CD8 positive T-cells decrease neurogenesis and induce anxiety-like behaviour following hepatitis B vaccination.

Mounting evidence indicates the involvement of peripheral immunity in the regulation of brain function, influencing aspects such as neuronal development, emotion, and cognitive abilities. Previous studies from our laboratory have revealed that neonatal hepatitis B vaccination can downregulate hippocampal neurogenesis, synaptic plasticity and spatial learning memory. In the current post-epidemic era characterized by universal vaccination, understanding the impact of acquired immunity on neuronal function and neuropsychiatric disorders, along with exploring potential underlying mechanisms, becomes imperative. We employed hepatitis B vaccine-induced CD3 positive T cells in immunodeficient mice to investigate the key mechanisms through which T cell subsets modulate hippocampal neurogenesis and anxiety-like behaviours. Our data revealed that mice receiving hepatitis B vaccine-induced T cells exhibited heightened anxiety and decreased hippocampal cell proliferation compared to those receiving phosphate-buffered saline-T cells or wild-type mice. Importantly, these changes were predominantly mediated by infiltrated CD8+ T cells into the brain, rather than CD4+ T cells. Transcriptome profiling of CD8+ T cells unveiled that C-X-C motif chemokine receptor 6 positive (CXCR6+) CD8+ T cells were recruited into the brain through microglial and astrocyte-derived C-X-C motif chemokine ligand 16 (CXCL16). This recruitment process impaired neurogenesis and induced anxiety-like behaviour via tumour necrosis factor-α-dependent mechanisms. Our findings highlight the role of glial cell derived CXCL16 in mediating the recruitment of CXCR6+CD8+ T cell subsets into the brain. This mechanism represents a potential avenue for modulating hippocampal neurogenesis and emotion-related behaviours after hepatitis B vaccination.

Investigate the relationship between pulsed field ablation parameters and ablation outcomes.

BACKGROUND: Pulsed field ablation (PFA) is an emerging non-thermal ablation method. The primary challenge is the control of multiple parameters in PFA, as the interplay of these parameters remains unclear in terms of ensuring effective and safe tissue ablation. PURPOSE: This study employs the response surface method (RSM) to explore the interactions between various PFA parameters and ablation outcomes, and seeks to enhance the efficacy and safety of PFA. METHODS: In vivo experiments were conducted using rabbit liver for varying PFA parameters: pulse amplitude (PA), pulse interval (PI), number of pulse trains (NT), and number of pulses in a pulse train (NP). Ablation outcomes assessed included three ablation sizes, surface temperature, and muscle contraction strength. Additionally, histological analysis was performed on the ablated tissue. We analyzed the relationship between PFA parameters and ablation outcomes, and results were then compared with those from a simulation using an electric-thermal coupling PFA finite element model. RESULTS: A linear relationship between ablation outcomes and PFA parameters was established. PA and NT exhibited extremely significant (P < 0.0001) and significant effects (P < 0.05) on all ablation outcomes, respectively. NP showed an extremely significant impact (P < 0.0001) on surface temperature and muscle contraction strength, while PI significantly influenced (P < 0.05) muscle contraction strength alone. Histological analysis revealed that PFA produces controlled, well-defined areas of liver tissue necrosis. Surface temperature results from simulations and experiments were highly consistent (R2 > 0.97). CONCLUSIONS: This study clarifies the relationship between various PFA parameters and ablation outcomes, and aims to improve the efficacy and safety of PFA.

Experimental Study on Preparation of Inorganic Fibers from Circulating Fluidized Bed Boilers Ash.

The ash generated by Circulating Fluidized Bed (CFB) boilers is featured by its looseness and porosity, low content of glassy substances, and high contents of calcium (Ca) and sulfur (S), thus resulting in a low comprehensive utilization rate. Currently, the predominant treatment approach for CFB ash and slag is stacking, which may give rise to issues like environmental pollution. In this paper, CFB ash (with a CaO content of 7.64% and an SO3 content of 1.77%) was used as the main raw material. The high-temperature melting characteristics, viscosity-temperature characteristics, and initial crystallization temperature of samples with different acidity coefficients were investigated. The final drawing temperature range of the samples was determined, and mechanical property tests were conducted on the prepared inorganic fibers. The results show that the addition of dolomite powder has a significant reducing effect on the complete liquid phase temperature. The final drawing temperatures of the samples with different acidity coefficients range as follows: 1270-1318 °C; 1272-1351 °C; 1250-1372 °C; 1280-1380 °C; 1300-1382 °C; and 1310-1384 °C. The drawing temperature of this system is slightly lower than that of basalt fibers. Based on the test results of the mechanical properties of inorganic fibers, the Young's modulus of the inorganic fibers prepared through the experiment lies between 55 GPa and 74 GPa, which basically meets the performance requirements of inorganic fibers. Consequently, the method of preparing inorganic fibers by using CFB ash and dolomite powder is entirely feasible.

Influenza Vaccination Mediates SARS-CoV-2 Spike Protein Peptide-Induced Inflammatory Response via Modification of Histone Acetylation.

The effectiveness of coronavirus disease 2019 (COVID-19) vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain rapidly wanes over time. Growing evidence from epidemiological studies suggests that influenza vaccination is associated with a reduction in the risk of SARS-CoV-2 infection and COVID-19 severity. However, the underlying mechanisms remain elusive. Here, we investigate the cross-reactive immune responses of influenza vaccination to SARS-CoV-2 spike protein peptides based on in vitro study. Our data indicate enhanced activation-induced-marker (AIM) expression on CD4+ T cells in influenza-vaccination (IV)-treated peripheral blood mononuclear cells (PBMCs) upon stimulation with spike-protein-peptide pools. The fractions of other immune cell subtypes, including CD8+ T cells, monocytes, NK cells, and antigen-presenting cells, were not changed between IV-treated and control PBMCs following ex vivo spike-protein-peptide stimulation. However, the classical antiviral (IFN-γ) and anti-inflammatory (IL-1RA) cytokine responses to spike-protein-peptide stimulation were still enhanced in PBMCs from both IV-immunized adult and aged mice. Decreased expression of proinflammatory IL-1ß, IL-12p40, and TNF-α is associated with inhibited levels of histone acetylation in PBMCs from IV-treated mice. Remarkably, prior immunity to SARS-CoV-2 does not result in modification of histone acetylation or hemagglutinin-protein-induced cytokine responses. This response is antibody-independent but can be mediated by manipulating the histone acetylation of PBMCs. These data experimentally support that influenza vaccination could induce modification of histone acetylation in immune cells and reveal the existence of potential cross-reactive immunity to SARS-CoV-2 antigens, which may provide insights for the adjuvant of influenza vaccine to limit COVID-19-related inflammatory responses.

Effect of granulated biochar sphere on mineral nutrients in removing potentially toxic elements from contaminated agricultural soils.

Biochar (BC) granulation, yielding BC-based spheres, serves as an eco-friendly, cost-effective and efficient adsorbent for the removal of potential toxic elements (PTEs) from contaminated agricultural soils. The effect of BC-based spheres on mineral nutrients while effectively removing PTEs from contaminated soils is worth investigating. In this study, we utilized natural clay minerals, magnetic minerals and BC to produce water-hardened magnetic composite biochar sphere (WMBCS) that was capable of removing PTEs from composite contaminated agricultural soils. We explored the effect of WMBCS on minerals (Al, Ca, Fe, Mn, Na, Mg, Si, K, P, NH4+, and NO3-) in the removal of soil PTEs. WMBCS was a mineral nutrient-rich, recyclable, alkaline BC-based sphere that removes Cd (23.07-29.20 %), Pb (27.68-31.10 %), and As (26.17-37.48 %) from soils after three regeneration cycles. The effect of WMBCS on mineral nutrients varies depending on element type, BC and soil type. Compared to water-hardened magnetic composite phosphate modified biochar spheres (WMPBCS), water-hardened magnetic composite unmodified biochar spheres (WMUBCS) had more significant effect on Ca, Mg, Mn, Al and NH4+ in alkaline soils, but a greater effect on Ca, Mg, Mn, Fe and NO3- in acidic soils. Additionally, WMBCS displayed a more pronounced impact on mineral nutrients in alkaline soils than in acidic soils. The application of WMBCS reduced the accumulation of PTEs in wheat (18.40-84.70 %) and rice (27.96-88.66 %), but significantly inhibited seed germination and altered the uptake of mineral nutrients by seedlings due to its effects on soil physicochemical properties and mineral nutrient dynamics. Overall, WMBCS is suitable as a potential amendment for the remediation of soils co-contaminated with Cd, As, and Pb, but its effects on mineral nutrients cannot be overlooked, particularly in agricultural soils.

Lanternarene-Based Self-Sorting Double-Network Hydrogels for Flexible Strain Sensors.

Conductive flexible hydrogels have attracted immense attentions recently due to their wide applications in wearable sensors. However, the poor mechanical properties of most conductive polymer limit their utilizations. Herein, a double network hydrogel is fabricated via a self-sorting process with cationic polyacrylamide as the first flexible network and the lantern[33]arene-based hydrogen organic framework nanofibers as the second rigid network. This hydrogel is endowed with good conductivity (0.25 S m-1) and mechanical properties, such as large Young's modulus (31.9 MPa), fracture elongation (487%) and toughness (6.97 MJ m-3). The stretchability of this hydrogel is greatly improved after the kirigami cutting, which makes it can be used as flexible strain sensor for monitoring human motions, such as bending of fingers, wrist and elbows. This study not only provides a valuable strategy for the construction of double network hydrogels by lanternarene, but also expands the application of the macrocycle hydrogels to flexible electronics.

Comparing ECIRS with MPCNL for Complex Renal Calculi: A Retrospective Single-Centre Study on Efficacy and Safety.

BACKGROUND: Kidney stones, a common urinary system ailment, often necessitate surgical intervention. Endoscopic combined intrarenal surgery (ECIRS) and multi-channel percutaneous nephron lithotripsy (MPCNL) are key modalities for treating complex renal stones, prompting the need for a comparative analysis to enhance clinical decision-making. METHODS: Patients undergoing surgical treatment for complex kidney stones from April 2018 to April 2022 were divided into the control (MPCNL) and observation (ECIRS) groups. Propensity score matching was used to balance baseline data, and t-tests and chi-square tests were employed to compare the perioperative indicators between the two groups. RESULTS: A total of 210 patients were enrolled in this study for pre-observational comparison, and they were divided into the control group (110 patients) and observation group (100 patients). Following matching, each group comprised 85 patients. Pre-observational comparison revealed significant differences between the groups in age, disease duration, and stone diameter (p < 0.05). However, after matching, baseline data comparison showed no statistically significant differences (p > 0.05). Surgery-related parameters, including operation time, intraoperative blood loss, postoperative activity duration and hospital stay, did not significantly differ between the groups (p > 0.05). The observation group exhibited a significantly higher stone retention-free rate after initial treatment compared with the control group (p < 0.05), although overall stone clearance rates did not significantly differ between the groups (p > 0.05). We found no significant differences in perioperative complications between the two groups (p > 0.05). Moreover, the observation group experienced significantly lower postoperative pain levels at 6, 24 and 48 h compared with the control group (p < 0.001). CONCLUSIONS: Conclusively, ECIRS and MPCNL are viable options for treating complex renal calculi, with similar operation times, complication rates and stone clearance rates. ECIRS may offer advantages including lower postoperative pain and higher initial stone clearance rates than MPCNL. However, large-scale studies with long follow-up times are needed for validation.

A novel contact force sensing pulsed field ablation catheter in a porcine model.

BACKGROUND: Pulsed field ablation (PFA) has emerged as a novel non-thermal modality with highly myocardium-specific. However, the PFA catheter based on contact force (CF)-sensing has not been reported. The study aimed to evaluate the efficacy and safety of a novel CF-sensing PFA catheter. METHODS: First, different CF (5, 15, 25, and 35 g) of the novel PFA catheter were evaluated on lesion dimensions during ablation on right and left ventricle in two pigs. Next, this catheter was further evaluated on four typical sites of superior vena cava (SVC), cavotricuspid isthmus (CTI), right superior pulmonary vein (RSPV), and right inferior pulmonary vein (RIPV) for atrial ablation in another six pigs. Electrical isolation was evaluated immediately after ablation and 30-day survival. Chronic lesions were assessed via histopathology after euthanasia. Acute and chronic safety outcomes were observed peri- and post-procedurally. RESULTS: In ventricular ablation, increased CF from 5 to 15 g produced significantly greater lesion depth but nonsignificant increases from 15 to 35 g. In atrial ablation, the novel CF-sensing PFA deliveries produced an acute attenuation of local electrograms and formation of a continuous line of block in all 6 pigs. The ablation line remained sustained blockage at the 30-day survival period. The CF of SVC, CTI, RSPV, and RIPV was 9.4 ± 1.5, 14.5 ± 3.2, 17.2 ± 2.6, and 13.4 ± 2.8 g, respectively. Moreover, no evidence of damage to esophagus or phrenic nerve was observed. CONCLUSION: The novel CF-sensing PFA catheter potentiated efficient, safe, and durable ablation, without causing damage to the esophagus or phrenic nerve.

Biochar application for the remediation of soil contaminated with potentially toxic elements: Current situation and challenges.

Recently, biochar has garnered extensive attention in the remediation of soils contaminated with potentially toxic elements (PTEs) owing to its exceptional adsorption properties and straightforward operation. Most researchers have primarily concentrated on the effects, mechanisms, impact factors, and risks of biochar in remediation of PTEs. However, concerns about the long-term safety and impact of biochar have restricted its application. This review aims to establish a basis for the large-scale popularization of biochar for remediating PTEs-contaminated soil based on a review of interactive mechanisms between soil, PTEs and biochar, as well as the current situation of biochar for remediation in PTEs scenarios. Biochar can directly interact with PTEs or indirectly with soil components, influencing the bioavailability, mobility, and toxicity of PTEs. The efficacy of biochar in remediation varies depending on biomass feedstock, pyrolysis temperature, type of PTEs, and application rate. Compared to pristine biochar, modified biochar offers feasible solutions for tailoring specialized biochar suited to specific PTEs-contaminated soil. Main challenges limiting the applications of biochar are overdose and potential risks. The used biochar is separated from the soil that not only actually removes PTEs, but also mitigates the negative long-term effects of biochar. A sustainable remediation technology is advocated that enables the recovery and regeneration (95.0-95.6%) of biochar from the soil and the removal of PTEs (the removal rate of Cd is more than 20%) from the soil. Finally, future research directions are suggested to augment the environmental safety of biochar and promote its wider application.

New Straw Coating Material for Improving the Slow-Release Performance of Fertilizers.

In this work, we extracted cellulose from agricultural waste and produced a new straw coating material (ethyl cellulose, EC) through a series of modification operations. The slow-release properties of ethyl cellulose-coated urea (EU) and its absorption and utilization by plants were evaluated. The surface of EU can form a smooth and fine film, and the initial nutrient release rate is only 37.91% that of the uncoated fertilizer. Compared with common urea, the nitrogen of plants cultivated with EU increased by 17.69%, and the leached nitrogen decreased by 61.29%, indicating that EU can reduce nitrogen waste to the greatest extent and continuously supply nutrients to crops. Therefore, the application of EU could be a more practical, environmentally friendly, and sustainable alternative to nitrogen fertilizers.

A novel polarity configuration for enhancing ablation depth of pulsed field ablation: Design, modeling, and in vivo validation.

BACKGROUND: Pulsed field ablation (PFA) has been increasingly used to cut off the delivery of abnormal electrical signals in the treatment of cardiac arrhythmias. A successful cut off requires forming a layer of transmural damage on the heart wall, and this layer depends on the depth of ablation by PFA. PURPOSE: This study aims to propose a novel polarity configuration of PFA to increase the ablation depth in the treatment of cardiac arrhythmias. METHOD: A novel polarity configuration was designed for a multi-electrode system, where the number of electrodes is greater than two. The polarity configuration in such multi-electrode system is called the paired-electrode interlaced configuration (PIC). The existing configuration called the single-electrode interlaced configuration (SIC) was used to compare with the PIC. To both the SIC and PIC, a full-SIC or a full-PIC is called when all electrodes (anode, cathode) in a catheter is used otherwise partial-SIC or partial-PIC is called. By the comparison between the full-SIC and full-PIC, the benefit of the PIC was exhibited as opposed to the SIC, but an extra ablation step was added in the PIC in order to form a continuous ablation zone. The other comparative study was taken between a partial-PIC and a partial-SIC with the same number of ablation step. In this study, a rabbit model was built by infusing 0.4% saline solution (at 37°C) into the rabbit's abdominal cavity which surrounds the liver. This model was considered as a biometric environment of the heart, namely cardiac-mimetic model (CMM). RESULT: The experimental results have shown that the full-PIC is superior to the full-SIC in the ablation depth, specifically in both the maximum (4.14 ± 0.55 mm vs. 3.35 ± 0.26 mm, p < 0.01) and the minimum (3.18 ± 0.29 mm vs. 2.76 ± 0.28 mm, p < 0.05), and in the ablation width, specifically only in the maximum (8.27 ± 0.76 mm vs. 7.09 ± 0.51 mm, p = 0.019) under an identical ablation time (i.e., 5 s). It is noted that the minimum ablation width did not show a significant difference between the full-PIC and full-SIC (specifically, 5.61 ± 0.86 mm vs. 4.67 ± 0.73 mm, p = 0.069). Considering the lethal electric field threshold (LEFT) to be 600 V/cm for liver tissues, the maximum and minimum ablation depth generated by the full-PIC was found larger than that by the full-SIC (3.90 vs. 3.52 mm, and 3.03 vs. 2.48 mm, respectively) in the simulation. Meanwhile, similar experiment results by comparing the partial-PIC and partial-SIC have been obtained, which shows a significant increase in both the maximum ablation depth (4.81 ± 0.87 mm vs. 3.30 ± 0.73 mm, p < 0.001) and the maximum ablation width (8.19 ± 0.85 mm vs. 6.47 ± 1.13 mm, p = 0.001). CONCLUSIONS: (1) The electric field in the PIC is concentrated around the pair of electrodes, and the pattern of the field is a significant factor in the energy delivery along the direction of the depth. (2) The increase of the ablation depth can significantly expand the range of the tissue on the heart, where the PFA can apply, and can therefore readily form a layer of transmural damage on the heart wall at positions at which the wall is thicker.

Dissolvable Calcium Alginate Microfibers Produced via Immersed Microfluidic Spinning.

Fabrication of micro- and nanofibers are critical for a wide range of applications from microelectronics to biotechnology. Alginate microfibers with diameters of tens to hundreds of microns play an important role in tissue engineering and fibers of these diameters are impossible to fabricate via electrospinning and can only be produced via fluidic spinning. Typically, microfluidic spinning based on photopolymerization produces fibers that are not easily dissolvable, while fluidic spinning with chemical cross-linking employs complex setups of microfabricated chips or coaxial needles, aimed at precise control of the fiber diameter; however, fluidic spinning introduces significant cost and complexity to the microfluidic setup. We demonstrate immersed microfluidic spinning where a calcium alginate microfiber is produced via displacement of alginate solution through a single needle that is immersed in a cross-linking bath of calcium chloride solution. The resulting diameter of the fiber is characterized and the fiber diameter and topology of the deposited fiber is related to the concentration of the alginate solution (2 wt%, 4 wt%, and 6 wt%), needle gauge (30 g, 25 g, and 20 g), and the volumetric flow rate of the alginate solution (1 mL/min, 2 mL/min, and 2.7 mL/min). The resulting fiber diameter is smaller than the internal diameter of the needle and this dependence is explained by the continuity of the flow and increased rate of fall of the liquid jet upon its issuing from the needle. The fiber diameter (demonstrated diameter of fibers range from 100 microns to 1 mm) depends weakly on the volumetric flow rate and depends strongly on the needle diameter. It also seems that for a smaller needle size, a greater concentration of alginate results in smaller diameter fibers and that this trend is not evident as the needle diameter is increased. In terms of topology of the deposited fiber, the higher wt% alginate fiber produces larger loops, while smaller wt% alginate solution yields a denser topology of the overlaid fiber loops. These fibers can be dissolved in DMEM/EDTA/DSC solution in 20-30 min (depending on the fiber diameter), leaving behind the hollow channels in the hydrogel matrix. We believe that the demonstrated simple setup of the immersed microfluidic spinning of the calcium alginate microfibers will be useful for creating tissue constructs, including the vascularized tissue implants.

Issues in deep peak regulation for circulating fluidized bed combustion: Variation of NOx emissions with boiler load.

In order to improve the consumption of renewable energies, certain amounts of circulating fluidized bed (CFB) boiler units should assume the task of deep peak regulation. However, the effect of CFB boiler load on pollutant emissions such as NOx still needs to be clarified. In this paper, the NOx emission characteristics of two industrial-scale CFB boilers within a wide load range (35%-100%) were further analyzed by using a comprehensive one-dimensional, two-phase CFB mathematical model. Simulation results reveal that, when the load ratio decreases, the NOx emission decreases first and then increases. The non-monotonic variation trend is also confirmed by the operational data collected from the SC-350 boiler. However, for different boilers, the load ratio corresponding to the turning point of NOx emission may be different, e.g., for the 135 MWe super high steam pressure boiler, it is about 40%, while for the 350 MWe supercritical boiler is 50%. On the one hand, the decrease in boiler load leads to a decline in the furnace temperature, which contributes to reducing NOx emission due to the decrease of volatile yields, the lower conversion rate of Vol-N to NOx, and the enhancement of the overall NO reduction on chars. On the other hand, at low loads, the excess air coefficient is generally set to high values, and air staging is weakened, resulting in adverse effects on the NOx emission control. In addition, when the CFB boiler operates at low loads, the solid circulation loop performance usually worsens, and the heat loss caused by incomplete combustion may increase. This study points out that high NOx emission is an unavoidable issue in the process of deep peak regulation for CFB boilers.

Artificial Intelligence Algorithms Enable Automated Characterization of the Positive and Negative Dielectrophoretic Ranges of Applied Frequency.

The present work describes the phenomenological approach to automatically determine the frequency range for positive and negative dielectrophoresis (DEP)-an electrokinetic force that can be used for massively parallel micro- and nano-assembly. An experimental setup consists of the microfabricated chip with gold microelectrode array connected to a function generator capable of digitally controlling an AC signal of 1 V (peak-to-peak) and of various frequencies in the range between 10 kHz and 1 MHz. The suspension of latex microbeads (3-µm diameter) is either attracted or repelled from the microelectrodes under the influence of DEP force as a function of the applied frequency. The video of the bead movement is captured via a digital camera attached to the microscope. The OpenCV software package is used to digitally analyze the images and identify the beads. Positions of the identified beads are compared for successive frames via Artificial Intelligence (AI) algorithm that determines the cloud behavior of the microbeads and algorithmically determines if the beads experience attraction or repulsion from the electrodes. Based on the determined behavior of the beads, algorithm will either increase or decrease the applied frequency and implement the digital command of the function generator that is controlled by the computer. Thus, the operation of the study platform is fully automated. The AI-guided platform has determined that positive DEP (pDEP) is active below 500 kHz frequency, negative DEP (nDEP) is evidenced above 1 MHz frequency and the crossover frequency is between 500 kHz and 1 MHz. These results are in line with previously published experimentally determined frequency-dependent DEP behavior of the latex microbeads. The phenomenological approach assisted by live AI-guided feedback loop described in the present study will assist the active manipulation of the system towards the desired phenomenological outcome such as, for example, collection of the particles at the electrodes, even if, due to the complexity and plurality of the interactive forces, model-based predictions are not available.

IUGR with catch-up growth programs impaired insulin sensitivity through LRP6/IRS-1 in male rats.

Intrauterine growth restriction combined with postnatal accelerated growth (CG-IUGR) could lead to long-term detrimental metabolic outcomes characterized by insulin resistance. As an indispensable co-receptor of Wnt signaling, LRP6 plays a critical role in the susceptibility of metabolic disorders. However, whether LRP6 is involved in the metabolic programing is still unknown. We hypothesized that CG-IUGR programed impaired insulin sensitivity through the impaired LRP6-mediated Wnt signaling in skeletal muscle. A CG-IUGR rat model was employed. The transcriptional and translational alterations of the components of the Wnt and the insulin signaling in the skeletal muscle of the male CG-IUGR rats were determined. The role of LRP6 on the insulin signaling was evaluated by shRNA knockdown or Wnt3a stimulation of LRP6. Compared with controls, the male CG-IUGR rats showed an insulin-resistant phenotype, with impaired insulin signaling and decreased expression of LRP6/ß-catenin in skeletal muscle. LRP6 knockdown led to reduced expression of the IR-ß/IRS-1 in C2C12 cell line, while Wnt3a-mediated LRP6 expression increased the expression of IRS-1 and IGF-1R but not IR-ß in the primary muscle cells of male CG-IUGR rats. The impaired LRP6/ß-catenin/IGF-1R/IRS-1 signaling is probably one of the critical mechanisms underlying the programed impaired insulin sensitivity in male CG-IUGR.

Attenuated Salmonella carrying plasmid co-expressing HPV16 L1 and siRNA-E6 for cervical cancer therapy.

Human papillomavirus (HPV) infection is the major etiological factor for cervical cancer. HPV prophylactic vaccines based on L1 virus-like particles have been considered as an effective prevention method. However, existing recombination vaccines are too expensive for developing countries. DNA vaccines might be a lower-cost and effective alternative. In this study, a plasmid (pcDNA3.1-HPV16-L1) and a co-expressing plasmid (pcDNA3.1-HPV16-L1-siE6) carried by attenuated Salmonella were constructed and their prevention and treatment effect on cervical cancer were observed, respectively. The results showed that pcDNA3.1-HPV16-L1 carried by attenuated Salmonella could induce the production of HPV16-L1 antibodies, IL-2 and INF-γ in mice serum, which presented its prevention effect on HPV. Subsequently, E6 and E7 gene silencing by pCG-siE6 inhibited the growth of cervical cancer both in vitro and in vivo. Furthermore, L1 up-regulation and E6/E7 down-regulation caused by co-expressing plasmid (pcDNA3.1-HPV16-L1-siE6) contributed to a significant anti-tumor effect on the mice. This study suggests that pcDNA3.1-HPV16-L1-siE6 carried by attenuated Salmonella has a synergistic effect of immune regulation and RNA interference in cervical cancer treatment.

[Progress in PiggyBac transposition system research and its application in the gene modified T cell in tumor immunotherapy].

The tumor immunotherapy with gene modified T cells has made inspiring progress in recent years. Foreign gene transduction is the key link before the adoptive transfer of T cells. Advances in this field enhance T cells vitality and achieve precise targeted killing of tumor cells. T cell gene modification technology needs to strike a balance between transduction efficiency, safety, and cost. Transposons are with low immunogenicity, easy to manufacture, and cost-effective. They integrate the gene of interest into the target cell genome and allow stable and durable expression. Active transposons in mammalian cells include PiggyBac (PB), Sleeping Beauty (SB) and Tol2. Among them, the PB transposition system enables seamless genome editing with large gene load, high transposition activity, and strong structural plasticity. This article summarizes the structure, mechanism, characteristics, and transduction efficiency of PB transposition system, as well as its application and prospect in chimeric antigen receptor-engineered T cell therapy.

Cognitive Behavioral Therapy for Autism Spectrum Disorders: A Systematic Review.

CONTEXT: In several studies, authors have reported on cognitive behavioral therapy (CBT) for children and adolescents with autism spectrum disorders (ASDs), but inconsistent treatment effectiveness was revealed from these studies. OBJECTIVE: To evaluate the effectiveness of CBT on the symptoms of ASD and social-emotional problems in children or adolescents with ASD by using a meta-analytic approach. DATA SOURCES: Data sources included PubMed, Embase, and the Cochrane Library. STUDY SELECTION: We selected randomized controlled trials (RCTs) in which authors reported effectiveness of CBT on the symptoms of ASD and social-emotional problems in children or adolescents with ASD from database inception to May 2019. DATA EXTRACTION: For each study, 2 authors extracted data on the first author's surname, publication year, country, sample size, mean age, CBT target, intervention, outcome measurement, follow-up duration, and investigated outcomes. RESULTS: Forty-five RCTs and 6 quasi RCTs of 2485 children and adolescents with ASDs were selected for the final meta-analysis. There was no significant difference between CBT and control for symptoms related to ASD based on self-reported outcomes (standard mean difference: -0.09; 95% confidence interval: -0.42 to 0.24; P = .593), whereas CBT significantly improved the symptoms related to ASD based on informant-reported outcomes, clinician-rated outcomes, and task-based outcomes. Moreover, the pooled standard mean differences indicated that CBT has no significant effect on symptoms of social-emotional problems based on self-reported outcomes. LIMITATIONS: The quality of included studies was low to modest, significant heterogeneity among the included studies for all investigated outcomes was detected, and publication bias was inevitable. CONCLUSIONS: These findings indicate that CBT may significantly improve the symptoms of ASD and social-emotional problems in children or adolescents with ASD.

Guided Healing of Damaged Microelectrodes via Electrokinetic Assembly of Conductive Carbon Nanotube Bridges.

The subject of healing and repair of damaged microelectrodes has become of particular interest as the use of integrated circuits, energy storage technologies, and sensors within modern devices has increased. As the dimensions of the electrodes shrink together with miniaturization of all the elements in modern electronic devices, there is a greater risk of mechanical-, thermal-, or chemical-induced fracture of the electrodes. In this research, a novel method of electrode healing using electrokinetically assembled carbon nanotube (CNT) bridges is presented. Utilizing the previously described step-wise CNT deposition process, conductive bridges were assembled across ever-larger electrode gaps, with the width of electrode gaps ranging from 20 microns to well over 170 microns. This work represents a significant milestone since the longest electrically conductive CNT bridge previously reported had a length of 75 microns. To secure the created conductive CNT bridges, they are fixed with a layer of electrodeposited polypyrrole (a conductive polymer). The resistance of the resulting CNT bridges, and its dependence on the size of the electrode gap, is evaluated and explained. Connecting electrodes via conductive CNT bridges can find many applications from nanoelectronics to neuroscience and tissue engineering.

Guided Electrokinetic Assembly of Polystyrene Microbeads onto Photopatterned Carbon Electrode Arrays.

Assembly of microdevices from constituent parts currently relies on slow serial steps via direct assembly processes such as pick-and-place operations. Template Electrokinetic Assembly (TEA), a guided, noncontact assembly process, is presented in this work as a promising alternative to serial assembly processes. To characterize the process and its implementation of electrokinetic, dielectrophoretic, and electro-osmotic phenomena, we conducted studies to examine the assembly of polymer microparticles at specific locations on glassy carbon interdigitated electrode arrays (IDEAs). The IDEAs are coated with a layer of lithographically patterned resist, so that when an AC electric field is applied to the IDEA, microparticles suspended in the aqueous solution are attracted to the open regions of the electrodes not covered by photoresist. Interplay between AC electro-osmosis and dielectrophoretic forces guides 1 and 5 µm diameter polystyrene beads to assemble in regions, or "wells", uncovered by photoresist atop the electrodes. It was discovered that AC electro-osmosis under an applied frequency of 1 kHz is sufficient to effectively agglomerate 1 µm beads in the wells, whereas a stepwise process involving the application of a 1 MHz signal, followed by a 1 kHz signal, is required for the positioning of 5 µm beads, which are mainly affected by dielectrophoretic forces. Permanent entrapment of the microparticles is then demonstrated via the electropolymerization process of the conducting polymer polypyrrole.