The Ameliorate Effect of Endomorphin 1 on the Mice Nephrotoxicity Induced by Cadmium

AbstractTo wonder whether endomorphin 1(EM1), the antioxidative peptide, can protect against the renal toxicology of cadmium (Cd), which probably related to the oxidative injury.MethodsIn vivo assays have been designed and performed, such as the measurement of oxidative damage parameters and the index of antioxidative system.ResultData from our study demonstrated the effect of EM1 could ameliorate the increased concentration of lipid peroxidation products and protein carboxylatio and increase the content of antioxidative system, the antioxidant capacity of EM1 probably relate to its structure.ConclusionOur study first demonstrated the nephrotoxicity induced by Cd can be suppressed by the treatment of EM1

Structure-activity Study of Endomorphins Analogs with C- terminal Substitution

AbstractAims: To further wonder the influence of C-terminal residues on the pharmacological4 activities.Methods: The in vitro and in vivo opioid activities of C-terminal substitution analogs [L-Tic] EM1 and [L-Tic] EM2 were investigated using radioligand binding assay, guinea pig ileum (GPI) assay, mouse vas deferens (MVD) assay, systemic arterial pressure (SAP) assay and tail-flick test.Results: Our data showed that the analogs produced a higher δ-opioid affinity but low colon-opioid affinity, dose-dependent but reduced analgesic activities and cardiovascular effect comparing with those of EMs. Moreover, these effects induced by the analogs can be inhibited by naloxone, indicating an opioid mechanism.Conclusion: These results provided suggestive evidences that the substitution of C-terminal residue may play an important role in the regulation of opioid affinities and pharmacological activities

AutoFocusFormer: Image Segmentation off the Grid

Real world images often have highly imbalanced content density. Some areas are very uniform, e.g., large patches of blue sky, while other areas are scattered with many small objects. Yet, the commonly used successive grid downsampling strategy in convolutional deep networks treats all areas equally. Hence, small objects are represented in very few spatial locations, leading to worse results in tasks such as segmentation. Intuitively, retaining more pixels representing small objects during downsampling helps to preserve important information. To achieve this, we propose AutoFocusFormer (AFF), a local-attention transformer image recognition backbone, which performs adaptive downsampling by learning to retain the most important pixels for the task. Since adaptive downsampling generates a set of pixels irregularly distributed on the image plane, we abandon the classic grid structure. Instead, we develop a novel point-based local attention block, facilitated by a balanced clustering module and a learnable neighborhood merging module, which yields representations for our point-based versions of state-of-the-art segmentation heads. Experiments show that our AutoFocusFormer (AFF) improves significantly over baseline models of similar sizes.Comment: CVPR 202

Gray Matter Atrophy Is Associated With Cognitive Impairment in Patients With Presbycusis: A Comprehensive Morphometric Study

Presbycusis (PC) is characterized by bilateral sensorineural hearing loss at high frequencies and speech-perception difficulties in noisy environments and has a strikingly detrimental impact on cognitive function. As the neural consequences of PC may involve the whole brain, we hypothesized that patients with PC would show structural alterations not only in the auditory cortex but also in the cortexes involved in cognitive function. The purpose of this study was to use surface-based morphometry (SBM) analysis to elucidate whole-brain structural differences between patients with PC and age-matched normal hearing controls. Three-dimensional T1-weighted MR images of 26 patients with mild PC and 26 age-, sex- and education-matched healthy controls (HCs) were acquired. All participants underwent a battery of neuropsychological tests. Our results revealed gray matter atrophy in several auditory cortical areas, nodes of the default mode network (DMN), including the bilateral precuneus and inferior parietal lobule, the right posterior cingulate cortex (PCC), and the right insula of patients with PC compared to that in the HCs. Our findings also revealed that hearing loss was associated with reduced gray matter volume in the right primary auditory cortex of patients with PC. Moreover, structural alterations in the nodes of the DMN were associated with cognitive impairments in PC patients. Additionally, this study provides evidence that a thicker right insula is associated with better speech perception in patients with PC. Based on these findings, we argue that the onset of PC seems to trigger its own cascade of conditions, including a need for increased cognitive resources during speech comprehension, which might lead to auditory and cognition-related cortical reorganization

Downregulation of Long Non-coding RNA FALEC Inhibits Gastric Cancer Cell Migration and Invasion Through Impairing ECM1 Expression by Exerting Its Enhancer-Like Function

Long non-coding RNAs (lncRNAs) have been shown to play important roles in many human diseases. However, their functions and mechanisms in tumorigenesis and development remain largely unknown. Here, we demonstrated that focally amplified lncRNA in epithelial cancer (FALEC) was upregulated and significantly correlated with lymph node metastasis, TNM stage in gastric cancer (GC). Further experiments revealed that FALEC knockdown significantly inhibited GC cells migration and invasion in vitro. Mechanistic investigations demonstrated that small interfering RNA-induced silencing of FALEC decreased expression of the nearby gene extracellular matrix protein 1 (ECM1) in cis. Additionally, ECM1 and FALEC expression were positively correlated, and high levels of ECM1 predicted shorter survival time in GC patients. Our results suggest that the downregulation of FALEC significantly inhibited the migration and invasion of GC cells through impairing ECM1 expression by exerting an enhancer-like function. Our work provides valuable information and a novel promising target for developing new therapeutic strategies in GC