The role of lysosomal peptidases in glioma immune escape: underlying mechanisms and therapeutic strategies

Glioblastoma is the most common primary malignant tumor of the central nervous system, which has the characteristics of strong invasion, frequent recurrence, and rapid progression. These characteristics are inseparable from the evasion of glioma cells from immune killing, which makes immune escape a great obstacle to the treatment of glioma, and studies have confirmed that glioma patients with immune escape tend to have poor prognosis. The lysosomal peptidase lysosome family plays an important role in the immune escape process of glioma, which mainly includes aspartic acid cathepsin, serine cathepsin, asparagine endopeptidases, and cysteine cathepsins. Among them, the cysteine cathepsin family plays a prominent role in the immune escape of glioma. Numerous studies have confirmed that glioma immune escape mediated by lysosomal peptidases has something to do with autophagy, cell signaling pathways, immune cells, cytokines, and other mechanisms, especially lysosome organization. The relationship between protease and autophagy is more complicated, and the current research is neither complete nor in-depth. Therefore, this article reviews how lysosomal peptidases mediate the immune escape of glioma through the above mechanisms and explores the possibility of lysosomal peptidases as a target of glioma immunotherapy

Polarization description of successive ferroelectric switching in hafnia

Intertwined ionic conduction and ferroelectric (FE) switching in HfO2 lead to extensive focuses. To describe its fundamental phenomena, we present a free-energy model describing the potential of ferroelectrics with successive FE switching paths, and extend the domain model of ionic conduction to ferroelectric domains. Associate theoretical analyses and first-principles calculations suggest a nesting-domain pattern with opposite piezoelectric loops during the nucleation-and-growth process in displacive FE-HfO2. A collective oxygen ion conduction mechanism is also proposed with a field-dependent ionic conductivity following the Merz's law. We conclude that the ionic conductibility is concomitant with the ferroelectricity in HfO2, and it may provide a new venue for pursuing low temperature fast oxide-ion conductors and artificial synapses.Comment: 26 page

Endovascular treatment of acute ischemic stroke with a fully radiopaque retriever: A randomized controlled trial

ObjectiveThe Neurohawk retriever is a new fully radiopaque retriever. A randomized controlled non-inferiority trial was conducted to compare the Neurohawk and the Solitaire FR in terms of safety and efficacy. In order to evaluate the efficacy and safety of endovascular treatment in acute ischemic stroke (AIS) caused by intracranial atherosclerotic disease (ICAD) larger vessel occlusion (LVO), a sub-analysis was performed.MethodsAcute ischemic stroke patients aged 18–80 years with LVO in the anterior circulation were randomly assigned to undergo thrombectomy with either the Neurohawk or the Solitaire FR. The primary efficacy endpoint was successful reperfusion (mTICI 2b-3) rate by the allocated retriever. A relevant non-inferiority margin was 12.5%. Safety outcomes were symptomatic intracranial hemorrhage (sICH) and all-cause mortality within 90 days. Secondary endpoints included first-pass effect (FPE), modified FPE, and favorable outcomes at 90 days. In subgroup analysis, the patients were divided into the ICAD group and non-ICAD group according to etiology, and baseline characteristics, angiographic, and clinical outcomes were compared.ResultsA total of 232 patients were involved in this analysis (115 patients in the Neurohawk group and 117 in the Solitaire group). The rates of successful reperfusion with the allocated retriever were 88.70% in the Neurohawk group and 90.60% in the Solitaire group (95%CI of the difference, −9.74% to 5.94%; p = 0.867). There were similar results in FPE and mFPE in both groups. The rate of sICH seemed higher in the Solitaire group (13.16% vs. 7.02%, p = 0.124). All-cause mortality and favorable outcome rates were comparable as well. In subgroup analysis, 58 patients were assigned to the ICAD group and the remaining 174 to the non-ICAD group. The final successful reperfusion and favorable outcome rates showed no statistically significant differences in two groups. Mortality within 90 days was relatively lower in the ICAD group (6.90% vs. 17.24%; p = 0.054).ConclusionThe Neurohawk retriever is non-inferior to the Solitaire FR in the mechanical thrombectomy of large vessel occlusion-acute ischemic stroke (LVO-AIS). The sub-analysis suggested that endovascular treatment including thrombectomy with the retriever and essential rescue angioplasty is effective and safe in AIS patients with intracranial atherosclerotic disease-larger vessel occlusion (ICAD-LVO).Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT04995757, number: NCT04995757

Mine Strata Pressure Characteristics and Mechanisms in Gob-Side Entry Retention by Roof Cutting under Medium-Thick Coal Seam and Compound Roof Conditions

Coal is among the most important energy sources, and gob-side entry retention by roof cutting (GERRC) is an innovative non-pillar mining technique that can effectively increase coal recovery rates and avoid coal wastage. To investigate the characteristics of mine strata pressure using the GERRC technique, a field case study under conditions involving a medium-thick coal seam and a compound roof was performed, and the mine strata behavior mechanisms were studied by theoretical analysis. Field monitoring shows that the distributions of the weighting step and strength along the longwall working face are asymmetrical. The periodic weighting length on the entry retaining side is longer than that on the other sides of the longwall working face, and the average increase is appropriately 4 m. Compared to the other sides of the longwall, on the entry retaining side, the periodic weighting strength is weaker, the average pressure is reduced by 2.1 MPa, and the peak pressure is reduced by 10.2 MPa. The lateral distance affected by roof cutting along the longwall is approximately 29.75 m, and the closer to the cutting slit, the more significant the roof cutting effect is. The retained entry becomes stable when it is more than 230 m behind the mining face, and the final cross section of the retained entry can meet the reuse demand of the next mining face. Theoretical analysis shows that the roof pressure mechanism in GERRC can be explained using cantilever beam theory. Within the area affected by roof cutting, the thickness of the immediate roof increases, and the suspension plate length of the roof immediately behind the longwall decreases. Then, the gangue pile in the goaf behind the longwall formed by the immediate roof’s collapse and expansion can support the main roof and other overlying strata much better. Therefore, the rotational breaking angle of the main roof is smaller, the periodic weighting step strength increases, and the periodic weighting decreases. According to the structural state of the surrounding rocks during the entire entry retaining process, the retained entry can be divided into coal support, dynamic pressure and stable entry areas

Numerical Simulation of the Flow and Heat Transfer Characteristics of Sweeping and Direct Jets on a Flat Plate with Film Holes

The internal heat transfer performance and flow structures of a sweeping jet and film composite cooling on a flat plate were numerically studied. Sweeping jet and film composite cooling consists of a fluidic oscillator and 20 cylindrical film holes; the direct jet is formed by removing the feedback from the fluidic oscillator, which is different from the traditional cylindrical nozzle. Four different mass flow rates of coolant were considered, and the inclination angle of the film hole was 30°. The Conjugate Heat Transfer method (CHT) and Unsteady Reynolds Averaged Navier Stokes equation (URANS) were employed. The results indicated that the flow resistance coefficients of the sweeping jet were larger than those of the direct jet, and the Nusselt number monotonously increased with the increase in the mass flow rate. Compared to the direct jet, the sweeping jet had a more spatially uniform heat removal rate, and the area-averaged Nusselt number was slightly lower. Therefore, the sweeping jet and film composite cooling caused the distribution of the flat plate heat transfer to be more uniform. It is worth noting that the novel direct jet nozzle in the present work had considerable area-averaged impingement cooling effectiveness