Microenvironment matters: In vitro 3D bone marrow niches differentially modulate survival, phenotype and drug responses of acute myeloid leukemia (AML) cells.

Acute myeloid leukemia (AML) is a deadly form of leukemia with ineffective traditional treatment and frequent chemoresistance-associated relapse. Personalized drug screening holds promise in identifying optimal regimen, nevertheless, primary AML cells undergo spontaneous apoptosis during cultures, invalidating the drug screening results. Here, we reconstitute a 3D osteogenic niche (3DON) mimicking that in bone marrow to support primary AML cell survival and phenotype maintenance in cultures. Specifically, 3DON derived from osteogenically differentiated mesenchymal stem cells (MSC) from healthy and AML donors are co-cultured with primary AML cells. The AML cells under the AML_3DON niche showed enhanced viability, reduced apoptosis and maintained CD33+ CD34-phenotype, associating with elevated secretion of anti-apoptotic cytokines in the AML_3DON niche. Moreover, AML cells under the AML_3DON niche exhibited low sensitivity to two FDA-approved chemotherapeutic drugs, further suggesting the physiological resemblance of the AML_3DON niche. Most interestingly, AML cells co-cultured with the healthy_3DON niche are highly sensitive to the same sample drugs. This study demonstrates the differential responses of AML cells towards leukemic and healthy bone marrow niches, suggesting the impact of native cancer cell niche in drug screening, and the potential of re-engineering healthy bone marrow niche in AML patients as chemotherapeutic adjuvants overcoming chemoresistance, respectively.

Design of novel broad-spectrum antiviral nucleoside analogues using natural bases ring-opening strategy.

The global prevalence of RNA virus infections has presented significant challenges to public health in recent years, necessitating the expansion of its alternative therapeutic library. Due to its evolutional conservation, RNA-dependent RNA polymerase (RdRp) has emerged as a potential target for broad-spectrum antiviral nucleoside analogues. However, after over half a century of structural modification, exploring unclaimed chemical space using frequently-used structural substitution methods to design new nucleoside analogues is challenging. In this study, we explore the use of the "ring-opening" strategy to design new base mimics, thereby using these base mimics to design new nucleoside analogues with broad-spectrum antiviral activities. A total of 29 compounds were synthesized. Their activity against viral RdRp was initially screened using an influenza A virus RdRp high-throughput screening model. Then, the antiviral activity of 38a was verified against influenza virus strain A/PR/8/34 (H1N1), demonstrating a 50% inhibitory concentration (IC50) value of 9.95 µM, which was superior to that of ribavirin (the positive control, IC50 = 11.43 µM). Moreover, 38a also has inhibitory activity against coronavirus 229E with an IC50 of 30.82 µM. In addition, compounds 42 and 46f exhibit an 82% inhibition rate against vesicular stomatitis virus at a concentration of 20 µM and hardly induce cytotoxicity in host cells. This work demonstrates the feasibility of designing nucleoside analogues with "ring-opening" bases and suggests the "ring-opening" nucleosides may have greater polarity, and designing prodrugs is an important aspect of optimizing their antiviral activity. Future research should focus on enhancing the conformational restriction of open-loop bases to mimic Watson-Crick base pairing better and improve antiviral activity.

Regulation of exercise ability and glycolipid metabolism by synthetic SR9009 analogues as new REV-ERB-α agonists.

SR9009 is an activator of REV-ERBs with diverse biological activities, including improving exercise tolerance and controlling skeletal muscle mass. To optimise the carbamate motif of SR9009, analogues of SR9009 were synthesised and evaluated. All of them showed REV-ERB-α agonist activities. Among them, 5a, 5f, 5 g, 5m, and 5p showed potencies equivalent to or slightly higher than the potency of SR9009 in vitro. These data indicate that the halogenated benzyl group is an indispensable active group in these compounds. 5m, 5p and SR9009 improved exercise tolerance in normal mice in vivo. Additionally, in hyperlipidemic mice, 5m and 5p not only improved exercise tolerance but also lowered blood lipid levels. 5m and 5p displayed stronger hypoglycaemic activity than SR9009.

Visible light-responsive polylactic acid@pullulan-chitosan/homojunction g-C3N4 bilayer antimicrobial films for fruit preservation.

The development of novel packaging materials with antimicrobial properties is crucial in preventing the microbial-induced spoilage of fruits, vegetables, and foodborne illnesses. In this study, homojunction g-C3N4 (HCN) photocatalysts with excellent photocatalytic performance were incorporated into a matrix consisting of pullulan/chitosan (Pul/CS). These photocatalysts were then electrostatically spun onto polylactic acid (PLA) films to fabricate PLA@Pul/CS/HCN nanofibrous composite films. The design of the bilayer films aimed to combine the physical properties of PLA film with the excellent antibacterial properties of nanofiber films, thereby achieving synergistic advantages. The incorporation of the HCN photocatalysts resulted in enhanced hydrophobicity, barrier function, and mechanical properties of the composite films. Under visible light irradiation, the PLA@Pul/CS/HCN films exhibited approximately 3.43 log and 3.11 log reductions of Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA), respectively, within 2 h. The excellent antimicrobial performance could be attributed to the synergistic effect of CS and the release of reactive oxygen species (ROS) from HCN. Moreover, the strawberries packaged in the PLA@Pul/CS/HCN film demonstrated diminished quality degradation and a prolonged shelf life following visible light irradiation treatment. This study will provide new insights into the exploration of safe and efficient antimicrobial food packaging.

The impacts of economy policy uncertainty on peer effects of firms R&D investment: Based on LDA machine learning and regression statistical modeling approach.

The Latent Dirichlet Allocation (LDA) model is used to extract the text themes of newspaper news and construct the Chinese Economic Policy Uncertainty (EPU) Index. On this basis, based on the relevant data of Chinese A-share listed companies from 2008 to 2020, this paper empirically analyzes the impact of EPU on peer effects of firms R&D investment, and finds that EPU will aggravate the peer effects of firms R&D investment. Furthermore, the moderating effect of manager's motivation to maintain reputation on the process of EPU influencing the peer effects of firms R&D investment was tested, and the mechanism of EPU influencing the peer effects of firms R&D investment through financial frictions was verified.

Sophisticated Structural Ceramics Shaped from 3D Printed Hydrogel Preceramic Skeleton.

Shaping ceramic materials into sophisticated architecture with 3D hierarchical structure is desirable in multiapplication yet remains challenge due to their brittle and stiff nature. Herein, a new method to achieve ceramic architectures with unsupported and large-spanning structure by shaping vat photopolymerization 3D printed hydrogel preceramic skeleton with unique flexible and deformable character is proposed. Specifically, the present photopolymerizable hydrogel preceramic achieves one stone, two birds: the photosensitive polymer matrix coupled with ceramic nanoparticles for the first shaping by vat photopolymerization 3D printing and the secondary plasticity of the 3D printed ceramic body through flexible shape deformation of hydrogel networks. Inorganic binder aluminum dihydrogen phosphate serves as hydrogel dispersion medium to achieve ultralow shrinkage photopolymerization ceramic. Compared with conventional polymer-derived photocuring ceramics, the linear shrinkage of lamina structure is solely 2%, and which of cubic ceramic structure is just 13.3%. More importantly, one 3D printed preceramic is conducted to reshape repeatedly myriad constructions, realizing reusability of intrinsic brittle ceramic, improving manufacturing fault tolerance rate. Finally, a variety of paradigms for ceramic structure applications are proposed toward stereo circuit, biomedicine, and catalytic applications, breaking the limitation of intrinsic brittleness of ceramic in high-precision manufacturing of complex ceramic devices.

Designing Chromane Derivatives as α2A-Adrenoceptor Selective Agonists via Conformation Constraint.

Enhancing the selectivity of alpha2-adrenoceptor (α2A-AR) agonists remains an unresolved issue. Herein, we reported the design of an α2A-AR agonist using the conformation constraint method, beginning with medetomidine. The structure-activity relationship indicated that the 8-substituent of chromane derivatives exerted the most pronounced effect on α2A-AR agonistic activity. Compounds A9 and B9 were identified as the most promising, exhibiting EC50 values of 0.78 and 0.23 nM, respectively. Their selectivity indexes surpassed dexmedetomidine (DMED) by 10-80 fold. In vivo studies demonstrated that both A9 and B9 dose-dependently increased the loss of righting reflex in mice, with ED50 values of 1.54 and 0.138 mg/kg, respectively. Binding mode calculations and mutation studies suggested the indispensability of the hydrogen bond between ASP1283.32 and α2A-AR agonist. In particular, A9 and B9 showed no dual reverse pharmacological effect, a characteristic exhibited by DMED in α2A-AR activation.

De novo synthesis of a novel hapten and development of a monoclonal antibody-based immunoassay for the detection of dichlorvos and trichlorfon.

The absence of high-affinity antibodies has hindered the development of satisfactory immunoassays for dichlorvos (DDVP) and trichlorfon (TCP), two highly toxic organophosphorus pesticides. Herein, the de novo synthesis of a novel anti-DDVP hapten was introduced. Subsequently, a specific anti-DDVP monoclonal antibody (Mab) was produced with satisfying affinity to DDVP (IC50: 12.4 ng mL-1). This Mab was highly specific to DDVP, and TCP could readily convert into DDVP under mild alkaline conditions. Leveraging this insight, an indirect competitive ELISA was successfully developed for simultaneous detection of DDVP and TCP. The limit of detection in rice, cabbage and apple for DDVP /TCP was found to be 12.1/14.6 µg kg-1, 7.3/8.8 µg kg-1 and 6.9/8.3 µg kg-1, respectively. This study not only provides an effective strategy for producing a high-quality anti-DDVP Mab but also affords a reliable and cost-effective tool suitable for high-throughput detection of DDVP and TCP in food samples.

Quality of Life and Glucose Regulation in Pediatric Patients with Type 1 Diabetes: A Study in the Ningxia Hui Autonomous Region.

Objective: In this study, we aimed to evaluate the current status of the quality of life (QOL) of pediatric patients and plasma glucose concentration regulation in children with type 1 diabetes (T1DM) in the Ningxia Hui autonomous region. Methods: The study involved children with T1DM admitted to the General Hospital of Ningxia Medical University between October 2011 and October 2021. The children and their parents completed general information and quality of life (QOL) questionnaires. The regulation of plasma glucose concentration was assessed based on HbA1c levels, and plasma glucose and QOL-influencing components were investigated. Results: Among the 136 pediatric patients diagnosed with T1DM, the mean glycated hemoglobin (HbA1c) level was recorded at 8.7% (7.2%, 10.5%). A breakdown of the patient cohort revealed that 44 patients (32.4%) demonstrated good regulation of plasma glucose, 33 patients (24.3%) exhibited acceptable glycemic control, and 59 patients (43.3%) displayed poor regulation of plasma glucose. The control of plasma glucose in pediatric patients diagnosed with T1DM was affected by the duration of the disease, the patient's age, the frequency of daily plasma glucose measurements, the use of CGM, diabetic ketoacidosis (DKA), and the education level of the mother. The control of plasma glucose, dietary management, DKA, the ability to learn, and health education are interfering factors of quality of life in children diagnosed with T1DM. Effective control of plasma glucose may ensure the QOL in children with T1DM, and DKA was the risk factor for QOL. Conclusion: In Ningxia, the regulation of plasma glucose in pediatric and adolescent patients with T1DM remains suboptimal, leading to poor QOL. There is a pressing need to enhance glucose regulation and QOL through comprehensive strategies, which include reinforced dietary management, rigorous monitoring of plasma glucose levels, and heightened health education levels.

Antimicrobial carbon dots/pectin-based hydrogel for promoting healing processes in multidrug-resistant bacteria-infected wounds.

Multidrug-resistant (MDR) bacterial infections have become a significant threat to global healthcare systems. Here, we developed a highly efficient antimicrobial hydrogel using environmentally friendly garlic carbon dots, pectin, and acrylic acid. The hydrogel had a porous three-dimensional network structure, which endowed it with good mechanical properties and compression recovery performance. The hydrogel could adhere closely to skin tissues and had an equilibrium swelling ratio of 6.21, indicating its potential as a wound dressing. In particular, the bactericidal efficacy following 24-h contact against two MDR bacteria could exceed 99.99 %. When the hydrogel was applied to epidermal wounds infected with methicillin-resistant Staphylococcus aureus (MRSA) on mice, a remarkable healing rate of 93.29 % was observed after 10 days. This was better than the effectiveness of the traditionally used antibiotic kanamycin, which resulted in a healing rate of 70.36 %. In vitro cytotoxicity testing and hemolysis assay demonstrated a high biocompatibility. This was further proved by the in vivo assay where no toxic side effects were observed on the heart, liver, spleen, lung, or kidney of mice. This eco-friendly and easy-to-prepare food-inspired hydrogel provides an idea for the rational use of food and food by-products as a wound dressing to control MDR bacterial infections.

Augmentation of scleral glycolysis promotes myopia through histone lactylation.

Myopia is characterized of maladaptive increases in scleral fibroblast-to-myofibroblast transdifferentiation (FMT). Scleral hypoxia is a significant factor contributing to myopia, but how hypoxia induces myopia is poorly understood. Here, we showed that myopia in mice and guinea pigs was associated with hypoxia-induced increases in key glycolytic enzymes expression and lactate levels in the sclera. Promotion of scleral glycolysis or lactate production induced FMT and myopia; conversely, suppression of glycolysis or lactate production eliminated or inhibited FMT and myopia. Mechanistically, increasing scleral glycolysis-lactate levels promoted FMT and myopia via H3K18la, and this promoted Notch1 expression. Genetic analyses identified a significant enrichment of two genes encoding glycolytic enzymes, ENO2 and TPI1. Moreover, increasing sugar intake in guinea pigs not only induced myopia but also enhanced the response to myopia induction via the scleral glycolysis-lactate-histone lactylation pathway. Collectively, we suggest that scleral glycolysis contributes to myopia by promoting FMT via lactate-induced histone lactylation.

Effects of Nonmagnetic Zn2+ Ion and RE Ion Substitution on the Magnetic Properties of Functional Nanomaterials Co1-yZnyRExFe2-xO4 (RE = La, Sm, Gd) by Sol-Gel.

Magnetic Functional Nanomaterials Co1-yZnyRExFe2-xO4 (RE (rare-earth) = La,Sm,Gd) were prepared using the sol-gel combustion method. XRD characterization confirms that the ferrite samples we synthesized are single-phase cubic structures. The variation in the average crystalline size and lattice parameter is related to RE ion doping. The Mössbauer spectra of CoRExFe2-xO4 are two sets of magnetic six-wire peaks that indicate the ferrimagnetic behavior of the sample. The calcination temperature greatly influences the absorption area of Mössbauer for CoFe2O4, indicating that the calcination temperature affects the iron ion content at the octahedral B and tetrahedral A sites. Additionally, scanning electron microscopy measurements of the substituted specimens reveal that the ferrite powders are nanoparticles. With an increase in RE ions, the coercivity increases, and the saturation magnetization changes obviously. The XRD characterization of Co0.7Zn0.3LaxFe2-xO4 shows that the main crystalline phase of the sample is the cubic spinel structure phase, and there are fewer secondary crystalline phases. The lattice parameter tends to decrease with the substitution of La3+ ions. The average grain size decreased significantly with the increase in La content. From ferrimagnetic state transition to relaxation behavior, the hyperfine magnetic field decreases in La concentration by room temperature Mössbauer spectra. With the substitution of La3+ ions, both the saturation magnetization and coercivity of the samples were reduced, and the coercivity of all samples was lower.

A safety study on ultra­high or moderate static magnetic fields combined with platycodin D against lung cancer.

Due to the serious side effects of chemotherapy drugs against lung cancer, and the antitumor properties and high safety of magnetic fields, the present study combined moderate or ultra-high intensity statics magnetic fields (SMFs) with platycodin D (PD) to explore the antitumor efficiency and biosafety. The antitumor effects of PD with or without moderate and ultra-high SMFs on A549 cells bearing mice were compared. Mouse body weight, food/water intake, hematology routine, blood biochemistry, tumor weight and tissues hematoxylin and eosin (H&E) staining were examined. Behavior was measured using the elevated plus maze, open field and vital signs tests. The combined targets of PD and SMFs were detected using RNA-sequencing (RNA-seq). The results showed that the antitumor effect of 22 Tesla (T) SMF group was 3.6-fold higher compared with that of the 2 mg/kg PD group (tumor growth inhibition=10.08%), while the antitumor effect of 150 mT SMF was only 1.56-fold higher compared with that of PD. Although PD reduced the food intake, there was no significant difference in body weight, water intake or food consumption among PD and SMF groups. Behavioral results indicated that PD ameliorated dysphoria in mice, but SMFs reduced this effect. However, no significant abnormalities were found in routine blood, blood biochemistry test, H&E staining or organ index, except renal index which was reduced by PD with or without SMFs. RNA-sequencing (RNA-seq) demonstrated that SMFs and PD synergistically targeted the expression of genes associated with tumor growth, inflammation and neurological disease. The present study showed the antitumor efficacy and biosafety of moderate or ultra-high SMF combined with PD, which exhibited only few side effects in the treatment of lung cancer, thus supporting further research for the clinical application of magnetic fields.

Effect of Cd2+ Substitution on Structural-Magnetic and Dielectric Properties of Ni-Cu-Zn Spinel Ferrite Nanomaterials by Sol-Gel.

CdxNi0.5-xCu0.2Zn0.3Fe2O4 (0 ≤ x ≤ 0.50) ferrite with a spinel structure was prepared using the sol-gel self-propagation method. The effects of Cd2+ doping on the structure, morphology, dielectric, and magnetic properties of Ni-Cu-Zn ferrite were examined using XRD, SEM, EDX, FTIR, MPMS, and dielectric tests. The cubic spinel structure was verified by XRD and FTIR analyses. The crystallite size and particle size information of the samples were obtained with XRD and SEM analysis. The sample particle size belonged to a class of nanoscale materials with a particle size range of 1-100 nm. The minor difference between the grain size and particle size indicated that the sample nanoparticles were composed of numerous microcrystals. The EDX spectra indicated that the samples contained all stoichiometric elements. MPMS was used to measure the hysteresis lines of the samples. According to the hysteresis line, the saturation magnetization intensity (Ms), coercivity (Hc), and magnetic moment (µB) of the sample increased and then decreased with the increase in cadmium concentration. The magnetization strength (Ms) is between 4-67 emu/g, and the coercivity (Hc) is between 9-46 Oe. The curves of the real part of the dielectric constant (ε'), the imaginary part of the dielectric constant (ε″), and the loss factor (tanδ) with frequency were measured in the frequency range 100 Hz-100 kHz by means of an impedance analyzer. The complex modulus spectrum was analyzed to understand the dynamics of the conduction process.

Structural and Magnetic Properties of Perovskite Functional Nanomaterials La1-xRxFeO3 (R = Co, Al, Nd, Sm) Obtained Using Sol-Gel.

Perovskite is the largest mineral on earth and has a variety of excellent physical and chemical properties. La1-xRxFeO3 (R = Co, Al, Nd, Sm) were synthesized using the sol-gel method and analyzed by XRD, TG-DTA, and VSM. With the increase in the Co2+ doping content, the diffraction peak drifted in the direction of a larger angle. The grain size of La1-xRxFeO3(R = Co) is mainly concentrated between 50.7 and 133.5 nm. As the concentration of Co2+ increased, the magnetic loop area and magnetization increased. La1-xRxFeO3(R = Al) is an orthorhombic perovskite structure, the grain size decreased with the increase in Al3+ doping concentration, and the minimum crystallite is 17.9 nm. The magnetic loop area and magnetization increased with the increase in Al3+ ion concentration. The enclosed area of the M-H curve of the sample decreased, and the ferromagnetic order gradually weakened and tended to be antiferromagnetic, which may be due to the increase in sintering temperature, decrease in the iron oxide composition, and changes in the magnetic properties. Proper doping can improve the magnetization of La1-xRxFeO3(R = Nd), refine the particles, and obtain better magnetic performance. As the Nd3+ ion concentration increased, the magnetic properties of the samples increased. Ms of La0.85Co0.15FeO3 prepared by different calcination time increases with the increase in calcination time. As the Sm3+ ion concentration increased, the magnetic properties of the samples increased. Proper doping can improve the magnetization of La1-xRxFeO3(R = Sm), refine the particles, and generate better magnetic performance.

Development of an ultrasensitive sandwich immunoassay for detecting small molecule semicarbazide.

Ultrasensitive sandwich immunoassays for detecting the small molecule semicarbazide (SEM) were developed based on derivatization. Several SEM derivatizing agents were synthesized by linking o-nitrobenzaldehyde (NBA) and biotin with dihydroxyalkanes (different lengths), which were then used to evaluate the distance effect of two epitopes. Sandwich ELISA for SEM derivatives was developed using an anti-SEM-NBA antibody and horseradish peroxidase-labeled avidin or anti-biotin antibody as a secondary conjugate. The advantageous distances of the two epitopes under the double-antibody sandwich and antibody-avidin sandwich modes were ≥12 and ≥13 Å, respectively. Under the distances, the sensitivities of the sandwich ELISA were no lower than those of competitive ELISA. The obtained optimal EC50 values were 11.2 pg/mL (double-antibody sandwich with the epitope distance ≥16 Å) and 7.3 pg/mL (antibody-avidin sandwich with the epitope distance ≥17 Å). Compared with competitive ELISA, the developed method achieved a 30-fold improvement in sensitivity, with simpler aquatic product pretreatment.

Polysaccharides from Armillariella tabescens mycelia mitigate DSS-induced ulcerative colitis via modulating intestinal microbiota in mice.

Polysaccharides from Armillariella tabescens mycelia (AT) have a potent anti-inflammatory effect. Nevertheless, the impact of AT on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) has not yet been illustrated. This study aimed to explore AT's impact on experimental UC mice and investigate its underlying mechanisms. Mice were given DSS, 0.2 g/kg AT or 0.4 g/kg AT for seven days, and the symptoms of UC were observed. The serum and colon samples were harvested to analyze the biochemical indices and inflammasome-related proteins. The feces were collected to analyze short-chain fatty acids (SCFAs) and gut microbiota. The present study found that AT improved the symptoms of UC, colonic oxidative stress, and inflammation. AT treatment elevated SCFAs contents and colonic barrier function. Furthermore, AT improved microbial community structure through the selective enrichment of beneficial bacterial species. In conclusion, these results underlined that AT improved DSS-induced colitis and inhibited colonic inflammation via regulating the intestinal microbial community and enhancing the colonic mucosal barrier.

Synthesis and characterization of pendant N,N-dimethylaminobenzaldehyde-functionalized chitosan Schiff base composite (CS@MABA) as a new sorbent for removal of Pb(II) ions from aqueous media.

In this work, new pendant N,N-dimethylaminobenzaldehyde-functionalized chitosan Schiff base composite (CS@MABA) was prepared from the simple and convenient condensation reaction between chitosan (CS) and N,N-dimethylaminobenzaldehyde (MABA) in ethanol-glacial acetic acid (1:1 v/v) and characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC) and scanning electron microscope (SEM). The as-prepared composite CS@MABA was applied for the removal of Pb(II) ions, due to the presence of imine, hydroxyl and phenyl groups, and the effects of important parameters such as solution pH, contact time and sorbent dosage on the removal percentage and adsorption capacity were investigated and discussed. The optimum conditions were found to be at pH 5, adsorbent dosage of 0.1 g, Pb(II) concentration of 50 mg/L and contact time of 60 min. The maximum Pb(II) removal percentage was found to be 94.28 % with the high adsorption capacity of 165 mg/g. The adsorption capacity of CS@MABA is remain 87 % after 5 adsorption-desorption cycles. The adsorption kinetic and isotherm studies indicated that the Pb(II) removal by CS@MABA follows a pseudo-first order and Langmuir models, respectively. Compared to similar compounds, the synthesized CS@MABA composite has shown a relatively high yield for removing Pb(II) ions. According to these results, the CS@MABA suggested for the sorption of other heavy metals.

Magnetic Fields Affect Alcoholic Liver Disease by Liver Cell Oxidative Stress and Proliferation Regulation.

It is well known that alcohol consumption leads to substantially increased free radical levels and health risks, which lacks effective treatment besides alcohol abstinence. Here, we compared different static magnetic field (SMF) settings and found that a downward quasi-uniform SMF of ~0.1 to 0.2 T could effectively alleviate alcohol-induced liver damage and lipid accumulation and improve hepatic function. SMFs of two different directions can reduce the inflammation, reactive oxygen species levels, and oxidative stress in the liver, while the downward SMF had more obvious effects. Moreover, we found that the upward direction SMF of ~0.1 to 0.2 T could inhibit DNA synthesis and regeneration in hepatocytes, which caused detrimental effects on the lifespan of "heavy drinking" mice. In contrast, the downward SMF prolongs survival of "heavy drinking" mice. On one hand, our study shows that ~0.1 to 0.2 T moderate quasi-uniform SMFs with a downward direction have great promises to be developed into a physical method to reduce alcohol-induced liver damage; on the other hand, although the internationally recognized upper limit for SMF public exposure is 0.4 T, people should also pay extra attention to SMF strength, direction, and inhomogeneity that could generate harmful effects on specific severe pathological conditions.

Early activation of Toll-like receptor-3 reduces the pathological progression of Alzheimer's disease in APP/PS1 mouse.

BACKGROUND: Toll-like receptor 3 (TLR3) plays an important role in the immune/inflammatory response in the nervous system and is a main pathological feature of Alzheimer's disease (AD). This study investigates the role of early activation of TLR3 in the pathophysiological process of AD. METHODS: In the experiment, the agonist of TLR3, Poly(I:C), was intraperitoneally injected into the APP/PS1 mouse model of AD and wild-type control mice starting from the age of 4 to 9 months. At the age of 14 months, behavioral tests were conducted. Western blot and immunohistochemistry staining were used to evaluate the level of amyloid ß-protein (Aß), the activation of inflammatory cells, and neuron loss. In addition, the levels of inflammatory cytokines were measured using a quantitative polymerase chain reaction. RESULTS: The results demonstrated that the early activation of TLR3 attenuated neuronal loss and neurobehavioral dysfunction. Moreover, the early activation of TLR3 reduced Aß deposition, inhibited the activation of microglia and astrocytes, and decreased the transcription of pro-inflammatory factors in the hippocampus. CONCLUSIONS: The results indicated that the activation of TLR3 by Poly (I:C) in the early stage of development of AD in a mouse model attenuated neuron loss and improved neurobehavioral functions. The underlying mechanisms could be attributed to its role in Aß clearance, the inhibition of glial cells, and the regulation of neuroinflammation in the hippocampus.