Mieap, a p53-Inducible Protein, Controls Mitochondrial Quality by Repairing or Eliminating Unhealthy Mitochondria

Maintenance of healthy mitochondria prevents aging, cancer, and a variety of degenerative diseases that are due to the result of defective mitochondrial quality control (MQC). Recently, we discovered a novel mechanism for MQC, in which Mieap induces intramitochondrial lysosome-like organella that plays a critical role in the elimination of oxidized mitochondrial proteins (designated MALM for Mieap-induced accumulation of lysosome-like organelles within mitochondria). However, a large part of the mechanisms for MQC remains unknown. Here, we report additional mechanisms for Mieap-regulated MQC. Reactive oxygen species (ROS) scavengers completely inhibited MALM. A mitochondrial outer membrane protein NIX interacted with Mieap in a ROS-dependent manner via the BH3 domain of NIX and the coiled-coil domain of Mieap. Deficiency of NIX also completely impaired MALM. When MALM was inhibited, Mieap induced vacuole-like structures (designated as MIV for Mieap-induced vacuole), which engulfed and degraded the unhealthy mitochondria by accumulating lysosomes. The inactivation of p53 severely impaired both MALM and MIV generation, leading to accumulation of unhealthy mitochondria. These results suggest that (1) mitochondrial ROS and NIX are essential factors for MALM, (2) MIV is a novel mechanism for lysosomal degradation of mitochondria, and (3) the p53-Mieap pathway plays a pivotal role in MQC by repairing or eliminating unhealthy mitochondria via MALM or MIV generation, respectively

Global, regional, and national incidence of six major immune-mediated inflammatory diseases: findings from the global burden of disease study 2019

Background The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. Methods We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. Findings In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. Interpretation The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively. Funding The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. The project funded by Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38)

Melting Heat Transfer Rheology in Bioconvection Cross Nanofluid Flow Confined by a Symmetrical Cylindrical Channel with Thermal Conductivity and Swimming Microbes

Peer reviewed: TrueNonlinear thermal transport of non-Newtonian polymer flows is an increasingly important area in materials engineering. Motivated by new developments in this area which entail more refined and more mathematical frameworks, the present analysis investigates the boundary-layer approximation and heat transfer persuaded by a symmetrical cylindrical surface positioned horizontally. To simulate thermal relaxation impacts, the bioconvection Cross nanofluid flow Buongiorno model is deployed. The study examines the magnetic field effect applied to the nanofluid using the heat generated, as well as the melting phenomenon. The nonlinear effect of thermosolutal buoyant forces is incorporated into the proposed model. The novel mathematical equations include thermophoresis and Brownian diffusion effects. Via robust transformation techniques, the primitive resulting partial equations for momentum, energy, concentration, and motile living microorganisms are rendered into nonlinear ordinary equations with convective boundary postulates. An explicit and efficient numerical solver procedure in the Mathematica 11.0 programming platform is developed to engage the nonlinear equations. The effects of multiple governing parameters on dimensionless fluid profiles is examined using plotted visuals and tables. Finally, outcomes related to the surface drag force, heat, and mass transfer coefficients for different influential parameters are presented using 3D visuals.</jats:p

Comparative Numerical Analysis for the Error Estimation of the Fluid Flow over an Inclined Axisymmetric Cylinder with a Gyrotactic Microbe

Peer reviewed: TrueAcknowledgements: Researcher Supporting Project number (RSPD2023R1060), King Saud University, Riyadh, Saudi Arabia.The numerical investigation of bioconvective nanofluid (NF) flow, which involves gyrotactic microbes and heat and mass transmission analysis above an inclined extending axisymmetric cylinder, is presented in this study. The study aims to investigate the bioconvection flow of nanofluid under the influence of heat sources/sinks. Through proper transformation, all partial differential equations are transformed into a non-linear ODE scheme. A new set of variables is presented in the directive to get the first-order convectional equations and then solved numerically using bvp4c MATLAB, embedded in the function. The proposed model is validated after calculating the error estimation and obtaining the residual error. The influence of various factors on the velocity, energy, concentration, and density of motile microorganisms is examined and studied. The analysis describes and addresses all physical measures of concentration such as Skin Friction (SF), Sherwood number, the density of motile microorganisms, and Nusselt number. To validate the present study, a comparison is conducted with previous studies, and excellent correspondence is found. In addition, the ND-Solve approach is utilized to confirm the bvp4c. The mathematical model is confirmed through error analysis. This study provides the platform for industrial applications such as cooling capacity polymers, heat exchange, and chemical production sectors

Door-to-door survey of major neurological disorders (project) in Al Quseir City, Red Sea Governorate, Egypt

Hamdy NA El Tallawy,1 Wafaa MA Farghaly,1 Tarek A Rageh,1 Ghaydaa A Shehata,1 Reda Badry,1 Nabil A Metwally,2 Esam A El Moselhy,2 Mahmoud Hassan,2 Mohamed A Sayed,3 Ahmed A Waris,1 Yaser Hamed,2 Islam Shaaban,2 Mohamed A Hamed,1 Mahmoud Raafat Kandil11Department of Neurology, Faculty of Medicine, Assiut University, Assiut, Egypt; 2Department of Neurology and Public Health, Faculty of Medicine, Al-Azhar University (Assiut branch), Assiut, Egypt; 3Department of Neurology, Faculty of Medicine, Sohag University, Sohag, EgyptAbstract: A door-to-door survey, including every household, was conducted for all inhabitants of Al Quseir City (33,283), Red Sea Governorate, Egypt by three specialists of neurology as well as nine senior staff members of neurology and 15 female social workers to assess the epidemiology of major neurological disorders. Over six phases, from July 1, 2009 to January 31, 2012, screening of all eligible people in the population was carried out, by which case ascertainment of all major neurological disorders included in the study was done according to the accepted definitions and diagnostic criteria of the World Health Organization. The order of frequency of prevalence of the studied neurological disorders was dementia (3.83% for those aged > 60 years), migraine (2.8% for those aged > 8 years), stroke (6.2/1000 for those aged > 20 years), epilepsy (5.5/1000), Parkinson&rsquo;s disease (452.1/100,000 for those aged > 40 years), cerebral palsy (3.6/1000 among children 37 years), chorea (21.03/100,000), athetosis (15/100,000), and multiple sclerosis (13.74/100,000). The incidence rates of stroke, epilepsy, and Bell&rsquo;s palsy were 181/100,000, 48/100,000, and 98.9/100,000 per year, respectively.Keywords: prevalence, incidence, neurological disorder