Seeing in crowds: Averaging first, then max.

Crowding, a fundamental limit in object recognition, is believed to result from excessive integration of nearby items in peripheral vision. To understand its pooling mechanisms, we measured subjects' internal response distributions in an orientation crowding task. Contrary to the prediction of an averaging model, we observed a pattern suggesting that the perceptual judgement is made based on choosing the largest response across the noise-perturbed items. A model featuring first-stage averaging and second-stage signed-max operation predicts the diverse errors made by human observers under various signal strength levels. These findings suggest that different rules operate to resolve the bottleneck at early and high-level stages of visual processing, implementing a combination of linear and nonlinear pooling strategies.

Visual statistical learning of naturalistic textures.

The visual system continuously adapts to the statistical properties of the environment. In this study, we demonstrated that training significantly enhanced subjects' perceptual sensitivity to co-occurrence statistics in naturalistic textures. The learning effect was specific to the statistical component and spatial location. By examining the time course of learning, we found that learning was accelerated at an untrained location. Our findings establish a link between statistical learning and visual perception, indicating multistage plasticity beyond V1 in the visual hierarchy. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Effect of hyperbaric oxygen on post-stroke depression.

BACKGROUND: In patients with post-stroke depression (PSD) in diabetes, the situation may be more complex, requiring simultaneous treatment of blood glucose, depressive symptoms, and neurological dysfunction. Hyperbaric oxygen (HBO) therapy can improve tissue oxygen content and improve the situation of ischemia and hypoxia, thus playing a role in protecting brain cells and restoring the function of brain cells. However, there are few studies on HBO therapy for patients with PSD. This study explores the clinical efficacy of such therapy for stroke complicated with depression and diabetes mellitus, and to provide reference and basis for clinical treatment and development through the application of relevant rating scales and laboratory test indicators. AIM: To evaluate the clinical effects of HBO therapy on patients with diabetes with PSD. METHODS: A total of 190 diabetic patients with PSD were randomly divided into observation and control groups (95 patients per group). The control group received escitalopram oxalate 10mg once a day for eight weeks. In addition, the ob-servation group was also given HBO therapy, once a day, five times a week, for eight weeks. The Montgomery Depression Rating Scale (MADRS), National Institutes of Health Stroke Scale (NIHSS), hypersensitive C-reactive protein, tumor necrosis factor (TNF)-α, and fasting glucose levels were compared. RESULTS: There were no significant differences in age, sex, or depression course between the groups (P > 0.05). After HBO treatment, MADRS scores in both groups decreased significantly (14.3 ± 5.2), and were significantly lower in the control group (18.1 ± 3.5). After HBO treatment, NIHSS scores in both groups decreased significantly, and scores in the observation group (12.2 ± 4.0) decreased more than in the control group (16.1 ± 3.4), the difference was statistically significant (P < 0.001). The levels of hypersensitive C-reactive protein and TNF-α in both groups were significantly decreased, and the observation group was significantly lower than the control group (P < 0.001). Fasting blood glucose levels in both groups decreased significantly, and those in the observation group decreased more (8.02 ± 1.10) than in the control group (9.26 ± 1.04), with statistical significance (t = -7.994, P < 0.001). CONCLUSION: HBO therapy can significantly improve depressive symptoms and neurological dysfunction in patients with PSD, and reduce the levels of hypersensitive C-reactive protein, TNF-α and fasting blood glucose.

Using a Multiple-Case Study Design to Explore the Worship Experiences of Black Families Affected by Dementia.

OBJECTIVES: The purpose of this multiple-case study was to report on the worship experiences of Black families affected by dementia. METHODS: Data were collected through participant observations of family caregivers (n = 4) and persons living with dementia (n = 4) during worship services and semi-structured interviews with the family caregivers over six months. Data were initially analyzed case-by-case, then across-cases. RESULTS: Four overarching themes emerged: Welcoming church culture, Community support from the church, Engagement during worship service, and Connectedness between the caregiver and their family member living with dementia. Family caregivers reported that their family member with dementia was attentive and expressed moments of clarity during and immediately after worship services. CONCLUSIONS: Worship services can be tailored to support families affected by dementia and can promote engagement of the person living with dementia with church activities and family members. CLINICAL IMPLICATIONS: Health practitioners are encouraged to acknowledge the influence of religious practices within Black families affected by dementia and integrate them into interdisciplinary care plans and programs.

Discovery of the First Potent IDO1/IDO2 Dual Inhibitors: A Promising Strategy for Cancer Immunotherapy.

Indoleamine 2,3-dioxygenase-1 (IDO1) plays an important role in tumor immune escape. However, unsatisfactory clinical efficacies of selective IDO1 inhibitors have impeded their further development, suggesting that they do not exert sufficient antitumor effects by selectively inhibiting IDO1. IDO2, an isoenzyme of IDO1, is overexpressed in some human tumors, and emerging evidence suggests that concomitant inhibition of IDO1/2 may have synergistic effects in cancer treatment, revealing a promising cancer immunotherapeutic strategy. Herein, we describe the discovery of compound 4t, the first inhibitor targeting both IDO1/2 that has excellent in vitro inhibitory activity (IDO1 IC50 = 28 nM and IDO2 IC50 = 144 nM). Notably, 4t (TGI = 69.7%) exhibited significantly stronger in vivo antitumor potency than epacadostat (TGI = 49.4%) in CT26 xenograft mouse models, highlighting the advantages of IDO1/2 dual inhibitors for tumor immunotherapy. Preliminary mechanistic studies in vivo further identified that 4t exerts its antitumor effect by inhibiting IDO1/2.

Curcumin Complex Analogues as Near-Infrared Fluorescent Probes for Monitoring all Aß Species in the Early Alzheimer's Disease Model.

Aggregation of amyloid ß-peptide (Aß) is closely related to the pathology of Alzheimer's disease (AD). In this pathology, the beginning stage is characterized by excessive accumulation of Aß monomers due to imbalanced Aß in the process of clearance. The Aß peptide exists in many forms such as soluble and insoluble Aß species, both of which coexist during the progression of AD and contribute to AD pathology. Thus, probes capable of monitoring all Aß species are highly desirable. While there are several fluorescent probes for detecting insoluble Aß, it is still challenging to monitor all Aß forms by using probes. Here, we describe a near-infrared fluorescent chemical probe, termed AD-1, developed through complexation of curcumin analogues with a stabilizer, which has good photophysical properties and shows high binding to all Aß species in solution tests. Furthermore, AD-1 exhibited good blood-brain barrier penetrating ability and low cytotoxicity. More importantly, it was successfully applied to 4-month-young APP/PS1 mice imaging noninvasively.

"Everything is Either Sent by God or Used by God": An Exploratory Study on the Impact of COVID-19 Upon the Religious Lives of Black Families Living with Dementia.

The purpose of this research study was to explore the impact of COVID-19 on church engagement for Black families affected by dementia in the USA. Semi-structured interviews were conducted with current caregivers, church leaders, and persons with dementia (n = 16). The following themes emerged: (a) Ability to continue religious practices, (b) Increased church engagement, (c) Importance of fellowship, (d) Role of technology, and (e) New normal. As the Internet becomes the new church building, online worship services enabled more families affected by dementia to engage. Many church leaders expressed the intent of continuing to provide online worship services post-pandemic. Families highlighted their need to fellowship with other congregants. Technology was perceived as a double-edged sword serving as both a motivator and a barrier to religious engagement. These findings will support faith leaders in understanding the needs of their congregants during the COVID-19 pandemic, such as allowing families living with dementia to continue engaging in religious practices and living in meaningful ways.

Design, synthesis and biological evaluation of novel molecules as potent PARP-1 inhibitors.

Two series of novel compounds with inhibition activity against PARP-1 were designed and synthesized. All target compounds were evaluated for their PARP-1 inhibition activity, and compounds with high PARP-1 inhibition activity were selected to assess for cellular assays in vitro. Among them, compound II-4 displayed impressive results in both PARP-1 enzyme inhibition with IC50 value of 0.51 nM and anti-proliferation activity against HCT116 and HCC1937 cell lines with IC50 values of 6.62 nM and 12.65 nM, respectively. Also, II-4 exhibited good metabolic stability in vitro with t1/2 of 173.25 min and CLint of 0.04 mL/min/mg. Prediction of molecular properties and protein docking were applied to structure design. Our study provides potential lead compounds and design directions for the development of PARP-1 inhibitors.

Discovery of novel PARP/PI3K dual inhibitors with high efficiency against BRCA-proficient triple negative breast cancer.

Co-targeting PARP and PI3K by PARP/PI3K dual inhibitors has been recognized as a promising chemotherapeutic strategy for the treatment of triple negative breast cancer (TNBC) in our previous work. To further explore novel and more potent PARP/PI3K dual inhibitors, a series of compounds were designed, synthesized and evaluated for their pharmacological properties, resulting in the candidate compound 12, a potent and highly selective PARP/PI3K dual inhibitor. Compared to Olaparib, compound 12 exhibits a superior antiproliferative profile against BRCA-proficient MDA-MB-468 cells. In MDA-MB-468 cell-derived xenograft model, compound 12 displayed excellent antitumor efficacy at a dose of 50 mg/kg, which is considerably more efficacious than the single administration of Olaparib or BKM120. Furthermore, compound 12 displayed good metabolic stability and high safety. Taken together, these results suggest that compound 12 as a novel PARP/PI3K dual inhibitor is worthy for further study.

Discovery of Novel Dual Poly(ADP-ribose)polymerase and Phosphoinositide 3-Kinase Inhibitors as a Promising Strategy for Cancer Therapy.

Concomitant inhibition of PARP and PI3K pathways has been recognized as a promising strategy for cancer therapy, which may expand the clinical utility of PARP inhibitors. Herein, we report the discovery of dual PARP/PI3K inhibitors that merge the pharmacophores of PARP and PI3K inhibitors. Among them, compound 15 stands out as the most promising candidate with potent inhibitory activities against both PARP-1/2 and PI3Kα/δ with pIC50 values greater than 8. Compound 15 displayed superior antiproliferative profiles against both BRCA-deficient and BRCA-proficient cancer cells in cellular assays. The prominent synergistic effects produced by the concomitant inhibition of the two targets were elucidated by comprehensive biochemical and cellular mechanistic studies. In vivo, 15 showed more efficacious antitumor activity than the corresponding drug combination (Olaparib + BKM120) in the MDA-MB-468 xenograft model with a tumor growth inhibitory rate of 73.4% without causing observable toxic effects. All of the results indicate that 15, a first potent dual PARP/PI3K inhibitor, is a highly effective anticancer compound.

Development of Near-Infrared Fluorescent Probes for Use in Alzheimer's Disease Diagnosis.

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder. Currently, there are no available treatments that can effectively stop or reverse the progression of the disease, and existing therapeutics can only alleviate the symptoms. Thus, it remains urgent to develop effective early-stage AD diagnostic methods. In recent years, the search for near-infrared fluorescent (NIRF) probes of AD hallmarks has become a promising research field. In this Review, we will focus on small-molecule NIRF probes used to detect ß-amyloid, tau proteins, and reactive oxygen species in vivo during the past 4 years. We believe that some new directions we raise herein will benefit the future development of NIRF probes in the field of AD research.

Design, synthesis and biological evaluation of novel 3H-imidazole [4,5-b] pyridine derivatives as selective mTOR inhibitors.

A series of 3H-imidazo [4,5-b] pyridines derivatives were designed and synthesized as selective mTOR inhibitors. The systematic optimization of the molecules resulted in the identification of two compounds 10d and 10n with nanomolar mTOR inhibitory activity and selectivity over PI3Kα. Besides, compounds 10d and 10n demonstrated attractive potency against human breast cancer cells (MCF-7) and human ovarian cancer cell (A2780).