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

Effect of Constructing a New Tunnel on the Adjacent Existed Tunnel in Weak Rock Mass: A Case Study

This study takes a new Shidao tunnel where the left line constructing in weak rock mass as a case study, and the effect of the new constructing tunnel on the existed tunnel are studied by the numerical analysis. High-precision field investigations are conducted to provide accurate parameters for the numerical model. The modified generalized Zhang-Zhu (GZZ) constitutive model is applied, and the numerical analysis results containing horizontal convergence displacement of side walls of the new constructing tunnel and a longitudinal crack in existed tunnel are validated by real-time monitoring. The vertical displacement of the vault, the horizontal displacement of the adjacent side wall, the plastic zone of the new constructing tunnel are studied. The effect of the new constructing tunnel on the existed tunnel is studied by analyzing the vertical displacement of the vault and the horizontal displacement of the adjacent side wall of the existed tunnel. During the constructing process of new tunnel, the maximum width variation of longitudinal crack is less than 0.3 mm. The maximum vertical displacement of the vault is less than 1 mm, and the maximum horizontal displacement of the adjacent side wall is less than 0.5 mm for the existed tunnel. Finally, the effects of tunnel spacing between new constructing and existed tunnels and geological condition represented by geological strength index (GSI) are investigated. The result shows that the maximum vertical displacements of the vault and the maximum horizontal displacement of adjacent side wall can reach −10.4 mm and −4.9 mm respectively when tunnel spacing is 0.5 d (d is actual spacing). When GSI is increased from 15 to 30, the maximum vertical displacement of the vault is reduced obviously

Effect of Constructing a New Tunnel on the Adjacent Existed Tunnel in Weak Rock Mass: A Case Study

This study takes a new Shidao tunnel where the left line constructing in weak rock mass as a case study, and the effect of the new constructing tunnel on the existed tunnel are studied by the numerical analysis. High-precision field investigations are conducted to provide accurate parameters for the numerical model. The modified generalized Zhang-Zhu (GZZ) constitutive model is applied, and the numerical analysis results containing horizontal convergence displacement of side walls of the new constructing tunnel and a longitudinal crack in existed tunnel are validated by real-time monitoring. The vertical displacement of the vault, the horizontal displacement of the adjacent side wall, the plastic zone of the new constructing tunnel are studied. The effect of the new constructing tunnel on the existed tunnel is studied by analyzing the vertical displacement of the vault and the horizontal displacement of the adjacent side wall of the existed tunnel. During the constructing process of new tunnel, the maximum width variation of longitudinal crack is less than 0.3 mm. The maximum vertical displacement of the vault is less than 1 mm, and the maximum horizontal displacement of the adjacent side wall is less than 0.5 mm for the existed tunnel. Finally, the effects of tunnel spacing between new constructing and existed tunnels and geological condition represented by geological strength index (GSI) are investigated. The result shows that the maximum vertical displacements of the vault and the maximum horizontal displacement of adjacent side wall can reach −10.4 mm and −4.9 mm respectively when tunnel spacing is 0.5 d (d is actual spacing). When GSI is increased from 15 to 30, the maximum vertical displacement of the vault is reduced obviously

Neural Network of Roof Cutting Blasting Parameters Based on Mines with Different Roof Conditions

The design and construction of roof cutting and blasting is a key part of the roof cutting pressure releasing gob-side entry retaining (RCPRGER) technology. In the existing research, the blasting parameters of roof cutting have been primarily determined by field tests. However, the disadvantages of field tests include a complicated process, which hinders the succession of related procedures, and an unstable roof cutting effect. Therefore, in this work, the authors attempt to use a mathematical analysis method to simplify the design process of the key parameters of roof cutting blasting. First, the mechanics process mechanism of surrounding rocks with roof cutting and pressure releasing is investigated, and the stress evolution process of the surrounding rock is divided into the following six stages: original rock stress state, excavation stress state, supporting stress state, roof cutting stress state, premining stress state, and postmining stress state. Furthermore, the relationship between roof cutting and entry retaining from the perspective of Mohr’s stress circle is discussed. Next, using four typical mines, including the Tashan, Yuanlin, Jinfeng, and Hengyuan coal mines, as examples, the existing design methods of roof cutting and blasting, geological data characteristics of each mine, distribution rule of roof cutting connectivity rate, and explosive charge structure of roof cutting blasting are summarized. Based on these results, the logic of roof cutting blasting design is obtained, the key indices affecting blasting design are determined, and the blasting design is defined as a complex fuzzy problem with multiple factors. Finally, based on the study of the above mechanics mechanism and blasting rule, a three-layer back propagation (BP) neural network, including six input units, nine hidden units, and three output units, is developed with the four typical mines as the sample space. This neural network realizes the rapid determination of the three key parameters pertaining to sealing length, blasthole spacing, and the explosive charge weight of a single hole. Through training, the calculation error is less than 0.48%, which considerably simplifies the design process of the blasting parameters. The charge structure parameters can also be determined according to this method. At present, the construction of this neural network has the shortcomings of limited sample space. This problem can be overcome by supplementing the sample size in the subsequent research and practice, which will improve the efficiency and accuracy of this design method and promote the application and development of the RCPRGER technology. The interdisciplinary research reported in this paper is an attempt that uses an intelligent algorithm to simplify the design process of roof cutting blasting in RCPRGER, and it represents not only an application development of the intelligent algorithm, but also a new step regarding the intelligent design of RCPRGER technology

Study and Application of Roof Cutting Pressure Releasing Technology in Retracement Channel Roof of Halagou 12201 Working Face

The retracement channel roof cutting (RCRC) technology can change the overburden structure actively by cutting off the roof of channel along the direction of working face tendency and make use of the gangue collapsing from roof cutting range to fill the goaf and weaken the mining pressure during the retracement process of working face. In order to solve the problems of high stress in surrounding rock and serious deformation of retracement channel in Halagou coal mine, it is the first time that the pressure releasing test is carried out on the 12201 working face by the method of the directional presplitting roof cutting in retracement channel. First, according to statics theory and energy theory, the stress state of hydraulic support and roof deformation mechanism of retracement channel are analyzed. Then the roof cutting design of retracement channel is determined according to the geological conditions of 12201 working face, and the cutting effect is analyzed by numerical simulation. Finally, the field test is carried out on the 12201 working face to verify the effect of pressure releasing by roof cutting. The result shows that, with the roof cutting design including the roof cutting height being 8m and roof cutting angle being 45°, the roof subsidence of the 12201 working face retracement channel in Halagou mine is reduced to 132.5mm, and the hydraulic support resistance is maintained at 1361KN. And there is no hydraulic support crushed; the deformation of the retracement channel is also small; namely, the effect of roof cutting for pressure releasing is obvious

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