Identifying the risk of depression in a large sample of adolescents: An artificial neural network based on random forest.

BACKGROUND: This study aims to develop an artificial neural network (ANN) prediction model incorporating random forest (RF) screening ability for predicting the risk of depression in adolescents and identifies key risk factors to provide a new approach for primary care screening of depression among adolescents. METHODS: The data were from a large cross-sectional study conducted in China from July to September 2021, enrolling 8635 adolescents aged 10-17 with their parents. We used the Patient health questionnaire (PHQ-9) to rate adolescent depression symptoms, using scales and single-item questions to collect demographic information and other variables. Initial model variables screening used the RF importance assessment, followed by building prediction model using the screened variables through the ANN. RESULTS: The rate of depression symptoms in adolescents was 24.6%, and the depression risk prediction model was built based on 70% of the training set and 30% of the test set. Ten variables were included in the final prediction model with a model accuracy of 85.03%, AUC of 0.892, specificity of 89.79%, and sensitivity of 70.81%. The top 10 significant factors of depression risk were adolescent rumination, adolescent self-esteem, adolescent mobile phone addiction, peer victimization, care in parenting styles, overprotection in parenting styles, academic pressure, conflict in parent-child relationship, parental rumination, and relationship between parents. CONCLUSIONS: The ANN model based on the RF effectively identifies depression risk in adolescents and provides a methodological reference for large-scale primary screening. Cross-sectional studies and single-item scales limit further improvements in model accuracy.

BLA-involved circuits in neuropsychiatric disorders.

The basolateral amygdala (BLA) is the subregion of the amygdala located in the medial of the temporal lobe, which is connected with a wide range of brain regions to achieve diverse functions. Recently, an increasing number of studies have focused on the participation of the BLA in many neuropsychiatric disorders from the neural circuit perspective, aided by the rapid development of viral tracing methods and increasingly specific neural modulation technologies. However, how to translate this circuit-level preclinical intervention into clinical treatment using noninvasive or minor invasive manipulations to benefit patients struggling with neuropsychiatric disorders is still an inevitable question to be considered. In this review, we summarized the role of BLA-involved circuits in neuropsychiatric disorders including Alzheimer's disease, perioperative neurocognitive disorders, schizophrenia, anxiety disorders, depressive disorders, posttraumatic stress disorders, autism spectrum disorders, and pain-associative affective states and cognitive dysfunctions. Additionally, we provide insights into future directions and challenges for clinical translation.

Nano-enzyme hydrogels for cartilage repair effectiveness based on ternary strategy therapy.

Designing artificial nano-enzymes for scavenging reactive oxygen species (ROS) in chondrocytes (CHOs) is considered the most feasible pathway for the treatment of osteoarthritis (OA). However, the accumulation of ROS due to the amount of nano-enzymatic catalytic site exposure and insufficient oxygen supply seriously threatens the clinical application of this therapy. Although metal-organic framework (MOF) immobilization of artificial nano-enzymes to enhance active site exposure has been extensively studied, artificial nano-enzymes/MOFs for ROS scavenging in OA treatment are still lacking. In this study, a biocompatible lubricating hydrogel-loaded iron-doped zeolitic imidazolate framework-8 (Fe/ZIF-8/Gel) centrase was engineered to scavenge endogenous overexpressed ROS synergistically generating dissolved oxygen and enhancing sustained lubrication for CHOs as a ternary artificial nano-enzyme. This property enabled the nano-enzymatic hydrogels to mitigate OA hypoxia and inhibit oxidative stress damage successfully. Ternary strategy-based therapies show excellent cartilage repair in vivo. The experimental results suggest that nano-enzyme-enhanced lubricating hydrogels are a potentially effective OA treatment and a novel strategy.

Prognostic value of genomic mutation signature associated with immune microenvironment in southern Chinese patients with esophageal squamous cell carcinoma.

The genomic landscape of esophageal squamous cell cancer (ESCC), as well as its impact on the regulation of immune microenvironment, is not well understood. Thus, tumor samples from 92 patients were collected from two centers and subjected to targeted-gene sequencing. We identified frequently mutated genes, including TP53, KMT2C, KMT2D, LRP1B, and FAT1. The most frequent mutation sites were ALOX12B (c.1565C > T), SLX4 (c.2786C > T), LRIG1 (c.746A > G), and SPEN (c.6915_6917del) (6.5%). Pathway analysis revealed dysregulation of cell cycle regulation, epigenetic regulation, PI3K/AKT signaling, and NOTCH signaling. A 17-mutated gene-related risk model was constructed using random survival forest analysis and showed significant prognostic value in both our cohort and the validation cohort. Based on the Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression (ESTIMATE) algorithm, the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm, and the MCPcounter algorithm, we found that the risk score calculated by the risk model was significantly correlated with stimulatory immune checkpoints (TNFSF4, ITGB2, CXCL10, CXCL9, and BTN3A1; p < 0.05). Additionally, it was significantly associated with markers that are important in predicting response to immunotherapy (CD274, IFNG, and TAMM2; p < 0.05). Furthermore, the results of immunofluorescence double staining showed that patients with high risk scores had a significantly higher level of M2 macrophage than those with low risk scores (p < 0.05). In conclusion, our study provides insights into the genomic landscape of ESCC and highlights the prognostic value of a genomic mutation signature associated with the immune microenvironment in southern Chinese patients with ESCC.

Oligo-residual disease in PD-1/PD-L1 inhibitor-treated metastatic non-small cell lung cancer: incidence, pattern of failure, and clinical value of local consolidative therapy.

OBJECTIVES: To investigate the feasibility and potential clinical value of local consolidative therapy (LCT) in PD-1/PD-L1 inhibitor-treated metastatic non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: PD-1/PD-L1 inhibitor-treated metastatic NSCLC patients with measurable disease in three academic centers were screened and those with adequate follow-up were included. Oligo-residual disease (ORD) was defined as residual tumors limited to three organs and five lesions evaluated at the best response among patients with partial response or stable disease after PD-1/PD-L1 inhibitors. Oligometastatic and multiple-metastatic disease (OMD/MMD) were similarly classified at baseline. Locoregional interventions, administered after effective treatment of PD-1/PD-L1 inhibitors and before initial disease progression, were defined as LCT. Patterns of initial progressive disease (PD) were classified as involving only residual sites (RP), only new sites (NP), or a combination of both (BP). RESULTS: Among the 698 patients included, ORD was documented in 73 (47.1%) of 155 patients with baseline OMD and 60 (11.0%) of 543 patients with baseline MMD. With a median follow-up of 31.0 (range, 6.0-53.0) months, 108 patients with ORD developed initial PD, with RP, NP, and BP occurring in 51 (47%), 23 (21.3%), and 34 (31.5%), respectively. Among the 133 patients with ORD, those receiving LCT (n = 43) had longer progression-free survival (HR = 0.58, 95% CI 0.40-0.85, p = 0.01) and overall survival (HR = 0.49, 95% CI 0.30-0.79, p < 0.0001). CONCLUSION: ORD occurs with a clinically relevant frequency among PD-1/PD-L1 inhibitor-treated metastatic NSCLC patients and LCT may provide extra survival benefits in those with ORD.

Immunosuppressant Agents as Add-On Therapy Failed to Improve the Outcome of Immunoglobulin A Nephropathy with Crescent Score C1.

Background The renoprotective benefits of adding immunosuppressant therapy to corticosteroid (CS) treatment for immunoglobulin A nephropathy (IgAN) patients with less than 25% crescent formation (C1) remains uncertain, warranting further research. Methods A retrospective study was conducted on IgAN patients with crescent C1 lesions confirmed by renal biopsy at Xinqiao Hospital between May 1, 2017, and May 1, 2020. Patients were stratified into either the CS treatment group or the CS combined with an additional immunosuppressant therapy group. Follow-up assessments were conducted within 24 months. Propensity score analysis was used to match patients receiving CS and CS+immunosuppressant drug treatment in a 1:1 ratio. Primary outcomes included changes in estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Subgroup analyses were performed to evaluate the benefits of different populations. Composite endpoint outcomes comprised a 30% eGFR decrease, end-stage kidney disease (ESKD) necessitating dialysis or transplant, or kidney disease-related mortality. Adverse events were also compared between the two groups. Results: 296 IgAN patients with C1 lesions were included in the analysis. Baseline characteristics indicated that IgAN patients in the CS+immunosuppressant group exhibited poorer renal function and higher UACR levels. Propensity score analysis effectively minimized the influence of baseline clinical characteristics, including age, serum creatinine, initial eGFR, UACR, and 24-hour proteinuria. Both treatment groups demonstrated continuous eGFR improvement and significant UACR reduction during follow-up, especially at 6 months. However, no significant differences in eGFR and UACR reduction rates were observed between the two groups throughout the entire follow-up period, both before and after matching. Subgroup analysis revealed improved eGFR in both treatment groups, notably among patients with an initial eGFR below 90 ml/min/1.73 m2. Conversely, IgAN patients with C1 lesions and a cellular crescent ratio exceeding 50% treated with CS and immunosuppressant therapy experienced a significant improvement in renal function and a decline in urinary protein creatinine ratio. Composite endpoint outcomes did not significantly differ between the two groups, while the incidence of adverse events was comparable. Conclusion Our findings suggest that the addition of immunosuppressant therapy to corticosteroid monotherapy did not confer significant therapeutic advantages in patients with C1 lesions compared to CS monotherapy, although some specific patient populations appeared to derive modest benefits from this combined approach.

New Directions for Advanced Targeting Strategies of EGFR Signaling in Cancer.

Epidermal growth factor (EGF)-EGF receptor (EGFR) signaling studies paved the way for a basic understanding of growth factor and oncogene signaling pathways and the development of tyrosine kinase inhibitors (TKIs). Due to resistance mutations and the activation of alternative pathways when cancer cells escape TKIs, highly diverse cell populations form in recurrent tumors through mechanisms that have not yet been fully elucidated. In this review, we summarize recent advances in EGFR basic research on signaling networks and intracellular trafficking that may clarify the novel mechanisms of inhibitor resistance, discuss recent clinical developments in EGFR-targeted cancer therapy, and offer novel strategies for cancer drug development.

Symptom networks analysis among people with Meniere's disease: Application for nursing care.

Objectives: This study aimed to explore and visualize the relationships among multiple symptoms in patients with Meniere's disease (MD) and aid clinical nurses in the design of accurate, individualized interventions. Methods: This study included 790 patients with MD at the Eye and ENT Hospital of Fudan University from October 2014 to December 2021. A self-designed symptom checklist was used to assess 15 MD-related symptoms and construct contemporaneous networks with all 15 symptoms in R software. Qgraph package and Fruchterman-Reingold layout were used for network visualization. Bootstrapping methods were performed to assess network accuracy and stability, and three centrality indices were adopted to describe relationships among symptoms. Results: Symptom networks showed good accuracy and stability. "Anxiety and nervousness"(98.2%), "aural fullness"(84.4%) and "tinnitus"(82.7%) were the common symptom in MD patients, while "tinnitus", "aural fullness" and "decline in word recognition", were more serious. MD patients with longer disease duration had higher prevalence and severity for all symptoms (P < 0.05). Symptom networks showed good accuracy and stability. "Decline in word recognition," "fatigue," and "anxiety and nervousness" were at the center of the symptom networks, which had the largest strength values and closeness. "Decline in word recognition," "headache," and "spatial discrimination and poor orientation" were the symptoms with the highest betweenness with the strongest bridging effect. The ≥1-year disease group exhibited higher centralities for "drop attack" and "anxiety and nervousness," and a lower centrality for "headache" compared with the <1-year disease group. Conclusions: The symptom networks of MD patients with varying disease durations were revealed. Clinicians and nurses must provide precision interventions tailored to modifying symptom severity and centrality. Nursing interventions should focus on word recognition issues and associated discomfort in MD patients with multiple symptoms.

Probing Glycerolipid Metabolism using a Caged Clickable Glycerol-3-Phosphate Probe.

In this study, we present the probe SATE-G3P-N3 as a novel tool for metabolic labeling of glycerolipids (GLs) to investigate lipid metabolism in yeast cells. By introducing a clickable azide handle onto the glycerol backbone, this probe enables general labeling of glycerolipids. Additionally, this probe contains a caged phosphate moiety at the glycerol sn-3 position to not only facilitate probe uptake by masking negative charge but also to bypass the phosphorylation step crucial for initiating phospholipid synthesis, thereby enhancing phospholipid labeling. The metabolic labeling activity of the probe was thoroughly assessed through cellular fluorescence microscopy, mass spectrometry (MS), and thin-layer chromatography (TLC) experiments. Fluorescence microscopy analysis demonstrated successful incorporation of the probe into yeast cells, with labeling predominantly localized at the plasma membrane. LCMS analysis confirmed metabolic labeling of various phospholipid species (PC, PS, PA, PI, and PG) and neutral lipids (MAG, DAG, and TAG), and GL labeling was corroborated by TLC. These results showcased the potential of the SATE-G3P-N3 probe in studying GL metabolism, offering a versatile and valuable approach to explore the intricate dynamics of lipids in yeast cells.

The Association of High Lipoprotein(a) Concentration and Risk of Ischaemic Stroke in Atrial Fibrillation Patients.

Background: Lipoprotein(a) [Lp(a)] is a well-established risk factor for ischaemic stroke (IS). It is unclear whether Lp(a) is associated with IS in patients with atrial fibrillation (AF). The aim of this study is to explore the association between the concentration of Lp(a) and the risk of IS in AF patients, hope to find the potential risk factor for the IS in AF patients. Methods: This study is a retrospective cohort study. The screened AF patients between January 2017 and July 2021 were matched at 1:1 by the propensity score matching (PSM) method in the Second Affiliated Hospital of Nanchang University. Associations between Lp(a) and ischaemic stroke were analysed using logistic regression models, stratified analysis and sensitivity analysis. Statistical analyses were conducted using IBM SPSS software. Results: The number of enrolled participates is 2258, which contains 1129 non-AF patients and 1129 AF patients. Among IS patients, the median Lp(a) concentration was higher than that of controls (17.03 vs. 15.36 mg/dL, P = 0.032). The Spearman rank-order correlation coefficients revealed significant positive relationships between IS and Lp(a) (P = 0.032). In addition, a significant increase in IS risk was associated with Lp(a) levels >30.00 mg/dL in unadjusted model [OR:1.263, 95% CI(1.046-1.523), P = 0.015], model 1 [OR:1.284, 95% CI(1.062,1.552), P = 0.010], model 2 [OR: 1.297, 95% CI(1.07,1.573). P = 0.008], and model 3 [OR: 1.290, 95% CI (1.064, 1.562). P = 0.009]. The stratified analysis indicated that this correlation was not affected by female sex [1.484 (1.117, 1.972), P = 0.006], age ≤ 60 [1.864 (1.067-3.254), P=0.029], hypertension [1.359 (1.074, 1.721), P = 0.011], or non-coronary heart disease (CHD) [1.388 (1.108, 1.738), P = 0.004]. Conclusion: High levels of Lp(a) were significantly related to IS in AF patients and may be a potential risk factor in the onset of an IS in AF patients.

Postoperative myopic shift and visual acuity rehabilitation in patients with bilateral congenital cataracts.

Background: This study aimed to explore the postoperative myopic shift and its relationship to visual acuity rehabilitation in patients with bilateral congenital cataracts (CCs). Methods: Bilateral CC patients who underwent cataract extraction and primary intraocular lens implantations before 6 years old were included and divided into five groups according to surgical ages (<2, 2-3, 3-4, 4-5, and 5-6 years). The postoperative myopic shift rates, spherical equivalents (SEs), and the best corrected visual acuity (BCVA) were measured and analyzed. Results: A total of 1,137 refractive measurements from 234 patients were included, with a mean follow-up period of 34 months. The postoperative mean SEs at each follow-up in the five groups were linearly fitted with a mean R2 = 0.93 ± 0.03, which showed a downtrend of SE with age (linear regression). Among patients with a follow-up of 4 years, the mean postoperative myopic shift rate was 0.84, 0.81, 0.68, 0.24, and 0.28 diopters per year (D/y) in the five age groups (from young to old), respectively. The BCVA of those with a surgical age of <2 years at the 4-year visit was 0.26 (LogMAR), and the mean postoperative myopic shift rate was 0.84 D/y. For patients with a surgical age of 2-6 years, a poorer BCVA at the 4-year visit was found in those with higher postoperative myopic shift rates (r = 0.974, p = 0.026, Pearson's correlation test). Conclusion: Performing cataract surgery for patients before 2 years old and decreasing the postoperative myopic shift rates for those with a surgical age of 2-6 years may benefit visual acuity rehabilitation.

Concomitant Near-Infrared Photothermy and Photoluminescence of Rod-Shaped Au52(PET)32 and Au66(PET)38 Synthesized Concurrently.

Gold nanoclusters exhibiting concomitant photothermy (PT) and photoluminescence (PL) under near-infrared (NIR) light irradiation are rarely reported, and some fundamental issues remain unresolved for such materials. Herein, we concurrently synthesized two novel rod-shaped Au nanoclusters, Au52(PET)32 and Au66(PET)38 (PET = 2-phenylethanethiol), and precisely revealed that their kernels were 4 × 4 × 6 and 5 × 4 × 6 face-centered cubic (fcc) structures, respectively, based on the numbers of Au layers in the [100], [010], and [001] directions. Following the structural growth mode from Au52(PET)32 to Au66(PET)38, we predicted six more novel nanoclusters. The concurrent synthesis provides rational comparison of the two nanoclusters on the stability, absorption, emission and photothermy, and reveals the aspect ratio-related properties. An interesting finding is that the two nanoclusters exhibit concomitant PT and PL under 785 nm light irradiation, and the PT and PL are in balance, which was explained by the qualitative evaluation of the radiative and non-radiative rates. The ligand effects on PT and PL were also investigated.

EGFR-ERK1/2 signaling and mitochondrial dynamics in seasonal ovarian steroidogenesis of the muskrats (Ondatra zibethicus).

The dynamic systems of mitochondria, including mitochondrial fusion and fission, are essential for ovarian endocrine and follicular development. Meanwhile, ERK1/2 signaling is an important mechanism mediating altered mitochondrial dynamics and steroidogenesis. The purpose of this study was to investigate the seasonal changes in ovarian steroidogenesis concerning EGFR-ERK1/2 signaling and mitochondrial dynamics of the muskrats (Ondatra zibethicus). The results showed that follicular development in the muskrats remained in the tertiary follicular stage during the non-breeding season, accompanied by a significant decrease in serum and ovarian concentrations of 17ß-estradiol and progesterone from the breeding season to the non-breeding season. EGF, EGFR, ERK1/2, p-ERK1/2, and mitochondrial dynamics regulators were mainly localized in granulosa cells and theca cells of muskrats during the breeding and non-breeding seasons. The mRNA levels of Egfr, Erk1/2, Mfn1/2, Opa1, Drp1, and steroidogenic enzymes in the ovaries were remarkably higher during the breeding season. The 17ß-estradiol concentrations in the serum and ovaries as well as the relative levels of Mfn1/2, Opa1, and Drp1 were positively associated with each other. Furthermore, transcriptomic analysis of the ovaries revealed that differentially expressed genes might be linked to steroid biosynthesis, estrogen signaling pathway, and mitochondrial membrane-related pathways. In conclusion, these results suggest that the up-regulation of mitochondrial dynamics regulators during the breeding season is closely associated with enhanced ovarian steroidogenesis in the muskrats, which may be regulated by upstream EGFR-ERK1/2 signaling.

Trade-off between Pore-Throat Structure and Mineral Composition in Modulating the Stability of Soil Organic Carbon.

The preservation of soil organic carbon (OC) is an effective way to decelerate the emission of CO2 emission. However, the coregulation of pore structure and mineral composition in OC stabilization remains elusive. We employed the in situ nondestructive oxidation of OC by low-temperature ashing (LTA) combined with near edge X-ray absorption fine structure (NEXAFS), high-resolution microtomography (µ-CT), field emission electron probe microanalysis (FE-EPMA) with C-free embedding, and novel Cosine similarity measurement to investigate the C retention in different aggregate fractions of contrasting soils. Pore structure and minerals contributed equally (ca. 50%) to OC accumulation in macroaggregates, while chemical protection played a leading role in C retention with 53.4%-59.2% of residual C associated with minerals in microaggregates. Phyllosilicates were discovered to be more prominent than Fe (hydr)oxides in C stabilization. The proportion of phyllosilicates-associated C (52.0%-61.9%) was higher than that bound with Fe (hydr)oxides (45.6%-55.3%) in all aggregate fractions tested. This study disentangled quantitatively for the first time a trade-off between physical and chemical protection of OC varying with aggregate size and the different contributions of minerals to OC preservation. Incorporating pore structure and mineral composition into C modeling would optimize the C models and improve the soil C content prediction.

Multi-resource dynamic coordinated planning of flexible distribution network.

The flexible distribution network presents a promising architecture to accommodate highly integrated distributed generators and increasing loads in an efficient and cost-effective way. The distribution network is characterised by flexible interconnections and expansions based on soft open points, which enables it to dispatch power flow over the entire system with enhanced controllability and compatibility. Herein, we propose a multi-resource dynamic coordinated planning method of flexible distribution network that allows allocation strategies to be determined over a long-term planning period. Additionally, we establish a probabilistic framework to address source-load uncertainties, which mitigates the security risks of voltage violations and line overloads. A practical distribution network is adopted for flexible upgrading based on soft open points, and its cost benefits are evaluated and compared with that of traditional planning approaches. By adjusting the acceptable violation probability in chance constraints, a trade-off between investment efficiency and operational security can be realised.

Regulation and Role of Adiponectin Secretion in Rat Ovarian Granulosa Cells.

Adiponectin is an important adipokine involved in glucose and lipid metabolism, but its secretion and potential role in regulating glucose utilization during ovarian development remains unclear. This study aims to investigate the mechanism and effects of follicle-stimulating hormones (FSHs) on adiponectin secretion and its following impact on glucose transport in the granulosa cells of rat ovaries. A range of experimental techniques were utilized to test our research, including immunoblotting, immunohistochemistry, immunofluorescence, ELISA, histological staining, real-time quantitative PCR, and transcriptome analysis. The immunohistochemistry results indicated that adiponectin was primarily located in the granulosa cells of rat ovaries. In primary granulosa cells cultured in vitro, both Western blot and immunofluorescence assays demonstrated that FSH significantly induced adiponectin secretion within 2 h of incubation, primarily via the PKA signaling pathway rather than the PI3K/AKT pathway. Concurrently, the addition of the AdipoR1/AdipoR2 dual agonist AdipoRon to the culture medium significantly stimulated the protein expression of GLUT1 in rat granulosa cells, resulting in enhanced glucose absorption. Consistent with these in vitro findings, rats injected with eCG (which shares structural and functional similarities with FSH) exhibited significantly increased adiponectin levels in both the ovaries and blood. Moreover, there was a notable elevation in mRNA and protein levels of AdipoRs and GLUTs following eCG administration. Transcriptomic analysis further revealed a positive correlation between the expression of the intraovarian adiponectin system and glucose transporter. The present study represents a novel investigation, demonstrating that FSH stimulates adiponectin secretion in ovarian granulosa cells through the PKA signaling pathway. This mechanism potentially influences glucose transport (GLUT1) and utilization within the ovaries.

Associations between perceived usefulness and willingness to use smart healthcare devices among Chinese older adults: The multiple mediating effect of technology interactivity and technology anxiety.

Objective: This study aims to explore the mediating roles of technological interactivity and technological anxiety in the relationship between perceived usefulness and the willingness to use a smart health device to provide insight into the decision-making process of older adults in relation to the adoption of smart devices. Methods: A cross-sectional survey was conducted in Jiangsu, China involving 552 older adults. The study utilized structural equation modeling (SEM) to analyze the relationship between the independent variable 'perceived usefulness' and the dependent variable 'willingness to use.' It also examined the multiple mediating effects of technological interactivity and technological anxiety between the independent and dependent variables. Results: The results indicate that the direct effect of perceived usefulness on willingness to use was insignificant. However, technological interactivity completely mediated the relationship between perceived usefulness and willingness to use. Additionally, technological interactivity and technological anxiety were found to have a serial mediating effect on the impact of perceived usefulness on willingness to use smart healthcare devices. Conclusions: These findings suggest that increasing older adults' intention to use smart healthcare devices requires not only raising awareness of their usefulness, but also addressing technological anxiety and enhancing the interactivity of these devices to improve the overall user experience.

Intercalated and Surface-Adsorbed Phosphate Anions in NiFe Layered Double-Hydroxide Catalysts Synergistically Enhancing Oxygen Evolution Reaction Activity.

The oxygen evolution reaction (OER), a crucial semireaction in water electrolysis and rechargeable metal-air batteries, is vital for carbon neutrality. Hindered by a slow proton-coupled electron transfer, an efficient catalyst activating the formation of an O-H bond is essential. Here, we proposed a straightforward one-step hydrothermal procedure for fabricating PO43--modified NiFe layered double-hydroxide (NiFe LDH) catalysts and investigated the role of PO43- anions in enhancing OER. Phosphate amounts can efficiently regulate LDH morphology, crystallinity, composition, and electronic configuration. The optimized sample showed a low overpotential of 267 mV at 10 mA cm-2. Density functional theory calculations revealed that intercalated and surface-adsorbed PO43- anions in NiFe LDH reduced the Gibbs free energy in the rate-determining step of *OOH formation, balancing oxygen-containing intermediate adsorption/dissociation and promoting the OER. Intercalated phosphate ions accelerated precatalyst dehydrogenation kinetics, leading to a rapid reconstruction into active NiFe oxyhydroxide species. Surface-adsorbed PO43- interacted favorably with adsorbed *OOH on the active Ni sites, stabilizing *OOH. Overall, the synergistic effects of intercalated and surface-adsorbed PO43- anions significantly contributed to enhanced OER activity. Achieving optimal catalytic activity requires a delicate equilibrium between thermodynamic and kinetic factors by meticulously regulating the quantity of introduced PO43- ions. This endeavor will facilitate a deeper comprehension of the influence of anions in electrocatalysis for OER.

O-GlcNAcylation Facilitates the Interaction between Keratin 18 and Isocitrate Dehydrogenases and Potentially Influencing Cholangiocarcinoma Progression.

Glycosylation plays a pivotal role in the intricate landscape of human cholangiocarcinoma (CCA), actively participating in key pathophysiological processes driving tumor progression. Among the various glycosylation modifications, O-linked ß-N-acetyl-glucosamine modification (O-GlcNAcylation) emerges as a dynamic regulator influencing diverse tumor-associated biological activities. In this study, we employed a state-of-the-art chemical proteomic approach to analyze intact glycopeptides, unveiling the critical role of O-GlcNAcylation in orchestrating Keratin 18 (K18) and its interplay with tricarboxylic acid (TCA) cycle enzymes, specifically isocitrate dehydrogenases (IDHs), to propel CCA progression. Our findings shed light on the mechanistic intricacies of O-GlcNAcylation, revealing that site-specific modification of K18 on Ser 30 serves as a stabilizing factor, amplifying the expression of cell cycle checkpoints. This molecular event intricately fosters cell cycle progression and augments cellular growth in CCA. Notably, the interaction between O-GlcNAcylated K18 and IDHs orchestrates metabolic reprogramming by down-regulating citrate and isocitrate levels while elevating α-ketoglutarate (α-KG). These metabolic shifts further contribute to the overall tumorigenic potential of CCA. Our study thus expands the current understanding of protein O-GlcNAcylation and introduces a new layer of complexity to post-translational control over metabolism and tumorigenesis.

Bioinspired In-Sensor Multimodal Fusion for Enhanced Spatial and Spatiotemporal Association.

Multimodal perception can capture more precise and comprehensive information compared with unimodal approaches. However, current sensory systems typically merge multimodal signals at computing terminals following parallel processing and transmission, which results in the potential loss of spatial association information and requires time stamps to maintain temporal coherence for time-series data. Here we demonstrate bioinspired in-sensor multimodal fusion, which effectively enhances comprehensive perception and reduces the level of data transfer between sensory terminal and computation units. By adopting floating gate phototransistors with reconfigurable photoresponse plasticity, we realize the agile spatial and spatiotemporal fusion under nonvolatile and volatile photoresponse modes. To realize an optimal spatial estimation, we integrate spatial information from visual-tactile signals. For dynamic events, we capture and fuse in real time spatiotemporal information from visual-audio signals, realizing a dance-music synchronization recognition task without a time-stamping process. This in-sensor multimodal fusion approach provides the potential to simplify the multimodal integration system, extending the in-sensor computing paradigm.