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Abstract Renal inflammation and fibrosis are the common pathways leading to progressive chronic kidney disease (CKD). We previously identified hematopoietic cell kinase (HCK) as upregulated in human chronic allograft injury promoting kidney fibrosis; however, the cellular source and molecular mechanisms are unclear. Here, using immunostaining and single cell sequencing data, we show that HCK expression is highly enriched in pro-inflammatory macrophages in diseased kidneys. HCK-knockout (KO) or HCK-inhibitor decreases macrophage M1-like pro-inflammatory polarization, proliferation, and migration in RAW264.7 cells and bone marrow-derived macrophages (BMDM). We identify an interaction between HCK and ATG2A and CBL, two autophagy-related proteins, inhibiting autophagy flux in macrophages. In vivo, both global or myeloid cell specific HCK-KO attenuates renal inflammation and fibrosis with reduces macrophage numbers, pro-inflammatory polarization and migration into unilateral ureteral obstruction (UUO) kidneys and unilateral ischemia reperfusion injury (IRI) models. Finally, we developed a selective boron containing HCK inhibitor which can reduce macrophage pro-inflammatory activity, proliferation, and migration in vitro, and attenuate kidney fibrosis in the UUO mice. The current study elucidates mechanisms downstream of HCK regulating macrophage activation and polarization via autophagy in CKD and identifies that selective HCK inhibitors could be potentially developed as a new therapy for renal fibrosis.

Background: Teratomas are totipotent tumors commonly seen in gonadal and extragonadal region. Gastric teratomas are very rare and account for

Abstract Tissue architecture is a prerequisite for its biological functions. Recapitulating the three‐dimensional (3D) tissue structure represents one of the biggest challenges in tissue engineering. Two‐dimensional (2D) tissue fabrication methods are currently in the main stage for tissue engineering and disease modeling. However, due to their planar nature, the created models only represent very limited out‐of‐plane tissue structure. Here compressive buckling principle is harnessed to create 3D biomimetic cell‐laden microstructures from microfabricated planar patterns. This method allows out‐of‐plane delivery of cells and extracellular matrix patterns with high spatial precision. As a proof of principle, a variety of polymeric 3D miniature structures including a box, an octopus, a pyramid, and continuous waves are fabricated. A mineralized bone tissue model with spatially distributed cell‐laden lacunae structures is fabricated to demonstrate the fabrication power of the method. It is expected that this novel approach will help to significantly expand the utility of the established 2D fabrication techniques for 3D tissue fabrication. Given the widespread of 2D fabrication methods in biomedical research and the high demand for biomimetic 3D structures, this method is expected to bridge the gap between 2D and 3D tissue fabrication and open up new possibilities in tissue engineering and regenerative medicine.

The glomerulus is a compact cluster of capillaries responsible for blood filtration and initiating urine production in the renal nephrons. A trilaminar structure in the capillary wall forms the glomerular filtration barrier (GFB), composed of glycocalyx-enriched and fenestrated endothelial cells adhering to the glomerular basement membrane and specialized visceral epithelial cells, podocytes, forming the outermost layer with a molecular slit diaphragm between their interdigitating foot processes. The unique dynamic and selective nature of blood filtration to produce urine requires the functionality of each of the GFB components, and hence, mimicking the glomerular filter in vitro has been challenging, though critical for various research applications and drug screening. Research efforts in the past few years have transformed our understanding of the structure and multifaceted roles of the cells and their intricate crosstalk in development and disease pathogenesis. In this review, we present a new wave of technologies that include glomerulus-on-a-chip, three-dimensional microfluidic models, and organoids all promising to improve our understanding of glomerular biology and to enable the development of GFB-targeted therapies. Here, we also outline the challenges and the opportunities of these emerging biomimetic systems that aim to recapitulate the complex glomerular filter, and the evolving perspectives on the sophisticated repertoire of cellular signaling that comprise the glomerular milieu.

Frontal circuits play a critical role in motor, cognitive and affective processing, and their dysfunction may result in a variety of brain disorders. However, exactly which frontal domains mediate which (dys)functions remains largely elusive. We studied 534 deep brain stimulation electrodes implanted to treat four different brain disorders. By analyzing which connections were modulated for optimal therapeutic response across these disorders, we segregated the frontal cortex into circuits that had become dysfunctional in each of them. Dysfunctional circuits were topographically arranged from occipital to frontal, ranging from interconnections with sensorimotor cortices in dystonia, the primary motor cortex in Tourettes syndrome, the supplementary motor area in Parkinsons disease, to ventromedial prefrontal and anterior cingulate cortices in obsessive-compulsive disorder. Our findings highlight the integration of deep brain stimulation with brain connectomics as a powerful tool to explore couplings between brain structure and functional impairments in the human brain.

Emergency department visits and healthcare expenditures for pediatric atopic dermatitis have been increasing over the last two decades. There is a paucity of replicable quality improvement initiatives addressed at educating primary care and emergency medicine clinicians on this condition. The goal of this initiative was to improve clinician knowledge and comfort in the diagnosis and management of pediatric atopic dermatitis and superinfection. Clinicians were recruited via email from academic and community settings in Travis County, Texas, in 2020. They were sent a pre-intervention survey, a series of three quizzes, and a post-intervention survey. After each quiz, participants received performance feedback and various forms of multimodal education. Differences between the first and final quiz scores and clinician confidence levels were analyzed for statistical significance. Fifty-six clinicians completed the intervention. The average overall and treatment-specific scores increased significantly by 10% and 37%, respectively. Further, confidence levels improved significantly in the majority of clinicians. Clinician qualitative feedback revealed high satisfaction. Results from this educational quality improvement project have demonstrated that this is an effective and replicable resource for educating clinicians who manage pediatric atopic dermatitis in the emergency department and outpatient setting.

Objectives: This study aimed to evaluate linear measurements of the frontal sinus (FS) and sphenoid sinus (SS) for sex identification on cone beam computed tomography (CBCT) images. Methods: A comparative CBCT analysis was conducted on 200 full field of view (FOV) scans taken as part of routine dental investigations. Dimensions of the bilateral frontal and sphenoid sinuses were measured. Intra- and interobserver reliability were calculated. Independent t tests were used to compare the various parameters between sexes. Stepwise discriminant function analysis was used to determine sex. Additionally, the receiver operating characteristic (ROC) curve, area under the curve (AUC), sensitivity, and specificity were also determined. A p value

Brain rhythms can facilitate neural communication for the maintenance of brain function. Beta rhythms (13–35 Hz) have been proposed to serve multiple domains of human ability, including motor control, cognition, memory, and emotion, but the overarching organisational principles remain unknown. To uncover the circuit architecture of beta oscillations, we leverage normative brain data, analysing over 30 hr of invasive brain signals from 1772 channels from cortical areas in epilepsy patients, to demonstrate that beta is the most distributed cortical brain rhythm. Next, we identify a shared brain network from beta-dominant areas with deeper brain structures, like the basal ganglia, by mapping parametrised oscillatory peaks to whole-brain functional and structural MRI connectomes. Finally, we show that these networks share significant overlap with dopamine uptake as indicated by positron emission tomography. Our study suggests that beta oscillations emerge in cortico-subcortical brain networks that are modulated by dopamine. It provides the foundation for a unifying circuit-based conceptualisation of the functional role of beta activity beyond the motor domain and may inspire an extended investigation of beta activity as a feedback signal for closed-loop neurotherapies for dopaminergic disorders.

Introduction: The study aimed to determine the prevalence and associated factors of internet addiction (IA) among early adolescents during the COVID-19 pandemic in Kota Bharu, Kelantan, Malaysia. Methods: A cross-sectional online survey was conducted from February to April 2021 among adolescents in Kota Bharu, Kelantan. Participants completed the Malay Version of the Internet Addiction Test, the Depression, Anxiety and Stress Scale-21 and a sociodemographic information form. A multiple logistic regression analysis was performed to determine the associations between variables. Results: A total of 535 adolescents participated in this study. Among them, 65.9% were girls. The prevalence of IA among the participants was 48.6%. Male sex [adjusted odds ratio (AOR)=2.15, 95% confidence interval (CI)=1.30–3.57], internet usage at home (AOR=6.17, 95% CI=1.94–19.58), internet usage to watch/download music (AOR=2.50, 95% CI=1.52–4.12), internet usage to engage in social networking (AOR=2.29, 95% CI=1.19–4.40), inadequate parental/guardian bonding (AOR=2.19, 95% CI=1.31–3.65), depression (AOR=2.03, 95% CI=1.07–3.85), anxiety (AOR=2.79, 95% CI=1.64–4.76) and stress (AOR=4.67, 95% CI=2.00–10.91) were significantly associated with IA. Conclusion: IA was prevalent among Malaysian adolescents during the COVID-19 pandemic. Sex, internet usage profile and psychological factors were significant predictors of IA.