Mechanism of blood-brain barrier damage caused by the inhibition of Wnt7/β-catenin pathway induced by endoplasmic reticulum stress in cerebrovascular endothelial cells after stroke

Objective·To investigate whether the inactivation of Wnt7/β-catenin signaling causes the destruction of the blood-brain barrier (BBB) in cerebrovascular endothelial cells after ischemic stroke, and investigate whether endoplasmic reticulum stress bursts mediates the inhibition of Wnt7/β-catenin pathway.Methods·The model of middle cerebral artery occlusion (MCAO) in mice was established by a monofilament nylon suture with a round tip, which was used to temporarily occlude the middle cerebral artery for 60 min. MCAO model mice were intraperitoneally injected with the endoplasmic reticulum stress blocker 4-phenylbutyric acid (4-PBA) as 4-PBA+MCAO group. Sham surgery group (Sham group) was set. Twenty-four hours after MCAO, Evans blue (EB) was used to measure the BBB permeability. The brain water content was calculated by dry-wet weight ratio, and the adhesion of cerebrovascular endothelial cells and pericytes in mice was measured by immunofluorescence. Human brain microvascular endothelial cells (HBMECs) were used to establish an oxygen and glucose deprivation (OGD) model for 4 h, and then cultured with 4-PBA for 24 h. Cells were divided into blank control group, OGD group, and OGD+4-PBA group for CCK-8 assay to determine the cell viability. FITC-labeled bovine serum albumin (FITC-BSA) was used to detect the cell permeability. The secretion of platelet-derived growth factor β (PDGF-β) was measured by ELISA. Fluo-3 AM fluorescence probe was used to detect the fluorescence intensity of cells to assess intracellular Ca2+ concentration, and reactive oxygen species (ROS) content was measured by CM-H2DCFDA fluorescence probe to clarify the endoplasmic reticulum stress state. Western blotting was used to examine the expression of connexins, including zonula occludens-1 (ZO-1) and claudin-5, the expression of endoplasmic reticulum stress proteins, including CCAAT/enhancer-binding protein homologous protein (CHOP), glucose-regulated protein 78 (GRP78), and cysteine-containing aspartate-specific proteases-12 (Caspase-12), and the expression of Wnt7/β-catenin in HBMECs.Results·Compared with the Sham group, the brain water content of the infarction area of mice increased after MCAO, and the exudation of EB increased significantly (both P<0.05). The adhesion between cerebrovascular endothelial cells and pericytes in mice was reduced after the occurrence of MCAO. After intraperitoneal injection of 4-PBA in mice with MCAO, the degree of brain edema and the exudation of EB were reduced (both P<0.05), and the adhesion between cerebrovascular endothelial cells and pericytes increased. Compared with the HBMECs of the blank control group, the viability of HBMECs after OGD decreased, and the permeability of HBMECs increased (both P<0.05). OGD condition also led to decreased expression of connexins (ZO-1 and claudin-5), decreased secretion of PDGF-β in HBMECs, increased expression of endoplasmic reticulum stress proteins (CHOP, GRP78 and Caspase-12), up-regulated intracellular Ca2+ concentration and ROS content, and decreased expression of Wnt7 and β-catenin in HBMECs (all P<0.05). After HBMECs were cultured with 4-PBA, the damage of HBMECs caused by OGD was reduced, and the expression of connexins increased. The permeability of HBMECs was reduced, and the secretion of PDGF-β was promoted (all P<0.05). After 4-PBA treatment, the activity of Wnt7/β-catenin signaling was significantly restored in the OGD model of HBMECs (P<0.05).Conclusion·Wnt7/β-catenin signaling inactivation caused by endothelial reticulum stress bursts leads to cerebrovascular endothelial cell damage, which is the crucial pathway of BBB destruction after stroke

A predictive nomogram for assessing the likelihood of retrieving 12 lymph nodes after rectal cancer surgery: a single-center study

ObjectiveThe retrieval of 12 lymph nodes (LNs) remains a crucial criterion for accurate staging and prognosis evaluation in rectal cancer (RC). However, some patients fail to meet this threshold after surgery. This study developed a nomogram model based on clinical variables to predict the probability of retrieving 12 LNs postoperatively.MethodsPatients who underwent radical RC surgery at Shanxi Cancer Hospital between 2015 and 2020 were retrospectively analyzed. Continuous variables were converted into categorical variables. Chi-square tests were used to identify key factors influencing the retrieval of 12 LNs. Significant variables were incorporated into a nomogram model. The model’s discrimination ability was evaluated based on the receiver operating characteristic (ROC) curve, while model calibration was assessed using calibration plots. The clinical utility of the model was determined using decision curve analysis (DCA).ResultsA total of 2,724 RC patients were included; 1,906 cases were assigned to the training dataset, while 818 were assigned to the internal validation dataset. Chi-square analysis identified age, T stage, N stage, tumor size, Carcinoembryonic Antigen, CA19-9, hemoglobin, and platelet count as significant factors associated with 12 LN retrieval. The nomogram indicated that T stage, N stage, and tumor size contributed most significantly. The areas under the ROC curves of the model were 0.669 for the training dataset and 0.689 for the internal validation dataset. The calibration plots showed good agreement between the predicted probabilities and actual outcomes. The DCA curves demonstrated a favorable net benefit across a wide range of threshold probabilities.ConclusionThe nomogram model can effectively predict the likelihood of retrieving 12 LNs following RC surgery. The model also provides a valuable tool for preoperative risk stratification and personalized clinical decision-making

Refining models of archaic admixture in Eurasia with ArchaicSeeker 2.0

We developed a method, ArchaicSeeker 2.0, to identify introgressed hominin sequences and model multiple-wave admixture. The new method enabled us to discern two waves of introgression from both Denisovan-like and Neanderthal-like hominins in present-day Eurasian populations and an ancient Siberian individual. We estimated that an early Denisovan-like introgression occurred in Eurasia around 118.8–94.0 thousand years ago (kya). In contrast, we detected only one single episode of Denisovan-like admixture in indigenous peoples eastern to the Wallace-Line. Modeling ancient admixtures suggested an early dispersal of modern humans throughout Asia before the Toba volcanic super-eruption 74 kya, predating the initial peopling of Asia as proposed by the traditional Out-of-Africa model. Survived archaic sequences are involved in various phenotypes including immune and body mass (e.g., ZNF169), cardiovascular and lung function (e.g., HHAT), UV response and carbohydrate metabolism (e.g., HYAL1/HYAL2/HYAL3), while “archaic deserts” are enriched with genes associated with skin development and keratinization

Abnormal cerebellar activity and connectivity alterations of the cerebellar-limbic system in post-stroke cognitive impairment: a study based on resting state functional magnetic resonance imaging

BackgroundStroke is an important cause of cognitive impairment. Post-stroke cognitive impairment (PSCI) is a prevalent psychiatric disorder following stroke. However, the effects of PSCI on the cerebellum remain mostly unknown.MethodsA total of 31 PSCI patients and 31 patients without cognitive impairment after stroke were included in this study. The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) were administered to all participants. Analyses of ALFF, fALFF, and ReHo were employed to investigate alterations in brain neuronal activity, while limbic connectivity analysis was utilized to reflect changes within the abnormal connections within brain regions.ResultsWe found that ALFF values were increased in Cerebelum_7b_R, Cerebelum_Crus1_L. fALFF values were increased in Vermis_3. The ReHo values were increased in Cerebelum_8_R, Cerebelum_Crus2_R, Cerebelum_Crus1_L. The functional connection between Frontal_Mid_Orb_L and Cerebelum_Crus2_R brain regions was decreased. The functional connection between Hippocampus_L and Cerebelum_Crus2_R brain regions was decreased. The functional connection between Vermis_3 and Frontal_Med_Orb_L brain regions was decreased.ConclusionThe severity of cognitive impairment may influence the extent of functional connectivity disruption between the cerebellum and the limbic system. Furthermore, atypical alterations in neuronal activity within cerebellar regions are associated with cognitive decline

NTIRE 2024 Quality Assessment of AI-Generated Content Challenge

This paper reports on the NTIRE 2024 Quality Assessment of AI-Generated Content Challenge, which will be held in conjunction with the New Trends in Image Restoration and Enhancement Workshop (NTIRE) at CVPR 2024. This challenge is to address a major challenge in the field of image and video processing, namely, Image Quality Assessment (IQA) and Video Quality Assessment (VQA) for AI-Generated Content (AIGC). The challenge is divided into the image track and the video track. The image track uses the AIGIQA-20K, which contains 20,000 AI-Generated Images (AIGIs) generated by 15 popular generative models. The image track has a total of 318 registered participants. A total of 1,646 submissions are received in the development phase, and 221 submissions are received in the test phase. Finally, 16 participating teams submitted their models and fact sheets. The video track uses the T2VQA-DB, which contains 10,000 AI-Generated Videos (AIGVs) generated by 9 popular Text-to-Video (T2V) models. A total of 196 participants have registered in the video track. A total of 991 submissions are received in the development phase, and 185 submissions are received in the test phase. Finally, 12 participating teams submitted their models and fact sheets. Some methods have achieved better results than baseline methods, and the winning methods in both tracks have demonstrated superior prediction performance on AIGC

Cucinaqui. Il centro si riempie di sapori

LAUREA MAGISTRALELa tragedia del sisma Abruzzese è ancora viva nel ricordo dei suoi cittadini o di chiunque abbia visitato quei luoghi colpiti dal terremoto o semplicemente visto le immagini di quello che la forza della natura può compiere. Tre anni dopo la catastrofe, l’Aquila risulta essere una città fantasma. Passeggiando per il centro storico non si incontra praticamente nessuno, solo il silenzio regna indiscusso. Sono pochi i locali commerciali che sono riusciti a riaprire e solo grazie agli sforzi dei proprietari, con il rischio che falliscano da un momento all’altro perché coloro che abitavano la città, sono stati trasferiti nelle case d’emergenza costruite nei dintorni e raramente vi fanno visita, non hanno il pretesto per andare appositamente nelle vie del centro. Le poche persone che si vedono sono gli anziani o qualche ragazzo ma i cittadini soffrono nel vedere la loro città ferita e che nessuno se ne interessi. Alcune serate soprattutto quelle universitarie sembra di rivivere lo splendore di un tempo grazie ai locali notturni che riescono a riunire giovani che affollano le piazzette aperte, il corso e via Garibaldi. “Costruire significa dare corpo a nuovi modi di vivere” in questo modo Walter A. Gropius apre il suo discorso al II CIAM di Francoforte avviando così una stagione di continua sperimentazione sul tema dell’abitare temporaneo, tema che è stato affrontato nel progetto da un punto di vista innovativo,ovvero dove l’architettura non riesce a trovare soluzioni in tempi brevi e con soluzioni semplici per arrivare al cuore delle persone, entra in gioco la cultura del Design. Il progetto si rivolge direttamente ai cittadini del L’Aquila grazie a una serie di attività legate al tema della cucina. Infatti prendendo come spunto la gastronomia, ma soprattutto la tradizione culinaria radicata nel territorio abruzzese e notoriamente momento di riunione preferito da tutti i popoli, il progetto va ad inserirsi nel tessuto cittadino come un nuovo layer temporaneo per ridare vita alla città, ridare speranza ai cittadini promuovendo una collaborazione intergenerazionale tra giovani anziani e professionisti, auspicando che possibili visitatori esterni visitino L’Aquila come avrebbero fatto prima del terremoto.The wounds in Abruzzo citizens’ heart have not been healed after they witnessed the collapse of the city in 2009. People who have ever visited the ruined places after the earthquake are impressed by the force of nature. Three years after the disaster, L’Aquila turns out to be a ghost town. Walking through the history center, ‘empty’ is the word to describe what we see and what we feel. Only the silence reigns undisputed. Very few of the local businesses are able to reopen thanks to the efforts of the owners. However, they run the risk of failure at any moment because people who used to live in the city are transferred to the emergency houses built in the vicinity and they have no reason to go specifically back to the place of grief. The few people that can be seen are elderly people or some young guys, but most of the citizens are suffering from seeing the debris and knowing that no one is truly interested in it. During some evenings, especially those university evenings, the beautiful time seems to come back thanks to the nightclubs who bring so many young people to the the squares, il Corso and Via Garibaldi. “To build means to embody a new way of living” Walter A. Gropius started his discourse at the CIAM II in Frankfurt, setting up a new season of continuous experimentation around the theme of temporary housing. In our project, such theme has been developed from an innovative point of view: when Architecture is not able to find solutions in a short time or find simple ways that can touch people, Design needs to play a role. The project is targeted directly to the citizens of L'Aquila with a series of activities based on the theme of cooking. Taking inspiration from the food, especially the culinary tradition rooted in the Abruzzo region, which is known as people’s favorite moment of gathering, the project is going to integrate into the urban fabric as a new temporary layer in order to revitalize the city and to restore the hope for the citizens by promoting the collaboration between young people, elderly people and professionals, in the hope that visitors will visit L'Aquila again as they did or planned before the earthquake

DYNAMIC EXPLICIT FEM IN WHEELS RADIAL FATIGUE TEST

As the static implicit Finite Element Method（ FEM） is hard to simulate the wheels radial fatigue test accurately,this paper studies the simulated method with dynamic explicit FEM. It introduces the setting method of finite element,material performance parameter,tire,bolt pretention,weld,rotary drum,radial force,etc. It shown the distribution of stress and surface pressure of wheels,put forward a method to judge analysis result reasonable or not,and introduces the selection method of S-N curve for fatigue analysis. By comparing the FEA and test result,it knows that the dynamic explicit FEM setting method in this paper can get an idea analysis result