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Mitochondrial dysfunction has been increasingly recognized as a trigger for systemic lupus erythematosus (SLE). Recent bioinformatics studies have suggested Fam210b as a significant candidate for the classification and therapeutic targeting of SLE. To experimentally prove the role of Fam210b in SLE, we constructed Fam210b knockout (Fam210b-/-) mice using the CRISPR-Cas9 method. We found that approximately 15.68% of Fam210b-/- mice spontaneously developed lupus-like autoimmunity, which was characterized by skin ulcerations, splenomegaly, and an increase in anti-double-stranded DNA (anti-dsDNA) IgG antibodies and anti-nuclear antibodies(ANA). Single-cell sequencing showed that Fam210b was mainly expressed in erythroid cells. Critically, the knockout of Fam210b resulted in abnormal erythrocyte differentiation and development in the spleens of mice. Concurrently, the spleens exhibited an increased number of CD71+ erythroid cells, along with elevated levels of reactive oxygen species (ROS) in the erythrocytes. The co-culture of CD71+ erythroid cells and lymphocytes resulted in lymphocyte activation and promoted dsDNA and IgG production. In summary, Fam210b knockout leads to a low probability of lupus-like symptoms in mice through the overproduction of ROS in CD71+ erythroid cells. Thus, Fam210b reduction may serve as a novel key marker that triggers the development of SLE.
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Lupus Eritematoso Sistémico , Ratones Noqueados , Animales , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/metabolismo , Lupus Eritematoso Sistémico/patología , Ratones , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Anticuerpos Antinucleares , Membranas Mitocondriales/metabolismo , Células Eritroides/metabolismo , Células Eritroides/patología , Modelos Animales de Enfermedad , Inmunoglobulina G/metabolismo , Ratones Endogámicos C57BL , Bazo/metabolismo , Bazo/patología , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , FemeninoRESUMEN
Microglia-mediated inflammatory response is one key cause of many central nervous system diseases, like Alzheimer's disease. We hypothesized that a novel C15orf39 (MAPK1 substrate) plays a critical role in the microglial inflammatory response. To confirm this hypothesis, we used lipopolysaccharide (LPS)-and interferon-gamma (IFN-γ)-induced human microglia HMC3 cells as a representative indicator of the microglial in vitro inflammatory response. We found that C15orf39 was down-regulated when interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) expression increased in LPS/IFN-γ-stimulated HMC3 cells. Once C15orf39 was overexpressed, IL-6 and TNFα expression were reduced in LPS/IFN-γ-stimulated HMC3 cells. In contrast, C15orf39 knockdown promoted IL-6 and TNFα expression in LPS/IFN-γ-stimulated HMC3 cells. These results suggest that C15orf39 is a suppressive factor in the microglial inflammatory response. Mechanistically, C15orf39 interacts with the cytoplasmic protein arginine methyltransferase 2 (PRMT2). Thus, we termed C15orf39 a PRMT2 interaction protein (PRMT2 IP). Furthermore, the interaction of C15orf39 and PRMT2 suppressed the activation of NF-κB signaling via the PRMT2-IκBα signaling axis, which then led to a reduction in transcription of the inflammatory factors IL6 and TNF-α. Under inflammatory conditions, NF-κBp65 was found to be activated and to suppress C15orf39 promoter activation, after which it canceled the suppressive effect of the C15orf39-PRMT2-IκBα signaling axis on IL-6 and TNFα transcriptional expression. In conclusion, our findings demonstrate that in a steady condition, the interaction of C15orf39 and PRMT2 stabilizes IκBα to inhibit IL-6 and TNFα expression by suppressing NF-κB signaling, which reversely suppresses C15orf39 transcription to enhance IL-6 and TNFα expression in the microglial inflammatory condition. Our study provides a clue as to the role of C15orf39 in microglia-mediated inflammation, suggesting the potential therapeutic efficacy of C15orf39 in some central nervous system diseases.
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Inflamación , Interleucina-6 , Lipopolisacáridos , Microglía , Proteína-Arginina N-Metiltransferasas , Factor de Necrosis Tumoral alfa , Humanos , Línea Celular , Inflamación/metabolismo , Inflamación/genética , Inflamación/patología , Interferón gamma/metabolismo , Interferón gamma/farmacología , Interleucina-6/metabolismo , Interleucina-6/genética , Lipopolisacáridos/farmacología , Microglía/metabolismo , Microglía/efectos de los fármacos , FN-kappa B/metabolismo , Sistemas de Lectura Abierta , Proteína-Arginina N-Metiltransferasas/metabolismo , Proteína-Arginina N-Metiltransferasas/genética , Transducción de Señal , Factor de Necrosis Tumoral alfa/metabolismo , Cromosomas Humanos Par 15RESUMEN
Xiaoying Zhou, Wenting Su, Quanwei Bao, Yu Cui, Xiaoxu Li, Yidong Yang, Chengzhong Yang, Chengyuan Wang, Li Jiao, Dewei Chen, and Jian Huang. Nitric oxide ameliorates the effects of hypoxia in mice by regulating oxygen transport by hemoglobin. High Alt Med Biol. 00:00-00, 2024.-Hypoxia is a common pathological and physiological phenomenon in ischemia, cancer, and strenuous exercise. Nitric oxide (NO) acts as an endothelium-derived relaxing factor in hypoxic vasodilation and serves as an allosteric regulator of hemoglobin (Hb). However, the ultimate effects of NO on the hematological system in vivo remain unknown, especially in extreme environmental hypoxia. Whether NO regulation of the structure of Hb improves oxygen transport remains unclear. Hence, we examined whether NO altered the oxygen affinity of Hb (Hb-O2 affinity) to protect extremely hypoxic mice. Mice were exposed to severe hypoxia with various concentrations of NO, and the survival time, exercise capacity, and other physical indexes were recorded. The survival time was prolonged in the 5 ppm NO (6.09 ± 1.29 minutes) and 10 ppm NO (6.39 ± 1.58 minutes) groups compared with the 0 ppm group (4.98 ± 1.23 minutes). Hypoxia of the brain was relieved, and the exercise exhaustion time was prolonged when mice inhaled 20 ppm NO (24.70 ± 6.87 minutes vs. 20.23 ± 6.51 minutes). In addition, the differences in arterial oxygen saturation (SO2%) (49.64 ± 7.29% vs. 42.90 ± 4.30%) and arteriovenous SO2% difference (25.14 ± 8.95% vs. 18.10 ± 6.90%) obviously increased. In ex vivo experiments, the oxygen equilibrium curve (OEC) left shifted as P50 decreased from 43.77 ± 2.49 mmHg (0 ppm NO) to 40.97 ± 1.40 mmHg (100 ppm NO) and 38.36 ± 2.78 mmHg (200 ppm NO). Furthermore, the Bohr effect of Hb was enhanced by the introduction of 200 ppm NO (-0.72 ± 0.062 vs.-0.65 ± 0.051), possibly allowing Hb to more easily offload oxygen in tissue at lower pH. The crystal structure reveals a greater distance between Asp94ß-His146ß in nitrosyl -Hb(NO-Hb), NO-HbßCSO93, and S-NitrosoHb(SNO-Hb) compared to tense Hb(T-Hb, 3.7 Å, 4.3 Å, and 5.8 Å respectively, versus 3.5 Å for T-Hb). Moreover, hydrogen bonds were less likely to form, representing a key limitation of relaxed Hb (R-Hb). Upon NO interaction with Hb, hydrogen bonds and salt bridges were less favored, facilitating relaxation. We speculated that NO ameliorated the effects of hypoxia in mice by promoting erythrocyte oxygen loading in the lung and offloading in tissues.
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OBJECTIVE: Due to the complexity of drug-induced lupus (DIL) pathogenesis, more susceptibility factors need to be discovered. FAM210B is a new mitochondrial protein whose function has not been fully elucidated. This study will explore whether there is a correlation between FAM210B and the risk of DIL. METHODS: At first, we extracted three FAM210B genetic variants from the GTEx database (n = 948), and extracted their corresponding genome-wide association study (GWAS) summary statistics from DIL (101 DIL cases and 218691 controls). Then, we performed a Mendelian randomization (MR) study to evaluate the causal association of the expression of FAM210B with DIL using inverse-variance weighted (IVW), the weighted median, MR-Egger, and MR-PRESSO test. RESULTS: We successfully extracted three FAM210B single-nucleotide polymorphisms (SNPs) (rs116032784, rs34361943 and rs33923703) from the GTEx_Analysis_v8_eQTL data that can reduce FAM210B expression. The results of the MR analysis showed that genetically reduced expression of FAM210B was significantly associated with increased risk of DIL in European ancestry based on the IVW method (ß = 1.037, p = 0.001, odds ratio [OR] = 2.821, 95% confidence interval [CI]:1.495-5.322). CONCLUSION: MR analysis showed a causal relationship between FAM210B expression and the risk of DIL disease. Our results suggested that FAM210B may be a marker that can mark susceptibility of DIL in the future. It provides evidence for the study of DIL, but its specific mechanism of action in DIL needs to be further studied. Key Points â¢This is the first MR analysis to examine the association between FAM210B and DIL. â¢The findings of this study suggested that reduced FAM210B expression is associated with the increased risk of DIL. â¢FAM210B may be a marker that can mark susceptibility of DIL in the future.
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Proteínas de la Membrana , Análisis de la Aleatorización Mendeliana , Proteínas Mitocondriales , Humanos , Causalidad , Bases de Datos Factuales , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido SimpleRESUMEN
Sustainable retinal codelivery poses significant challenges technically, although it is imperative for synergistic treatment of wet age-related macular degeneration (wAMD). Here, a microemulsion-doped hydrogel (Bor/PT-M@TRG) is engineered as an intravitreal depot composing of temperature-responsive hydrogel (TRG) and borneol-decorated paeoniflorin (PF) & tetramethylpyrazine (TMP)-coloaded microemulsions (Bor/PT-M). Bor/PT-M@TRG, functioning as the "ammunition depot", resides in the vitreous and continuously releases Bor/PT-M as the therapeutic "bullet", enabling deep penetration into the retina for 21 days. A single intravitreal injection of Bor/PT-M@TRG yields substantial reductions in choroidal neovascularization (CNV, a hallmark feature of wAMD) progression and mitigates oxidative stress-induced damage in vivo. Combinational PF&TMP regulates the "reactive oxygen species/nuclear factor erythroid-2-related factor 2/heme oxygenase-1" pathway and blocks the "hypoxia inducible factor-1α/vascular endothelial growth factor" signaling in retina, synergistically cutting off the loop of CNV formation. Utilizing fluorescence resonance energy transfer and liquid chromatography-mass spectrometry techniques, they present compelling multifaceted evidence of sustainable retinal codelivery spanning formulations, ARPE-19 cells, in vivo eye balls, and ex vivo section/retina-choroid complex cell levels. Such codelivery approach is elucidated as the key driving force behind the exceptional therapeutic outcomes of Bor/PT-M@TRG. These findings highlight the significance of sustainable retinal drug codelivery and rational combination for effective treatment of wAMD.
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Pirazinas , Animales , Pirazinas/química , Pirazinas/administración & dosificación , Pirazinas/farmacología , Pirazinas/farmacocinética , Retina/efectos de los fármacos , Retina/metabolismo , Degeneración Macular/tratamiento farmacológico , Sistemas de Liberación de Medicamentos/métodos , Humanos , Neovascularización Coroidal/tratamiento farmacológico , Neovascularización Coroidal/metabolismo , Neovascularización Coroidal/patología , Ratones , Hidrogeles/química , Hidrogeles/farmacología , Estrés Oxidativo/efectos de los fármacos , Canfanos/química , Canfanos/farmacología , Ratones Endogámicos C57BL , Especies Reactivas de Oxígeno/metabolismoRESUMEN
This study aims to develop fatty acid metabolism-related molecular subtypes and construct a fatty acid metabolism-related novel model for bladder cancer (BCa) by bioinformatic profiling. Genome RNA-seq expression data of BCa samples from the TCGA database and GEO database were downloaded. We then conducted consensus clustering analysis to identify fatty acid metabolism-related molecular subtypes for BCa. Univariate and multivariate Cox regression analysis were performed to identify a novel prognostic fatty acid metabolism-related prognostic model for BCa. Finally, we identified a total of three fatty acid metabolismrelated molecular subtypes for BCa. These three molecular subtypes have significantly different clinical characteristics, PD-L1 expression levels, and tumor microenvironments. Also, we developed a novel fatty acid metabolism-related prognostic model. Patients with low-risk score have significantly preferable overall survival compared with those with high-risk score in the training, testing, and validating cohorts. The area under the ROC curve (AUC) for overall survival prediction was 0.746, 0.681, and 0.680 in the training, testing and validating cohorts, respectively. This model was mainly suitable for male, older, high-grade, cluster 2-3, any TCGA stage, any N-stage, and any T-stage patients. Besides, we selected FASN as a hub gene for BCa and further qRT-PCR validation was successfully conducted. In conclusion, we developed and successfully validated a novel fatty acid metabolism-related prognostic model for predicting outcome for BCa patients.
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Neoplasias de la Vejiga Urinaria , Humanos , Masculino , Neoplasias de la Vejiga Urinaria/genética , Análisis por Conglomerados , Biología Computacional , Bases de Datos Factuales , Ácidos Grasos/genética , Microambiente TumoralRESUMEN
M1 polarization of tumor-associated macrophages (TAMs) is a promising approach to breaking through therapeutic barriers imposed by the immunosuppressive tumor microenvironment (TME). As a clinically-used immunopotentiator for cancer patients after chemotherapies; however, the immunomodulatory mechanism and potential of polyporus polysaccharide (PPS) remains unclear. Here, we present mannose-decorated PPS-loaded superparamagnetic iron-based nanocomposites (Man/PPS-SPIONs) for synergistic M1 polarization of TAMs and consequent combinational anti-breast cancer therapy. Once internalized by M2-like TAMs, PPS released from Man/PPS-SPIONs induces the M1 polarization via IFN-γ secretion and downstream NF-κB pathway activating. The SPIONs within the nanocomposites mediate a Fenton reaction, producing OH· and activating the subsequent NF-κB/MAPK pathway, further facilitating the M1 polarization. The Man/PPS-SPIONs thereby establish a positive feedback loop of M1 polarization driven by the "IFN-γ-Fenton-NF-κB/MAPK" multi-pathway, leading to a series of anti-tumoral immunologic responses in the TME and holding promising potential in combinational anticancer therapies. Our study offers a new strategy to amplify TME engineering by combinational natural carbohydrate polymers and iron-based materials.
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A low-driving energy and bistable recoverable MEMS safety and arming device (S&A), based on microcasting technology and deep silicon etching technology, is proposed to meet safety system requirements. A force-electromagnetic combination solution is constructed for the Si MEMS S&A, with parameters and strength verified, ultimately achieving an S&A size of (13 × 13 × 0.4) mm. Additionally, a low-driving energy U-shaped electromagnetic coil (USEC) model is designed using microcasting technology, and an electrical-magnetic-mechanical coupling mathematical model is established to explore the relationship between design parameters and driving capacity and reliability. With a driving power of 8 V/0.5 A, the model achieves a stable electromagnetic driving force of 15 mN with a travel distance of 0.5 mm. Finally, the fabrication and testing of the USEC and S&A are carried out, with driving capability and S&A disarming ability tests conducted to verify the feasibility of the system design. Compared to the existing S&A, this scheme has the advantages of low-driving energy, recoverability, fast response speed, and strong adaptability.
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With the aim of achieving the combat technical requirements of super-quick (SQ) initiation and reliable self-destruction (SD) of a small-caliber projectile fuze, this paper describes a high-functional-density integrated (HFDI) inertial switch based on the "ON-OFF" state transition (i.e., almost no terminal ballistic motion). The reliable state switching of the HFDI inertial switch is studied via elastic-plastic mechanics and verified via both simulations and experiments. The theoretical and simulation results indicate that the designed switch can achieve the "OFF-ON" state transition in the internal ballistic system, and the switch can achieve the "ON-OFF" state transition in the simulated terminal ballistic system within 8 µs or complete the "ON-OFF" state transition as the rotary speed sharply decreases. The experimental results based on the anti-target method show the switch achieves the "ON-OFF" state transition on the µs scale, which is consistent with the simulation results. Compared with the switches currently used in small-caliber projectile fuzes, the HFDI inertial switch integrates more functions and reduces the height by about 44%.
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Information self-destruction devices represent the last protective net available to realize information security. The self-destruction device proposed here can generate GPa-level detonation waves through the explosion of energetic materials and these waves can cause irreversible damage to information storage chips. A self-destruction model consisting of three types of nichrome (Ni-Cr) bridge initiators with copper azide explosive elements was first established. The output energy of the self-destruction device and the electrical explosion delay time were obtained using an electrical explosion test system. The relationships between the different copper azide dosages and the assembly gap between the explosive and the target chip with the detonation wave pressure were obtained using LS-DYNA software. The detonation wave pressure can reach 3.4 GPa when the dosage is 0.4 mg and the assembly gap is 0.1 mm, and this pressure can cause damage to the target chip. The response time of the energetic micro self-destruction device was subsequently measured to be 23.65 µs using an optical probe. In summary, the micro-self-destruction device proposed in this paper offers advantages that include low structural size, fast self-destruction response times, and high energy-conversion ability, and it has strong application prospects in the information security protection field.
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BACKGROUND: Conventional dissolving microneedles (DMNs) face significant challenges in anti-melanoma therapy due to the lack of active thrust to achieve efficient transdermal drug delivery and intra-tumoral penetration. METHODS: In this study, the effervescent cannabidiol solid dispersion-doped dissolving microneedles (Ef/CBD-SD@DMNs) composed of the combined effervescent components (CaCO3 & NaHCO3) and CBD-based solid dispersion (CBD-SD) were facilely fabricated by the "one-step micro-molding" method for boosted transdermal and tumoral delivery of cannabidiol (CBD). RESULTS: Upon pressing into the skin, Ef/CBD-SD@DMNs rapidly produce CO2 bubbles through proton elimination, significantly enhancing the skin permeation and tumoral penetration of CBD. Once reaching the tumors, Ef/CBD-SD@DMNs can activate transient receptor potential vanilloid 1 (TRPV1) to increase Ca2+ influx and inhibit the downstream NFATc1-ATF3 signal to induce cell apoptosis. Additionally, Ef/CBD-SD@DMNs raise intra-tumoral pH environment to trigger the engineering of the tumor microenvironment (TME), including the M1 polarization of tumor-associated macrophages (TAMs) and increase of T cells infiltration. The introduction of Ca2+ can not only amplify the effervescent effect but also provide sufficient Ca2+ with CBD to potentiate the anti-melanoma efficacy. Such a "one stone, two birds" strategy combines the advantages of effervescent effects on transdermal delivery and TME regulation, creating favorable therapeutic conditions for CBD to obtain stronger inhibition of melanoma growth in vitro and in vivo. CONCLUSIONS: This study holds promising potential in the transdermal delivery of CBD for melanoma therapy and offers a facile tool for transdermal therapies of skin tumors.
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Although air pollutions cause human diseases, no epidemiological study has investigated the effect of exposure to air pollutants on brain diseases in the general population. Our objective was to examine the association between tropospheric airborne pollutants and human health risk and global burden, especially, attributable to indoor formaldehyde (FA) pollution in China. The data of tropospheric pollutants, such as: CO, NO, O3, PM2.5 or PM10, SO2, and FA in China, 2013-2019, which were derived from the database of satellite remote-sensing, were first calculated and then analyzed them according to satellite cloud pictures. The rate of prevalence, incidence, deaths, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) of the Chinese population was obtained from the Global Burden of Diseases (GBD 2010). A linear regression analysis was used to evaluate the relationship between tropospheric FA concentrations and GBD indexes of human brain diseases, the numbers of fire plot, the average summer temperature, population density and car sales in China from 2013 to 2019. Our results showed that the levels of tropospheric FA could reflect the degree of indoor air FA pollution on a nationwide scale in China; in particular, only tropospheric FA exhibited a positive correlation with the rates of both prevalence and YLDs in brain diseases including: Alzheimer's disease (AD) and brain cancer, but not in Parkinson's disease and depression. In particular, the spatial-temporal changes in tropospheric FA levels were consistent with the geographical distribution of FA exposure-induced AD and brain cancer in both sex old adults with age (60-89). In addition, summer average temperature, car sales and population density were positively correlated with tropospheric FA levels in China, 2013-2019. Hence, mapping of tropospheric pollutants could be used for air quality monitoring and health risk assessment.
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Enfermedad de Alzheimer , Neoplasias Encefálicas , Personas con Discapacidad , Contaminantes Ambientales , Adulto , Humanos , Años de Vida Ajustados por Calidad de Vida , Factores de Riesgo , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/epidemiología , China/epidemiologíaRESUMEN
Sustained retina drug delivery and rational drug combination are considered essential for enhancing the efficacy of therapy for wet age-related macular degeneration (wAMD) due to the conservative structure of the posterior ocular segment and the multi-factorial pathological mechanism. Designing a drug co-delivery system that can simultaneously achieve deep penetration and long-lasting retention in the vitreous is highly desired, yet remains a huge challenge. In this study, we fabricated Bor/RB-M@TRG as an intravitreal-injectable hydrogel depot for deep penetration into the posterior ocular segment and long-lasting distribution in the retinal pigment epithelium (RPE) layer. The Bor/RB-M@TRG consisted of borneol-decorated rhein and baicalein-coloaded microemulsions (Bor/RB-M, the therapy entity) and a temperature-responsive hydrogel matrix (the intravitreal depot). Bor/RB-M exhibited the strongest in vitro anti-angiogenic effects among all the groups studied, which is potentially associated with improved cellular uptake, as well as the synergism of rhein and baicalein, acting via anti-angiogenic and anti-oxidative stress pathways, respectively. Importantly, a single intravitreal (IVT) injection with Bor/RB-M@TRG displayed significant inhibition against the CNV of wAMD model mice, compared to all other groups. Particularly, coumarin-6-labeled Bor/RB-M@TRG (Bor/C6-M@TRG) could not only deeply penetrate into the retina but also stably accumulate in the RPE layer for at least 14 days. Our design integrates the advantages of borneol-decorated microemulsions and hydrogel depots, offering a promising new approach for clinically-translatable retinal drug delivery and synergistic anti-wAMD treatment.
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Hidrogeles , Retina , Animales , Ratones , AntraquinonasRESUMEN
BACKGROUND: A recent Mendelian randomization (MR) did not support an effect of the lead interleukin-6 receptor (IL-6 R) variant on risk of pulmonary arterial hypertension (PAH). Thus, we used two sets of genetic instrumental variants (IVs) and publicly available PAH genome-wide association studies (GWAS) to reassess the genetic causal link between IL-6 signaling and PAH. METHODS: Six independent IL-6 signaling and 34 independent soluble IL-6 receptor (sIL-6 R) genetic IVs from recent MR reports and PAH GWAS including 162,962 European individuals were used to perform this two-sample MR study. RESULTS: We found that as IL-6 signaling genetically increased, the risk of PAH reduced using IVW (odds ratio [OR] = 0.023, 95% confidence interval [CI]: 0.0013-0.393; p = .0093) and weighted median (OR = 0.033, 95% CI: 0.0024-0.467; p = .0116). Otherwise, as sIL-6 R genetically increased, the risk of PAH increased using IVW (OR = 1.34, 95% CI: 1.16-1.56; p = .0001), weighted median (OR = 1.36, 95% CI: 1.10-1.68; p = .005), MR-Egger (OR = 1.43, 95% CI: 1.05-1.94; p = .03), and weighted mode (OR = 1.35, 95% CI for OR: 1.12-1.63; p = .0035). CONCLUSION: Our analysis suggested the causal link between genetically increased sIL-6 R and increased risk of PAH and between genetically increased IL-6 signaling and reduced risk of PAH. Thus, higher sIL-6 R levels may be a risk factor for patients with PAH, whereas higher IL-6 signaling may be a protective factor for patients with PAH.
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Hipertensión Arterial Pulmonar , Humanos , Interleucina-6 , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Factores de RiesgoRESUMEN
A microelectromechanical systems (MEMS) solid-state logic control chip with three layers-diversion layer, control layer, and substrate layer-is designed to satisfy fuse miniaturization and integration requirements. A mathematical model is established according to the heat conduction equation, and the limit conditions of different structures are presented. The finite element multi-physical field simulation method is used to simulate the size and the action voltage of the diversion layer of the control chip. Based on the surface silicon process, fuse processing, and testing with the MEMS solid-state fuse-logic control chip, a diversion layer constant current, maximum current resistance test, and a control layer of different bridge area sizes, the bridge area size is 200 × 30 µm, and the minimum electrical explosion voltage is 23.6 V. The theoretical calculation results at 20 V and 100 µF demonstrate that the capacitor energy is insufficient to support the complete vaporization of the bridge area, but can be partially vaporized, consistent with the experimental results.
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Cicatriz , Trasplante de Piel , Humanos , Cicatriz/cirugía , Cicatrización de Heridas , DermisRESUMEN
Observational studies have suggested a suspected association between varicella-zoster virus (VZV) infection and multiple sclerosis (MS), but the connection has remained unclear. The aim of the present study is to evaluate the causal relationship between chickenpox which is caused by VZV infection and MS. We performed a two-sample Mendelian randomization analysis to investigate the association of chickenpox with MS using summary statistics from genome-wide association studies (GWAS). The GWAS summary statistics data for chickenpox was from the 23andMe cohort including 107 769 cases and 15 982 controls. A large summary of statistical data from the International Multiple Sclerosis Genetics Consortium (IMSGC) was used as the outcome GWAS data set, including 14 802 MS cases and 26 703 controls. We found evidence of a significant association between genetically predicted chickenpox and risk of MS (odds ratio [OR] = 35.27, 95% confidence interval [CI] = 22.97-54.17, p = 1.46E-59). Our findings provided evidence indicating a causal effect of chickenpox on MS. Further elucidations of this association and underlying mechanisms are needed for identifying feasible interventions to promote MS prevention.
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Varicela , Esclerosis Múltiple , Humanos , Varicela/epidemiología , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple/genética , Análisis de la Aleatorización Mendeliana , Estudio de Asociación del Genoma Completo , Herpesvirus Humano 3/genética , Polimorfismo de Nucleótido SimpleRESUMEN
Information self-destruction modules (ISDMs) play a vital role in the information security area. In this paper, an ISDM based on the integration of a micro-thermoelectric generation mechanism (M-TEGM) with energetic materials (EMs) is proposed. On the basis of energy conversion relationship, an open-loop electromotive force is induced, and this energy will drive the EMs to release the detonation wave and realize information storage module self-destruction. During the tests, under the temperature difference (100 K), the open-loop electromotive force (3.86 V) is induced by the M-TEGM and can drive the EMs (0.37 mg copper azide) to generate a detonation wave (GPa) in 3.4 µs, which can physically destroy the information storage modules. This ISDM has advantages that include rapid response times, low drive energy compared with traditional information security technology.
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Some viruses, such as varicella zoster virus, are associated with severe dementia. The present study aims to identify the causal link between chickenpox and dementia. To date, the largest publicly available genome-wide association study (GWAS) for chickenpox (710 cases and 211 856 controls from European individuals) and for dementia (5933 cases and 212 859 controls from European individuals) were used to performed this two-sample Mendelian randomization (MR) study. We found no significant pleiotropy or heterogeneity in all seven selected chickenpox genetic instrumental variants in dementia GWAS. Of seven chickenpox genetic variants, two are located in the intergenic region and five are located in intron. We found that as chickenpox genetically increased, dementia risk increased based on an inverse-variance weighted analysis (ß = 0.070, 95% confidence interval [CI] for ß: 0.014-0.126; odds ratio [OR] = 1.073, 95% CI for OR: 1.015-1.134; p = 0.014) and weighted median (ß = 0.071, 95% CI for ß: 0.002-0.141; OR = 1.074, 95% CI for OR: 1.002-1.152; p = 0.045). Reverse MR analysis showed no causal effect of dementia on chickenpox. Our analysis suggests a causal effect of genetically increased chickenpox on dementia risk. Thus, chickenpox may be a potential risk factor for dementia.
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Varicela , Demencia , Humanos , Análisis de la Aleatorización Mendeliana , Estudio de Asociación del Genoma Completo , Varicela/epidemiología , Polimorfismo de Nucleótido Simple , Demencia/epidemiología , Demencia/genéticaRESUMEN
BACKGROUND: Low-value care provides little or no benefit, causes harm and incurs unnecessary costs. Low-value care for coronary heart disease (CHD) is particularly prevalent in the US and China. Identifying low-value care services is the first step in reducing these services. There is currently limited data on identifying a comprehensive CHD low-value care list in the US and China. We aimed to identify and compare low-value care recommendations for CHD prevention, diagnosis, and treatment in the US and China. METHODS: Clinical practice guidelines (CPGs) related to CHD in the US and China were screened for do-not-do recommendations stating that specific services should be avoided. The similarities and discrepancies of low-value care recommendations for CHD between the two countries were then compared. RESULTS: We found a total of 38 low-value care recommendations in 6 Chinese CPGs and 98 recommendations in 11 US CPGs. In the US, the most common types of low-value care recommendations were therapeutic medications (44, 44.9%), followed by therapeutic procedures (27, 27.6%), diagnostic imaging (16, 16.3%), diagnostic testing (9, 9.2%) and primary prevention (2, 2.0%). In China, the most common types were therapeutic medications (18, 47.4%), followed by therapeutic procedures (13, 34.2%), diagnostic testing (4, 10.5%), and diagnostic imaging (3, 7.9%). CONCLUSION: In this study, a comprehensive list of low-value care for CHD in the US and China was established and potentially become the important targets for de-implementation for both countries. The findings may have important implications for other countries, especially low-and middle-income countries, to reduce low-value care for CHD.