Silica Nanoparticle Exposure Implicates ß-Amyloid (1-42) Inbound and the Accelerating Alzheimer's Disease Progression in Mice Overexpressing Mutated Forms of Human Amyloid Precursor Protein and Presenilin 1 Genes.

The increasing nanoparticle (NP) applications in the biomedical field have become an emerging concern regarding human health. NP exposure may play a role in the accelerating Alzheimer's disease (AD) progression; however, the etiology of this disorder is complex and remains largely unclear. Here, we identified that intravenous injection of silica NPs (SiNPs) caused the blood-brain barrier breakdown via downregulating tight junction-related gene expressions. Meanwhile, SiNPs upregulate the transport receptor for advanced glycation end products (RAGE) that govern the ß-amyloid (Aß) influx to the brain; however, low-density lipoprotein receptor-related protein 1 (LRP1) that controls the efflux of Aß from the brain was not affected. Consequently, an increase in Aß burden in the brain of SiNP-challenged APP/PS1 mice was found. Intriguingly, plasma apolipoprotein E (ApoE) adsorbed on the surface of SiNPs partially relieves this effect. Using ApoE knockout (ApoE-/-) mice, we confirmed that SiNPs covered with serum without ApoE showed further elevated AD symptoms. Together, this study offered a compilation of data to support the potential risk factors of NP exposure and AD pathology.

Malaria sporozoites evade host complement attack.

Complement is the first line of the host innate immune response against bacterial and viral infections; however, its role in the development of the malaria liver stage remains undefined. We found that sporozoite infection by either a mosquito bite or intravenous injection activated systemic complement, but neither depletion of C3 nor knockout of C3 had a significant effect on malaria liver stage development. Incubation of mouse serum with trypsin-treated sporozoites, but not naive sporozoites, led to the deposition of a membrane attack complex (MAC) on the surface of sporozoites and greatly reduced the number of exo-erythrocytic forms (EEF). Further studies have shown that the recruitment of complement H factor (CFH) may be associated with the prevention of MAC deposition on the surface of naïve sporozoites. Our data strongly suggest that sporozoites can escape complement attacks and provide us with a novel strategy to prevent malaria infection.

Influence of the laser pulse time profile on residual stress characteristics in laser shock peening.

In this paper, residual stress and plastic deformation of TC4 titanium alloys and AA7075 aluminum alloys after laser shock peening (LSP) with the laser pulses that have the same energy and peak intensity but different time profiles have been studied. The results show that the time profile of the laser pulse has a significant influence on LSP. The difference between the results of LSP with varying laser input mode has been contributed to the shock wave caused by different laser pulse. In LSP, the laser pulse with a positive-slope triangular time profile could induce a more intense and deeper residual stress distribution in metal targets. Residual stress distribution changing with laser time profiles suggests that shaping the laser time profile is a potential residual stress control strategy for LSP. This paper comprises the first step of this strategy.

The distinctive role of membrane fibrinogen-like protein 2 in the liver stage of rodent malaria infections.

Viral infection often induce the expression of murine fibrinogen-like protein 2 (mFGL2) triggering immune coagulation, which causes severe liver pathogenesis via increased fibrin deposition and thrombosis in the microvasculature. We aimed to investigate the role of mFGL2 in the liver stage of malaria infections. We reveal that infection with malaria sporozoites also induces increased expression of mFGL2 and that this expression is primarily located within the liver Kupffer and endothelial cells. In addition, we report that inhibition of FGL2 has no significant effect on immune coagulation but increases the expression of inflammatory cytokines in the livers of infected mice. Interestingly, FGL2 deficiency had no significant impact on the development of liver stage malaria parasites or the pathogenesis of the infected liver. In contrast to viral infections, we conclude that mFGL2 does not contribute to either parasite development or liver pathology during these infections, revealing the unique features of this protein in liver-stage malaria infections.

Evolution of laser-induced bulk damage in KDP crystal.

Pinpoint damage is the main type of bulk damage in potassium dihydrogen phosphate (KDP) crystals in high-power lasers. Using time-resolved microimaging, we observed the complete dynamic evolution of pinpoint damage in a KDP crystal. We analyzed changes in the patterns of dark zones formed by decreasing probe transmittance in transient images throughout the process. The mechanical properties of stress waves in KDP crystals were further studied by a depolarized shadowgraph experiment and theoretical simulation. The dynamic evolution of mechanical stress waves was observed, and the correlation between mechanical failure due to stress waves and the static characteristic damage morphology was established.

Investigation of stress wave and damage morphology growth generated by laser-induced damage on rear surface of fused silica.

In this study, stress wave and damage morphology on the rear surface of silica during laser induced damage with cumulative UV pump shots is investigated. Time resolved imaging system, along with stress induced birefringence detecting, is used to demonstrate the development of stress wave. The properties of three types of stress waves, namely, compressive wave (P-wave), shear wave (S-wave), and Rayleigh wave (R-wave) are recorded and studied during the damage process. The experimental and simulated results indicated that R-wave exhibits the highest intensity among all the three stress waves. Because the R-wave is mainly localized at the region near the surface, it is responsible for the mechanical damage along the surface; in addition, it rapidly increases the damage diameter, which was observed from the front view of the damage.

Investigation of sub-phonon lifetime pulse amplification in active frequency matching stimulated Brillouin scattering.

We demonstrate Brillouin amplification of sub-phonon lifetime Stokes pulses based on an active frequency matching method. The main purpose is to extend Brillouin amplification to further applications requiring shorter pulse widths and break the phonon lifetime limit. A combination of theoretical simulations and experiments is used to achieve this goal. As a result, the Brillouin transient gain is identified as the key parameter to achieve sub-phonon lifetime Brillouin amplification. The experimental results agree well with the theoretical simulation.

Novel chitosan-based flocculants for chromium and nickle removal in wastewater via integrated chelation and flocculation.

Carboxylated chitosan (CPCTS) is used as substrates in the design and synthesis of CPCTS-based flocculants through UV-initiated polymerization techniques. The synthesized flocculants are applied to remove Cr and Ni ions from chromic acid lotion and electroplating wastewater through two-stage flocculation. This study investigates the effect of flocculant dosage, pH, reaction time, and stirring speed on the removal efficiency of Cr and Ni ions. Results indicated that the total Cr removal ratios by CPCTS-graft-polyacrylamide-co-sodium xanthate (CAC) and CPCTS-graft-poly [acrylamide-2-Acrylamido-2-methylpropane sulfonic acid] (CPCTS-g-P(AM-AMPS)) are 94.7% and 94.6%, respectively. The total Ni removal efficiencies by CAC and CPCTS-g-P(AM-AMPS) are 99.3% and 99.4%, respectively. The two-stage flocculation with CPCTS-based flocculants could reduce the total concentrations of Cr and Ni to 1.0 mg/L and 0.5 mg/L, respectively. The relationship of removal capacity and structural properties between the flocculants with different functional groups is established through Fourier transform infrared spectroscopy, nuclear magnetic resonance, scanning electron microscopy, and X-ray diffraction. The micro-interfacial behavior between the colloidal particles and the solution during the integrated chelation-flocculation are elucidated. Thus, CPCTS-based flocculants could be a potential material for the removal of high amounts of Cr and Ni ions in industrial wastewater.

Increased expression of pleiotrophin is a prognostic marker for patients with gastric cancer.

UNLABELLED: BACKGROUND/AIMs: Pleiotrophin (PTN) have been demonstrated to play an important role in the development of human gastric cancer. However, the prognostic value remains unclear. The aim of this study was to investigate whether expression of PTN has prognostic relevance in human gastric cancer. METHODOLOGY: Immunohistochemistry was used to investigate the expression of PTN proteins in 178 patients with gastric cancer. The level of PTN mRNA in gastric cancer tissues and paratumor tissues were evaluated in 52 paired cases by quantitative real-time polymerase chainreaction(qRT-PCR). Survival analysis by the Kaplan-Meier method was performed to assess prognostic significance. RESULTS: The expression level of PTN in gastric cancer tissues was significantly higher (P<0.001) than those in paratumor tissues according to the immunohistochemistry analysis, which was confirmed by qRT-PCR analysis. Additionally, the overexpression of PTN was significantly associated with the tumor site (P=0.001), Lauren's classification (P<0.001),histologic differentiation(P=0.014),depth of invasion(P<0.001), TNM stage (P=0.003),and lymph node metastasis (P=0.002). Moreover, the Cox proportional- hazards regression analysis revealed that the increased expression of PTN was an independent prognostic factor for poor recurrence-free survival(RFS) and overall survival(OS)(both P<0.001). CONCLUSIONS: These findings indicated that the expression of PTN is significantly correlated with prognosis in gastric cancer patients, suggesting that the expression of PTN may be used as an independent prognostic marker.

CD8+ Trms against malaria liver-stage: prospects and challenges.

Attenuated sporozoites provide a valuable model for exploring protective immunity against the malarial liver stage, guiding the design of highly efficient vaccines to prevent malaria infection. Liver tissue-resident CD8+ T cells (CD8+ Trm cells) are considered the host front-line defense against malaria and are crucial to developing prime-trap/target strategies for pre-erythrocytic stage vaccine immunization. However, the spatiotemporal regulatory mechanism of the generation of liver CD8+ Trm cells and their responses to sporozoite challenge, as well as the protective antigens they recognize remain largely unknown. Here, we discuss the knowledge gap regarding liver CD8+ Trm cell formation and the potential strategies to identify predominant protective antigens expressed in the exoerythrocytic stage, which is essential for high-efficacy malaria subunit pre-erythrocytic vaccine designation.

Research on the aerodynamic characteristics of dragonfly leading edge.

Dragonflies are some of the most stable and maneuverable flying organisms. To explore the mechanism of how dragonfly leading edges enhance flight lift, this article conducts a detailed study on the leading edge veins and the microstructures on them of dragonfly wings. Observations have discovered the special leading edge vein and the regularly distributed microstructures on the leading edge vein. A biomimetic model has been established, and computational fluid dynamics (CFD) simulation analysis has been conducted on the biomimetic model. The analysis explores the effects of microstructure characteristics, distribution patterns, and positions on the aerodynamic characteristics of dragonfly gliding. The analysis shows that the leading edge structure influences the incoming flow, simultaneously promotes the formation of the leading edge vortex (LEV), and increases the lift-to-drag ratio by up to 4%. A wing prototype featuring biomimetic microstructures is subsequently fabricated and tested in wind tunnel experiments. Compared with a control group without leading edge structures, the airflow passing through the biomimetic structures is influenced by the shape and arrangement of these structures. The smoother transition of the leading edge vein's shape facilitates the flow of air. The microstructures primarily filter and accelerate the airflow. The spacing of the microstructures affects the stability of the airflow, thereby influencing aerodynamic performance. Additionally, the middle-row arrangement of microstructures is more beneficial for gliding conditions, while the upper-row arrangement is more advantageous for flapping conditions. These findings enhance our understanding of insect wings and advance micro aerial vehicle applications. RESEARCH HIGHLIGHTS: This study observed the leading-edge veins and microstructures of dragonfly wings in detail. Using a biomimetic model and computational fluid dynamics (CFD) simulations, it was found that these leading-edge structures promote the formation of leading-edge vortices (LEV), increasing the lift-to-drag ratio by up to 4%. Wind tunnel experiments demonstrated that wings with biomimetic microstructures significantly improved airflow smoothness and lift compared with control wings. Additionally, the arrangement of microstructures greatly affects airflow stability and aerodynamic performance, with middle-row arrangements being more beneficial for gliding and upper-row arrangements for flapping conditions. These findings enhance our understanding of insect wings and provide innovative guidance for designing efficient micro aerial vehicles.

Adverse drug events associated with linezolid administration: a real-world pharmacovigilance study from 2004 to 2023 using the FAERS database.

Introduction: Linezolid is an oxazolidinone antibiotic that is active against drug-resistant Gram-positive bacteria and multidrug-resistant Mycobacterium tuberculosis. Real-world studies on the safety of linezolid in large populations are lacking. This study aimed to determine the adverse events associated with linezolid in real-world settings by analyzing data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Methods: We retrospectively extracted reports on adverse drug events (ADEs) from the FAERS database from the first quarter of 2004 to that of 2023. By using disproportionality analysis including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), along with the multi-item gamma Poisson shrinker (MGPS), we evaluated whether there was a significant association between linezolid and ADE. The time to onset of ADE was further analyzed in the general population and within each age, weight, reporting population, and weight subgroups. Results: A total of 11,176 reports of linezolid as the "primary suspected" drug and 263 significant adverse events of linezolid were identified, including some common adverse events such as thrombocytopenia (n = 1,139, ROR 21.98), anaemia (n = 704, ROR 7.39), and unexpected signals that were not listed on the drug label such as rhabdomyolysis (n = 90, ROR 4.33), and electrocardiogram QT prolonged (n = 73, ROR 4.07). Linezolid-induced adverse reactions involved 27 System Organ Class (SOC). Gender differences existed in ADE signals related to linezolid. The median onset time of all ADEs was 6 days, and most ADEs (n = 3,778) occurred within the first month of linezolid use but some may continue to occur even after a year of treatment (n = 46). Conclusion: This study reports the time to onset of adverse effects in detail at the levels of SOC and specific preferred term (PT). The results of our study provide valuable insights for optimizing the use of linezolid and reducing potential side effects, expected to facilitate the safe use of linezolid in clinical settings.

ZIF-8-Derived Carbon In-Situ Encapsulated Hollow Mn2SiO4 Sub-Microspheres as Anode for Lithium-Ion Batteries with Ultrahigh Capacity and Excellent Rate Performance.

Manganese silicate (Mn2SiO4) possesses a more suitable volume expansion (186%) compared to SiOx-based materials and is also characterized by low cost, environmental friendliness, and considerable theoretical capacity. Hollow Mn2SiO4 sub-microspheres encapsulated by a highly continuous network of conductive carbon (MSC) are prepared by the self-templating method and subsequent ZIF-8-derived carbon coating. The as-prepared Mn2SiO4@C hybrid under optimal conditions (MSC-2) can provide a high capacity of 1343 mA h g-1 at 0.2 A g-1 and an excellent rate performance of 434 mA h g-1 at 10 A g-1. Even after 500 cycles, MSC-2 can still maintain a considerable specific capacity of 554 mA h g-1 at a high current density of 5.0 A g-1. Additionally, the full cell assembled with MSC-2 anode and LiFePO4 cathode (MSC-2//LFP) possesses a robust energy density of 218 W h kg-1, excellent power density of 2.5 kW kg-1, and good cycling stability.

Surface Cleanliness Maintenance with Laminar Flow Based on the Characteristics of Laser-Induced Sputtering Particles in High-Power Laser Systems.

In high-power laser systems, the primary cause of contamination of optical components and degradation of spatial cleanliness is laser-induced sputtering of particles. To mitigate this problem, laminar flow is frequently utilized to control the direction and transport of these particles. This study characterizes the properties of laser-induced sputtering particles, including their flying trend, diameter range, and velocity distribution at varying time intervals. A time-resolved imaging method was employed to damage the rear surface of fused silica using a 355 nm Nd: YAG pump laser. The efficacy of laminar flow in controlling these particles was then assessed, with a particular focus on the influence of laminar flow direction, laminar flow velocity, particle flight height, and particle diameter. Our results indicate that the optimal laminar flow velocity for preventing particle invasion is highly dependent on the maximum particle attenuation distance (or safety distance), which can vary by up to two orders of magnitude. Furthermore, a laminar flow velocity of 0.5 m/s can effectively prevent particle sedimentation. Future research will aim to optimize laminar flow systems based on these findings to achieve high surface cleanliness in high-power laser systems with minimal energy consumption.

Exercise improved bone health in aging mice: a role of SIRT1 in regulating autophagy and osteogenic differentiation of BMSCs.

Introduction: This study was designed to investigate the effect of running exercise on improving bone health in aging mice and explore the role of the SIRT1 in regulating autophagy and osteogenic differentiation of Bone marrow Mesenchymal Stem Cells (BMSCs). Methods: Twelve-month-old male C57BL/6J mice were used in this study as the aging model and were assigned to treadmill running exercise for eight weeks. Non-exercise male C57BL/6J mice of the same old were used as aging control and five-month-old mice were used as young controls. BMSCs were isolated from mice and subjected to mechanical stretching stimulation in vitro. Results: The results showed that aging mice had lower bone mass, bone mineral density (BMD), and autophagy than young mice, while running exercise improved BMD and bone mass as well as upregulated autophagy in bone cells. Mechanical loading increased osteogenic differentiation and autophagy in BMSCs, and knockdown of SIRT1 in BMSCs demonstrated that SIRT1-regulated autophagy involved the mechanical loading activation of osteogenic differentiation. Conclusion: Taken together, this study revealed that exercise improved bone health during aging by activating bone formation, which can be attributed to osteogenic differentiation of BMSCs through the activation of SIRT1-mediated autophagy. The mechanisms underlying this effect may involve mechanical loading.

A real-world pharmacovigilance study of mepolizumab in the FDA adverse event reporting system (FAERS) database.

Mepolizumab is primarily used in the treatment of asthma, eosinophilic granulomatosis with polyangiitis, eosinophilia syndrome, and chronic rhinitis with nasal polyps. The information about its adverse drug reactions is mainly derived from clinical trials, and there is a shortage of real-world studies with extensive sample sizes. In this study, the U.S. FDA's Adverse Event Reporting System (FAERS) database was analyzed to evaluate the side effects of mepolizumab. A total of 18,040 reports of mepolizumab-associated adverse events were identified from the FDA Adverse Event Reporting System database. Multiple disproportionality analysis algorithms were used to determine the significance of these AEs. The study identified 198 instances of mepolizumab-induced AEs, including some important AEs not mentioned in the product labeling. The time to onset of adverse reactions was also analyzed, with a median time of 109 days. Most AEs occurred within the first month of mepolizumab use, but some may still occur after 1 year of treatment. Gender-specific analysis showed different high-risk AEs for females (digestive and neurological side effects) and males (serious adverse effects leading to hospitalization and death). The findings mentioned provide valuable insights on optimizing the use of mepolizumab, enhancing its effectiveness, and minimizing potential side effects. This information will greatly contribute to the practical implementation of the drug in clinical settings.

An overview of brain-like computing: Architecture, applications, and future trends.

With the development of technology, Moore's law will come to an end, and scientists are trying to find a new way out in brain-like computing. But we still know very little about how the brain works. At the present stage of research, brain-like models are all structured to mimic the brain in order to achieve some of the brain's functions, and then continue to improve the theories and models. This article summarizes the important progress and status of brain-like computing, summarizes the generally accepted and feasible brain-like computing models, introduces, analyzes, and compares the more mature brain-like computing chips, outlines the attempts and challenges of brain-like computing applications at this stage, and looks forward to the future development of brain-like computing. It is hoped that the summarized results will help relevant researchers and practitioners to quickly grasp the research progress in the field of brain-like computing and acquire the application methods and related knowledge in this field.

Niobium Tungsten Oxides for Electrochromic Devices with Long-Term Stability.

There is a keen interest in the use of electrochromic materials because they can regulate light and heat, thereby reducing the cooling and heating energy. However, the long response time, short cycle life, and high power consumption of an electrochromic film hinder its development. Here, we report an electrochromic material of complex niobium tungsten oxides. The Nb18W16O93 thin films in the voltage range of 0 to -1.5 V show good redox kinetics with the coloration time of 4.7 s and bleaching time of 4.0 s, respectively. The electrochromic device based on the Nb18W16O93 thin film has an optical modulation of 53.1% at a wavelength of 633 nm, with the coloration efficiency of ∼46.57 cm2 C-1. An excellent electrochemical stability of 78.1% retention after 8000 cycles is also achieved. These good performances are due to the fast and stable Li-ion intercalation/extraction in the open framework of Nb18W16O93 with multiple ion positions. Our work provides a strategy for electrochromic materials with fast response time and good cycle stability.

Synergistic Optimization Strategy Involving Sandwich-like MnO2@rGO and Laponite-Modified PAM for High-Performance Zinc-Ion Batteries and Zinc Dendrite Suppression.

Optimization of the cathode structure and exploration of a novel electrolyte system are important approaches for achieving high-performance zinc-ion batteries (ZIBs) and zinc dendrite suppression. Herein, a quasi-solid-state ZIB combining a sandwich-like MnO2@rGO cathode, a laponite (Lap)-modified polyacrylamide (PAM) hydrogel electrolyte, and an electrodeposited zinc anode is designed and constructed by a synergistic optimization strategy. The MnO2 composite prepared through the intercalation of rGO shows developed mesopores, providing accessible ion transport channels and exhibiting a high electrical conductivity. Thanks to the high dispersion of Lap nanoplates in the hydrogel and good charge-averaging effect, the Zn//PAM-5%Lap//Zn symmetrical battery exhibits a consistent low-voltage polarization of less than 60 mV within 2000 h without a short-circuit phenomenon or any over-potential rise, indicating a stable zinc peeling/plating process. The optimized quasi-solid-state ZIB delivers a high reversible capacity of 291 mA h g-1 at a current density of 0.2 A g-1 due to the synergistic effect of each component of ZIB. Even at a high rate of 2 A g-1, it still maintains a high reversible capacity of 97 mA h g-1 after 2000 cycles, indicating its excellent electrochemical performance. Furthermore, the assembled flexible battery performs excellently in terms of damage and bending resistance.

[Construction and Identification of Acute Myeloid Leukemia NOD/SCID Mouse Model by Tail Vein Injection of THP-1 Cells].

OBJECTIVE: To construct NOD/SCID mouse leukemia model by using THP-1 cells. METHODS: Eighteen female NOD/SCID mice aged 3 to 4 weeks were randomly divided into control group, model group A and model group B (6 in each group). Before inoculation, each mouse was intraperitoneally injected with cyclophosphamide 2 mg/(kg·d) for 2 d, and the mice in model groups were inoculated with cells within 24 h after pretreatment. The mice in model group were inoculated with THP-1 cell suspension in logarithmic growth phase by 1×107 cells/group (group A) and 5×106 cells/group (group B), the mice in the control group were injected with the same amount of normal saline in the tail vein. The general situation was observed, blood routine test and peripheral blood leukocyte classification were performed at 7, 14, 21, 28 d of inoculation before the pre-treatment, and at the time sacrifice. Before dying, tissue of mice were collected and histological examination was performed. RESULTS: Pilereation, droopiness and hypkinesia could be observed from d 7 and d 10 of inoculation cells in model group. Compared with the control group, the body weight of the mice in model group A and B decreased significantly after 21 days of inoculation (P<0.01), and the white blood cell counts increased significantly after 28 days of modeling (P<0.01). Among them, the above-mentioned presentation in inoculation of 1×107 group A was the most significant. Histopathological sections showed diffuse infiltration of leukemia cells in the spleen of the model group. The immunohistochemistry results indicated that the leukemia cells were positive for anti-human CD13, which confirmed the successful establishment of the model. CONCLUSION: After pretreatment with intraperitoneal injection of CTX in NOD/SCID mice, the injection of 1×107 or 5×106 THP-1 cells in tail vein of each mouse can successfully construct an acute myeloid leukemia animal model. The tumor formation is more much faster by injection of high concentration THP-1 cells.