Continuous Injection Research Articles

Uric acid mediates kidney tubular inflammation through the LDHA/ROS/NLRP3 pathway

ABSTRACT Purpose Hyperuricemia (HUA) is an important factor leading to chronic kidney disease (CKD). The kidney tubular inflammatory response is activated in HUA. This study aimed to investigate whether lactate dehydrogenase A (LDHA) is involved in mediating uric acid-induced kidney tubular inflammatory response. Methods In vivo, an HUA mouse model was established by continuous intraperitoneal injection of potassium oxonate (PO) for one week. A total of 18 C57BL/6J male adult mice were divided into three groups: control group, HUA group, and HUA+oxamate group, with six mice in each group. Oxamate was intraperitoneally injected into the mice one hour after PO injection. In vitro, an HUA model was simulated by stimulating HK-2 cells with uric acid. Oxamate and tempol inhibited LDHA and reactive oxygen species (ROS) in HK-2 cells. Results In HUA mice, blood uric acid levels were significantly elevated. LDHA in kidney tubular cells was significantly increased in both in vivo and in vitro HUA models, accompanied by an increase in kidney tubular inflammation and ROS. Mechanistically, LDHA mediates uric acid-induced inflammation to kidney tubular cells through the ROS/NLRP3 pathway. Pharmacologic inhibition of LDHA or ROS in kidney tubular cells can significantly ameliorate inflammation response caused by uric acid. Conclusions LDHA in kidney tubular cells significantly was increased in HUA models. LDHA mediates kidney inflammation response induced by uric acid through the ROS/NLRP3 pathway. This study may provide a new intervention target for preventing kidney tubular inflammation caused by uric acid.

Study of recovery factor and CO(2) storage behavior in a reservoir using numerical simulation

In this study, the behavior of the recovery factor during the displacement and storage phases of carbon dioxide (CO2) in an Ecuadorian reservoir was investigated by numerical simulation. Continuous injection and CO2 WAG methods were used. The methodology included field data collection, creation of a static reservoir model, configuration of the PVT model with CMG software, construction of a dynamic model in GEM-CMG based on rock-fluid properties, and evaluation of CO2 injection scenarios. After a screening analysis, the optimal scenario was identified and the performance of the recovery factor over time was studied. The results indicated that, during the 8 years of simulation, the recovery factor with continuous injection was 28%, while with the WAG method it reached 31%. It was concluded that WAG was the most efficient method. Regarding storage, it was observed that continuous injection was able to store 83% of the CO2 in the reservoir.

Iron chelation therapy failed to improve cardiac dysfunction caused by mitochondrial injury in rats with iron overload cardiomyopathy a 7T Cardiac MR research in vivo

Abstract Purpose To assess the efficacy of iron chelation therapy in improving cardiac function in iron overload cardiomyopathy (IOC) rats by using Cardiac magnetic resonance feature-tracking (CMR-FT). Methods The IOC rat model was induced by intraperitoneal injection of iron dextran over 2 months. Subsequently, 7 rats with IOC were assigned as IOC group to receive continued intraperitoneal injections of saline for an additional 2 months, while another group of 5 rats received intraperitoneal injections of deferoxamine (DFO) for the same duration, forming the IOC+DFO group. Meanwhile, a control group consisting of 7 healthy rats received intraperitoneal injections of saline for the entire duration of 4 months. All rats underwent a 7T CMR scan to assess cardiac function, myocardial iron overload, and myocardial fibrosis via cine, T2 mapping, and late gadolinium enhancement (LGE) scanning, respectively. The cardiac function analysis included left ventricular ejection fraction (LVEF) and left ventricular global longitudinal strain (GLS) using cine images. Following CMR scans, all rats underwent open-chest blood collection to detect serum iron levels, and cardiac gross specimens were then subjected to pathological staining, including hematoxylin and eosin (HE) for cardiomyocytes injury, Prussian blue for iron deposition , and Masson staining for myocardial fibrosis. Furthermore, the ultrastructure of cardiomyocyte was examined using transmission electron microscopy (TEM). Results The T2 value, measured in the septum wall at the mid-layer of the LV, and LVEF, and GLS exhibited a significant decrease in the IOC or IOC+DFO group, compared to the control group, while there were no significant difference observed between the IOC and IOC+DFO group (Fig. 1A, B, C). Myocardial fibrosis was not detected in the LGE images in both IOC and IOC+DFO group. Compared to the control group (37.5±12.5μmol/L) , serum iron levels were significantly elevated in the IOC group (368.6±181.0μmol/L) and in chelation treatment group (106.1±32.2μmol/L). Histological examination with HE staining revealed a normal arrangement of myocardial cells in all rats, without cellular degeneration or necrosis. Prussian blue staining highlighted the presence of iron particles within the myocardial interstitium in the IOC and IOC+DFO groups. Masson staining demonstrated intact myocardial muscle bundles without any evidence of myocardial fibrosis. Transmission electron microscopy (TEM) revealed myocardial mitochondria injury, characterized by ruptured outer membranes, reduced cristae, and vacuolization. Conclusions Following iron chelation therapy, the excessive iron burden in the bloodstream was alleviated. However, myocardial iron overload persisted in IOC rats, with no significant improvement in cardiac function observed. This persistence may be attributed to mitochondrial injury. The findings underscore the importance of monitoring cardiac dysfunction in patients with iron overload.CMR parameters analysis in IOC rats

Numerical modelling of CO2-in-water emulsion injection into a water-saturated core

Depressurization method shows promise for methane hydrate (MH) reservoir production, but the reformation of hydrates due to a lack of geothermal heat presents a significant challenge for commercial production. This study proposes a novel approach for MH gas recovery by injecting a CO2-in-water (C/W) emulsion into an MH reservoir aquifer. The exothermic nature of CO2 hydrate formation and liquid CO2 dissolution in water in this method provides heat to the MH layer, effectively preventing hydrate reformation. Subsequently, 1-D numerical models were developed and implemented using the MATLAB Reservoir Simulation Toolbox (MRST). These models were rigorously validated against experimental data under homogeneous conditions and varying injection schemes. The investigation indicated that the average volume fraction of CO2 hydrate within the hydrate particles was found to be 55% of the volume of liquid CO2 droplets. The alternating C/W emulsion injection increased the driving force for CO2 dissolution in water, thereby promoting subsequent hydrate particle decomposition and CO2 hydrate dissolution in water, which effectively mitigated blockage within the porous medium. In conclusion, water alternating C/W emulsion injection, along with the continuous injection of a low volume fraction of liquid CO2 within the C/W emulsion, exhibits promising potential for sustained injection and provides adequate heat to the MH layer, preventing hydrate reformation. Furthermore, the developed numerical model reasonably predicts the behavior of various injection schemes. This developed model can be used for devising long term sub-seabed carbon capture and storage development plan.

Coupled hydro-mechanical model for underground hydrogen storage undergoing cyclic injection and production

ABSTRACT Excess renewable energy can be used to generate and store hydrogen underground, offering a secure and econimical solution to the intermittency challenges of renewable energy sources. The success of underground storage relies on understanding and controlling the geo-mechanical integrity of storage sites during cyclic loadings. While geological deformation during natural gas and carbon dioxide storage is well studied, few have investigated pore pressure and in-situ stress variations during cyclic loading, which is unique to underground hydrogen storage sites. This paper presents a predictive analytical model for the pore pressure and stress changes during cyclic loading. The model was derived based on continuous point source injection, a basic hydro-mechanical model while applying the superposition to consider the cyclic loading. The developed model was evaluated for hydrogen and natural gas subjected to cyclic injection and production. Comparing hydrogen and natural gas storage cases can offer valuable insights into the behavior of hydrogen since the deformation of natural gas storage is more studied. Finally, analytical solutions for both storage cases were validated by numerical models with discrepancies between the models amounting to less than 1%. Comparative analysis of the results from 3 to 99 cycles of injection and production for both hydrogen and methane demonstrates that rise in cycle numbers leads to a corresponding rise in stress accumulation in the system. Neglecting the stress accumulation during these cycles can lead to significant geomechanical issues, potentially compromising the storage system’s safety and integrity.

Detection of extended gamma-ray emission in the vicinity of Cl Danks 1 and 2

Abstract We report the detection of high-energy gamma-ray emission towards the G305 star-forming region. Using almost 15 years of observation data from Fermi Large Area Telescope, we detected an extended gamma-ray source in this region with a significance of ∼13σ. The gamma-ray radiation reveals a clear pion-bump feature and can be fitted with the power law parent proton spectrum with an index of −2.5. The total cosmic ray (CR) proton energy in the gamma-ray production region is estimated to be the order of $10^{49}\ \rm erg$. We further derived the CR radial distribution from both the gamma-ray emission and gas distribution and found it roughly obeys the 1/r type profile, though a constant profile is not ruled out. This is consistent with other similar systems and expected from the continuous injection of CRs by the central powerful young massive star cluster Danks 1 or Danks 2 in this region. Together with former detections of similar gamma-ray structures, such as Cygnus cocoon, Westerlund 1, Westerlund 2, NGC 3603, and W40, the detection supports the hypothesis that young massive star clusters are CR accelerators.

Enhancing insulating properties of glass-fiber reinforced polymers using plasma fluorination-modified boron nitride nanosheets

The insulation failure of glass fiber-reinforced polymers (GFRP) limits their use in high-voltage insulation fields. In this study, boron nitride nanosheets (BNNS) were prepared using ball-milling and further fluorinated via dielectric barrier discharge (DBD) plasma treatment. The GFRP nanocomposites were fabricated using different filler types and doping concentrations. The test results indicated that fluorinated BNNS (F-BNNS) displays good dispersion and interfacial compatibility, enhances the interfacial bonding strength of the “fiber-matrix-filler” ternary system in GFRP, and reduces the internal defects of materials. In addition, the insulating properties of the composites were related to the filler concentration. Adding a trace amount of F-BNNSs increased the flashover and breakdown voltages of the GFRP by up to 28.77% and 21.62%, respectively. The results of molecular dynamics simulations and trap distribution calculations showed that plasma fluorination of BNNS increases the bandgap and deep trap energy level at the interface. The extremely strong charge-binding ability of the deep traps inhibits continuous charge injection and regulates carrier migration, which improves the insulating properties of the composites. The results of this study provide a novel, environmentally friendly, and efficient solution for improving the insulating properties of GFRP.

Impregnate Carbonation: CO2-Guided In Situ Growth of Robust Superhydrophobic Structures on Concrete Surfaces.

Superhydrophobic surfaces applying on concrete can greatly improve the durability of concrete by preventing the damage from water. However, traditional design of superhydrophobic concrete surfaces by external coating encounters to problems of flaking and poor surface robustness, while that by adding hydrophobic agents or particles faces the challenges of strength damage of concrete. Drawing inspiration from the carbonation phenomenon of concrete, here a new design of in situ growing superhydrophobic structures on concrete is proposed: The concrete sample is impregnated into Mg2+-containing silane-water system with continuous CO2 injection. The contact angle of the concrete surface achieves 171.9° without obvious strength decrease after 120 min, which are mainly attributed to the formation of CaxMg1-xCO3 crystals with micro-nano-structures and the reduction of carbonates surface energy by silane. This superhydrophobic concrete structure can be divided into a superhydrophobic-hydrophobic-hydrophilic three layers structure, providing the stable water-proof protection under mechanical fatigue, capillary water absorption, UV aging, sulfate attack, and impurity water impact tests due to the in situ growing robust superhydrophobic structures. Furthermore, it captures 29.80gm-2 CO2 during the reaction process, providing new insights for the design and preparation of eco-friendly superhydrophobic concrete.

Structured Jet Model for Multiwavelength Observations of the Jetted Tidal Disruption Event AT 2022cmc

AT 2022cmc is a recently documented tidal disruption event that exhibits a luminous jet, accompanied by fast-declining X-ray and long-lasting radio and millimeter emission. Motivated by the distinct spectral and temporal signatures between the X-ray and radio observations, we propose a multizone model involving relativistic jets with different Lorentz factors. We systematically study the evolution of faster and slower jets in an external density profile, considering the continuous energy injection rate associated with time-dependent accretion rates before and after the mass fallback time. We investigate time-dependent multiwavelength emission from both the forward shock (FS) and reverse shock (RS) regions of the fast and slow jets, in a self-consistent manner. Our analysis demonstrates that the energy injection rate can significantly impact the jet evolution and subsequently influence the lightcurves. We find that the X-ray spectra and lightcurves could be described by electron synchrotron emission from the RS of the faster jet, in which the late-time X-ray upper limits, extending to 400 days after the disruption, could be interpreted as a jet break. Meanwhile, the radio observations can be interpreted as a result of synchrotron emission from the FS region of the slower jet. We also discuss prospects for testing the model with current and future observations.

An integrated dynamic modeling workflow for acid gas and CO2 geologic storage screening in saline aquifers with faults: A case study in Western Canada

This study investigates the feasibility of storing the acid gas produced from the oil and gas facilities in Southern Saskatchewan into the Basal Sand aquifer using a coupled wellbore-aquifer-compositional reservoir model. The simulations investigate the pressure change around the fault in proximity of the primary storage location incorporating the influence of reservoir permeability, fault transmissibility, and wellbore configuration, on the factors critical to safe and efficient storage, such as plume migration, pressure changes, and CO2 storage capacity. A compositional fluid model created using an equation of state was integrated into the reservoir model. Simultaneous incorporation of fault transmissibility, phase solubility, water salinity, temporal in-situ hysteresis and structural trapping, and in-situ compositional tracking of individual gas components is considered as the main novelty of this work. The main challenge of the study was the lack of available data to characterize the aquifer. To this end, a comprehensive workflow of reservoir studies and modeling was applied to reduce the uncertainties and evaluate the site selection. The Basal sand scoping models reveal that the aquifer is expected to handle the required disposal volume given its extent. The injected acid gas plume migrates laterally and preferentially towards the northwest, away from the fault, owing to the aquifer's geological structure. CO2 remains entirely in the supercritical state, offering storage advantages due to its lower volume. The reservoir permeability significantly impacts the pressure patterns with lower permeability formations triggering higher wellhead injection pressures. Substantial pressure increases around the sealing fault can be observed. Pressure changes of 110 kPa (16 psi) to over 400 kPa (58 psi) were observed at the fault segment after 20 years of continuous gas injection for the expected range of reservoir properties. Mitigation strategies to minimize the increase in fault pressure entail relocating the injection site away from the fault or utilizing a horizontal well trajectory and using an observation well near the fault for monitoring any pressure buildup and slippage.

Continuous Treatment with IncobotulinumtoxinA Despite Presence of BoNT/A Neutralizing Antibodies: Immunological Hypothesis and a Case Report.

Botulinum Neurotoxin A (BoNT/A) is a bacterial protein that has proven to be a valuable pharmaceutical in therapeutic indications and aesthetic medicine. One major concern is the formation of neutralizing antibodies (nAbs) to the core BoNT/A protein. These can interfere with the therapy, resulting in partial or complete antibody (Ab)-mediated secondary non-response (SNR) or immunoresistance. If titers of nAbs reach a level high enough that all injected BoNT/A molecules are neutralized, immunoresistance occurs. Studies have shown that continuation of treatment of neurology patients who had developed Ab-mediated partial SNR against complexing protein-containing (CPC-) BoNT/A was in some cases successful if patients were switched to complexing protein-free (CPF-) incobotulinumtoxinA (INCO). This seems to contradict the layperson's basic immunological understanding that repeated injection with the same antigen BoNT/A should lead to an increase in antigen-specific antibody titers. As such, we strive to explain how immunological memory works in general, and based on this, we propose a working hypothesis for this paradoxical phenomenon observed in some, but not all, neurology patients with immunoresistance. A critical factor is the presence of potentially immune-stimulatory components in CPC-BoNT/A products that can act as immunologic adjuvants and activate not only naïve, but also memory B lymphocyte responses. Furthermore, we propose that continuous injection of a BoN/TA formulation with low immunogenicity, e.g., INCO, may be a viable option for aesthetic patients with existing nAbs. These concepts are supported by a real-world case example of a patient with immunoresistance whose nAb levels declined with corresponding resumption of clinical response despite regular INCO injections.

Numerical Investigation of Heterogeneous Calcite Distributions in MICP Processes

Microbially induced calcite precipitation (MICP) is a sustainable and environmentally friendly technology with applications in soil stabilization, concrete crack repair, and wastewater treatment. This study presents an improved Darcy-scale numerical model to simulate the MICP processes in heterogeneous porous media. It focuses on the effects of porosity heterogeneity, characterized by average porosity and correlation length, as well as injection strategies. Both average porosity and correlation length are critical factors influencing mass transport and calcite distribution during MICP treatment. An increase in average porosity leads to significant reductions in transport distance and total calcite mass. Notably, in the case of low averaged porosity, a larger correlation length results in more heterogeneous calcite distributions. However, there exists an upper threshold value of the initial averaged porosity (ϕ0=0.45) above which the heterogeneity of the calcite does not present clear dependence on the correlation length. Additionally, injection strategies significantly impact the consolidation effects. Compared to continuous injection, using the phased injection strategy can greatly improve the precipitated calcite area and mass due to its high utility and the efficiency of reactants.

Microscale insights into enzyme-induced carbonate precipitation in rock-based microfluidic chips

Biomineralisation technology shows promise for sealing subsurface fractures, but understanding its microscale mechanisms in real rock fractures remains incomplete. In this study, a microfluidic chip incorporating real rock slices was utilised to conduct enzymatically induced carbonate precipitation (EICP) experiments using a one-phase continuous injection strategy. Real-time observations revealed grey flocs forming and clustering into aggregates susceptible to transport by flow. Calcium carbonate (CaCO3) crystals that formed on rock and polydimethylsiloxane surfaces effectively filled and bridged fractures, leading to a significant pressure drop. Rough surfaces can provide additional sites for solute attachment and heterogeneous nucleation of calcium carbonate. High velocities and small apertures generally promoted floc formation and reduced crystal growth. Precipitation content gradually increased with a decreasing rate. Lower estimated precipitation efficiency was obtained in smaller, high-flow fractures. Precipitates on rock interfaces induced eddies and significant pressure drops within narrow pore throats. Crystal growth displayed a two-stage development: an initial increase followed by a decrease, varying across different facets (the surfaces or orientations of the growing crystals). Growth competition will occur when two or more neighbouring crystals come into contact with diverse grain orientations. The findings provide valuable microscale insights into microscale processes governing EICP within real rock fractures, contributing to evaluation of its efficacy in subsurface fracture sealing applications.

Very Large and Long-lasting Anisotropies Caused by Sunward Streaming Energetic Ions: Solar Orbiter and STEREO A Observations

The anisotropy of energetic particles provides essential information to help resolve the underlying fundamental physics of their spatial distributions, injection, acceleration, and transport processes. In this work, we report an energetic ion enhancement that is characterized by very large and long-lasting anisotropies observed by STEREO A and Solar Orbiter, which are nearly aligned along the same nominal Parker spiral. This ion enhancement appears at the rising phase of a widespread solar energetic particle event that was associated with the farside coronal mass ejection on 2022 February 15. According to our analysis, the long-lasting anisotropy resulted from the continuous injection of energetic ions from a well-connected particle source located beyond the STEREO A’s orbit. Solar Orbiter also observed an interval of very large anisotropy dominated exclusively by sunward streaming ions but with the additional implication that it detected the very early phase of ion injections onto magnetic field lines that newly connected to the particle source, which is likely the first reported event of this kind. These results further illustrate how energetic particle anisotropy information, in particular from multiple observer locations, can be used to disentangle the sources and transport processes of energetic ions, even when their heliospheric context is not simple.

Analysis of dynamic characteristics and influencing factors of CO2 low-permeability coal reservoir sequestration

ABSTRACT Abandoned coal seams can be an important carrier for CO2 geological storage. Considering the gas seepage-diffusion and physical adsorption coupling characteristics in the process of CO2 adsorption and storage in coal and rock, a two-dimensional model of coupled flow-solidity for geological storage of CO2 in low-permeability reservoir with double voids was established by introducing the Zhang Hongbin model algorithm and adding the Klinkenberg effect and the compression effect of the rock skeleton in coal reservoirs in the controlling equation for rock deformation. The coupled flow-solid model was solved by using the PDE equation of COMSOL Multiphics program, and the simulation results difference between the new model and the traditional model in terms of sequestration dynamics were compared. The dynamic characteristic of reservoir gas pressure, formation stress, permeability and sequestration density in the process of CO2 geologic sequestration and injection were analyzed, and the influences of injection pressure and injection well diameter on the amount of CO2 sequestration were explored. The results show that the new model is more reasonable for calculating reservoir gas pressure and permeability compared with the Palmer-Mansoori model (PM model), and can simulate the free-state seepage movement of CO2 in the fracture system as well as its physical adsorption process compared with the single-heavy pore medium model. With continuous CO2 injection, the maximum sequestration density was raised to a limit value of about 1000 kg/m3 after 1 year. The date of reaching the limit of the sequestration volume was advanced by about 45 d when the positive pressure of the injected gas was increased from 10 kPa to 50 kPa. This model can reproduce the main parameters including, when affecting the effect, and realize the calculation of parameters such as CO2 density reaching the limit value, sealing limit day, sealing limit amount, which can provide a theoretical basis for further deep understanding of CO2 geological sealing law and scientific development of gas injection scheme.

The Need for Separate Testing with Acetylcholine for the Assessment of Endothelial Dysfunction and Coronary Artery Spasm.

Intracoronary acetylcholine (ACH) testing is clinically useful to diagnose the presence of the coronary vasomotor disorders coronary endothelial dysfunction and coronary epicardial/microvascular spasm. In Western countries, continuous intracoronary injection of ACH for 2-3 minutes without a pacemaker is the usual method, while rapid injection of ACH for 20-30 seconds with a pacemaker is the traditional procedure in Japan. Coronary microvascular spasm is often observed in Western populations, whereas coronary epicardial spasm is frequently seen in Japanese subjects. Methodological differences between Western and Japanese protocols may lead to the opposite prevalence of coronary vasomotor disorders. This article discusses the optimal method for diagnosing endothelial dysfunction and epicardial/microvascular spasm based on previous reports, and compares intracoronary ACH testing performed by Western cardiologists with that by Japanese physicians.

Stretchable, transparent and multifunctional PVC-gel heater: a novel approach to skin-mountable, wearable thermal devices

Electric heaters based on functional materials and innovative designs have been developed for various applications. In this paper, we propose a soft dielectric heater (SDH) using polyvinyl chloride-gel (PVC-gel) as the dielectric heater and hydrogel as stretchable electrodes. Under an AC voltage, the leakage current in the PVC-gel leads to continuous injection and discharge of charges, causing the polarized plasticizers and flexible PVC chains to vibrate and collide, thereby generating heat through dielectric heating. Furthermore, the SDH generates a uniform temperature distribution even under strains up to 400%. Besides, high transmittance over 86% across the visible range renders it suitable for wearable or skin-mountable heaters from an esthetic viewpoint. Its capacitor-like structure achieves a scalable design, enabling extension from a singular cell to a row/column addressable and pixelated array of heaters. The 5 × 5 SDH array can deliver varied thermal information and sensations while maintaining performance even when stretched.

Manipulation of lasing modes in a deformed octagonal microcavity laser

We have demonstrated a deformed octagonal microcavity semiconductor laser with manipulated lasing modes for bistable operation and direct modulation. There are two sets of degenerated four-bounced modes, S01 and S02, in the octagonal microcavity, and the degeneracy between them is broken by introducing a square hole into the center of the cavity. In the deformed octagonal microcavity laser, mode S01 dominates the lasing process during the current rising process. However, mode S02 also lases when the current decreases and interacts nonlinearly with S01, which is caused by the non-uniform distribution of the refractive index induced by the square-ring-shaped current injection. We observe a counterclockwise bistable hysteresis loop with continuous injection current ranging from 31 to 13 mA at 288 K. We also study the small-signal modulation response of the laser at high and low states with different injection currents. By utilizing the photon-photon resonance effect between modes S01 and S02, we effectively increased the 3-dB bandwidth of the laser from 12 GHz to 16.2 GHz.

Fingolimod alleviates type 2 diabetes associated cognitive decline by regulating autophagy and neuronal apoptosis via AMPK/mTOR pathway

This study aimed to reveal the role of fingolimod (FTY720) in mice with type 2 diabetes-associated cognitive decline and explore its potential neuroprotective mechanism. Mice were divided into five groups: normal control, normal control + FTY720 (1.0 mg/kg/day), type 2 diabetes mellitus, type 2 diabetes mellitus + low-dose FTY720 (0.5 mg/kg/day), and type 2 diabetes mellitus + high-dose FTY720 (1.0 mg/kg/day). Different doses of FTY720 were administered daily for 8 weeks after the induction of type 2 diabetes using a four-week high-fat diet feeding combined with continuous low-dose intraperitoneal injections of streptozotocin. After 8 weeks of treatment, the body weights and fasting blood glucose levels of mice from the five groups were compared. Morris water maze and new object recognition tests were used to evaluate cognitive function. Pathological changes in the hippocampal CA1 region were observed using haematoxylin-eosin and Nissl staining, and the ultrastructure of the hippocampal neurones was assessed using transmission electron microscopy. The expression levels of autophagy- and apoptosis-related proteins, such as LC3, Beclin-1, P62, Bax, and Bcl-2, in the mice hippocampus were detected by western blotting. Simultaneously, AMPK/mTOR signaling pathway proteins were detected to understand the potential mechanism. FTY720 had no significant effect on the body weight or fasting blood glucose levels in mice with type 2 diabetes. However, both FTY720 doses improved the cognitive function and hippocampal damage. In addition, the results suggested that FTY720 dramatically decreased P62 and Bax levels and increased LC3 II/LC3 I ratio, Beclin-1, and Bcl-2 expression in the hippocampus of type 2 diabetic mice. FTY720 also affected the expression of the AMPK/mTOR signaling pathway. Thus, FTY720 improved cognitive function and hippocampal pathological changes in type 2 diabetic mice without affecting fasting blood glucose levels. Our results show that FTY720 may exert neuroprotective effects in vivo by enhancing hippocampal autophagy and inhibiting apoptosis via the AMPK/mTOR signaling pathway.

Soft photon heating: a semi-analytic framework and applications to 21-cm cosmology

ABSTRACT The presence of an abundant population of low-frequency photons at high redshifts (such as a radio background) can source leading order effects on the evolution of the matter and spin temperatures through rapid free–free absorptions. This effect, known as soft photon heating, can have a dramatic impact on the differential brightness temperature, $\Delta T_{\rm b}$, a central observable in 21-cm cosmology. Here, we introduce a semi-analytic framework to describe the dynamics of soft photon heating, providing a simplified set of evolution equations and a useful numerical scheme which can be used to study this generic effect. We also perform quasi-instantaneous and continuous soft photon injections to elucidate the different regimes in which soft photon heating is expected to impart a significant contribution to the global 21-cm signal and its fluctuations. We find that soft photon backgrounds produced after recombination with spectral index $\gamma \gt 3.0$ undergo significant free–free absorption, and therefore this heating effect cannot be neglected. The effect becomes stronger with steeper spectral index, and in some cases the injection of a synchrotron-like spectrum ($\gamma = 3.6$) can suppress the amplitude of $\Delta T_{\rm b}$ relative to the standard model prediction (where an additional radio background is absent), making the global 21-cm signal even more difficult to detect in these scenarios.