Nonvolatile Multistate Manipulation of Topological Magnetism in Monolayer CrI3 through Quadruple-Well Ferroelectric Materials.

Nonvolatile multistate manipulation of two-dimensional (2D) magnetic materials holds promise for low dissipation, highly integrated, and versatile spintronic devices. Here, utilizing density functional theory calculations and Monte Carlo simulations, we report the realization of nonvolatile and multistate control of topological magnetism in monolayer CrI3 by constructing multiferroic heterojunctions with quadruple-well ferroelectric (FE) materials. The Pt2Sn2Te6/CrI3 heterojunction exhibits multiple magnetic phases upon modulating FE polarization states of FE layers and interlayer sliding. These magnetic phases include Bloch-type skyrmions and ferromagnetism, as well as a newly discovered topological magnetic structure. We reveal that the Dzyaloshinskii-Moriya interaction (DMI) induced by interfacial coupling plays a crucial role in magnetic skyrmion manipulation, which aligns with the Fert-Levy mechanism. Moreover, a regular magnetic skyrmion lattice survives when removing a magnetic field, demonstrating its robustness. The work sheds light on an effective approach to nonvolatile and multistate control of 2D magnetic materials.

Self-Assembly of Ultrathin, Ultrastrong Layered Membranes by Protic Solvent Penetration.

Flexible membranes with ultrathin thickness and excellent mechanical properties have shown great potential for broad uses in solid polymer electrolytes (SPEs), on-skin electronics, etc. However, an ultrathin membrane (<5 µm) is rarely reported in the above applications due to the inherent trade-off between thickness and antifailure ability. We discover a protic solvent penetration strategy to prepare ultrathin, ultrastrong layered films through a continuous interweaving of aramid nanofibers (ANFs) with the assistance of simultaneous protonation and penetration of a protic solvent. The thickness of a pure ANF film can be controlled below 5 µm, with a tensile strength of 556.6 MPa, allowing us to produce the thinnest SPE (3.4 µm). The resultant SPEs enable Li-S batteries to cycle over a thousand times at a high rate of 1C due to the small ionic impedance conferred by the ultrathin characteristic and regulated ionic transportation. Besides, a high loading of the sulfur cathode (4 mg cm-2) with good sulfur utilization was achieved at a mild temperature (35 °C), which is difficult to realize in previously reported solid-state Li-S batteries. Through a simple laminating process at the wet state, the thicker film (tens of micrometers) obtained exhibits mechanical properties comparable to those of thin films and possesses the capability to withstand high-velocity projectile impacts, indicating that our technique features a high degree of thickness controllability. We believe that it can serve as a valuable tool to assemble nanomaterials into ultrathin, ultrastrong membranes for various applications.

Millimeter-wave over fiber integrated sensing and communication system using self-coherent OFDM.

Orthogonal frequency-division multiplexing (OFDM) waveform is highly preferred as a dual-function candidate for integrated sensing and communication (ISAC) systems. However, the sensitivity to both carrier frequency offset (CFO) and phase noise greatly impedes its applications in millimeter-wave ISAC systems. Here, we propose and experimentally demonstrate a photonic millimeter-wave ISAC system employing the virtual-carrier-aided self-coherent OFDM technique, wherein a digitally-generated local oscillator is transmitted along with the OFDM signal. Then, a compact CFO-immune and phase noise-immune envelope detection method is implemented for down-converting millimeter-wave communication and radar echo signals. In experiments, a V-band ISAC system is successfully implemented with a simplified remote radio unit, using the remote photonic millimeter-wave heterodyning up-conversion for downlink and the envelope detection-assisted down-conversion for uplink (or radar echoes). In the converged transmission link with a 5-km fiber link and 2-m space link, the Kramers-Kronig (KK) receiver supports a communication data rate up to 16-Gbit/s by mitigating signal-signal beat interference (SSBI). More significantly, the SSBI leads to negligible effects on the sensing performance when classic matched filtering is adopted for target identification. Consequently, a 4.8-cm range resolution and a 4-mm range accuracy are obtained for the radar sensing function.

Alternative models to support weight loss in chronic musculoskeletal conditions: effectiveness of a physiotherapist-delivered intensive diet programme for knee osteoarthritis, the POWER randomised controlled trial.

OBJECTIVES: To determine if physiotherapists can deliver a clinically effective very low energy diet (VLED) supplementary to exercise in people with knee osteoarthritis (OA) and overweight or obesity. METHODS: 88 participants with knee OA and body mass index (BMI) >27 kg/m2 were randomised to either intervention (n=42: VLED including two daily meal replacement products supplementary to control) or control (n=46: exercise). Both interventions were delivered by unblinded physiotherapists via six videoconference sessions over 6 months. The primary outcome was the percentage change in body weight at 6 months, measured by a blinded assessor. Secondary outcomes included BMI, waist circumference, waist-to-hip ratio, self-reported measures of pain, function, satisfaction and perceived global change, and physical performance tests. RESULTS: The intervention group lost a mean (SD) of 8.1% (5.2) body weight compared with 1.0% (3.2) in the control group (mean (95% CI) between-group difference 7.2% (95% CI 5.1 to 9.3), p<0.001), with significantly lower BMI and waist circumference compared with control group at follow-up. 76% of participants in the intervention group achieved ≥5% body weight loss and 37% acheived ≥10%, compared with 12% and 0%, respectively, in the control group. More participants in the intervention group (27/38 (71.1%)) reported global knee improvement than in the control group (20/42 (47.6%)) (p=0.02). There were no between-group differences in any other secondary outcomes. No serious adverse events were reported. CONCLUSION: A VLED delivered by physiotherapists achieved clinically relevant weight loss and was safe for people with knee OA who were overweight or obese. The results have potential implications for future service models of care for OA and obesity. TRIAL REGISTRATION NUMBER: NIH, US National Library of Medicine, Clinicaltrials.gov NCT04733053 (1 February 2021).

The JMJD3 histone demethylase inhibitor GSK-J1 ameliorates lipopolysaccharide-induced inflammation in a mastitis model.

Jumonji domain-containing 3 (JMJD3/KDM6B) is a histone demethylase that plays an important role in regulating development, differentiation, immunity, and tumorigenesis. However, the mechanisms responsible for the epigenetic regulation of inflammation during mastitis remain incompletely understood. Here, we aimed to investigate the role of JMJD3 in the lipopolysaccharide (LPS)-induced mastitis model. GSK-J1, a small molecule inhibitor of JMJD3, was applied to treat LPS-induced mastitis in mice and in mouse mammary epithelial cells in vivo and in vitro. Breast tissues were then collected for histopathology and protein/gene expression examination, and mouse mammary epithelial cells were used to investigate the mechanism of regulation of the inflammatory response. We found that the JMJD3 gene and protein expression were upregulated in injured mammary glands during mastitis. Unexpectedly, we also found JMJD3 inhibition by GSK-J1 significantly alleviated the severity of inflammation in LPS-induced mastitis. These results are in agreement with the finding that GSK-J1 treatment led to the recruitment of histone 3 lysine 27 trimethylation (H3K27me3), an inhibitory chromatin mark, in vitro. Furthermore, mechanistic investigation suggested that GSK-J1 treatment directly interfered with the transcription of inflammatory-related genes by H3K27me3 modification of their promoters. Meanwhile, we also demonstrated that JMJD3 depletion or inhibition by GSK-J1 decreased the expression of toll-like receptor 4 and negated downstream NF-κB proinflammatory signaling and subsequently reduced LPS-stimulated upregulation of Tnfa, Il1b, and Il6. Together, we propose that targeting JMJD3 has therapeutic potential for the treatment of inflammatory diseases.

Role of Adrenomedullin 2/Intermedin in the Pathogenesis of Neovascular Age-Related Macular Degeneration.

Adrenomedullin 2 (AM2; also known as intermedin) is a member of the adrenomedullin (AM) peptide family. Similarly to AM, AM2 partakes in a variety of physiological activities. AM2 has been reported to exert protective effects on various organ disorders; however, its significance in the eye is unknown. We investigated the role of AM2 in ocular diseases. The receptor system of AM2 was expressed more abundantly in the choroid than in the retina. In an oxygen-induced retinopathy model, physiological and pathologic retinal angiogenesis did not differ between AM2-knockout (AM2-/-) and wild-type mice. In contrast, in laser-induced choroidal neovascularization, a model of neovascular age-related macular degeneration, AM2-/- mice had enlarged and leakier choroidal neovascularization lesions, with exacerbated subretinal fibrosis and macrophage infiltration. Contrary to this, exogenous administration of AM2 ameliorated the laser-induced choroidal neovascularization-associated pathology and suppressed gene expression associated with inflammation, fibrosis, and oxidative stress, including that of VEGF-A, VEGFR-2, CD68, CTGF, and p22-phox. The stimulation of human adult retinal pigment epithelial (ARPE) cell line 19 cells with TGF-ß2 and TNF-α induced epithelial-to-mesenchymal transition (EMT), whereas AM2 expression was also elevated. The induction of EMT was suppressed when the ARPE-19 cells were pretreated with AM2. A transcriptome analysis identified 15 genes, including mesenchyme homeobox 2 (Meox2), whose expression was significantly altered in the AM2-treated group compared with that in the control group. The expression of Meox2, a transcription factor that inhibits inflammation and fibrosis, was enhanced by AM2 treatment and attenuated by endogenous AM2 knockout in the early phase after laser irradiation. The AM2 treatment of endothelial cells inhibited endothelial to mesenchymal transition and NF-κB activation; however, this effect tended to be canceled following Meox2 gene knockdown. These results indicate that AM2 suppresses the neovascular age-related macular degeneration-related pathologies partially via the upregulation of Meox2. Thus, AM2 may be a promising therapeutic target for ocular vascular diseases.

Photonic super-resolution millimeter-wave joint radar-communication system using self-coherent detection.

A millimeter-wave (MMW) joint radar-communication (JRC) system with super-resolution is proposed and experimentally demonstrated, using optical heterodyne upconversion and self-coherent detection downconversion techniques. The point lies in the designed coherent dual-band constant envelope linear frequency modulation-orthogonal frequency division multiplexing (LFM-OFDM) signal with opposite phase modulation indexes for the JRC system. Then the self-coherent detection, as a simple and low-cost means, is accordingly facilitated for both de-chirping of MMW radar and frequency downconversion reception of MMW communication, which circumvents costly high-speed mixers along with MMW local oscillators and, more significantly, achieves the real-time decomposition of radar and communication information. Furthermore, a super-resolution radar range profile is realized through the coherent fusion processing of dual-band JRC signals. In experiments, a dual-band LFM-OFDM JRC signal centered at 54 GHz and 61 GHz is generated. The two bands feature an identical instantaneous bandwidth of 2 GHz and carry an OFDM signal of 1 Gbaud, which helps to achieve a 6-Gbit/s data rate for communication and a 1.76-cm range resolution for radar.

Investigations into ferroptosis in methylmercury-induced acute kidney injury in mice.

Methylmercury (MeHg) is a highly poisonous form of mercury and a risk factor for kidney impairment in humans that currently has no effective means of therapy. Ferroptosis is a non-apoptotic metabolic cell death linked to numerous diseases. It is currently unknown whether ferroptosis takes part in MeHg-induced kidney damage. Here, we established a model of acute kidney injury (AKI) in mice by gavage with different doses of MeHg (0, 40, 80, 160 µmol/kg). Serological analysis revealed elevated levels of UA, UREA, and CREA; H&E staining showed variable degrees of renal tubule injury; qRT-PCR detection displayed increased expression of KIM-1 and NGAL in the groups with MeHg treatment, indicated that MeHg successfully induced AKI. Furthermore, MDA levels enhanced in renal tissues of mice with MeHg exposure whereas GSH levels decreased; ACSL4 and PTGS2 nucleic acid levels elevated while SLC7A11 levels reduced; transmission electron microscopy illustrated that the density of the mitochondrial membrane thickened and the ridge reduced considerably; protein levels for 4HNE and TfR1 improved since GPX4 levels declined, all these results implying the involvement of ferroptosis as a result of MeHg exposure. Additionally, the observed elevation in the protein levels of NLRP3, p-p65, p-p38, p-ERK1/2, and KEAP1 in tandem with downregulated Nrf2 expression levels indicate the involvement of the NF-κB/NLRP3/MAPK/Nrf2 pathways. All the above findings suggested that ferroptosis and the NF-κB/NLRP3/MAPK/Nrf2 pathways are implicated in MeHg-induced AKI, thereby providing a theoretical foundation and reference for future investigations into the prevention and treatment of MeHg-induced kidney injury.

Immune Response of Inactivated Rabies Vaccine Inoculated via Intraperitoneal, Intramuscular, Subcutaneous and Needle-Free Injection Technology-Based Intradermal Routes in Mice.

Inoculation routes may significantly affect vaccine performance due to the local microenvironment, antigen localization and presentation, and, therefore, final immune responses. In this study, we conducted a head-to-head comparison of immune response and safety of inactivated rabies vaccine inoculated via intraperitoneal (IP), intramuscular (IM), subcutaneous (SC) and needle-free injection technology-based intradermal (ID) routes in ICR mice. Immune response was assessed in terms of antigen-specific antibodies, antibody subtypes and neutralizing antibodies for up to 28 weeks. A live rabies virus challenge was also carried out to evaluate vaccine potency. The dynamics of inflammatory cell infiltration at the skin and muscle levels were determined via histopathological examination. The kinetics and distribution of a model antigen were also determined by using in vivo fluorescence imaging. Evidence is presented that the vaccine inoculated via the ID route resulted in the highest antigen-specific antibody and neutralizing antibody titers among all administration routes, while IP and IM routes were comparable, followed by the SC route. Antibody subtype analysis shows that the IP route elicited a Th1-biased immune response, while SC and IM administration elicited a prominent Th2-type immune response. Unexpectedly, the ID route leads to a balanced Th1 and Th2 immune response. In addition, the ID route conferred effective protection against lethal challenge with 40 LD50 of the rabies CVS strain, which was followed by IP and IM routes. Moreover, a one-third dose of the vaccine inoculated via the ID route provided comparable or higher efficacy to a full dose of the vaccine via the other three routes. The superior performance of ID inoculation over other routes is related to longer local retention at injection sites and higher lymphatic drainage. Histopathology examination reveals a transient inflammatory cell infiltration at ID and IM injection sites which peaked at 48 h and 24 h, respectively, after immunization, with all side effects disappearing within one week. These results suggest that needle-free injection technology-based ID inoculation is a promising strategy for rabies vaccination in regard to safety and efficacy.

The pollution control effect of the atmospheric environmental policy in autumn and winter: Evidence from the daily data of Chinese cities.

The pollution control effect of seasonal environmental regulation policies in developing countries still lacks empirical evidence. In 2017, China implemented its first Atmospheric Environmental Policy in Autumn and Winter (AEPAW) to coordinate efforts among cities in reducing air pollutant emissions. Taking the daily panel data of 174 cities in northern China from July 2017 to July 2020 as samples, this paper empirically examines the pollution control effect of the AEPAW using a difference-in-differences model, a difference-in-difference-in-differences model, and a regression discontinuity design. The results show that the AEPAW significantly improves air quality in autumn and winter, with the air quality index decreasing by 5.6% on average by reducing PM2.5, PM10, SO2, and O3 emissions. However, the AEPAW only creates a short-term "policy-induced blue sky", and there exists a phenomenon of "retaliatory pollution" after the AEPAW ends. Besides, the pollution control effect of the AEPAW is moderated by the heterogeneity of the national "Two Sessions" and the Central Environmental Protection Inspection. The implementation of the AEPAW also has a significant spillover effect on air pollution control in surrounding areas. The net benefit from the AEPAW is estimated to be approximately US$ 670 million per year. These findings not only have practical significance for strengthening the comprehensive control of air pollution in China, but also give some important references for other developing countries.

Age at adiposity rebound and the relevance for obesity: a systematic review and meta-analysis.

OBJECTIVES: To understand the sex difference in age at adiposity rebound (AR), integrate the prevalence of early AR (EAR), and provide a quantitative association between early age at AR and overweight/obesity. METHODS: Literature review was conducted in different databases, including the Web of Science, PubMed, EMBASE, Wiley, Chinese National Knowledge Infrastructure, and ScienceDirect databases up to August 2021. Studies that reported data related to AR were considered for inclusion. Pooled effect sizes and their respective 95% confidence intervals (CIs) were calculated using random effects models, depending on the size of heterogeneity. Heterogeneity was tested by using the I2 statistics. RESULTS: 28 studies with a combined sample size of 106,397 people were included in the final meta-analysis. Girls had a significantly earlier age of AR than boys (mean difference = 3.38 months; 95% CI 2.14-4.63). The overall prevalence of EAR was 40% (95% CI 31% to 50%), and the prevalence in girls was 5% higher than that in boys based on the definition of age at AR < 5.0-5.1 years. The overall pooled prevalence of EAR showed an increasing trend by child's birth year [1934-1973]: 29% (95% CI 22% to 37%), 1991-2001: 35% (95% CI 26% to 44%), and 2002-2009: 52% (95% CI 40-63%). Early age at AR (age at AR < 5.0-5.1 years) was associated with a significantly increased risk of overweight/obesity (OR = 5.07; 95% CI 3.60-7.12), overweight (OR = 3.10; 95% CI 1.69-5.70), and obesity (OR = 6.97; 95% CI 4.32-11.26) from the preschool period to adulthood. CONCLUSIONS: The overall prevalence of EAR is increasing, and girls experience AR earlier than boys. The early age at AR in children may be an early and effective marker of obesity.

RoF distributed antenna architecture and reinforcement learning empowered real-time EMI immunity for highly reliable railway communication: publisher's note.

The publisher's note contains a correction to [Opt. Express2932333 (2021)10.1364/OE.438439]. The article was corrected on 17 June 2022.

Millimeter-wave joint radar and communication system based on photonic frequency-multiplying constant envelope LFM-OFDM.

The joint radar and communication (JRC) system providing both large-capacity transmission and high-resolution ranging will play a pivotal role in the next-generation wireless networks (e.g., 6G and beyond) and defense applications. Here, we propose and experimentally demonstrate a novel photonics-assisted millimeter-wave (mm-wave) JRC system with a multi-Gbit/s data rate for communication function and centimeter-level range resolution for radar function. The key is the design of the intermediate-frequency (IF) JRC signal through the angle modulation of the linear frequency modulation (LFM) radar carrier using orthogonal frequency division multiplexing (OFDM) communication signal, inspired by the idea of constant-envelope OFDM (CE-OFDM). This IF angle-modulated waveform facilitates the broadband photonic frequency (phase)-multiplying scheme to generate mm-wave JRC signal with multiplied instantaneous bandwidth and phase modulation index for high-resolution LFM radar and noise-robust CE-OFDM communication. It is with fixed low power-to-average power ratio to render robustness against the nonlinear distortions. In proof-of-concept experiments, a 60-GHz JRC signal with an instantaneous bandwidth over 10-GHz is synthesized through a CE-LFM-OFDM signal encoded with a 2-GBaud 16-QAM OFDM signal. Consequently, a 1.5-cm range resolution of two-dimension imaging and an 8-Gbit/s data rate are achieved for both radar and communication functions, respectively. Furthermore, the proposed JRC system is able to achieve higher radar range resolution and better anti-noise communication, when using higher-order photonic frequency multiplying.

Sex-specific association between placental inflammatory cytokine mRNA expression and preschoolers' behavioral development: The Ma'anshan birth cohort study.

BACKGROUND: Placental inflammation may contribute to brain abnormalities and childhood neuropsychiatric disorders, but limited knowledge is available on the association of placental inflammatory cytokine levels and offspring's behavioral development. This study aimed to examine the sex-specific association between placental inflammatory cytokine mRNA expression and preschoolers' behavioral development. METHODS: 3474 pregnant women were recruited as the initial study population in the Ma'anshan birth cohort (MABC) study. Placentas (n = 2519) were collected during childbirth, and the mRNA expression of IL-8, IL-1ß, CRP, TNF-α, IL-6, IL-10, and IL-4 was assessed. The Child Behavior Checklist 1.5-5 (CBCL 1.5-5) was used to assess children's behavioral development at 4 years old. A T-score ≥ 60 on summary scales or a score ≥ 65 on syndrome scales was regarded as the borderline clinical range. Multiple linear regression models and binary logistic regression models were applied to explore the sex-specific associations between placental inflammatory cytokines mRNA transcript levels and preschoolers' behavioral development. RESULTS: Sex-specific associations between placental inflammatory cytokines mRNA expression and preschoolers' behavioral development were observed. There was a positive association between IL-8 and CBCL scores for boys on anxious/depressed problems, aggressive behaviors, externalizing problems and total problems. Logistic regression models showed that high levels of IL-8 were associated with a higher risk of girls' emotionally reactive problems and sleep problems compared to low/medium levels. High TNF-α was correlated with increased sleep problem scores in boys, and medium TNF-α (vs. low levels) was associated with an increased risk of girls' externalizing problems. Medium levels of CRP, IL-1ß, and IL-6 were found to be associated with a decreased risk of girls' behavioral problems compared to low/high levels. For anti-inflammatory cytokines, medium IL-10 and IL-4 (vs. low levels) were observed to be associated with a lower risk of internalizing problems in boys and externalizing problems in girls, respectively. High IL-10 was correlated with decreased attention problem scores in boys. CONCLUSION: This study indicates that placental inflammatory cytokine mRNA expression of IL-8, CRP, TNF-α, IL-1ß, IL-4 and IL-10 may be associated with preschoolers' behavioral development in a sex-specific manner.

Zinc oxide nanoparticles (ZnO-NPs) exhibit immune toxicity to crucian carp (Carassius carassius) by neutrophil extracellular traps (NETs) release and oxidative stress.

Zinc oxide nanoparticles (ZnO-NPs) are widely used in sunscreens, cosmetics, paint, construction materials, and other products. ZnO-NPs released into the environment can harm aquatic creatures and pose a health risk to humans through the food chain. ZnO-NPs are toxic to fish, but there are few reports on its immunotoxicity on crucian carp (Carassius carassius). In this study, ZnO-NPs increased the biochemical indexes of the liver in serum, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT). In histopathological observation, many inflammatory cells were filled in the liver's central vein stimulated by ZnO-NPs. Furthermore, ZnO-NPs could increase malondialdehyde (MDA) level, lessen superoxide dismutase (SOD) level, and elevate the level of neutrophil extracellular traps (NETs). However, deoxyribonuclease I (DNase I) alleviated all biochemical indexes and histopathological changes. Immunofluorescence in vitro confirmed that NETs were composed of citrullinated histone 3, myeloperoxidase, and neutrophil elastase. ZnO-NPs-increased NETs were dependent on reactive oxygen species (ROS) and nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase and were also related to partial processes of glycolysis. Our study confirms that ZnO-NPS has a toxic effect on the liver of crucian carp. DNase I can prevent liver damage caused by ZnO-NPs, which provides a new insight into the immunotoxicity of ZnO-NPs to fish.

RoF distributed antenna architecture- and reinforcement learning-empowered real-time EMI immunity for highly reliable railway communication.

Highly reliable wireless train-ground communication immune to the electromagnetic interferences (EMIs) is of critical importance for the security and efficiency of high-speed railways (HSRs). However, the rapid development of HSRs (>52,000 km all over the world) brings great challenges on the conventional EMIs mitigation strategies featuring non-real-time and passive. In this paper, the convergence of radio-over-fiber distributed antenna architecture (RoF-DAA) and reinforcement learning technologies is explored to empower a real-time, cognitive and efficient wireless communication solution for HSRs, with strong immunity to EMIs. A centralized communication system utilizes the RoF-DAA to connect the center station (CS) and distributed remote radio units (RRUs) along with the railway track-sides to collect electromagnetic signals from environments. Real-time recognition of EMIs and interactions between the CS and RRUs are enabled by the RoF link featuring broad bandwidth and low transmission loss. An intelligent proactive interference avoidance scheme is proposed to perform EMI-immunity wireless communication. Then an improved Win or learn Fast-Policy Hill Climbing (WoLF-PHC) multi-agent reinforcement learning algorithm is adopted to dynamically select and switch the operation frequency bands of RRUs in a self-adaptive mode, avoiding the frequency channel contaminated by the EMIs. In proof-of-concept experiments and simulations, EMIs towards a single RRU and multiple RRUs in the same cluster and towards two adjacent RRUs in distinct clusters are effectively avoided for the Global System for Mobile communications-Railway (GSM-R) system in HSRs. The proposed system has a superior performance in terms of circumventing either static or dynamic EMIs, serving as an improved cognitive radio scheme to ensuring high security and high efficiency railway communication.

Bongkrekic acid induced neutrophil extracellular traps via p38, ERK, PAD4, and P2X1-mediated signaling.

Bongkrekic acid (BKA) produced by pseudomonas cocovenenans is a deadly toxin, and is mainly found in spoiled or fermented foods. However, less is known on its immunotoxicity. Neutrophil extracellular traps (NETs) are a novel effector mechanism of neutrophils against invading pathogens, but excessive NETs also contribute to tissue damage. This study aimed to investigate NET formation triggered by BKA in murine neutrophils, and describe its characteristics and potential mechanisms. Our results showed that BKA triggered NET formation via co-localization of DNA and histone or MPO by immunostaining. Moreover, BKA-triggered NET formation was dose- and time-dependent via NET quantification based on Picogreen-derived fluorescence intensities. Furthermore, BKA increased ROS production in neutrophils. Pharmacological inhibition indicated that BKA-triggered NET formation was associated with ROS-p38 and -ERK signaling pathways, but independent on NADPH oxidase. Besides, PAD4 and P2X1 receptor also mediated BKA-triggered NET formation. To our knowledge, all these findings provide for the first time an initial understanding of BKA on innate immunity, which might be helpful for further investigation on BKA immunotoxicity.

Ultracompact silicon polarization splitter-rotator using a dual-etched and tapered coupler.

The polarization splitter-rotator (PSR) plays a significant role in telecom, Datacom, and quantum circuits to meet significant requirements for polarization processing and multiplexing. We design an ultracompact PSR based on a silicon asymmetrical directional coupler (ADC). One waveguide of the ADC is gradually etched in two levels along the coupling region and the S-bend. A trapezoidal taper on the top of the dual-etched waveguide is first formed to satisfy the phase-matching condition for the TM-TE mode conversion, such that the TM mode is cross-coupled from the input waveguide without etching. Then, the etching width gradually increases in the S-bend and the following to achieve a single-mode waveguide for further removal of the residual TM mode. In this way, a high extinction ratio can be achieved for the polarization mode splitting in an ultracompact silicon ADC. For the designed PSR with a total length of about 24 µm, the simulation results reveal that the minimum extinction ratio is greater than 30, 20, or 15 dB within the bandwidth of 33, 100, or 150 nm, respectively, while the maximum polarization conversion loss is less than 0.4, 0.9, or 1 dB.

Ultracompact silicon polarization splitter-rotator using dual-etched and tapered coupler: publisher's note.

This publisher's note corrects the Funding section in Appl. Opt.59, 9540 (2020)APOPAI0003-693510.1364/AO.404741.

Protein and mRNA Delivery Enabled by Cholesteryl-Based Biodegradable Lipidoid Nanoparticles.

Developing safe and efficient delivery systems for therapeutic biomacromolecules is a long-standing challenge. Herein, we report a newly developed combinatorial library of cholesteryl-based disulfide bond-containing biodegradable cationic lipidoid nanoparticles. We have identified a subset of this library which is effective for protein and mRNA delivery in vitro and in vivo. These lipidoids showed comparable transfection efficacies but much lower cytotoxicities compared to the Lpf2k in vitro. In vivo studies in adult mice demonstrated the successful delivery of genome engineering protein and mRNA molecules in the skeletal muscle (via intramuscular injection), lung and spleen (via intravenous injection), and brain (via lateral ventricle infusion).