Pericytes in Alzheimer's disease: Key players and therapeutic targets.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder that leads to progressive cognitive decline and neuropathological changes. Pericytes, which are vessel mural cells on the basement membrane of capillaries, play a crucial role in regulating cerebrovascular functions and maintaining neurovascular unit integrity. Emerging research substantiates the involvement of pericytes in AD. This review provides a comprehensive overview of pericytes, including their structure, origin, and markers and various functions within the central nervous system. Emphatically, the review explores the intricate mechanisms through which pericytes contribute to AD, including their interactions with amyloid beta and apolipoprotein E, as well as various signaling pathways. The review also highlights potential for targeted pericyte therapy for AD, with a focus on stem cell therapy and drug treatments. Future research directions include the classification of pericyte subtypes, studies related to aging, and the role of pericytes in exosome-related mechanisms in AD pathology. In conclusion, this review consolidates current knowledge on the pivotal roles of pericytes in AD and their potential as therapeutic targets, providing valuable insights for future research and clinical interventions aimed at addressing the impact of AD on patients' lives.

Targeting mitophagy for neurological disorders treatment: advances in drugs and non-drug approaches.

Mitochondria serve as a vital energy source for nerve cells. The mitochondrial network also acts as a defense mechanism against external stressors that can threaten the stability of the nervous system. However, excessive accumulation of damaged mitochondria can lead to neuronal death. Mitophagy is an essential pathway in the mitochondrial quality control system and can protect neurons by selectively removing damaged mitochondria. In most neurological disorders, dysfunctional mitochondria are a common feature, and drugs that target mitophagy can improve symptoms. Here, we reviewed the role of mitophagy in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, stroke, and traumatic brain injuries. We also summarized drug and non-drug approaches to promote mitophagy and described their therapeutic role in neurological disorders in order to provide valuable insight into the potential therapeutic agents available for neurological disease treatment. However, most studies on mitophagy regulation are based on preclinical research using cell and animal models, which may not accurately reflect the effects in humans. This poses a challenge to the clinical application of drugs targeting mitophagy. Additionally, these drugs may carry the risk of intolerable side effects and toxicity. Future research should focus on the development of safer and more targeted drugs for mitophagy.

Experimental observation of the electron beam focusing effect induced by plasma currents with opposite directions.

We report on the experimental observation of the focusing effect of a 50MeV accelerator electron beam in a gas-discharge plasma target. The plasma is generated by igniting an electric discharge in two collinear quartz tubes, with the currents up to 1.5kA flowing in opposite directions in either of the two tubes. In such plasma current configuration, the electron beam is defocused in the first discharge tube and focused with a stronger force in the second one. With symmetric plasma currents, asymmetric effects are, however, induced on the beam transport process and the beam radius is reduced by a factor of 2.6 compared to the case of plasma discharge off. Experimental results are supported by two-dimensional particle-in-cell simulations.

Coexistence of Ferroelectriclike Polarization and Dirac-like Surface State in TaNiTe_{5}.

By combining angle-resolved photoemission spectroscopy, scanning tunneling microscopy, atomic force microscope based piezoresponse force microscopy and first-principles calculations, we have studied the low-energy band structure, atomic structure, and charge polarization on the surface of a topological semimetal candidate TaNiTe_{5}. Dirac-like surface states were observed on the (010) surface by angle-resolved photoemission spectroscopy, consistent with the first-principles calculations. On the other hand, piezoresponse force microscopy reveals a switchable ferroelectriclike polarization on the same surface. We propose that the noncentrosymmetric surface relaxation observed by scanning tunneling microscopy could be the origin of the observed ferroelectriclike state in this novel material. Our findings provide a new platform with the coexistence of a ferroelectriclike surface charge distribution and novel surface states.

Full convolutional network based multiple side-output fusion architecture for the segmentation of rectal tumors in magnetic resonance images: A multi-vendor study.

PURPOSE: Accurate segmentation of rectal tumors is a basic and crucial task for diagnosis and treatment of rectal cancer. To avoid tedious manual delineation, an automatic rectal tumor segmentation model is proposed. METHODS: A pretrained Resnet50 model was introduced for feature extraction. To reduce the complexity of the model, all layers after the 13th residual block of ResNet50 were removed, and three side-output modules were added to the hidden layer of ResNet50 to guide multiscale feature learning. The final boundaries of tumors were determined by fusion of the predictions from side-output modules. The proposed model was compared with two other models, and the effects of different region of interest (ROI) sizes, loss functions, and side-output fusion strategy were also evaluated. RESULTS: The models were trained and evaluated on data from four clinical centers; T2-weighted magnetic resonance images (T2W-MRIs) from 461 patients in the first clinical center were used for training, while T2W-MRIs from 51 patients in the same clinical center and 56 patients in three other clinical centers were used for performance evaluation. The proposed model was superior to the two other models and achieved an average Dice similarity coefficient of 82.39%, sensitivity of 86.32%, specificity of 92.25%, and Hausdorff distance of 12.10 px. In addition, when the ROI contained rectal tumors, the smaller the ROI size, the higher the segmentation accuracy. For a certain ROI size, there were no considerable differences in segmentation results among the loss functions. Compared to the models with single side-output module, the proposed model performed better. CONCLUSIONS: The results show that the proposed model has potential clinical applications in rectal cancer treatment, particularly with regard to therapeutic response evaluation and preoperative planning.

Method for Calculating the Bending Angle of Puncture Needle in Preoperative Planning for Transjugular Intrahepatic Portal Systemic Shunt (TIPS).

Transjugular Intrahepatic Portal Systemic Shunt is a comprehensive interventional therapy for portal hypertension. During this intervention, puncturing from hepatic vein into portal vein is a difficult step. Selecting puncture needle with a proper bending angle is vital to accurate puncture. Thus, this prospective study provides a method to calculate the angle of the puncture needle using preinterventional contrast-enhanced CT imaging. According to the geometrical characteristics of puncture needle, Bezier curve equation was adopted to describe its bending part. By testing whether each point in a specific region satisfied the equation set of Bezier curves, the possible position of needle tip was obtained. Then, the bending angle of puncture needle was obtained by calculating curvature. The method was evaluated in 13 patients from 2 centers showing now a success rate of 100% and a duration of the procedure of 141 and 161 minutes. The method based on Bezier curve equation for calculating a proper bending angle of puncture needle was proven to be effective. And the clinical study is preliminary and additional work for clinical evaluation is necessary.

Pathological changes of the three clinical types of laryngeal burns based on a canine model.

OBJECTIVE: The study was designed to examine pathological changes of inhalational laryngeal burns of three clinical types: congestive, oedematous and obstructive. METHODS: A total of 18 healthy, male, adult Beagle dogs were randomly assigned to inhale hot dry air at room temperature (group C), 80°C (Group 1), 160°C (Group 2) or 320°C (Group 3) for 20min to induce inhalation injury. Each larynx was evaluated and scored based on the 'clinical scoring and typing system of laryngeal burns at early stage'. Tissue samples of the epiglottis, laryngeal vestibule, vocal folds and infraglottic cavity of the larynx were observed microscopically and evaluated based on a 'pathological scoring system'. RESULTS: Pathological changes of the larynxes of groups 1 and 2 were primarily characterised by slight atrophy of the mucosa and mild oedema of the submucosal tissues. Group 3 larynxes showed two distinct pathological changes: oedematous and atrophic types. The larynxes of the atrophic type showed lower clinical scores (29.5±0.7 vs. 44.3±2.1) but higher pathological scores (18.6±3.2 vs. 13.7±1.8) than the larynxes of the oedematous type. CONCLUSION: Severe laryngeal burns could manifest as severe laryngeal oedema or atrophic change. The laryngeal burns of the atrophic type might suggest an unsatisfactory prognosis, although it had less risk of laryngeal obstruction at an early stage.

Polymorphisms of killer cell immunoglobulin-like receptor gene: possible association with susceptibility to or clearance of hepatitis B virus infection in Chinese Han population.

AIM: To explore whether killer cell immunoglobulin-like receptors (KIR) gene polymorphisms are associated with susceptibility to persistent hepatitis B virus (HBV) infection or HBV clearance. METHODS: Fifteen known KIR genes were determined in 150 chronic hepatitis B patients, 251 spontaneously recovered controls, and 412 healthy controls by the sequence specific primer polymerase chain reaction (SSP-PCR) method. KIR genotype frequency (gf) differences were tested for significance by two-tailed Fisher exact test or chi(2) test. Multifactorial analysis was also performed by logistic analysis (the SAS system). RESULTS: Framework genes KIR2DL4, KIR3DL2, KIR3DL3, and KIRZ were present in all individuals. The frequencies of KIR2DS2 and KIR2DS3 were higher in chronic hepatitis B patients, than in both healthy and spontaneously recovered controls. The frequencies of activating KIR2DS1, KIR3DS1, and the inhibitory KIR2DL5 were higher in spontaneously recovered controls than in chronic hepatitis B patients and healthy controls. CONCLUSION: KIR polymorphisms may be associated with susceptibility to HBV infection or HBV clearance. It could be suggested that KIR2DS2 and KIR2DS3 were HBV-susceptive genes, which induced a persistent yet weak inflammatory reaction that resulted in continuous injury of live tissues and chronic hepatitis. KIR2DS1, KIR3DS1, and KIR2DL5, on the other hand, may be protective genes that facilitated the clearance of HBV.