Proton energy enhancement by optimizing a laser pulse profile.

Based on current laboratory laser parameters and the low density target that is induced by the inevitable prepulse, we propose what we believe to be a new scheme to enhance the proton energy by employing a laser pulse with two different peak intensities. Initially, the lower-intensity peak of the laser pulse P1, irradiates the low-density plasma target induced by the prepulse to form a significantly denser plasma target. Such a compressed high-density target is critical for supporting the subsequent main pulse P2 with higher peak intensity to drive proton acceleration. As an example, particle-in-cell (PIC) simulations reveal that when using a circularly polarized (CP) flat-top P1 with a peak intensity of approximately 1.71 × 10 19 W/cm2, full-width at half-maximum(FWHM) duration of 325 fs and a CP P2 with a peak intensity of 1.54 × 10 22 W/cm2, FWHM duration of 26.5 fs, and focal spot radius of 4 µm successively acting on a target with an initial density of 8nc, protons with cut-off energy of 940 MeV can be obtained from the cascaded acceleration scheme. Compared with the case without P1, the cutoff energy increased by 340 MeV. Owing to the intervention of P1, this scheme overcomes the limitation of laser contrast and is more feasible to be implemented experimentally.

Inactivated vaccine dosage and serum IgG levels correlate with persistent COVID-19 infections in hematologic malignancy patients during the Omicron Surge in China.

PURPOSE: The essence of this scholarly work was to carefully outline the key factors intensifying the virulence and protracted contagion of COVID-19, particularly among individuals afflicted with hematologic malignancies (HM), in an epoch predominantly governed by the Omicron variant. METHODS: Adults with HM diagnosed with COVID-19 from November 2022 to February 2023 were monitored in this retrospective study. Patient blood samples yielded biochemical data, and COVID-19 was confirmed through RNA or antigen testing. The factors affecting severity and infection duration were examined using both univariate and multivariate logistic regression analyses. For calculating the overall survival probabilities, the Kaplan-Meier product limit approach was employed. RESULTS: In the examined cohort, 133 individuals diagnosed with HM and concomitantly infected with COVID-19 were scrutinized. Of the participants, 29.3% (39 patients) were classified as Severe/Critical, while the other 70.7% (94 patients) were categorized as Non-severe. A significant difference was observed in vaccination status: 61.7% of patients in the Non-severe group had received at least a two-dose vaccine regimen, whereas 61.5% of the Severe/Critical group had either minimal or only one dose of vaccination. The data analysis revealed that elevated C-reactive protein levels (≥ 100 mg/L) significantly raised the risk of severe/critical conditions in HM patients with COVID-19, as determined by advanced multivariate logistic regression. The odds ratio was 3.415 with a 95% confidence interval of 1.294-9.012 (p = 0.013). Patients who continued to have positive nucleic acid tests and ongoing symptoms beyond 30 days were categorized as having a persistent infection, whereas those who achieved infection control within this timeframe were categorized as having infection recovery. Of the HM cohort, 11 did not survive beyond 30 days after diagnosis. The results from a competing risk model revealed that increased interleukin-6 levels (HR: 2.626, 95% CI: 1.361-5.075; p = 0.004) was significantly associated with persistent infection. Conversely, receiving more than two vaccine doses (HR: 0.366, 95% CI: 0.158-0.846; p = 0.019), and having high IgG levels (≥ 1000 mg/dl) (HR: 0.364, 95% CI: 0.167-0.791; p = 0.011), were associated with infection recovery. There was a notable disparity in survival rates between patients with persistent infections and infection recovery, with those in the non-persistent group demonstrating superior survival outcomes (P < 0.001). CONCLUSIONS: In conclusion, the study determined that HM patients with COVID-19 and increased C-reactive protein levels had a higher likelihood of severe health outcomes. Persistent infection tended to be more prevalent in those with vaccine dosages (< 2 doses), lower IgG levels, and higher interleukin-6 levels.

Research Advances in the Treatment of Bone Marrow Edema Syndrome.

Bone marrow edema syndrome (BMES) is a relatively uncommon clinical condition. It has been poorly reported in the literature. Hence, doctors are not sufficiently aware of the disease and are prone to misdiagnosis and mistreatment, which can undoubtedly prolong the course of the disease, reduce the quality of life of patients and even affect their function. This paper reviews the literature and summarizes the treatment options for bone marrow edema syndrome, such as symptomatic treatment, extracorporeal shock waves therapy (ESWT), pulsed electromagnetic fields (PEFs), hyperbaric oxygen (HBO), vitamin D, iloprost, bisphosphonates, denosumab, and surgery, etc. This informs clinicians in treating bone marrow edema syndrome, hopefully improving patients' quality of life and shortening the duration of their disease.

Static and Dynamic Plantar Pressure Distribution in 94 Patients with Different Stages of Unilateral Knee Osteoarthritis Using the Footscan® Platform System: An Observational Study.

BACKGROUND Plantar pressure analysis is widely used in the study of knee osteoarthritis (KOA). The present study aimed to investigate the static and dynamic plantar pressure distribution in patients with different stages of unilateral KOA using the Footscan® platform system. MATERIAL AND METHODS We recruited 94 patients aged 61.75±7.23 years old with different stages of unilateral KOA for static and dynamic analysis using the Footscan® platform system. The static pressure (%) of the left, right, anterior, posterior, and the pelvic rotation (°) was assessed. The peak pressure (PP, kPa) was investigated in 10 areas of the foot: medial heel (MH), lateral heel (LH), midfoot (MF), first to fifth metatarsals (M1-M5), hallux (T1), and toes 2-5 (T2-5). The correlation between KOA stages and plantar pressure distributions was investigated. RESULTS The results revealed that static pressure on the unaffected side and pelvic rotation were positively correlated with KOA stages. In addition, there was a positive correlation between KOA stages and PP of M5, MF, and LH zones on the affected side and PP of M2, M3, and M4 zones on the unaffected side, and a negative correlation between KOA stages and PP of T1 and T2-5 zones on the affected side. CONCLUSIONS With the progression of KOA, static plantar pressure tends to distributed on the unaffected side, and the dynamic plantar pressure tends to be distributed laterally on both feet. The plantar pressure distributions in unilateral KOA patients are abnormal and are closely related to the severity of KOA.

COVID-19 and risk spillovers of China's major financial markets: Evidence from time-varying variance decomposition and wavelet coherence analysis.

COVID-19 has influenced financial markets drastically; however, this influence has received little attention, particularly in China. This study investigates risk spillovers across China's financial and shipping markets through dynamic spillover measures based on time-varying parameter vector autoregression and generalized forecast error variance decompositions. Stock, fund, and futures markets are identified as major risk senders, whereas other markets are identified as major risk receivers. Surprisingly, bonds, gold, and shipping are safe havens that facilitate portfolio optimization. Furthermore, using wavelet coherence analysis, we find that the coherence between dynamic total spillover and COVID-19 varies across time and frequency domains.

UV-enhanced NO2gas sensors based on In2O3/ZnO composite material modified by polypeptides.

This present study reported a high-performance gas sensor, based on In2O3/ZnO composite material modified by polypeptides, with a high sensibility to NO2, where the In2O3/ZnO composite was prepared by a one-step hydrothermal method. A series of results through material characterization technologies showed the addition of polypeptides can effectively change the morphology and size of In2O3/ZnO crystals, and effectively improve the sensing performance of the gas sensors. Due to the single shape and small size, In2O3/ZnO composite modified by polypeptides increased the active sites on the surface. At the same time, the gas sensing properties of four different ratios of polypeptide-modified In2O3/ZnO gas sensors were tested. It was found that the In2O3/ZnO-10 material showed the highest response, excellent selectivity, and good stability at room temperature under UV light. In addition, the response of the In2O3/ZnO-10 gas sensor showed a strong linear relationship with the NO2gas concentration. When the NO2gas concentration was 20 ppm, the response time was as quick as 19 s, and the recovery time was 57 s. Finally, based on the obtained experimental characterization results and energy band structure analysis, a possible gas sensing mechanism is proposed.

Polymerized Naphthalimide Derivatives as Remarkable Electron-Transport Layers for Inverted Organic Solar Cells.

Two polymerized naphthalimide derivatives, named as N-TBHOB and N-DBH, are prepared by quaternization. They exhibit excellent performance as electron-transport layers (ETLs) in inverted organic solar cells (i-OSCs). The results indicate N-TBHOB with a reticulated structure owns a superior performance on electron extraction, electron transport, thickness tolerance, and less carrier recombination compared with N-DBH with linear structure. The i-OSCs based on N-TBHOB with PTB7-Th:PC71 BM as the active layer achieve power conversion efficiencies (PCEs) of 10.72% and 10.03% under the thickness of 11 and 48 nm respectively, which indicates N-TBHOB possesses better thickness tolerance than most of organic ETLs in i-OSCs. N-TBHOB also shows more competent performance than N-DBH and ZnO in nonfullerene i-OSCs for comprehensively improved Jsc , Voc , and fill factor (FF) values. Its i-OSC with PM6:Y6 blend presents a high PCE of 16.78%. The study provides an efficient strategy to prepare ETLs by combining conjugated and nonconjugated units with a reticulated structure in the backbone for high-performance i-OSCs.

Non-equilibrium spin-transport properties of Co/phosphorene/Co MTJ with non-collinear electrodes under mechanical bending.

Monolayer phosphorene has outstanding mechanical flexibility, making it rather attractive in flexible spintronics that are based on 2D materials. Here, we report a first-principles study on non-equilibrium electronic-transport properties of the Co/phosphorene/Co magnetic tunnel junction (MTJ) with two α-Co electrodes. The magnetic moments of the two electrodes are considered in the parallel configuration (PC) and the anti-parallel configuration (APC). The tunneling current through the MTJ is investigated at a small bias from 0 to 40 mV when mechanical bending is applied on the MTJ with different central angle (θ) values. For both the PC and APC, the tunneling current increases evidently and monotonously with increasing mechanical bending for 25° < θ < 40°, as compared to that without bending, which is mainly due to the reduced tunnel barrier. In the PC, the spin-injection efficiency (SIE) of the current is largely increased at a small bias from 0 to 40 mV for 25° ≤ θ ≤ 30° with a maximum of 90%, while the SIE is overall increased under all mechanical bending angles for the APC. The tunnel magnetoresistance is decreased with an increasing bias voltage, which can be largely enhanced for θ ≥ 25°, especially at small bias. Our results indicate that the Co/phosphorene/Co MTJ has promising applications in flexible low-power spintronic devices.

Tunable assembly of hybrid colloids induced by regioselective depletion.

Assembling colloidal particles using site-selective directional interactions into predetermined colloidal superlattices with desired properties is broadly sought after, but challenging to achieve. Herein, we exploit regioselective depletion interactions to engineer the directional bonding and assembly of non-spherical colloidal hybrid microparticles. We report that the crystallization of a binary colloidal mixture can be regulated by tuning the depletion conditions. Subsequently, we fabricate triblock biphasic colloids with controlled aspect ratios to achieve regioselective bonding. Without any surface treatment, these biphasic colloids assemble into various colloidal superstructures and superlattices featuring optimized pole-to-pole or centre-to-centre interactions. Additionally, we observe polymorphic crystallization, quantify the abundancy of each form using algorithms we developed and investigate the crystallization process in real time. We demonstrate selective control of attractive interactions between specific regions on an anisotropic colloid with no need of site-specific surface functionalization, leading to a general method for achieving colloidal structures with yet unforeseen arrangements and properties.

The value of a new prognostic model developed by lymphocyte-monocyte ratio and platelet-monocyte ratio in peripheral T-cell lymphoma.

Peripheral T-cell lymphoma(PTCL) is a group of lymphoproliferative tumors originated from post-thymic T cells or mature natural killer (NK) cells. It shows highly aggressive clinical behaviour, resistance to conventional chemotherapy, and a poor prognosis. Although a few prognostic models of PTCL have been established in retrospective studies, some high-risk patients still can not be screened out. Therefor we retrospectively studied 347 newly diagnosed PTCL patients and assessed the prognostic role of lymphocyte-monocyte ratio (LMR) and platelet-monocyte ratio (PMR) in the complete response (CR) and survival of PTCL patients. Patients with LMR ≤ 1.68 and PMR ≤ 300 achieved a lower CR rate and a poor survival. In multivariate analysis, LMR ≤ 1.68 (HR = 1.751, 95% CI 1.158-2.647, p < 0.05) and PMR ≤ 300 (HR = 1.762, 95% CI 1.201-2.586, p < 0.05) were independently associated with short survival. On this basis, a new prognostic model of PTCL was established to screen out high-risk patients. In our "Peripheral Blood Score (PBS)" model, three groups were identified at low risk (178 patients, 51.3%, score 0), intermediate risk (85 patients, 24.5%, score 1), and high risk (84 patients, 24.2%, score 2), having a 1-year OS of 86%, 55.3% and 22.6% (p < 0.05), and a 3-year OS of 43.4%, 20% and 13.1% (p < 0.05), respectively. Optimal strategies for identifying high-risk patients with PTCL are urgently needed. Our new PBS model is simple, inexpensive and widely available to screen out the high risk patients.

Fatal hemorrhagic pneumonia in patients with hematologic diseases and Stenotrophomonas maltophilia bacteremia: a retrospective study.

BACKGROUND: Fatal hemorrhagic pneumonia is one of the most severe manifestations of Stenotrophomonas maltophilia (SM) infections. Here, we aimed to investigate the clinical characteristics of SM bacteremia and to identify the risk factors of hemorrhagic pneumonia caused by SM in patients with hematologic diseases. METHODS: The clinical records of 55 patients diagnosed with hematologic diseases and SM bacteremia were retrospectively reviewed. We compared patients' clinical characteristics and outcomes between the hemorrhagic pneumonia group and non-hemorrhagic pneumonia group. RESULTS: Twenty-seven (49.1%) patients developed hemorrhagic pneumonia. The overall mortality rate of SM bacteremia was 67.3%. Hemorrhagic pneumonia (adjusted HR 2.316, 95% CI 1.140-4.705; P = 0.020) was an independent risk factor of 30-day mortality in hematological patients with SM bacteremia. Compared with the non-hemorrhagic pneumonia group, patients in the hemorrhagic pneumonia group were older and showed clinical manifestations as higher proportions of isolated SM in sputum culture, neutropenia and elevated procalcitonin (PCT). Multivariate analysis showed that neutropenia, high levels of PCT, prior tigecycline therapy within 1 month were independent risk factors associated with hemorrhagic pneumonia. CONCLUSIONS: Neutropenia, high level of PCT and prior tigecycline therapy within 1 month were significant independent predictors of hemorrhagic pneumonia in hematologic patients with SM bacteremia. Due to no effective antibiotics to prevent hemorrhagic pneumonia, prophylaxis of SM infection and its progression to hemorrhagic pneumonia is particularly important.

Self-Regulated Particle Swarm Multi-Task Optimization.

Population based search techniques have been developed and applied to wide applications for their good performance, such as the optimization of the unmanned aerial vehicle (UAV) path planning problems. However, the search for optimal solutions for an optimization problem is usually expensive. For example, the UAV problem is a large-scale optimization problem with many constraints, which makes it hard to get exact solutions. Especially, it will be time-consuming when multiple UAV problems are waiting to be optimized at the same time. Evolutionary multi-task optimization (EMTO) studies the problem of utilizing the population-based characteristics of evolutionary computation techniques to optimize multiple optimization problems simultaneously, for the purpose of further improving the overall performance of resolving all these problems. EMTO has great potential in solving real-world problems more efficiently. Therefore, in this paper, we develop a novel EMTO algorithm using a classical PSO algorithm, in which the developed knowledge transfer strategy achieves knowledge transfer between task by synthesizing the transferred knowledges from a selected set of component tasks during the updating of the velocities of population. Two knowledge transfer strategies are developed along with two versions of the proposed algorithm. The proposed algorithm is compared with the multifactorial PSO algorithm, the SREMTO algorithm, the popular multifactorial evolutionary algorithm and a classical PSO algorithm on nine popular single-objective MTO problems and six five-task MTO problems, which demonstrates its superiority.

Evolutionary Multi-Objective One-Shot Filter Pruning for Designing Lightweight Convolutional Neural Network.

Deep neural networks have achieved significant development and wide applications for their amazing performance. However, their complex structure, high computation and storage resource limit their applications in mobile or embedding devices such as sensor platforms. Neural network pruning is an efficient way to design a lightweight model from a well-trained complex deep neural network. In this paper, we propose an evolutionary multi-objective one-shot filter pruning method for designing a lightweight convolutional neural network. Firstly, unlike some famous iterative pruning methods, a one-shot pruning framework only needs to perform filter pruning and model fine-tuning once. Moreover, we built a constraint multi-objective filter pruning problem in which two objectives represent the filter pruning ratio and the accuracy of the pruned convolutional neural network, respectively. A non-dominated sorting-based evolutionary multi-objective algorithm was used to solve the filter pruning problem, and it provides a set of Pareto solutions which consists of a series of different trade-off pruned models. Finally, some models are uniformly selected from the set of Pareto solutions to be fine-tuned as the output of our method. The effectiveness of our method was demonstrated in experimental studies on four designed models, LeNet and AlexNet. Our method can prune over 85%, 82%, 75%, 65%, 91% and 68% filters with little accuracy loss on four designed models, LeNet and AlexNet, respectively.

Two-Dimensional (2D) or Quasi-2D Superstructures from DNA-Coated Colloidal Particles.

This contribution describes the synthesis of colloidal di-patch particles functionalized with DNA on the patches and their assembly into colloidal superstructures via cooperative depletion and DNA-mediated interactions. The assembly into flower-like Kagome, brick-wall like monolayer, orthogonal packed single or double layers, wrinkled monolayer, and colloidal honeycomb superstructures can be controlled by tuning the particles' patch sizes and assembly conditions. Based on these experimental results, we generate an empirical phase diagram. The principles revealed by the phase diagram provide guidance in the design of two-dimensional (2D) materials with desired superstructures. Our strategy might be translatable to the assembly of three-dimensional (3D) colloidal structures.

Polyunsaturated fatty acid supplement alleviates depression-incident cognitive dysfunction by protecting the cerebrovascular and glymphatic systems.

INTRODUCTION: Depression, the most prevalent mood disorder, has high comorbidity with cerebrovascular disease and cognitive decline. However, there is little understanding of the cellular mechanisms involved in depression and its comorbid cerebrovascular damage and cognition impairment. Here, we tested the prediction that the chronic unpredictable mild stress (CUMS) mouse model would manifest in disturbed glymphatic function and that dietary supplementation with polyunsaturated fatty acids (PUFA) could ameliorate these deficits while alleviating the depression-associated cognitive decline. METHODS: To test the treatment effects of PUFA or Es on behaviours, we applied the tail suspension, open field, and sucrose preference tests to assess depressive symptoms, and applied the Morris water maze test to assess cognition in groups of control, chronic unpredictable mild stress (CUMS), PUFA, and escitalopram (Es) treatment. We measured the extracellular concentrations of dopamine (DA), 5-hydroxytryptamine (5-HT) and noradrenaline (NA) in microdialysates from prefrontal cortex (PFC) by liquid chromatography mass spectrometry. Glia cells and inflammatory factors were analysed with fluorescent immunochemistry and western blot, respectively. We tested brain vasomotor function with two-photon and laser speckle imaging in vivo, and measured glymphatic system function by two-photon imaging in vivo and fluorescence tracer imaging ex vivo, using awake and anesthetized mice. Besides, we monitored cortical spreading depression by laser speckle imaging system. AQP4 depolarization is analysed by fluorescent immunochemistry and western blot. RESULTS: We confirmed that CUMS elicited depression-like and amnestic symptoms, accompanied by decreased monoamines neurotransmitter concentration in PFC and upregulated neuroinflammation markers. Moreover, CUMS mice showed reduced arterial pulsation and compliance in brain, and exhibited depolarized expression of AQP4, thus indicating glymphatic dysfunction both in awake and anesthetized states. PUFA supplementation rescued depression-like behaviours of CUMS mice, reduced neuroinflammation and cerebrovascular dysfunction, ultimately improved cognitive performance, all of which accompanied by restoring glymphatic system function. In contrast, Es treatment alleviated only the depression-like behavioural symptoms, while showing no effects on glymphatic function and depression-incident cognitive deficits. CONCLUSIONS: The CUMS depression model entails suppression of the glymphatic system. PUFA supplementation rescued most behavioural signs of depression and the associated cognitive dysfunction by restoring the underlying glymphatic system disruption and protecting cerebral vascular function.

Wireless Systems and Networks in the IoT.

This Special Issue is focused on breakthrough developments in the field of Wireless Systems and Networks in the IoT. The selected contributions report current scientific progress in a wide range of topics covering clock error compensation in sensor networks, backscatter communication networks, Radio-Frequency Identification (RFID)-based inventory management, resource allocation in Long-Term Evolution (LTE)/LTE-A, (Long Range Wide-Area Network (LoRaWAN) modeling and key generation for the IoT.

Aspirin inhibits adipogenesis of tendon stem cells and lipids accumulation in rat injury tendon through regulating PTEN/PI3K/AKT signalling.

Tendon injury repairs are big challenges in sports medicine, and fatty infiltration after tendon injury is very common and hampers tendon injury healing process. Tendon stem cells (TSCs), as precursors of tendon cells, have shown promising effect on injury tendon repair for their tenogenesis and tendon extracellular matrix formation. Adipocytes and lipids accumulation is a landmark event in pathological process of tendon injury, and this may induce tendon rupture in clinical practice. Based on this, it is important to inhibit TSCs adipogenesis and lipids infiltration to restore structure and function of injury tendon. Aspirin, as the representative of non-steroidal anti-inflammatory drugs (NSAIDs), has been widely used in tendon injury for its anti-inflammatory and analgesic actions, but effect of aspirin on TSCs adipogenesis and fatty infiltration is still unclear. Under adipogenesis conditions, TSCs were treated with concentration gradient of aspirin. Oil red O staining was performed to observe changes of lipids accumulation. Next, we used RNA sequencing to compare profile changes of gene expression between induction group and aspirin-treated group. Then, we verified the effect of filtrated signalling on TSCs adipogenesis. At last, we established rat tendon injury model and compared changes of biomechanical properties after aspirin treatment. The results showed that aspirin decreased lipids accumulation in injury tendon and inhibited TSCs adipogenesis. RNA sequencing filtrated PTEN/PI3K/AKT signalling as our target. After adding the signalling activators of VO-Ohpic and IGF-1, inhibited adipogenesis of TSCs was reversed. Still, aspirin promoted maximum loading, ultimate stress and breaking elongation of injury tendon. In conclusion, by down-regulating PTEN/PI3K/AKT signalling, aspirin inhibited adipogenesis of TSCs and fatty infiltration in injury tendon, promoted biomechanical properties and decreased rupture risk of injury tendon. All these provided new therapeutic potential and medicine evidence of aspirin in treating tendon injury and tendinopathy.

Simultaneous polarization transformation and amplification of multi-petawatt laser pulses in magnetized plasmas.

With increasing laser peak power, the generation and manipulation of high-power laser pulses become a growing challenge for conventional solid-state optics due to their limited damage threshold. As a result, plasma-based optical components that can sustain extremely high fields are attracting increasing interest. Here, we propose a type of plasma waveplate based on magneto-optical birefringence under a transverse magnetic field, which can work under extremely high laser power. Importantly, this waveplate can simultaneously alter the polarization state and boost the peak laser power. It is demonstrated numerically that an initially linearly polarized laser pulse with 5 petawatt peak power can be converted into a circularly polarized pulse with a peak power higher than 10 petawatts by such a waveplate with a centimeter-scale diameter. The energy conversion efficiency of the polarization transformation is about 98%. The necessary waveplate thickness is shown to scale inversely with plasma electron density ne and the square of magnetic field B0, and it is about 1 cm for ne = 3 × 1020 cm-3 and B0 = 100 T. The proposed plasma waveplate and other plasma-based optical components can play a critical role for the effective utilization of multi-petawatt laser systems.

Control of laser light by a plasma immersed in a tunable strong magnetic field.

The interaction between laser light and an underdense plasma immersed in a spatio-temporally tunable magnetic field is studied analytically and numerically. The transversely nonuniform magnetic field can serve as a magnetic channel, which can act on laser propagation in a similar way to the density channel. The envelope equation for laser intensity evolution is derived, which contains the effects of magnetic channel and relativistic self-focusing. Due to the magnetic field applied, the critical laser power for relativistic self-focusing can be significantly reduced. Theory and particle-in-cell simulations show that a weakly relativistic laser pulse can propagate with a nearly constant peak intensity along the magnetic channel for a distance much longer than its Rayleigh length. By setting the magnetic field tunable in both space and time, the simulation further shows that the magnetized plasma can then act as a lens of varying focal length to control the movement of laser focal spot, decoupling the laser group velocity from the light speed c in vacuum.

Expression of human Tau40 in the medial entorhinal cortex impairs synaptic plasticity and associated cognitive functions in mice.

Entorhinal cortex (EC) is the initial brain region that suffers abnormal tau in Alzheimer's disease (AD). Whether overexpression of human tau (htau40) in EC disrupts cognitive function and synaptic plasticity in AD has not been fully elucidated. To investigate the effects of htau40 on the pathology and associated mechanisms of early stage of AD in mice, an adeno-associated virus-based htau40 transduced in medial EC (mEC) mouse model was established. The results showed that htau40 restrictedly expressed in mEC after transduction. The memory function and long-term potentiation (LTP) of dentate gyrus (DG) were significantly impaired by overexpression of htau40 in mEC after transduction at 3 and 6 months. However, the abnormities of neurons and neurotransmitters in mEC started at just 1 month after transduction. The resting membrane potential was increased and paired pulse facilitates was depressed, but the action potential amplitude, threshold, and half width did not alter after htau40 transduction at 1 month. The levels of inhibitory neurotransmitters were up regulated whereas level of lactate was decreased. Our study demonstrated that htau40 in mEC impaired cognition and synaptic plasticity of perforant path (PP)-DG, which simulated early stage of AD and elucidated the mechanism of that htau40 overexpression in mEC may be associated with the development of AD.