Rosmarinic acid liposomes suppress ferroptosis in ischemic brain via inhibition of TfR1 in BMECs.

BACKGROUND: Iron deposition and ferroptosis are involved in ischemic stroke injury, but the choice of drugs for treatment is limited. PURPOSE: To investigate the potential neuroprotective effects of Rosmarinic acid (RosA) encapsulated within nanoliposomes (RosA-LIP) on ischemic stroke. METHODS: Wild-type (WT) and TfR1EC cKO (specific knockout of the TfR1 gene in BMECs) mice used to establish a dMCAO model, with simultaneous administration of RosA-LIP (20 mg/kg/d, i.p.) or RosA (20 mg/kg/d, i.p.). RESULTS: The successful synthesis of RosA-LIP resulted in enhanced stability and precise delivery in both the serum and brain. The administration of RosA-LIP effectively mitigated ischemia-induced behavioral abnormalities and pathological damage. RosA-LIP inhibited ferroptosis by ameliorating mitochondrial abnormalities, increasing GPX4 levels, and decreasing ACSL4/LPCAT3/Lox-dependent lipid peroxidation. RosA-LIP effectively improved blood‒brain barrier (BBB) permeability, increased tight junctions (TJs) protein expression and reduced iron levels in ischemic tissue and brain microvascular endothelial cells (BMECs) by modulating FPN1 and TfR1 levels. Furthermore, RosA-LIP suppressed TfR1 to attenuate ACSL4/LPCAT3/Lox-mediated ferroptosis in TfR1EC cKO mice subjected to dMCAO. CONCLUSION: RosA-LIP effectively increased the brain level of RosA and protected against ferroptosis through the regulation of TfR1 in BMECs.

Cardiomyocyte-specific overexpression of FPN1 diminishes cardiac hypertrophy induced by chronic intermittent hypoxia.

The significance of iron in myocardial mitochondria function cannot be underestimated, because deviations in iron levels within cardiomyocytes may have profound detrimental effects on cardiac function. In this study, we investigated the effects of ferroportin 1 (FPN1) on cardiac iron levels and pathological alterations in mice subjected to chronic intermittent hypoxia (CIH). The cTNT-FPN1 plasmid was administered via tail vein injection to induce the mouse with FPN1 overexpression in the cardiomyocytes. CIH was established by exposing the mice to cycles of 21%-5% FiO2 for 3 min, 8 h per day. Subsequently, the introduction of hepcidin resulted in a reduction in FPN1 expression, and H9C2 cells were used to establish an IH model to further elucidate the role of FPN1. First, FPN1 overexpression ameliorated CIH-induced cardiac dysfunction, myocardial hypertrophy, mitochondrial damage and apoptosis. Second, FPN1 overexpression attenuated ROS levels during CIH. In addition, FPN1 overexpression mitigated CIH-induced cardiac iron accumulation. Moreover, the administration of hepcidin resulted in a reduction in FPN1 levels, further accelerating the CIH-induced levels of ROS, LIP and apoptosis in H9C2 cells. These findings indicate that the overexpression of FPN1 in cardiomyocytes inhibits CIH-induced cardiac iron accumulation, subsequently reducing ROS levels and mitigating mitochondrial damage. Conversely, the administration of hepcidin suppressed FPN1 expression and worsened cardiomyocyte iron toxicity injury.

Circular RNA circPHF16 enhances IL-17A expression and secretion by sequestering miR-378a-3p to activate the IL6ST axis in Graves' disease.

Interleukin-17A (IL-17A) plays a pivotal role in the pathogenesis of Graves' disease (GD), an autoimmune disorder affecting thyroid function, but the detailed regulatory mechanisms remain elusive. Circular RNAs (circRNAs) have emerged as key regulators of IL-17A expression and secretion in autoimmune diseases, yet their specific role in GD, especially within CD4 + T lymphocytes, are not well understood. In this study, a circRNA, circPHF16 (hsa_circ_0090364) was found to be highly expressed in the peripheral blood mononuclear cells and serum of GD patients. In vitro experiments in Jurkat T cells revealed that silencing of circPHF16 suppressed IL-17A expression and secretion, while overexpression of circPHF16 had the opposite effect. Furthermore, bioinformatics analysis demonstrated a circPHF16/miR-378a-3p/IL6ST pathway, in which circPHF16 regulates IL6ST expression, which, in turn, influences IL-17A expression and secretion by interacting with miR-378a-3p. In vivo studies in a mouse model of GD showed similar trends in molecular expression levels, consistent with competitive endogenous RNA interactions. Together the results of the study identify circPHF16 as a potential target in the development of new strategies for GD diagnosis and treatment, and thus, offer a theoretical foundation for clinical therapeutic approaches in GD.

Accurate Prediction of the Magnetic Ordering Temperature of Ultralow-Temperature Magnetic Refrigerants.

Adiabatic demagnetization refrigeration is known to be the only cryogenic refrigeration technology that can achieve ultralow temperatures (≪1 K) at gravity-free conditions. The key indexes to evaluate the performance of magnetic refrigerants are their magnetic entropy changes (-ΔSm) and magnetic ordering temperature (T0). Although, based on the factors affecting the -ΔSm of magnetic refrigerants, one has been able to judge if a magnetic refrigerant has a large -ΔSm, how to accurately predict their T0 remains a huge challenge due to the fact that the T0 of magnetic refrigerants is related to not only magnetic exchange but also single-ion anisotropy and magnetic dipole interaction. Here, we, taking GdCO3F (1), Gd(HCOO)F2, Gd2(SO4)3·8H2O, GdF3, Gd(HCOO)3 and Gd(OH)3 as examples, demonstrate that the T0 of magnetic refrigerants with very weak magnetic interactions and small anisotropy can be accurately predicted by integrating mean-field approximation with quantum Monte Carlo simulations, providing an effective method for predicting the T0 of ultralow-temperature magnetic refrigerants. Thus, the present work lays a solid foundation for the rational design and preparation of ultralow-temperature magnetic refrigerants in the future.

Rosmarinic Acid Liposomes Downregulate Hepcidin Expression via BMP6-SMAD1/5/8 Pathway in Mice with Iron Overload.

The objective of this study is to examine the potential protective effect of rosmarinic acid (RosA) encapsulated within nanoliposomes (RosA-LIP) on hepatic damage induced by iron overload. The characteristics, stability, and release of RosA-LIP in vitro were identified. The mice were randomly assigned to five groups: Control, Model, Model+DFO (DFO), Model+RosA (RosA), and Model+RosA-LIP (RosA-LIP). The iron overload model was induced by administering iron dextran (i.p.). The DFO, RosA, and RosA-LIP groups received iron dextran and were subsequently treated with DFO, RosA, and RosA-LIP for 14 days. We developed a novel formulation of RosA-LIP that exhibited stability and controlled release properties. Firstly, RosA-LIP improved liver function and ameliorated pathological changes in a mouse model of iron overload. Secondly, RosA-LIP demonstrated the ability to enhance the activities of T-SOD, GSH-Px, and CAT, while reducing the levels of MDA and 4-HNE, thereby effectively mitigating oxidative stress damage induced by iron overload. Thirdly, RosA-LIP reduced hepatic iron levels by downregulating FTL, FTH, and TfR1 levels. Additionally, RosA-LIP exerted a suppressive effect on hepcidin expression through the BMP6-SMAD1/5/8 signaling pathway. Furthermore, RosA-LIP upregulated FPN1 expression in both the liver and duodenum, thereby alleviating iron accumulation in these organs in mice with iron overload. Notably, RosA exhibited a comparable iron chelation effect, and RosA-LIP demonstrated superior efficacy in mitigating liver damage induced by excessive iron overload. RosA-LIP exhibited favorable sustained release properties, targeted delivery, and efficient protection against iron overload-induced liver damage. A schematic representation of the proposed protective mechanism of rosmarinic acid liposome during iron overload. Once RosA-LIP is transported into cells, RosA is released. On the one hand, RosA attenuates the BMP6-SMAD1/5/8-SMAD4 signaling pathway activation, leading to inhibiting hepcidin transcription. Then, the declined hepcidin contacted the inhibitory effect of FPN1 in hepatocytes and duodenum, increasing iron mobilization. On the other hand, RosA inhibits TfR1 and ferritin expression, which decreases excessive iron and oxidative damage.

The Spectral Response of the Dual Microdisk Resonator Based on BaTiO3 Resistive Random Access Memory.

With the resistive random access memory (ReRAM) devices based on the Al/BaTiO3 (BTO)/ITO structure fabricated at hand, by cross-analyzing the resistive memory characteristics in terms of various barium titanate (BTO) film thicknesses, it is found that the device with 60 nm thick BTO can be switched more than 425 times, while the corresponding SET/RESET voltage, the on-off ratio, and the retention time are -0.69 V/0.475 V, 102, and more than 104 seconds, respectively. Furthermore, the aforementioned ReRAM with a low switching voltage and low power consumption is further integrated with a waveguide resonator in the form of a dual microdisk aligned in a parallel fashion. As the separation gap between the two microdisks is fixed at 15 µm, the ReRAM-mediated dual disk resonator would render a 180° phase reversal between the spectral outputs of the through-port and drop-port. If the gap is shortened to 10 and 5 µm, the expected phase reversal could also be retrieved due to the selective combinations of different memory states associated with each of the two ReRAM microdisks as witnessed by a series of characterization measurements.

Comparison between hospital- and community-acquired septic shock in children: a single-center retrospective cohort study.

BACKGROUND: We explored the differences in baseline characteristics, pathogens, complications, outcomes, and risk factors between children with hospital-acquired septic shock (HASS) and community-acquired septic shock (CASS) in the pediatric intensive care unit (PICU). METHODS: This retrospective study enrolled children with septic shock at the PICU of Beijing Children's Hospital from January 1, 2016, to December 31, 2019. The patients were followed up until 28 days after shock or death and were divided into the HASS and CASS group. Logistic regression analysis was used to identify risk factors for mortality. RESULTS: A total of 298 children were enrolled. Among them, 65.9% (n = 91) of HASS patients had hematologic/oncologic diseases, mainly with Gram-negative bacterial bloodstream infections (47.3%). Additionally, 67.7% (n = 207) of CASS patients had no obvious underlying disease, and most experienced Gram-positive bacterial infections (30.9%) of the respiratory or central nervous system. The 28-day mortality was 62.6% and 32.7% in the HASS and CASS groups, respectively (P < 0.001). Platelet [odds ratio (OR) = 0.996, 95% confidence interval (CI) = 0.992-1.000, P = 0.028], positive pathogen detection (OR = 3.557, 95% CI = 1.307-9.684, P = 0.013), and multiple organ dysfunction syndrome (OR = 10.953, 95% CI = 1.974-60.775, P = 0.006) were risk factors for 28-day mortality in HASS patients. Lactate (OR = 1.104, 95% CI = 1.022-1.192, P = 0.012) and mechanical ventilation (OR = 8.114, 95% CI = 1.806-36.465, P = 0.006) were risk factors for 28-day mortality in patients with CASS. CONCLUSIONS: The underlying diseases, pathogens, complications, prognosis, and mortality rates varied widely between the HASS and CASS groups. The predictors of 28-day mortality were different between HASS and CASS pediatric patients with septic shock.

Bidirectional Coupler Study for Chip-Based Spectral-Domain Optical Coherence Tomography.

A chip-based spectral-domain optical coherence tomography (SD-OCT) system consists of a broadband source, interferometer, and spectrometer. The optical power divider flatness in the interferometer's wavelength is crucial to higher signal-to-noise ratios. A Mach-Zehnder directional coupler (MZDC) structure could be utilized to smoothly maximize the splitting ratio of 50:50 on a silicon platform, with a sub-micrometer of decoupler optical path difference insensitive to the process variation up to 20 nanometers. However, the optical signal reflected from the reference and sample will go back to the same interferometer MZDC. The so-called bidirectional coupler MZDC will not illustrate a flat optical power response in the operating wavelength range but could still demonstrate at least 20 dB signal-to-noise ratio improvement in OCT after the echelle grating spectrum compensation is applied. For maintaining the axial resolution and sensitivity, the echelle grating is also insensitive to process shifts such as MZDC and could be further utilized to compensate a 3 dB bidirectional MZDC structure for a broad and flat 100 nm wavelength response in the interferometer-based on-chip SD-OCT.

A Gd-based borate-carbonate framework exhibiting a large magnetocaloric effect at a low magnetic field.

A 3D borate-carbonate framework, GdB(OH)4CO3 (1), was synthesized. Magnetic study reveals that its MCE is up to 33.5 J kg-1 K-1 at 2 K and 2 T, due to the introduction of a long magnetic exchange path of Gd-O-B-O-Gd leading to 1 exhibiting weak magnetic interaction.

Magnetocaloric Effect and Thermal Conductivity of a 3D Coordination Polymer of [Gd(HCOO)(C2O4)]n.

A 3D coordination polymer, [Gd(HCOO)(C2O4)]n was prepared. Its magnetocaloric effect (MCE) (32.7 J K-1 kg-1 at 2 K and 2 T) is significantly larger than that of commercial Gd3Ga5O12 (GGG) (14.6 J kg-1 K-1 at 2 K and 2 T), while its thermal conductivity (9.9 W m-1 K-1 at 3 K) is comparable to that of the commercial GGG (about 10 W m-1 K-1 at 3 K).

A PCR-free screen-printed magnetic electrode for the detection of circular RNA from hepatocellular cancer based on a back-splice junction.

Circular RNA (circRNA) has the potential to be applied to disease diagnosis and therapy. However, the currently available circRNA detection techniques are limited. This work proposes a sensitive and selective approach for circRNA detection based on gold nanoparticle-modified screen-printed magnetic electrodes (AuNPs-SPME). Magnetic beads (MBs) with capture probes based on specific back-splice junction (BSJ) sites were employed to identify and selectively isolate the target circRNA, which could be directly adsorbed onto the AuNPs-SPME. Then, the circRNA attached to the surface was detected by changes in the methylene blue redox signal. The simple and time-saving AuNPs-SPME is highly sensitive (LOD = 1.0 pM) to circCDYL, one of the biomarkers of hepatocellular cancer (HCC). The analytical performance of the method presented has also been verified in human serum samples, holding great promise for clinical diagnosis.

Selenium Level in Patients with Vitiligo: A Meta-Analysis.

BACKGROUND: It has been reported that deficiency of selenium can cause autoimmune disease. This meta-analysis was aimed at evaluating whether there exits an association between selenium level and vitiligo. METHODS: A comprehensive search was conducted on PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Med Online, and China VIP databases from the inception to February 12, 2019. The main outcome was the standardized mean difference (SMD) with 95% confidence interval (CI) in serum selenium level between vitiligo patients and healthy controls. RESULTS: A total of 8 studies with 305 vitiligo patients and 6156 healthy controls were included in this meta-analysis. The results showed that there was no significant difference in selenium level between vitiligo patients and healthy controls (SMD = 0.481, 95%CI = -0.642 to 1.604, Z = 0.840, P > 0.05). Further subgroup analysis stratified by area revealed that Asian vitiligo patients had decreased selenium level, while that finding was not observed in Caucasian patients (Asian: SMD = -0.303, 95%CI = -0.603 to -0.004, P < 0.05; Caucasian: SMD = 0.957, 95%CI = -0.752 to 2.665, P > 0.05). CONCLUSIONS: Although overall selenium level was similar between vitiligo patients and health controls, subgroup analysis showed decreased levels of selenium in Asian vitiligo patients. It may suggest a clinical tailored administration of selenium supplementation in Asian vitiligo patients.

New species of the tribe Meconematini (Orthoptera: Tettigoniidae: Meconematinae: Meconematini) from Sichuan, China.

Two new species of the subfamily Meconematinae are described, i.e. Neocyrtopsis (Neocyrtopsis) shimianensis Wang Shi, sp. nov. and Doicholobosa acuta Wang Shi, sp. nov. from Sichuan, China. All examined specimens are deposited in the Museum of Hebei University.

The emissions from co-firing of biomass and torrefied biomass with coal in a chain-grate steam boiler.

In this study, biomass of rice straw (RS) and wood (WD) and their torrefied biomass (RST and WDT) were used as solid biofuel (SBF) for co-firing individually with coal in a commercial continuous chain-grate steam boiler system, which was conducted at fixed input rate of heating value of mixture of SBF and coal and at fixed airflow rate. The effects of key system parameters on the gaseous and particulate pollutions and ash were examined. These include SBF type and blending ratio (RBL) of biomass (i.e., SBF) in the mixture of coal and biomass based on heating values for co-firing.The results indicated that wood, which possesses high heating value while less amount of ash, is more suitable for co-firing with coal than rice straw. Torrefaction can increase the heating value of biomass and homogenize its property, being beneficial to co-firing. Also, torrefaction can decompose the hydroxyl group of biomass, which makes biomass tending to possess hydrophobicity. This, in turn, helps the storage and transportation of biomass. Generally, adding the RS (with RBL = 5-10%), WD (2-15%), RST (2-10%) and WDT (2-20%), respectively, with coal decreases the emissions of NOx and SO2, but increases that of CO (except RST). The emission of HCl is little. The addition of biomass also increases the emission of fine particulate matters (PM) especially PM2.5 in the flue gases, raising PM2.5/PM100 from 34.87 to 78.35 wt.% (Case 50%WDT). These emissions for the Cases tested satisfy with Taiwanese emission standards of stationary sources which set limitations of NOx, SO2, CO and HCl < 350, 300, 2000 and 80 ppmv, while PM < 50 mg/m3, respectively. The results support the use of RS, WD, RST and WDT for co-firing with coal.Implications: This study examined the suitability of using solid bio-fuels to co-fire with coal in an industrial chain-grate steam boiler system with a capacity of 100 kW, in order to achieve carbon-free emissions. Both biomass and torrefied biomass of solid bio-fuel were tested. The findings would be useful for proper design and rational operation of solid bio-fuel/coal co-firing combustion matching the appeal of sustainable material management and circular economy of biomass, and of adaptation of global warming induced by greenhouse gases. It also provides information for policy-makers to promote the co-firing application of biomass and related bio-waste materials.

Myeloid Acat1/Soat1 KO attenuates pro-inflammatory responses in macrophages and protects against atherosclerosis in a model of advanced lesions.

Cholesterol esters are a key ingredient of foamy cells in atherosclerotic lesions; their formation is catalyzed by two enzymes: acyl-CoA:cholesterol acyltransferases (ACATs; also called sterol O-acyltransferases, or SOATs) ACAT1 and ACAT2. ACAT1 is present in all body cells and is the major isoenzyme in macrophages. Whether blocking ACAT1 benefits atherosclerosis has been under debate for more than a decade. Previously, our laboratory developed a myeloid-specific Acat1 knockout (KO) mouse (Acat1-M/-M), devoid of ACAT1 only in macrophages, microglia, and neutrophils. In previous work using the ApoE KO (ApoE-/-) mouse model for early lesions, Acat1-M/-M significantly reduced lesion macrophage content and suppressed atherosclerosis progression. In advanced lesions, cholesterol crystals become a prominent feature. Here we evaluated the effects of Acat1-M/-M in the ApoE KO mouse model for more advanced lesions and found that mice lacking myeloid Acat1 had significantly reduced lesion cholesterol crystal contents. Acat1-M/-M also significantly reduced lesion size and macrophage content without increasing apoptotic cell death. Cell culture studies showed that inhibiting ACAT1 in macrophages caused cells to produce less proinflammatory responses upon cholesterol loading by acetyl low-density lipoprotein. In advanced lesions, Acat1-M/-M reduced but did not eliminate foamy cells. In advanced plaques isolated from ApoE-/- mice, immunostainings showed that both ACAT1 and ACAT2 are present. In cell culture, both enzymes are present in macrophages and smooth muscle cells and contribute to cholesterol ester biosynthesis. Overall, our results support the notion that targeting ACAT1 or targeting both ACAT1 and ACAT2 in macrophages is a novel strategy to treat advanced lesions.

Bifunctional Squaramide-Catalyzed Asymmetric [3 + 2] Cyclization of 2-(1-Methyl-2-oxoindolin-3-yl)malononitriles with Unsaturated Pyrazolones To Construct Spirooxindole-Fused Spiropyrazolones.

The present paper reports a highly stereoselective synthesis of spirooxindole-fused spiropyrazolones through the asymmetric [3 + 2] cyclization reaction of 2-(1-methyl-2-oxoindolin-3-yl)malononitriles with unsaturated pyrazolones under mild conditions. With only a 1 mol % bifunctional squaramide catalyst, a series of chiral dispirocyclic pyrazolone derivatives were attained in high yields (85-97%) with excellent stereoselectivities (up to >99% ee and in all cases >20:1 dr). Moreover, gram-scale synthesis and further transformation of the products were also demonstrated.