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.

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.

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.

Analyzing resilience influencing factors in the prefabricated building supply chain based on SEM-SD methodology.

The supply chain for prefabricated buildings (PB) currently grapples with pressing challenges. In order to ensure the safe and stable development of the prefabricated building supply chains (PBSC), this study aims to identify the key factors and internal mechanisms affecting the PBSC, and propose a supply chain resilience enhancement mechanism, so as to promote the sustainable development of the PB industry. The study combined a literature review and survey data to identify key resilience factors in PBSC. A Structural Equation Model (SEM) was used to explore the relationships between these factors. System dynamics were applied to create a simulation model, assessing the resilience impact level and conducting sensitivity analysis. The results show that the transportation and procurement processes are the most significant factors influencing supply chain resilience. The external environmental factors wielded a more pronounced impact on the overall evaluation of supply chain resilience than the delivery and use processes, but delivery and use processes are more sensitive. The study uses the Pressure-State-Response (PSR) model to suggest strategies for enhancing supply chain resilience. This study contributes to more sustainable and efficient construction practices by offering an innovative theoretical framework to analyze the factors influencing PBSC resilience and proposing enhancement strategies.

Characterisation and comparison of enzymatically prepared donkey milk whey protein hydrolysates.

This study evaluated the structural characteristics, processing properties, and antioxidant properties of hydrolysates prepared from donkey milk (DM) whey protein using different proteases (Alcalase, Neutrase, papain, and Flavourzyme). The results showed that enzymatic hydrolysis significantly increased hydrolysate solubility and reduced average particle size compared to those of DM whey protein. Neutrase and Flavourzyme hydrolysates exhibited higher degrees of hydrolysis (DH), along with elevated emulsification properties and surface hydrophobicity. The choice of protease influenced secondary and tertiary protein structures and amino acid composition. Enzymatic hydrolysis led to decreased molecular weight of DM whey proteins. Moreover, all hydrolysates exhibited higher fluorescence intensity at λmax compared to DM whey protein, implying distinct properties due to the varied impacts of the four proteases on DM whey protein structure. The preparation of hydrolysates from DM whey proteins using proteases contributes to the development of integrated-value DM products.

Construction of an Exercise Intervention Program for Patients with Sarcopenic Obesity: A Delphi Method Study.

Purpose: Construct an exercise intervention program for patients with sarcopenic obesity. Material and Methods: Based on the COM-B theoretical model and evidence-based principles, the program was constructed using qualitative methods of literature analysis and Delphi method. The Delphi panel consisted of 15 experts from the fields of clinical medicine, rehabilitation medicine, medical technology, and nursing. Results: Fifteen experts were consulted, and the consultation recovery rate was 100%; the authority coefficient of the 1st round was 0.83, with coefficients of variation ranging from 0.00 to 0.27, and importance scores ranging from (4.13±1.13) to (5±0); the authority coefficient of the 2nd round was 0.82, with coefficients of variation ranging from 0.00 to 0.20, and importance scores ranging from (4.53±0.64) to (5±0); Kendall's harmony coefficient was 0.102, 0.115, respectively, and the differences were statistically significant(P < 0.05). The constructed exercise intervention program for patients with sarcopenic obesity included 4 primary indicators, 12 secondary indicators, and 28 tertiary indicators. Conclusion: The constructed exercise intervention program for patients with sarcopenic obesity is scientific, feasible and generalizable, and can provide useful reference for related personnel to develop exercise programs for patients with sarcopenic obesity.

Imaging diagnostics of pulmonary ground-glass nodules: a narrative review with current status and future directions.

Background and Objective: The incidence rate of lung cancer, which also has the highest mortality rates for both men and women worldwide, is increasing globally. Due to advancements in imaging technology and the growing inclination of individuals to undergo screening, the detection rate of ground-glass nodules (GGNs) has surged rapidly. Currently, artificial intelligence (AI) methods for data analysis and interpretation, image processing, illness diagnosis, and lesion prediction offer a novel perspective on the diagnosis of GGNs. This article aimed to examine how to detect malignant lesions as early as possible and improve clinical diagnostic and treatment decisions by identifying benign and malignant lesions using imaging data. It also aimed to describe the use of computed tomography (CT)-guided biopsies and highlight developments in AI techniques in this area. Methods: We used PubMed, Elsevier ScienceDirect, Springer Database, and Google Scholar to search for information relevant to the article's topic. We gathered, examined, and interpreted relevant imaging resources from the Second Affiliated Hospital of Nanchang University's Imaging Center. Additionally, we used Adobe Illustrator 2020 to process all the figures. Key Content and Findings: We examined the common signs of GGNs, elucidated the relationship between these signs and the identification of benign and malignant lesions, and then described the application of AI in image segmentation, automatic classification, and the invasiveness prediction of GGNs over the last three years, including its limitations and outlook. We also discussed the necessity of conducting biopsies of persistent pure GGNs. Conclusions: A variety of imaging features can be combined to improve the diagnosis of benign and malignant GGNs. The use of CT-guided puncture biopsy to clarify the nature of lesions should be considered with caution. The development of new AI tools brings new possibilities and hope to improving the ability of imaging physicians to analyze GGN images and achieving accurate diagnosis.

Tartronic Acid as a Potential Inhibitor of Pathological Calcium Oxalate Crystallization.

Kidney stones are a pervasive disease with notoriously high recurrence rates that require more effective treatment strategies. Herein, tartronic acid is introduced as an efficient inhibitor of calcium oxalate monohydrate (COM) crystallization, which is the most prevalent constituent of human kidney stones. A combination of in situ experimental techniques and simulations are employed to compare the inhibitory effects of tartronic acid with those of its molecular analogs. Tartronic acid exhibits an affinity for binding to rapidly growing apical surfaces of COM crystals, thus setting it apart from other inhibitors such as citric acid, the current preventative treatment for kidney stones. Bulk crystallization and in situ atomic force microscopy (AFM) measurements confirm the mechanism by which tartronic acid interacts with COM crystal surfaces and inhibits growth. These findings are consistent with in vivo studies that reveal the efficacy of tartronic acid is similar to that of citric acid in mouse models of hyperoxaluria regarding their inhibitory effect on stone formation and alleviating stone-related physical harm. In summary, these findings highlight the potential of tartronic acid as a promising alternative to citric acid for the management of calcium oxalate nephropathies, offering a new option for clinical intervention in cases of kidney stones.

The prognostic implications and tumor-suppressive functions of CYR61 in estrogen receptor-positive breast cancer.

Due to the therapeutic resistance of endocrine therapy and the limited efficacy of immune checkpoint inhibitors in estrogen receptor (ER)-positive breast cancer (BRCA), there is an urgent need to develop novel prognostic markers and understand the regulation of the tumor immune microenvironment (TIME). As a matricellular protein, CYR61 has been shown to either promote or suppress cancer progression depending on cancer types. However, how CYR61 functions in ER-positive BRCA remains elusive. In this study, we comprehensively analyzed the expression of CYR61 in BRCA based on the TCGA and METABRIC databases. Our findings showed that the expression of CYR61 is downregulated in different subtypes of BRCA, which is associated with elevated promoter methylation levels and predicts bad clinical outcomes. By comparing the high or low CYR61 expression groups of ER-positive BRCA patients, we found that CYR61 is intimately linked to the expression of genes involved in tumor-suppressive pathways, such as the TGF-ß and TNF signaling pathways, and genes related to cytokine-receptor interaction that may regulate cancer immunity. Moreover, reduced CYR61 expression is associated with an altered TIME that favors cancer progression. Finally, experimental analyses ascertained that CYR61 is downregulated in clinical BRCA tissues compared to matched normal breast tissues. Furthermore, CYR61 is able to impede the proliferation and colony formation of ER-positive BRCA cells. In summary, our study reveals that CYR61 could serve as a novel prognostic marker for ER-positive BRCA, and function as an inhibitor of cancer progression by both acting on cancer cells and remodeling the TIME.