How well do models of visual cortex generalize to out of distribution samples?

Unit activity in particular deep neural networks (DNNs) are remarkably similar to the neuronal population responses to static images along the primate ventral visual cortex. Linear combinations of DNN unit activities are widely used to build predictive models of neuronal activity in the visual cortex. Nevertheless, prediction performance in these models is often investigated on stimulus sets consisting of everyday objects under naturalistic settings. Recent work has revealed a generalization gap in how predicting neuronal responses to synthetically generated out-of-distribution (OOD) stimuli. Here, we investigated how the recent progress in improving DNNs' object recognition generalization, as well as various DNN design choices such as architecture, learning algorithm, and datasets have impacted the generalization gap in neural predictivity. We came to a surprising conclusion that the performance on none of the common computer vision OOD object recognition benchmarks is predictive of OOD neural predictivity performance. Furthermore, we found that adversarially robust models often yield substantially higher generalization in neural predictivity, although the degree of robustness itself was not predictive of neural predictivity score. These results suggest that improving object recognition behavior on current benchmarks alone may not lead to more general models of neurons in the primate ventral visual cortex.

EP300-ZNF384 transactivates IL3RA to promote the progression of B-cell acute lymphoblastic leukemia.

The EP300-ZNF384 fusion gene is an oncogenic driver in B-cell acute lymphoblastic leukemia (B-ALL). In the present study, we demonstrated that EP300-ZNF384 substantially induces the transcription of IL3RA and the expression of IL3Rα (CD123) on B-ALL cell membranes. Interleukin 3 (IL-3) supplementation promotes the proliferation of EP300-ZNF348-positive B-ALL cells by activating STAT5. Conditional knockdown of IL3RA in EP300-ZF384-positive cells inhibited the proliferation in vitro, and induced a significant increase in overall survival of mice, which is attributed to impaired propagation ability of leukemia cells. Mechanistically, the EP300-ZNF384 fusion protein transactivates the promoter activity of IL3RA by binding to an A-rich sequence localized at -222/-234 of IL3RA. Furthermore, forced EP300-ZNF384 expression induces the expression of IL3Rα on cell membranes and the secretion of IL-3 in CD19-positive B precursor cells derived from healthy individuals. Doxorubicin displayed a selective killing of EP300-ZNF384-positive B-ALL cells in vitro and in vivo. Collectively, we identify IL3RA as a direct downstream target of EP300-ZNF384, suggesting CD123 is a potent biomarker for EP300-ZNF384-driven B-ALL. Targeting CD123 may be a novel therapeutic approach to EP300-ZNF384-positive patients, alternative or, more likely, complementary to standard chemotherapy regimen in clinical setting.

Association of Triglyceride-Glucose Index With Cognitive Function and Brain Atrophy: A Population-Based Study.

OBJECTIVE: To investigate the associations of triglyceride-glucose (TyG) index, a reliable surrogate marker for insulin resistance, with the function of various cognitive domains and brain structures among older adults. DESIGN: A population-based cross-sectional study. SETTING: Older adults living in the rural communities in China. PARTICIPANTS: About 4,541 rural-dwelling dementia-free participants (age ≥65 years; 56.37% women) undertook examinations in March-September 2018 for MIND-China. MEASUREMENTS: TyG index was calculated as ln[fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. A neuropsychological test battery was used to assess memory, attention, verbal fluency, and executive function. Volumetric brain measures were assessed on magnetic resonance imaging (MRI) in a subsample (n = 1,019). Data were analyzed with restricted cubic spline and multivariable general linear models. RESULTS: An inverted J-shaped association was observed between TyG index and z-scores of multiple cognitive domains, such that among individuals with TyG index ≥8.57 (median), a higher TyG index was significantly associated with lower z-scores of memory, attention, verbal fluency, executive function, and global cognition (all p < 0.05); among people with TyG index <8.57, a higher TyG index was significantly associated with a higher executive function z-score (p < 0.05), but not with any of the other examined cognitive domains. In the MRI subsample, a higher TyG index was significantly associated with lower volumes of total brain tissue, gray matter, and white matter as well as greater cerebrospinal fluid volume (p < 0.05), but not with white matter hyperintensity volume. CONCLUSIONS: Insulin resistance, as indicated by a high TyG index, was associated with poor function in multiple cognitive domains and global brain atrophy.

RNA-seq analysis of small intestine transcriptional changes induced by starvation stress in piglets.

Piglets may experience a variety of stress injuries, but the molecular regulatory mechanisms underlying these injuries are not well understood. In this study, we analysed the ileum of Large White (LW) and Mashen (MS) piglets at different times of starvation using chemical staining and transcriptome analysis. The intestinal barrier of piglets was damaged after starvation stress, but the intestinal antistress ability of MS piglets was stronger than LW piglets. A total of 8021 differentially expressed genes (DEGs) were identified in two breeds. Interestingly, the immune capacity (CHUK, TLR3) of MS piglets increased significantly after short-term starvation stress, while energy metabolism (NAGS, PLA2G12B, AGCG8) was predominant in LW piglets. After long-term starvation stress, the level of energy metabolism (PLIN5, PLA2G12B) was significantly increased in MS piglets. The expression of immune (HLA-DQB1, IGHG4, COL3A1, CD28, LAT) and disease (HSPA1B, MINPPI, ADH1C, GAL3ST1) related genes were significantly increased in two breeds of piglets. These results suggest that short-term stress mainly enhances immunity and energy metabolism in piglets, while long-term starvation produces greater stress on piglets, making it difficult for them to compensate for the damage to their bodies through self-regulation. This information can help improve the stress resistance of piglets through molecular breeding.

Multimorbidity, cognitive phenotypes, and Alzheimer's disease plasma biomarkers in older adults: A population-based study.

INTRODUCTION: To examine the burden and clusters of multimorbidity in association with mild cognitive impairment (MCI), dementia, and Alzheimer's disease (AD)-related plasma biomarkers among older adults. METHODS: This population-based study included 5432 participants (age ≥60 years); of these, plasma amyloid beta (Aß), total tau, and neurofilament light chain (NfL) were measured in a subsample (n = 1412). We used hierarchical clustering to generate five multimorbidity clusters from 23 chronic diseases. We diagnosed dementia and MCI following international criteria. Data were analyzed using logistic and linear regression models. RESULTS: The number of chronic diseases was associated with dementia (multivariable-adjusted odds ratio = 1.22; 95% confidence interval [CI] = 1.11 to 1.33), AD (1.13; 1.01 to 1.26), vascular dementia (VaD) (1.44; 1.25 to 1.64), and non-amnestic MCI (1.25; 1.13 to 1.37). Metabolic cluster was associated with VaD and non-amnestic MCI, whereas degenerative ocular cluster was associated with AD (p < 0.05). The number of chronic diseases was associated with increased plasma Aß and NfL (p < 0.05). DISCUSSION: Multimorbidity burden and clusters are differentially associated with subtypes of dementia and MCI and AD-related plasma biomarkers in older adults. HIGHLIGHTS: We used hierarchical clustering to generate five clusters of multimorbidity. The presence and load of multimorbidity were associated with dementia and mild cognitive impairment. Multimorbidity clusters were differentially associated with subtypes of dementia and Alzheimer's disease plasma biomarkers.

Cardiometabolic multimorbidity, peripheral biomarkers, and dementia in rural older adults: The MIND-China study.

INTRODUCTION: Evidence has emerged that cardiometabolic multimorbidity (CMM) is associated with dementia, but the underlying mechanisms are poorly understood. METHODS: This population-based study included 5704 older adults. Of these, data were available in 1439 persons for plasma amyloid-ß (Aß), total tau, and neurofilament light chain (NfL) and in 1809 persons for serum cytokines. We defined CMM following two common definitions used in previous studies. Data were analyzed using general linear, logistic, and mediation models. RESULTS: The presence of CMM was significantly associated with an increased likelihood of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) (p < 0.05). CMM was significantly associated with increased plasma Aß40, Aß42, and NfL, whereas CMM that included visceral obesity was associated with increased serum cytokines. The mediation analysis suggested that plasma NfL significantly mediated the association of CMM with AD. DISCUSSION: CMM is associated with dementia, AD, and VaD in older adults. The neurodegenerative pathway is involved in the association of CMM with AD. HIGHLIGHTS: The presence of CMM was associated with increased likelihoods of dementia, AD, and VaD in older adults. CMM was associated with increased AD-related plasma biomarkers and serum inflammatory cytokines. Neurodegenerative pathway was partly involved in the association of CMM with AD.

Subsurface Single-atom Catalyst Enabled by Mechanochemical Synthesis for Oxidation Chemistry.

Single-atom catalysts have garnered significant attention due to their exceptional atom utilization and unique properties. However, the practical application of these catalysts is often impeded by challenges such as sintering-induced instability and poisoning of isolated atoms due to strong gas adsorption. In this study, we employed the mechanochemical method to insert single Cu atoms into the subsurface of Fe2O3 support. By manipulating the location of single atoms at the surface or subsurface, catalysts with distinct adsorption properties and reaction mechanisms can be achieved. It was observed that the subsurface Cu single atoms in Fe2O3 remained isolated under both oxidation and reduction environments, whereas surface Cu single atoms on Fe2O3 experienced sintering under reduction conditions. The unique properties of these subsurface single-atom catalysts call for innovations and new understandings in catalyst design.

Metabolic modulation of immune checkpoints and novel therapeutic strategies in cancer.

Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) or programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1)-based immune checkpoint inhibitors (ICIs) have led to significant improvements in the overall survival of patients with certain cancers and are expected to benefit patients by achieving complete, long-lasting remissions and cure. However, some patients who receive ICIs either fail treatment or eventually develop immunotherapy resistance. The existence of such patients necessitates a deeper understanding of cancer progression, specifically nutrient regulation in the tumor microenvironment (TME), which includes both metabolic cross-talk between metabolites and tumor cells, and intracellular metabolism in immune and cancer cells. Here we review the features and behaviors of the TME and discuss the recently identified major immune checkpoints. We comprehensively and systematically summarize the metabolic modulation of tumor immunity and immune checkpoints in the TME, including glycolysis, amino acid metabolism, lipid metabolism, and other metabolic pathways, and further discuss the potential metabolism-based therapeutic strategies tested in preclinical and clinical settings. These findings will help to determine the existence of a link or crosstalk between tumor metabolism and immunotherapy, which will provide an important insight into cancer treatment and cancer research.

Circ_0001589/miR-1248/HMGB1 axis enhances EMT-mediated metastasis and cisplatin resistance in cervical cancer.

Cervical cancer is the fourth most common malignant tumors in female worldwide. Cirular RNAs (circRNA) represent a new class of regulatory RNA and play a pivotal role in the carcinogenesis and development of tumors. However, their functions have not been fully elucidated in cervical cancer. In this study, we identified an upregulated circRNA, circ_0001589, both in fresh clinical samples and tissue microarray of cervical cancer. Transwell assay and cell apoptosis assay by flow cytometry demonstrated circ_0001589 promotes epithelial-mesenchymal transition (EMT)-mediated cell migration and invasion, and enhanced cisplatin resistance in vitro. In addition, in nude mice model, circ_0001589 increased the number of lung metastases and recovered xenograft growth from cisplatin treatment in vivo. Mechanistically, RNA pull-down assay, RNA immunoprecipitation, and dual-luciferase reporter assay disclosed that circ_0001589 function as an competing endogenous RNA to sponge miR-1248, which directly target the 3' untranslated region of high mobility group box-B1 (HMGB1). Thereby, circ_0001589 upregulated HMGB1 protein expression and accelerate cervical cancer progression. The rescue experiments also revealed that miR-1248 overexpression or HMGB1 knockdown partially reversed the regulatory functions of circ_0001589 on cell migration, invasion, and cisplatin resistance. In summary, our findings suggest the upregulation of circ_0001589 promoted EMT-mediated cell migration and invasion, and enhanced cisplatin resistance via regulating miR-1248/HMGB1 axis in cervical cancer. These results provided new evidence for understanding the carcinogenesis mechanism and finding new therapeutic target for cervical cancer.

Association of Lifelong Cognitive Reserve with Dementia and Mild Cognitive Impairment among Older Adults with Limited Formal Education: A Population-Based Cohort Study.

INTRODUCTION: Early-life educational attainment contributes to cognitive reserve (CR). We investigated the associations of lifelong CR with dementia and mild cognitive impairment (MCI) among older people with limited formal education. METHODS: This population-based cohort study included 2,127 dementia-free participants (≥60 years; 59.4% women; 81.5% with no or elementary school) who were examined at baseline (August-December 2014) and follow-up (March-September 2018). Lifelong CR score at baseline was generated from six lifespan intellectual factors. Dementia, MCI, and their subtypes were defined according to the international criteria. Data were analyzed using Cox proportional-hazards models. RESULTS: During the total of 8,330.6 person-years of follow-up, 101 persons were diagnosed with dementia, including 74 with Alzheimer's disease (AD) and 26 with vascular dementia (VaD). The high (vs. low) tertile of lifelong CR score was associated with multivariable-adjusted hazards ratios (95% confidence interval) of 0.28 (0.14-0.55) for dementia and 0.18 (0.07-0.48) for AD. The association between higher CR and reduced AD risk was significant in people aged 60-74 but not in those aged ≥75 years (p for interaction = 0.011). Similarly, among MCI-free people at baseline (n = 1,635), the high (vs. low) tertile of lifelong CR score was associated with multivariable-adjusted hazard ratios of 0.51 (0.38-0.69) for MCI and 0.46 (0.33-0.64) for amnestic MCI. Lifelong CR was not related to VaD or non-amnestic MCI. DISCUSSION: High lifelong CR is associated with reduced risks of dementia and MCI, especially AD and amnestic MCI. It highlights the importance of lifelong CR in maintaining late-life cognitive health even among people with no or limited education.

NAT10-mediated RNA acetylation enhances HNRNPUL1 mRNA stability to contribute cervical cancer progression.

N4-acetylcytidine (ac4C) is a lately discovered nucleotide modification that has been shown to be closely implicated in cancer. N-acetyltransferase10(NAT10) acts as an enzyme that regulates mRNA acetylation modifications. Currently, the role of NAT10-mediated RNA acetylation modification in cervical cancer remains to be elucidated. On the basis of transcriptome analysis of TCGA and GEO open datasets (GSE52904, GSE29570, GSE122697), NAT10 is upregulated in cervical cancer tissues and correlated with poor prognosis. Knockdown of NAT10 suppressed the cell proliferation, invasion, and migration of cervical cancer cells. The in vivo oncogenic function of NAT10 was also confirmed in xenograft models. Combined RNA-seq and acRIP-seq analysis revealed HNRNPUL1 as the target of NAT10 in cervical cancer. NAT10 positively regulate HNRNPUL1 expression by promoting ac4C modification and stability of HNRNPUL1 mRNA. Furthermore, depletion of HNRNPUL1 suppressed the cell division, invasion, and migration of cervical cancer. HNRNPUL1 overexpression partially restored cellular function in cervical cancer cells with NAT10 knockdown. Thus, this study demonstrates that NAT10 contributes to cervical cancer progression by enhancing HNRNPUL1 mRNA stability via ac4C modification, and NAT10-ac4C-HNRNPUL1 axis might be a potential target for cervical cancer therapy.

Resting heart rate, cognitive function, and inflammation in older adults: a population-based study.

BACKGROUND: Emerging evidence has linked elevated resting heart rate (RHR) with poor cognitive function in older adults, but the mechanisms underlying their association are poorly understood. METHODS: This population-based cross-sectional study included 4510 dementia-free participants (age ≥ 65 years; 56.9% females; 38.3% no formal education) in the baseline examination of the Multidomain Interventions to Delay Dementia and Disability in Rural China study. Of these, 1,386 had data on serum proinflammatory cytokines and adhesion molecules. RHR was measured using 12-lead electrocardiograph. We used the Mini-Mental State Examination (MMSE) and a neuropsychological test battery to assess cognitive function. Data were analyzed using the general linear and restricted cubic splines models. RESULTS: People with high RHR were more likely to have cardiometabolic diseases and worse cognitive function (p < 0.05). There was an inverted J-shaped association of RHR with MMSE and attention scores. Having RHR ≥ 80 bpm (vs. 60-69 bpm) was significantly associated with the multivariable-adjusted ß coefficients of - 0.58 [95% confidence interval (CI), - 1.00, - 0.16] for MMSE score and - 0.08 (- 0.15, - 0.01) for attention score. In the serum biomarker subsample, RHR was linearly associated with serum interleukin-6 (IL-6) (ß coefficient = 0.19; 95%CI 0.14, 0.24), IL-8 (0.08; 0.02, 0.13), IL-10 (0.09; 0.04, 0.15), tumor necrosis factor-α (0.06; 0.01, 0.11), monocyte chemotactic protein-1 (0.09; 0.04, 0.15), intercellular adhesion molecule-1 (0.16; 0.11, 0.22), and vascular cell adhesion molecule-1 (0.11; 0.06, 0.16). CONCLUSIONS: There is an inverted J-shaped association of RHR with attention and global cognition. Poor cognitive function and high RHR may be linked through systemic low-grade inflammation and endothelial injury.

Mild cognitive impairment among rural-dwelling older adults in China: A community-based study.

BACKGROUND: Epidemiological studies of mild cognitive impairment (MCI) and subtypes of MCI have rarely focused on rural residents in China. METHODS: This population-based study included 5068 participants (age ≥60 years) who were living in rural communities. We defined MCI, amnestic MCI (aMCI), and non-amnestic MCI (naMCI) following the Petersen's criteria that integrated neuropsychological assessments with in-person clinical evaluations. RESULTS: The overall prevalence of MCI, aMCI, and naMCI was 26.48%, 22.30%, and 4.18%, respectively. The prevalence of MCI increased with age. The adjusted odds ratio (OR) of MCI was 0.71 (95% confidence interval [CI] 0.61 to 0.82) for primary school (vs. illiteracy), 0.30 (0.24 to 0.39) for middle school or above, 1.35 (1.09 to 1.67) for being farmers, 0.65 (0.54 to 0.78) for alcohol consumption, 1.43 (1.20 to 1.70) for stroke history, and 1.14 (0.95 to 1.36) for any apolipoprotein E (APOE) ε4 allele (vs ε3/ε3). CONCLUSIONS: MCI affects over one-fourth of rural older adults in China. Overall MCI was associated with demographic factors, non-alcohol consumption, and stroke, but not with APOE genotype and cardiometabolic factors.

Anosmia, mild cognitive impairment, and biomarkers of brain aging in older adults.

Olfactory impairment is a potential marker for prodromal dementia, but the underlying mechanisms are poorly understood. This population-based study included 4214 dementia-free participants (age ≥65 years). Olfaction was assessed using the 16-item Sniffin' Sticks identification test. In the subsamples, we measured plasma amyloid beta (Aß)40, Aß42, total tau, and neurofilament light chain (NfL; n = 1054); and quantified hippocampal, entorhinal cortex, and white matter hyperintensity (WMH) volumes, and Alzheimer's disease (AD)-signature cortical thickness (n = 917). Data were analyzed with logistic and linear regression models. In the total sample, mild cognitive impairment (MCI) was diagnosed in 1102 persons (26.2%; amnestic MCI, n = 931; non-amnestic MCI, n = 171). Olfactory impairment was significantly associated with increased likelihoods of MCI, amnestic MCI, and non-amnestic MCI. In the subsamples, anosmia was significantly associated with higher plasma total tau and NfL concentrations, smaller hippocampal and entorhinal cortex volumes, and greater WMH volume, and marginally with lower AD-signature cortical thickness. These results suggest that cerebral neurodegenerative and microvascular lesions are common neuropathologies linking anosmia with MCI in older adults.

Self-reported sleep characteristics associated with dementia among rural-dwelling Chinese older adults: a population-based study.

BACKGROUND: Sleep characteristics associated with dementia are poorly defined and whether their associations vary by demographics and APOE genotype among older adults are unclear. METHODS: This population-based cross-sectional study included 4742 participants (age ≥ 65 years, 57.1% women) living in rural China. Sleep parameters were measured using the self-rated questionnaires of the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE). Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria, and the National Institute on Aging-Alzheimer's Association criteria for Alzheimer's disease (AD). Data were analysed using multiple logistic and general linear regression models. RESULTS: Dementia was diagnosed in 173 participants (115 with AD). Multivariable-adjusted odds ratio (OR) of dementia was 1.71 (95%CI, 1.07-2.72) for sleep duration ≤4 h/night (vs. > 6-8 h/night), 0.76 (0.49-1.18) for > 4-6 h/night, 1.63 (1.05-2.55) for > 8 h/night, 1.11 (1.03-1.20) for lower sleep efficiency (per 10% decrease), and 1.85 (1.19-2.89) for excessive daytime sleepiness. Very short sleep duration (≤4 h/night), lower sleep efficiency, and excessive daytime sleepiness were significantly associated with being diagnosed with AD (multivariable-adjusted OR range = 1.12-2.07; p < 0.05). The associations of sleep problems with dementia and AD were evident mainly among young-old adults (65-74 years) or APOE ε4 carriers. Among dementia-free participants, these sleep characteristics were significantly associated with a lower MMSE score. CONCLUSIONS: Self-reported sleep problems in dementia are characterized by very short or long sleep duration, low sleep efficiency, and excessive daytime sleepiness, especially among young-old people and APOE ε4 carriers. TRIAL REGISTRATION: ChiCTR1800017758 (Aug 13, 2018).

Simultaneous zygotic inactivation of multiple genes in mouse through CRISPR/Cas9-mediated base editing.

In vivo genetic mutation has become a powerful tool for dissecting gene function; however, multi-gene interaction and the compensatory mechanisms involved can make findings from single mutations, at best difficult to interpret, and, at worst, misleading. Hence, it is necessary to establish an efficient way to disrupt multiple genes simultaneously. CRISPR/Cas9-mediated base editing disrupts gene function by converting a protein-coding sequence into a stop codon; this is referred to as CRISPR-stop. Its application in generating zygotic mutations has not been well explored yet. Here, we first performed a proof-of-principle test by disrupting Atoh1, a gene crucial for auditory hair cell generation. Next, we individually mutated vGlut3 (Slc17a8), otoferlin (Otof) and prestin (Slc26a5), three genes needed for normal hearing function. Finally, we successfully disrupted vGlut3, Otof and prestin simultaneously. Our results show that CRISPR-stop can efficiently generate single or triple homozygous F0 mouse mutants, bypassing laborious mouse breeding. We believe that CRISPR-stop is a powerful method that will pave the way for high-throughput screening of mouse developmental and functional genes, matching the efficiency of methods available for model organisms such as Drosophila.

Oxytocin signalling in dendritic cells regulates immune tolerance in the intestine and alleviates DSS-induced colitis.

BACKGROUND: Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) that is associated with immune dysfunction. Recent studies have indicated that the neurosecretory hormone oxytocin (OXT) has been proven to alleviate experimental colitis. METHODS: We investigated the role of OXT/OXT receptor (OXTR) signalling in dendritic cells (DCs) using mice with specific OXTR deletion in CD11c+ cells (OXTRflox/flox×CD11c-cre mice) and a dextran sulfate sodium (DSS)-induced colitis model. RESULTS: The level of OXT was abnormal in the serum or colon tissue of DSS-induced colitis mice or the plasma of UC patients. Both bone marrow-derived DCs (BMDCs) and lamina propria DCs (LPDCs) express OXTR. Knocking out OXTR in DCs exacerbated DSS-induced acute and chronic colitis in mice. In contrast, the injection of OXT-pretreated DCs significantly ameliorated colitis. Mechanistically, OXT prevented DC maturation through the phosphatidylinositol 4,5-bisphosphate 3-kinase (Pi3K)/AKT pathway and promoted phagocytosis, adhesion and cytokine modulation in DCs. Furthermore, OXT pre-treated DCs prevent CD4+ T cells differentiation to T helper 1 (Th1) and Th17. CONCLUSIONS: Our results suggest that OXT-induced tolerogenic DCs efficiently protect against experimental colitis via Pi3K/AKT pathway. Our work provides evidence that the nervous system participates in the immune regulation of colitis by modulating DCs. Our findings suggest that generating ex vivo DCs pretreated with OXT opens new therapeutic perspectives for the treatment of UC in humans.

The Electrophilicity of Surface Carbon Species in the Redox Reactions of CuO-CeO2 Catalysts.

Electronic metal-support interactions (EMSI) describe the electron flow between metal sites and a metal oxide support. It is generally used to follow the mechanism of redox reactions. In this study of CuO-CeO2 redox, an additional flow of electrons from metallic Cu to surface carbon species is observed via a combination of operando X-ray absorption spectroscopy, synchrotron X-ray powder diffraction, near ambient pressure near edge X-ray absorption fine structure spectroscopy, and diffuse reflectance infrared Fourier transform spectroscopy. An electronic metal-support-carbon interaction (EMSCI) is proposed to explain the reaction pathway of CO oxidation. The EMSCI provides a complete picture of the mass and electron flow, which will help predict and improve the catalytic performance in the selective activation of CO2 , carbonate, or carbonyl species in C1 chemistry.

Parenterally Delivered Methionyl-Methionine Dipeptide During Pregnancy Enhances Mammogenesis and Lactation Performance Over Free Methionine by Activating PI3K-AKT Signaling in Methionine-Deficient Mice.

BACKGROUND: Pregnancy-induced hypoaminoacidemia, l-methionine (Met) included, disturbs embryogenesis and may also affect breast function. Supplementation with the dipeptide l-methionyl-Met (Met-Met) may improve lactation performance. OBJECTIVE: We compared the effects of supplemental Met or Met-Met during pregnancy on mammogenesis and lactogenesis and investigated underlying mechanisms. METHODS: In experiment 1, 9-wk-old ICR mice (n = 72, ∼30 g) were divided into 3 groups. During the first 17 days of pregnancy (DP), the Control group was fed a diet with Met (8.2 g/kg) and saline was intraperitoneally injected, the Met group was fed a Met-devoid diet and 35% of the Met (92-mmo l Met) as contained in the Control diet was intraperitoneally injected, and the Met-Met group was fed the same diet and 70-mmo l Met plus 11-mmo l Met-Met was intraperitoneally injected. All animals were fed the Control diet after DP17 and during lactation. Mammogenesis, lactogenesis, transcriptome at DP17, and milk performance during lactation were examined. In experiment 2, 9-wk-old ICR mice (n = 55, ∼30 g) at DP0 were injected through the teat with adeno-associated virus for overexpression/inhibition of phosphoinositide-3-kinase regulatory subunit 1 (Pik3r1), divided into the Control, Met, and Met-Met groups and received the same treatment as experiment 1 to examine mammogenesis and lactogenesis at DP17. RESULTS: In experiment 1, compared with the Met group, the Met-Met group showed higher (P < 0.05) mammary epithelium percentage (42%) and αS1-casein expression (84%) at DP17, milk yield (34%) and energy concentrations (8.7%) during lactation; transcriptomic analysis illustrated activated phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT) signaling in the mammary glands of the Met-Met group (P-adj < 0.001). In experiment 2, overexpression of Pik3r1 enhanced (P < 0.05) the protective effect of Met-Met over Met on mammogenesis and ß-casein expression. CONCLUSION: Met-Met is more effective than Met in promoting mammogenesis and lactogenesis mainly by activation of PI3K-AKT signaling in Met-deficient mice.

The power of the Functional Activities Questionnaire for screening dementia in rural-dwelling older adults at high-risk of cognitive impairment.

AIM: A simple approach to detecting dementia in its early stages may help improve patient care. We therefore aimed to assess the power of the Functional Activities Questionnaire (FAQ) for screening dementia among rural-dwelling older adults who are at high-risk for cognitive impairment. METHODS: This study included 961 participants at a high-risk for dementia who had been identified from a population-based survey of Chinese rural residents. All participants were aged 65 years and older and positive for cognitive impairment according to the Mini-Mental State Examination or the Ascertain Dementia 8-item Informant Questionnaire screening tests. The FAQ scale was used to evaluate daily activities. Dementia was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria. Receiver operating characteristic curve analyses were used to determine the FAQ's optimal cut-offs for dementia. The power (or accuracy) of the FAQ for screening dementia was analyzed in the total sample and in subgroups categorized by age, gender, and educational level. RESULTS: Of the 961 participants, 84 (8.7%) were clinically diagnosed with dementia. Among individuals who were positive for cognitive impairment on the Mini-Mental State Examination or the Ascertain Dementia 8-item Informant Questionnaire, the parameters for an FAQ cut-off score ≥6 as a means of discriminating those with dementia from those without dementia were area under curve = 0.899, sensitivity = 94.1%, specificity = 75.1%, positive likelihood ratio = 3.78, and accuracy = 0.768. The discriminant abilities of the FAQ scale varied with age, gender, and educational level. The discriminant parameters of the FAQ scale were similar overall among individuals who were positive on either the Mini-Mental State Examination or the Ascertain Dementia 8-item Informant Questionnaire test alone. CONCLUSION: The FAQ scale has high discriminative power to screen for dementia among rural older residents with suspected cognitive impairment.