyte nuclear factor 1α (HNF1α) is a key transcriptional factor that plays a significant role in regulating hepatocyte differentiation and liver function. The reduced expression of HNF1α is a critical event in the development of HCC, but the underlying mechanism for its degradation remains elusive. In this study, we discovered that the expression of TRIM8 was upregulated in HCC tissues, and was positively correlated with aggressive tumor behavior of HCC and shorter survival of HCC patients. Overexpression of TRIM8 promoted the proliferation, colony formation, invasion, and migration of HCC cells, while TRIM8 knockdown or knockout exerted the opposite effects. RNA sequencing revealed that TRIM8 knockout suppresses several cancer-related pathways, including Wnt/ß-catenin and TGF-ß signaling in HepG2 cells. TRIM8 directly interacts with HNF1α, promoting its degradation by catalyzing polyubiquitination on lysine 197 in HCC cells. Moreover, the cancer-promoting effects of TRIM8 in HCC were abolished by the HNF1α-K197R mutant in vitro and in vivo. These data demonstrated that TRIM8 plays an oncogenic role in HCC progression through mediating the ubiquitination of HNF1α and promoting its protein degradation, and suggests targeting TRIM8-HNF1α may provide a promising therapeutic strategy of HCC.

miR-221-3p as a potential biomarker of chronic periodontitis and its regulatory effect on inflammatory response.

PURPOSE: To explore the function of miR-221-3p in the development and course of chronic periodontitis (CP) and offer a fresh avenue for CP diagnosis and management. METHODS: miR-221-3p expression was detected by RT-qPCR. The clinical diagnostic value of miR-221-3p in CP patients was analyzed by receiver operating characteristic (ROC). ELISA was used to determine the IL-1ß and IL-6 in CP subjects and healthy controls. Pearson correlation analysis was performed with miR-221-3p. PDLCs were induced by LPS, transfected with miR-221-3p mimics, and their expression was analyzed for the effects of IL-1ß, and IL-6. RESULTS: The miR-221-3p expression was lower in the gingival sulcus fluid GCF of CP subjects compared to healthy controls. miR-221-3p showed high potential for clinical diagnosis in CP patients by ROC analysis, with high specificity and sensitivity. miR-221-3p was negatively correlated with Probing pocket depth (PD), Attachment loss (AL), Plaque index (PI), and Bleeding index (BI), and negatively correlated with inflammatory factors IL-1ß and IL-6. In LPS-induced PDLCs, IL-1ß and IL-6 were significantly increased, whereas miR-221-3p was significantly downregulated. Overexpression of miR-221-3p inhibited the production of inflammatory factors IL-1ß and IL-6 in LPS-induced PDLCs. CLINICAL SIGNIFICANCE: miR-221-3p expression may be a potential biological marker for the diagnosis of chronic periodontitis and provide a new direction for its treatment of chronic periodontitis.

Pirfenidone and nintedanib exert additive antifibrotic effects by the SPP1-AKT pathway in macrophages and fibroblasts.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disease with high mortality rates. It has been shown that pirfenidone (PFD) and nintedanib (Ofev) can slow down the decline in lung function of IPF patients, but their efficacy remains suboptimal. Some studies have suggested that the combination of PFD and Ofev may yield promising results. However, there is a lack of research on the combined application of these two medications in the treatment of IPF. A mouse model of bleomycin-induced (BLM) pulmonary fibrosis was established to investigate the impact of combination therapy on pulmonary fibrosis of mice. The findings demonstrated a significant reduction in lung tissue damage in mice treated with the combination therapy. Subsequent transcriptome analysis identified the differential gene secreted phosphoprotein 1 (SPP1), which was found to be associated with macrophages and fibroblasts based on multiple immunofluorescence staining results. Analysis of a phosphorylated protein microarray indicated that SPP1 plays a regulatory role in macrophages and fibroblasts via the AKT pathway. Consequently, the regulation of macrophages and fibroblasts in pulmonary fibrosis by the combination of PFD and Ofev is mediated by SPP1 through the AKT pathway, potentially offering a novel therapeutic option for IPF patients. Further investigation into the targeting of SPP1 for the treatment of pulmonary fibrosis is warranted.

Dynamic molecular signatures of acute myocardial infarction based on transcriptomics and metabolomics.

Acute myocardial infarction (AMI) commonly precedes ventricular remodeling, heart failure. Few dynamic molecular signatures have gained widespread acceptance in mainstream clinical testing despite the discovery of many potential candidates. These unmet needs with respect to biomarker and drug discovery of AMI necessitate a prioritization. We enrolled patients with AMI aged between 30 and 70. RNA-seq analysis was performed on the peripheral blood mononuclear cells collected from the patients at three time points: 1 day, 7 days, and 3 months after AMI. PLC/LC-MS analysis was conducted on the peripheral blood plasma collected from these patients at the same three time points. Differential genes and metabolites between groups were screened by bio-informatics methods to understand the dynamic changes of AMI in different periods. We obtained 15 transcriptional and 95 metabolite expression profiles at three time points after AMI through high-throughput sequencing. AMI-1d: enrichment analysis revealed the biological features of 1 day after AMI primarily included acute inflammatory response, elevated glycerophospholipid metabolism, and decreased protein synthesis capacity. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) might stand promising biomarkers to differentiate post-AMI stage. Anti-inflammatory therapy during the acute phase is an important direction for preventing related pathology. AMI-7d: the biological features of this stage primarily involved the initiation of cardiac fibrosis response and activation of platelet adhesion pathways. Accompanied by upregulated TGF-beta signaling pathway and ECM receptor interaction, GP5 help assess platelet activation, a potential therapeutic target to improve haemostasis. AMI-3m: the biological features of 3 months after AMI primarily showed a vascular regeneration response with VEGF signaling pathway, NOS3 and SHC2 widely activated, which holds promise for providing new therapeutic approaches for AMI. Our analysis highlights transcriptional and metabolomics signatures at different time points after MI, which deepens our understanding of the dynamic biological responses and associated molecular mechanisms that occur during cardiac repair.

Detection of pTDP-43 via routine muscle biopsy: A promising diagnostic biomarker for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP-43 aggregates. Recent evidence has been indicated that phosphorylated TDP-43 (pTDP-43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP-43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP-43 detectable in routine biopsied muscles? (ii) Can detection of pTDP-43 aggregation discriminate between ALS and non-ALS patients? (iii) Can pTDP-43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non-ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP-43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP-43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non-ALS controls (16/54; p < 0.001). The pTDP-43 aggregates were mainly close to the sarcolemma. Using a semi-quantified pTDP-43 aggregates score, we applied a cut-off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP-43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof-of-concept for the detection of pTDP-43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS.

Electronic Structure Modulation Via Iron-Incorporated NiO to Boost Urea Oxidation/Oxygen Evolution Reaction.

The urea-assisted water splitting not only enables a reduction in energy consumption during hydrogen production but also addresses the issue of environmental pollution caused by urea. Doping heterogeneous atoms in Ni-based electrocatalysts is considered an efficient means for regulating the electronic structure of Ni sites in catalytic processes. However, the current methodologies for synthesizing heteroatom-doped Ni-based electrocatalysts exhibit certain limitations, including intricate experimental procedures, prolonged reaction durations, and low product yield. Herein, Fe-doped NiO electrocatalysts were successfully synthesized using a rapid and facile solution combustion method, enabling the synthesis of 1.1107 g within a mere 5 min. The incorporation of iron atoms facilitates the modulation of the electronic environment around Ni atoms, generating a substantial decrease in the Gibbs free energy of intermediate species for the Fe-NiO catalyst. This modification promotes efficient cleavage of C-N bonds and consequently enhances the catalytic performance of UOR. Benefiting from the tunability of the electronic environment around the active sites and its efficient electron transfer, Fe-NiO electrocatalysts only needs 1.334 V to achieve 50 mA cm-2 during UOR. Moreover, Fe-NiO catalysts were integrated into a dual electrode urea electrolytic system, requiring only 1.43 V of cell voltage at 10 mA cm-2.

[Exosomes derived from bone marrow mesenchymal stem cells regulate NF-κB pathway and reduce lung ischemia-reperfusion injury in rats by miR-335].

This study aimed to investigate the effect of exosomes derived from bone marrow mesenchymal stem cells (BMSCs-EXO) on lung ischemia-reperfusion injury (IRI) in rats and to explore the role of miR-335. The model of rat lung IRI was established by clipping the hilum of left lung for 60 min and opening for 180 min. Forty Sprague-Dawley rats were randomly divided into sham group, IRI group, IRI+PBS group, IRI+EXO group, and IRI+miR-335 inhibitor EXO (IRI+inhibitor-EXO) group (n = 8). Rats in the sham group underwent thoracotomies without IRI. Rats in the IRI group were used to establish IRI model without any additional treatment. In the IRI+PBS, IRI+EXO, and IRI+inhibitor-EXO groups, the rats were used to establish IRI model and given PBS, EXO from BMSCs without any treatment, and EXO from BMSCs with miR-335 inhibitor treatment before reperfusion, respectively. Blood gases were analyzed during the experiment. Lung tissue wet/dry ratio (W/D), interleukin 1ß (IL-1ß), tumor necrosis factor α (TNF-α), myeloperoxidase (MPO), malondialdehyde (MDA), and superoxide dismutase (SOD) were measured at the end of reperfusion. Mitochondria were observed by electron microscopy and the Flameng scores were counted. Lung histopathology and apoptosis (TUNEL staining) were observed by light microscopy, and the lung injury scores (LIS) and apoptosis index (AI) were detected. The miR-335 expression was detected by RT-qPCR, and the expression of caspase-3, cleaved-caspase-3, caspase-9, cleaved-caspase-9, and NF-κB proteins were detected by Western blot at the end of reperfusion. The results showed that compared with the sham group, the oxygenation index, pH, and base excess (BE) were significantly lower in the IRI group and IRI+PBS group after reperfusion, whereas those indices were significantly higher in the IRI+EXO group than those in the IRI+PBS group (P < 0.05). Compared with the sham group, there were significant increases in W/D, IL-1ß, TNF-α, MPO, MDA, LIS, AI, Flameng score, caspase-3, cleaved-caspase-3, caspase-9, and cleaved-caspase-9, however significant decreases in the SOD, miR-335 and NF-κB in the IRI group (P < 0.05). These indices in the IRI and IRI+PBS groups showed no significant differences. Compared with the IRI+PBS group, there were significant decreases in W/D, IL-1ß, TNF-α, MPO, MDA, LIS, AI, Flameng score, caspase-3, cleaved-caspase-3, caspase-9, and cleaved-caspase-9, however significant increases in the SOD, miR-335 and NF-κB in the IRI+EXO group (P < 0.05). While, the changes of the above mentioned indices were reversed in the IRI+inhibitor-EXO group compared with IRI+EXO group, which were still better than those in the IRI+PBS group (P < 0.05). The results suggest that BMSCs-EXO could attenuate lung IRI in rats, activate NF-κB pathway, and maintain mitochondrial stability by up-regulating miR-335.

SRY-Box transcription factor 9 triggers YAP nuclear entry via direct interaction in tumors.

The translocation of YAP from the cytoplasm to the nucleus is critical for its activation and plays a key role in tumor progression. However, the precise molecular mechanisms governing the nuclear import of YAP are not fully understood. In this study, we have uncovered a crucial role of SOX9 in the activation of YAP. SOX9 promotes the nuclear translocation of YAP by direct interaction. Importantly, we have identified that the binding between Asp-125 of SOX9 and Arg-124 of YAP is essential for SOX9-YAP interaction and subsequent nuclear entry of YAP. Additionally, we have discovered a novel asymmetrical dimethylation of YAP at Arg-124 (YAP-R124me2a) catalyzed by PRMT1. YAP-R124me2a enhances the interaction between YAP and SOX9 and is associated with poor prognosis in multiple cancers. Furthermore, we disrupted the interaction between SOX9 and YAP using a competitive peptide, S-A1, which mimics an α-helix of SOX9 containing Asp-125. S-A1 significantly inhibits YAP nuclear translocation and effectively suppresses tumor growth. This study provides the first evidence of SOX9 as a pivotal regulator driving YAP nuclear translocation and presents a potential therapeutic strategy for YAP-driven human cancers by targeting SOX9-YAP interaction.

[Evidence mapping of Chinese patent medicines in treatment of premature ventricular contractions].

This study employed evidence mapping to systematically sort out the clinical studies about the treatment of premature ventricular contractions with Chinese patent medicines and to reveal the distribution of evidence in this field. The articles about the treatment of premature ventricular contractions with Chinese patent medicines were searched against PubMed, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP with the time interval from January 2016 to December 2022. Evidence was analyzed and presented by charts and graphs combined with text. According to the inclusion and exclusion criteria, 164 papers were included, including 147 interventional studies, 4 observational studies, and 13 systematic reviews. A total of 27 Chinese patent medicines were involved, in which Shensong Yangxin Capsules and Wenxin Granules had high frequency. There were off-label uses in clinical practice. In recent years, the number of articles published in this field showed a decreasing trend. Eight types of outcome indicators were used in interventional studies. Ambulatory electrocardiography, clinical response rate, safety, and echocardiography had high frequency, while the rate of ß-blocker decompensation, major cardiovascular events, and pharmaceutical economic indicators were rarely reported. The evaluation was one-sided. The low quality of the included articles reduced the reliability of the findings. In the future, the clinical use of medicines should be standardized, and the quality of clinical studies should be improved. Comprehensive clinical evaluation should be carried out to provide a sound scientific basis for the treatment of premature ventricular contractions with Chinese patent medicines.

Intracavity spatially modulated metasurfaces for a wavelength-tunable figure-9 vortex fiber laser.

Intracavity optical metasurfaces with compact and flexible light manipulation capabilities, effectively enrich the implementation of miniaturized and user-friendly orbital angular momentum (OAM) laser sources. Here we demonstrate a wavelength-tunable figure-9 Yb-doped vortex fiber laser solely with standard non-polarization-maintaining single-mode fibers, which utilizes a gap-surface plasmon (GSP) metasurface as the intracavity mode regulation component to generate OAM beams, extending the avenues and related applications for cost-effective OAM laser sources. Gained by the broadband operation range of the metasurface, the figure-9 fiber laser could emit OAM light with center wavelength tunable from 1020 nm to 1060 nm and of high mode purity (about 90%). OAM beams with different topological charges such as l = ±1 have been obtained by changing the metasurface design. The proposed fiber laser with the intracavity GSP metasurface provides a reliable and customized output of OAM beams at the laser source, holding great promise for a wide range of applications in optical communications, sensing, and super-resolution imaging.

Analysis of the chemical characteristics and causes of high total hardness of groundwater in Jianghan Plain, China.

Familiarity with the chemical characteristics of regional groundwater can provide important guidance and reference for the development of regional groundwater exploitation. Jianghan Plain has been reported to have high groundwater total hardness (TH), resulting in the inability of local groundwater to be directly used as drinking water. In order to explore the causes of high TH, the paper analyzed the hydrochemical characteristics of shallow groundwater in Jianghan Plain combined with software of SPSS, JMP, and PHEEQC. The results showed that the cations in the groundwater in the area were mainly Ca2+, while the anions were mainly HCO3-. 20% of groundwater exceed the China national guideline for TH (i.e., 450 mg/L). The groundwater chemistry in the study area was controlled by three main factors of dissolution of carbonate rocks, human activities, and redox conditions, among which the interaction between water and rock had the greatest impact. The water carbonate rock interaction within Jianghan Plain was affected by various factors such as water flow and aquifers and showed a gradually weakening trend from west to east. This work not only strengthened the understanding of the causes of the high TH of groundwater in the region, but also provided reference value for regional groundwater environmental management.

A Long-Term Follow-Up Study on the Auditory Performance and Speech Intelligibility of Mandarin-Speaking Prelingually Deaf Children With Isolated Large Vestibular Aqueduct Syndrome After Cochlear Implantation.

PURPOSE: The purpose of this study was to evaluate the auditory performance and speech perception of 104 children with isolated large vestibular aqueduct syndrome (LVAS) and 523 children with no inner ear malformation (IEM) for 5 years after cochlear implantation, in order to explore whether isolated LVAS can affect the long-term hearing and speech rehabilitation of deaf children after cochlear implantation. METHOD: A cohort study was established consisting of 627 children who underwent cochlear implantation at Beijing Tongren Hospital from 1999 to 2016. The children were examined at 0, 6, 12, 24, 36, 48, and 60 months after cochlear implantation to assess their auditory performance and speech perception using the Categories of Auditory Performance (CAP) and Speech Intelligibility Rating (SIR) questionnaires. RESULTS: The CAP scores of the isolated LVAS group increased significantly during the baseline to the 24th month, after which they gradually rose until reaching the plateau during the 24th to the 60th month. The CAP scores of the non-IEM group increased significantly during the baseline to the 36th month and then increased steadily. The SIR scores went up significantly during the baseline to the 48th month, and increased in a gradual manner in other stages of isolated LVAS evaluation. In comparison, The SIR scores of non-IEM group grew remarkably from the baseline to the 60th month. There were no significant differences in the CAP or SIR scores between isolated LVAS and non-IEM groups in each stage of evaluation, with the only exception being the CAP score at baseline month after cochlear implantation. CONCLUSIONS: The CAP and SIR questionnaires are helpful tools for quantifying the early hearing and speech skills of younger prelingually deafened cochlear implant recipients. This long-term follow-up study shows that the speech and hearing development of children in isolated LVAS and non-IEM groups follow similar patterns, and isolated LVAS does not affect the long-term rehabilitation of deaf children after cochlear implantation.

Electrically tunable topological phase transition in non-Hermitian optical MEMS metasurfaces.

Exceptional points (EPs), unique junctures in non-Hermitian open systems where eigenvalues and eigenstates simultaneously coalesce, have gained notable attention in photonics because of their enthralling physical principles and unique properties. Nonetheless, the experimental observation of EPs, particularly within the optical domain, has proven rather challenging because of the grueling demand for precise and comprehensive control over the parameter space, further compounded by the necessity for dynamic tunability. Here, we demonstrate the occurrence of optical EPs when operating with an electrically tunable non-Hermitian metasurface platform that synergizes chiral metasurfaces with piezoelectric MEMS mirrors. Moreover, we show that, with a carefully constructed metasurface, a voltage-controlled spectral space can be finely tuned to access not only the chiral EP but also the diabolic point characterized by degenerate eigenvalues and orthogonal eigenstates, thereby allowing for dynamic topological phase transition. Our work paves the way for developing cutting-edge optical devices rooted in EP physics and opening uncharted vistas in dynamic topological photonics.

Supported Platinum Nanoparticles Catalyzed Carbon-Carbon Bond Cleavage of Polyolefins: Role of the Oxide Support Acidity.

Supported platinum nanoparticle catalysts are known to convert polyolefins to high-quality liquid hydrocarbons using hydrogen under relatively mild conditions. To date, few studies using platinum grafted onto various metal oxide (MxOy) supports have been undertaken to understand the role of the acidity of the oxide support in the carbon-carbon bond cleavage of polyethylene under consistent catalytic conditions. Specifically, two Pt/MxOy catalysts (MxOy = SrTiO3 and SiO2-Al2O3; Al = 3.0 wt %, target Pt loading 2 wt % Pt ∼1.5 nm), under identical catalytic polyethylene hydrogenolysis conditions (T = 300 °C, P(H2) = 170 psi, t = 24 h; Mw = ∼3,800 g/mol, Mn = ∼1,100 g/mol, D = 3.45, Nbranch/100C = 1.0), yielded a narrow distribution of hydrocarbons with molecular weights in the range of lubricants (Mw = < 600 g/mol; Mn < 400 g/mol; D = 1.5). While Pt/SrTiO3 formed saturated hydrocarbons with negligible branching, Pt/SiO2-Al2O3 formed partially unsaturated hydrocarbons (<1 mol % alkenes and ∼4 mol % alkyl aromatics) with increased branch density (Nbranch/100C = 5.5). Further investigations suggest evidence for a competitive hydrocracking mechanism occurring alongside hydrogenolysis, stemming from the increased acidity of Pt/SiO2-Al2O3 compared to Pt/SrTiO3. Additionally, the products of these polymer deconstruction reactions were found to be independent of the polyethylene feedstock, allowing the potential to upcycle polyethylenes with various properties into a value-added product.