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Sarcoidosis is a systemic granulomatous disease characterized by non-caseating epithelioid cell granulomas. One of its immunological hallmarks is the differentiation of CD4 + naïve T cells into Th1/Th17 cells, accompanied by the release of numerous pro-inflammatory cytokines. The TL1A/DR3 signaling pathway plays a crucial role in activating effector lymphocytes, thereby triggering pro-inflammatory responses. The primary aim of this investigation was to scrutinize the impact of anti-TL1A monoclonal antibody on the dysregulation of Th1/Th17 cells and granuloma formation in sarcoidosis. Initially, the abnormal activation of the TL1A/DR3 signaling pathway in pulmonary tissues of sarcoidosis patients was confirmed using qPCR and immunohistochemistry techniques. Subsequently, employing a murine model of sarcoidosis, the inhibitory effects of anti-TL1A monoclonal antibody on the TL1A/DR3 signaling pathway in sarcoidosis were investigated through qPCR, immunohistochemistry, and Western blot experiments. The influence of anti-TL1A monoclonal antibody on granulomas was assessed through HE staining, while their effects on sarcoidosis Th1/Th17 cells and associated cytokine mRNA levels were evaluated using flow cytometry and qPCR, respectively. Immunofluorescence and Western blot experiments corroborated the inhibitory effects of anti-TL1A monoclonal antibody on the aberrant activation of the PI3K/AKT signaling pathway in sarcoidosis. The findings of this study indicate that the TL1A/DR3 signaling pathway is excessively activated in sarcoidosis. Anti-TL1A monoclonal antibody effectively inhibit this abnormal activation in sarcoidosis, thereby alleviating the dysregulation of Th1/Th17 cells and reducing the formation of pulmonary granulomas. This effect may be associated with the inhibition of the downstream PI3K/AKT signaling pathway. Anti-TL1A monoclonal antibody hold promise as a potential novel therapeutic intervention for sarcoidosis.
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Anticuerpos Monoclonales , Granuloma , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Sarcoidosis , Transducción de Señal , Células TH1 , Células Th17 , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral , Animales , Células TH1/inmunología , Células Th17/inmunología , Transducción de Señal/efectos de los fármacos , Humanos , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/inmunología , Granuloma/inmunología , Granuloma/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/inmunología , Femenino , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/metabolismo , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/inmunología , Masculino , Sarcoidosis/inmunología , Sarcoidosis/tratamiento farmacológico , Ratones , Adulto , Persona de Mediana Edad , Miembro 25 de Receptores de Factores de Necrosis Tumoral/metabolismo , Miembro 25 de Receptores de Factores de Necrosis Tumoral/inmunología , Pulmón/inmunología , Pulmón/patología , Citocinas/metabolismo , Citocinas/inmunología , Modelos Animales de Enfermedad , Ratones Endogámicos BALB CRESUMEN
BACKGROUND: Abdominal computed tomography (CT) scan is a crucial imaging modality for creating cross-sectional images of the abdominal area, particularly in cases of abdominal trauma, which is commonly encountered in traumatic injuries. However, interpreting CT images is a challenge, especially in emergency. Therefore, we developed a novel deep learning algorithm-based detection method for the initial screening of abdominal internal organ injuries. METHODS: We utilized a dataset provided by the Kaggle competition, comprising 3,147 patients, of which 855 were diagnosed with abdominal trauma, accounting for 27.16% of the total patient population. Following image data pre-processing, we employed a 2D semantic segmentation model to segment the images and constructed a 2.5D classification model to assess the probability of injury for each organ. Subsequently, we evaluated the algorithm's performance using 5k-fold cross-validation. RESULTS: With particularly noteworthy performance in detecting renal injury on abdominal CT scans, we achieved an acceptable accuracy of 0.932 (with a positive predictive value (PPV) of 0.888, negative predictive value (NPV) of 0.943, sensitivity of 0.887, and specificity of 0.944). Furthermore, the accuracy for liver injury detection was 0.873 (with PPV of 0.789, NPV of 0.895, sensitivity of 0.789, and specificity of 0.895), while for spleen injury, it was 0.771 (with PPV of 0.630, NPV of 0.814, sensitivity of 0.626, and specificity of 0.816). CONCLUSIONS: The deep learning model demonstrated the capability to identify multiple organ injuries simultaneously on CT scans and holds potential for application in preliminary screening and adjunctive diagnosis of trauma cases beyond abdominal injuries.
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Traumatismos Abdominales , Aprendizaje Profundo , Tomografía Computarizada por Rayos X , Humanos , Traumatismos Abdominales/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Masculino , Femenino , Adulto , Algoritmos , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
Sepsis is a systemic inflammatory response syndrome caused by trauma or infection, which can lead to multiple organ dysfunction. In severe cases, sepsis can also progress to septic shock and even death. Effective treatments for sepsis are still under development. This study aimed to determine if targeting the PI3K/Akt signaling with CAL-101, a PI3K p110δ inhibitor, could alleviate lipopolysaccharide (LPS)-induced sepsis and contribute to immune tolerance. Our findings indicated that CAL-101 treatment improved survival rates and alleviated the progression of LPS-induced sepsis. Compared to antibiotics, CAL-101 not only restored the Th17/regulatory T cells (Treg) balance but also enhanced Treg cell function. Additionally, CAL-101 promoted type 2 macrophage (M2) polarization, inhibited TNF-α secretion, and increased IL-10 secretion. Moreover, CAL-101 treatment reduced pyroptosis in peritoneal macrophages by inhibiting caspase-1/gasdermin D (GSDMD) activation. This study provides a mechanistic basis for future clinical exploration of targeted therapeutics and immunomodulatory strategies in the treatment of sepsis.
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Fosfatidilinositol 3-Quinasa Clase I , Ratones Endogámicos C57BL , Piroptosis , Sepsis , Linfocitos T Reguladores , Células Th17 , Animales , Ratones , Fosfatidilinositol 3-Quinasa Clase I/antagonistas & inhibidores , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacología , Piroptosis/efectos de los fármacos , Sepsis/inmunología , Sepsis/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/efectos de los fármacos , Células Th17/inmunología , Células Th17/efectos de los fármacosRESUMEN
A remarkable feature of disordered solids distinct from crystals is the violation of the Debye scaling law of the low-frequency vibrational density of states. Because the low-frequency vibration is responsible for many properties of solids, it is crucial to elucidate it for disordered solids. Numerous recent studies have suggested power-law scalings of the low-frequency vibrational density of states, but the scaling exponent is currently under intensive debate. Here, by classifying disordered solids into stable and unstable ones, we find two distinct and robust scaling exponents for non-phononic modes at low frequencies. Using the competition of these two scalings, we clarify the variation of the scaling exponent and hence reconcile the debate. Via the study of both ordinary and ultra-stable glasses, our work reveals a comprehensive picture of the low-frequency vibration of disordered solids and sheds light on the low-frequency vibrational features of ultra-stable glasses on approaching the ideal glass.
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Atopic dermatitis (AD) is a chronic skin condition with intense pruritus, eczema, and dry skin. The recurrent intense pruritus and numerous complications in patients with AD can profoundly affect their quality of life. Obesity is one of its comorbidities that has been confirmed to be the hazard factor of AD and also worsen its severity. Nevertheless, the specific mechanisms that explain the connection between obesity and AD remain incompletely recognized. Recent studies have built hopes on various adipokines to explain this connection. Adipokines, which are disturbed by an obese state, may lead to immune system imbalances in people with AD and promote the development of the disease. This review focuses on the abnormal expression patterns of adipokines in patients with AD and their potential regulatory molecular mechanisms associated with AD. The connection between AD and obesity is elucidated through the involvement of adipokines. This conduces to the in-depth exploration of AD pathogenesis and provides a new perspective to develop therapeutic targets.
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Dermatitis Atópica , Humanos , Calidad de Vida , Obesidad , Prurito , AdipoquinasRESUMEN
Background: This study aimed to explore the risk factors and clinical characteristics of granulomatous mastitis (GM) using a case-control study and establish and validate a clinical prediction model (nomogram). Methods: This retrospective case-control study was conducted in three hospitals in China from June 2017 to December 2021. A total of 1634 GM patients and 186 healthy women during the same period were included and randomly divided into the modeling and validation groups in a 7:3 ratio. To identify the independent risk factors of GM, univariate and multivariate logistic analyses were conducted and used to develop a nomogram. The prediction model was internally and externally validated using the Bootstrap technique and validation cohort. The receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the discrimination and calibration of the prediction model. Decision curve analysis (DCA) and clinical impact curve (CIC) were used to evaluate the clinical significance of the model. Results: The average age of GM patients was 33.14 years (mainly 20-40). The incidence was high within five years from delivery and mainly occurred in the unilateral breast. The majority of the patients exhibited local skin alterations, while some also presented with systemic symptoms. On multivariate logistic analysis, age, high prolactin level, sex hormone intake, breast trauma, nipple discharge or invagination, and depression were independent risk factors for GM. The mean area under the curve (AUC) in the modeling and validation groups were 0.899 and 0.889. The internal and external validation demonstrated the model's predictive ability and clinical value. Conclusion: Lactation-related factors are the main risk factors of GM, leading to milk stasis or increased ductal secretion. Meanwhile, hormone disorders could affect the secretion and expansion of mammary ducts. All these factors can obstruct or injure the duct, inducing inflammatory reactions and immune responses. Additionally, blunt trauma, depressed mood, and diet preference can accelerate the process. The nomogram can effectively predict the risk of GM.
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The efficient depolymerization of polyesters under mild conditions remains a significant challenge. Herein, we demonstrate a highly efficient strategy for the degradation of a diverse array of waste polyesters as low to 80 °C, 1â bar H2 . The key to the success of this transformation relied on the initial transesterification of macromolecular polyester into more degradable oligomeric fragments in the presence of CH3 OH and the subsequent hydrogenation by the use of the rationally designed quinaldine-based Ru complex. Controlled experiments and preliminary mechanistic studies disclosed the quinaldine-based catalysts could be hydrogenated to the eventually active species, which has been confirmed by X-ray diffraction analysis and directly used as a catalyst in the hydrogenolysis of polyester. The strong viability and high activity of this new species in protic solvent were explained in detail. Besides, the crucial role of CH3 OH in promoting reaction efficiency during the whole process was also elucidated. The synthetic utility of this method was further illustrated by preparing 1,4-cyclohexanedimethanol (CHDM) from waste polyethylene terephthalate (PET).
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Brassinosteroids (BRs) are phytohormones that play numerous roles in a plant's response to environmental stress. While BES/BZR transcription factors are essential components in BR signaling, their role in regulating postharvest fruit responses to cold stress is largely unknown. In this study, the application of 24-epibrassinolide (EBR) to peaches alleviated chilling injury (CI) during postharvest cold storage. We further characterized a key BES/BZR gene, PpBZR1, which regulates peach cold resistance. Transient expression PpBZR1 in peaches showed that PpBZR1 inhibits PpVIN2 expression and VIN activity, resulting in an elevated level of sucrose, which protects fruit from CI. Arabidopsis thaliana expressing PpBZR1 that had a high germination and seedling survival rate at low temperatures, which may be due to higher level of sucrose and lower oxidative damage. Mechanistically, we confirmed that PpBZR1 directly binds to the PpVIN2 promoter and functions as a negative regulator for sucrose metabolism. In addition, PpCBF1/5/6 were induced by EBR treatment and AtCBFs were upregulated in PpBZR1 transgenic Arabidopsis thaliana. Combined with previous findings, we hypothesize that PpBZR1 regulates PpVIN2 and may also be mediated by CBF. In conclusion, PpBZR1 expression is induced by EBR treatment during cold storage, which futher inhibite sucrose degradation gene PpVIN2 transcription via direct binding its promoter and indirectly regulating PpVIN2, resulting in slower sucrose degradation and higher chilling tolerance of peach.
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Arabidopsis , Prunus persica , Factores de Transcripción/genética , Prunus persica/genética , Respuesta al Choque por Frío , Arabidopsis/genética , Frutas/genéticaRESUMEN
Under a sufficiently large load, a solid material will flow via rearrangements, where particles change neighbors. Such plasticity is most easily described in the athermal, quasistatic limit of zero temperature and infinitesimal loading rate, where rearrangements occur only when the system becomes mechanically unstable. For disordered solids, the instabilities marking the onset of rearrangements have long been believed to be fold instabilities, in which an energy barrier disappears and the frequency of a normal mode of vibration vanishes continuously. Here, we report that there exists another, anomalous, type of instability caused by the breaking of a "stabilizing bond," whose removal creates an unstable vibrational mode. For commonly studied systems, such as those with harmonic finite-range interparticle interactions, such "discontinuous instabilities" are not only inevitable, they often dominate the modes of failure. Stabilizing bonds are a subset of all the bonds in the system and are prevalent in disordered solids generally. Although they do not trigger discontinuous instabilities in systems with vanishing stiffness at the interaction cutoff, they are, even in those cases, local indicators of incipient mechanical failure. They therefore provide an accurate structural predictor of instabilities not only of the discontinuous type but of the fold type as well.
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Strain-controlled isotropic compression gives rise to jammed packings of repulsive, frictionless disks with either positive or negative global shear moduli. We carry out computational studies to understand the contributions of the negative shear moduli to the mechanical response of jammed disk packings. We first decompose the ensemble-averaged, global shear modulus as ãGã=(1-F_{-})ãG_{+}ã+F_{-}ãG_{-}ã, where F_{-} is the fraction of jammed packings with negative shear moduli and ãG_{+}ã and ãG_{-}ã are the average values from packings with positive and negative moduli, respectively. We show that ãG_{+}ã and ã|G_{-}|ã obey different power-law scaling relations above and below pN^{2}â¼1. For pN^{2}>1, both ãG_{+}ãN and ã|G_{-}|ãNâ¼(pN^{2})^{ß}, where ßâ¼0.5 for repulsive linear spring interactions. Despite this, ãGãNâ¼(pN^{2})^{ß^{'}} with ß^{'}â³0.5 due to the contributions from packings with negative shear moduli. We show further that the probability distribution of global shear moduli P(G) collapses at fixed pN^{2} and different values of p and N. We calculate analytically that P(G) is a Γ distribution in the pN^{2}âª1 limit. As pN^{2} increases, the skewness of P(G) decreases and P(G) becomes a skew-normal distribution with negative skewness in the pN^{2}â«1 limit. We also partition jammed disk packings into subsystems using Delaunay triangulation of the disk centers to calculate local shear moduli. We show that the local shear moduli defined from groups of adjacent triangles can be negative even when G>0. The spatial correlation function of local shear moduli C(r[over â]) displays weak correlations for pn_{sub}^{2}<10^{-2}, where n_{sub} is the number of particles within each subsystem. However, C(r[over â]) begins to develop long-ranged spatial correlations with fourfold angular symmetry for pn_{sub}^{2}â³10^{-2}.
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Sarcoidosis is a multisystem inflammatory disease characterized by the development of Th1/Th17/regulatory T cells (Tregs)-related non-caseating granulomas. Phosphoinositide-3 kinases δ/γ (PI3Kδ/γ) play an important role in the maintenance of effective immunity, especially for Tregs homeostasis and stability. In the present study, superoxide dismutase A (SodA) stimulation was used to establish the sarcoidosis mouse model. The second immune stimulus was accompanied by CAL-101 (PI3Kδ inhibitor) or AS-605240 (PI3Kδ/γ inhibitor) treatment. To detect the effect of the PI3Kδ/γ inhibitor on the morphology of pulmonary granuloma and the activation of the PI3K signaling pathway, hematoxylin and eosin staining and immunofluorescence and western blotting was used, respectively. Fluorescence-activated cell sorting analysis and reverse transcription-quantitative PCR were adopted to detect the effect of the PI3Kδ/γ inhibitor on the SodA-induced sarcoidosis mouse model in respect to immune cell disorder and the function of Treg cells, with CD4+CD25- T cells and CD4+CD25+ T cells sorted by magnetic cell sorting. The results demonstrated that the inhibition of PI3Kδ/γ by transtracheal CAL-101/AS-605240 administration facilitated pulmonary granuloma formation. These therapeutic effects were associated with certain mechanisms, including suppressing the aberrantly activated PI3K/Akt signaling in both pulmonary granuloma and Tregs, particularly rescuing the suppressive function of Tregs. Notably, CAL-101 was more effective in immune modulation compared with AS-605240 and could overcome the aberrantly activated Akt in the lung and Tregs. These results suggest that PI3K/Akt signaling, especially the PI3Kδ subunit, can play a key role in optimal Tregs-mediated protection against pulmonary sarcoidosis. Therefore, transtracheal usage of PI3Kδ/γ inhibitors is an attractive therapy that may be developed into a new immune-therapeutic principle for sarcoidosis in the future.
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(1) Objective: To investigate the relationship between serum macrophage migration inhibitory factor (MIF) level and white matter hyperintensity (WMH) and executive function (EF) in cerebral small vascular disease (CSVD), and assess the impact and predictive value of MIF level and Fazekas scores in CSVD-related cognitive impairment (CI) (CSVD-CI); (2) Methods: A total of 117 patients with WMH admitted to the First Affiliated Hospital of Xinxiang Medical College from January 2022 to August 2022 were enrolled. According to the Montreal cognitive assessment (MoCA) scale, subjects were divided into a normal cognitive group and an impaired group. All subjects required serum MIF level, 3.0 T MRI, and neuropsychological evaluation to investigate the risk factors for CDVD-CI, analyze the correlation between MIF level, WMH, and EF, and to analyze the diagnostic value of MIF and WMH degree in predicting CSVD-CI; (3) Results: 1. Fazekas score and MIF level were the risk factors of CSVD-CI. 2. The Fazekas score was negatively correlated with MoCA score, positively correlated with Stroop C-Time, Stroop C-Mistake, Stroop interference effects (SIE)-Time, SIE-Mistake, and color trails test (CTT) interference effects (CIE) (B-A). 3. The MIF level was positively correlated with Fazekas score, Stroop C-Time, SIE-Time, CTT B-Time, and CIE (B-A), and negatively correlated with MoCA score. 4. Fazekas score and MIF level were significant factors for diagnosing CSVD-CI; (4) Conclusion: The Fazekas score and MIF level may be the risk factors of CSVD-CI, and they are closely correlated to CI, especially the EF, and they have diagnostic value for CSVD-CI.
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Due to the urgent demand for lithium-ion batteries (LIBs) with a high energy density, silicon (Si) possessing an ultrahigh capacity has aroused wide attention. However, its practical application is seriously hindered by enormous volume changes of the Si anode during cycling. Developing novel binders suitable for the Si anode has proven to be an effective strategy to improve its electrochemical performance. Herein, we constructed a three-dimensional network binder, in which the polyacrylic acid (PAA) long chains are cross-linked with one kind of amino acid, lysine (Lys). The abundant polar groups in PAA/Lys enable it to tightly adhere to the Si particles via hydrogen bonds, and the cross-linked structure prevents irreversible slipping of the PAA chains upon volume variation of the particles. The Si used was obtained from a sustainable route by recycling photovoltaic waste silicon. With high elasticity and strong adhesion, the PAA/Lys binder can effectively keep the structural integrity of the Si electrode and improve its electrochemical performance. The Si electrode using the PAA/Lys binder exhibits a good cycling stability (1008 mAh g-1 at 2 A g-1 after 250 cycles). Even with a high mass loading of 3.03 mg cm-2, the Si anode can remain stable for 100 cycles at a high fixed areal capacity of 3.03 mAh cm-2. This work gives a practical method to make stable Si electrodes using sustainable Si source and environmentally friendly amino acid-based binders.
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Based on theoretical analysis, this study empirically analyzes the mediating mechanism of how land rentals work on large-scale farmers to enhance soil conservation with survey data of 425 large-scale farmers in Shandong and Anhui Provinces, the main grain-producing regions of China, and further examines the moderating effect of agricultural extension services. The results show that: (1) The higher the land rentals, the greater the probability that large-scale farmers enhance soil conservation. (2) The mediating effect demonstrates that in a highly market-oriented rural land transfer market in China, the land lease term of large-scale farmers is longer with the increase of land rentals, thus motivating large-scale farmers to engage in soil conservation. (3) As shown by the moderating effect, agricultural extension services can further positively moderate the contribution of land lease term to large-scale farmers enhancing soil conservation. In order to encourage large-scale farmers to enhance soil conservation, on the one hand it is necessary to standardize the land transfer market and proactively guide large-scale farmers to extend the land lease term. On the other hand, it is indispensable to strengthen agricultural extension services and further broaden the access to soil conservation technologies for large-scale farmers.
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Conservación de los Recursos Naturales , Suelo , Humanos , Conservación de los Recursos Naturales/métodos , Agricultores , Agricultura/métodos , ChinaRESUMEN
Ti3C2Tx MXene has attracted considerable interest as a new emerging two-dimensional material for environmental remediation due to its high adsorption capacity. However, its use is greatly limited by its poor mechanical properties, low processability and recyclability, and the low dispersity of such powder materials. In this work, a porous adsorbent (C-CMP) containing cellulose nanocrystals (CNC), Ti3C2Tx MXene and polyvinyl alcohol (PVA) was prepared by a simple and environmentally-friendly foaming method. Glutaraldehyde was used as crosslinker to improve the mechanical properties and boost the adsorption efficiency of methylene blue (MB) molecules. Fourier transform infrared (FT-IR), elemental analysis (EDX) and thermogravimetric analysis (TGA) further confirmed that the preparation of the C-CMP foam and cross-linking reaction were successful. Scanning electron microscope (SEM) indicated that the macropores were distributed homogeneously. The adsorption experiment showed that maximum adsorption capacity of MB can reach 239.92 mg·g-1 which was much higher than anionic dye (methyl orange, 45.25 mg·g-1). The adsorption behavior fitted well with the Langmuir isotherm and pseudo-second-order kinetic models. Thermodynamic analysis indicated that the adsorption process was spontaneous and endothermic. Based on FT-IR, EDX and X-ray photoelectron spectroscopy (XPS) analysis, the adsorption mechanism between C-CMP and MB molecules was attributed to electrostatic interaction.
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Contaminantes Químicos del Agua , Purificación del Agua , Adsorción , Celulosa , Citidina Monofosfato , Cinética , Azul de Metileno/química , Espectroscopía Infrarroja por Transformada de Fourier , Contaminantes Químicos del Agua/química , Purificación del Agua/métodosRESUMEN
We investigate the mechanical response of jammed packings of circulo-lines in two spatial dimensions, interacting via purely repulsive, linear spring forces, as a function of pressure P during athermal, quasistatic isotropic compression. The surface of a circulo-line is defined as the collection of points that is equidistant to a line; circulo-lines are composed of a rectangular central shaft with two semicircular end caps. Prior work has shown that the ensemble-averaged shear modulus for jammed disk packings scales as a power law, ãG(P)ãâ¼P^{ß}, with ßâ¼0.5, over a wide range of pressure. For packings of circulo-lines, we also find robust power-law scaling of ãG(P)ã over the same range of pressure for aspect ratios Râ³1.2. However, the power-law scaling exponent ßâ¼0.8-0.9 is much larger than that for jammed disk packings. To understand the origin of this behavior, we decompose ãGã into separate contributions from geometrical families, G_{f}, and from changes in the interparticle contact network, G_{r}, such that ãGã=ãG_{f}ã+ãG_{r}ã. We show that the shear modulus for low-pressure geometrical families for jammed packings of circulo-lines can both increase and decrease with pressure, whereas the shear modulus for low-pressure geometrical families for jammed disk packings only decreases with pressure. For this reason, the geometrical family contribution ãG_{f}ã is much larger for jammed packings of circulo-lines than for jammed disk packings at finite pressure, causing the increase in the power-law scaling exponent for ãG(P)ã.
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For nonequilibrium systems, how to define temperature is one of the key and difficult issues to solve. Although effective temperatures have been proposed and studied to this end, it still remains elusive what they actually are. Here, we focus on the fluctuation-dissipation temperatures and report that such effective temperatures of slow-evolving systems represent characteristic temperatures of their equilibrium counterparts. By calculating the fluctuation-dissipation relation of inherent structures, we obtain a temperature-like quantity T IS For monocomponent crystal-formers, T IS agrees well with the crystallization temperature T c, while it matches with the onset temperature T on for glass-formers. It also agrees with effective temperatures of typical nonequilibrium systems, such as aging glasses, quasi-static shear flows, and quasi-static self-propelled flows. From the unique perspective of inherent structures, our study reveals the nature of effective temperatures and the underlying connections between nonequilibrium and equilibrium systems and confirms the equivalence between T on and T c.
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We investigate the mechanical response of jammed packings of repulsive, frictionless spherical particles undergoing isotropic compression. Prior simulations of the soft-particle model, where the repulsive interactions scale as a power law in the interparticle overlap with exponent α, have found that the ensemble-averaged shear modulus ãG(P)ã increases with pressure P as â¼P^{(α-3/2)/(α-1)} at large pressures. ãGã has two key contributions: (1) continuous variations as a function of pressure along geometrical families, for which the interparticle contact network does not change, and (2) discontinuous jumps during compression that arise from changes in the contact network. Using numerical simulations, we show that the form of the shear modulus G^{f} for jammed packings within near-isostatic geometrical families is largely determined by the affine response G^{f}â¼G_{a}^{f}, where G_{a}^{f}/G_{a0}=(P/P_{0})^{(α-2)/(α-1)}-P/P_{0}, P_{0}â¼N^{-2(α-1)} is the characteristic pressure at which G_{a}^{f}=0, G_{a0} is a constant that sets the scale of the shear modulus, and N is the number of particles. For near-isostatic geometrical families that persist to large pressures, deviations from this form are caused by significant nonaffine particle motion. We further show that the ensemble-averaged shear modulus ãG(P)ã is not simply a sum of two power laws, but ãG(P)ãâ¼(P/P_{c})^{a}, where a≈(α-2)/(α-1) in the Pâ0 limit and ãG(P)ãâ¼(P/P_{c})^{b}, where bâ³(α-3/2)/(α-1), above a characteristic pressure that scales as P_{c}â¼N^{-2(α-1)}.
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BACKGROUND: Type 1 diabetes (T1D) is a multiple factor autoimmune disease characterized by T cell-mediated immune destruction of islet ß cells. Autologous hematopoietic stem cell transplantation (AHSCT) has been a novel strategy for patients with new-onset T1D, but not for those with a later diagnosis. Disturbance of regulatory T cells (Tregs) likely contributes to poor response after transplantation in later-stage T1D. Inhibition of phosphoinositide 3-kinases (PI3K)/Akt signaling maintains Tregs' homeostasis. METHODS: We built a later-stage streptozotocin (STZ)-induced T1D mouse model. Syngeneic bone marrow transplantation (syn-BMT) was performed 20 days after the onset of diabetes in combination with BKM120 (a PI3K inhibitor). Meanwhile, another group of STZ-diabetic mice were transplanted with bone marrow cells cocultured with BKM120 in vitro for 24 h. Fasting glucose and glucose tolerance were recorded during the entire experimental observation after syn-BMT. Samples were collected 126 days after syn-BMT. Hematoxylin and eosin (H&E) staining was used to detect the effect of PI3K inhibitor combined with syn-BMT on morphology of the T1D pancreas. CD4+CD25- T cells and CD4+CD25+ T cells were sorted by magnetic cell sorting (MACS), then fluorescence activated cell sorting (FACS) and quantitative real-time PCR (qPCR) were used to detect the effect of PI3K inhibitor on modulating immune disorder and restoring the function of Treg cells. RESULTS: Our investigation showed syn-BMT in combination with BKM120 effectively maintained normoglycemia in later-stage T1D. The disease remission effects may be induced by the rebalance of Th17/Tregs dysregulation and restoration of Tregs' immunosuppressive function by BKM120 after syn-BMT. CONCLUSIONS: These results may reveal important connections for PI3K/Akt inhibition and Tregs' homeostasis in T1D after transplantation. AHSCT combining immunoregulatory strategies such as PI3K inhibition may be a promising therapeutic approach in later-stage T1D.
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Objective@#To explore the association of the frequency of domestic violence witness in childhood with the quality of life (QOL) of college students, and to provide a reference for improving the quality of life of students who domestic violence witness in childhood.@*Methods@#In October 2018, a total of 4 034 college students from four universities in Hefei, Anhui Province, were selected to participate in this study. The Conflict Tactics Scales Short Form (CTS2SF) and the World Health Organization Quality of Life-Brief (WHOQOL-BREF) were used to assess the effect of witnessing domestic violence in childhood on the QOL of college students. Multiple linear regression was used to analyze the relationship between the different frequencies of witnessing domestic violence in childhood and the QOL of college students.@*Results@#The mean scores of the subjective assessment of QOL, health subjective assessment, physiology, psychology, social relationships, and environment were (14.06±3.25) (13.42±3.47) (12.61±2.02) (14.09±2.62) (13.72±2.71) (13.77±2.46), respectively. The multiple linear regression model showed that, witnessing domestic violence in childhood was negatively correlated with the QOL of college students (P<0.01). Although occasional expose to severe family violence in childhood was not associated with the health subjective assessment and the environmental dimensions, the different frequencies of witnessing domestic violence in childhood were negatively correlated with the QOL of college students (P<0.05).@*Conclusion@#Frequency of domestic violence witness in childhood is associated with the mean scores of the QOL of college students. It is necessary to explore effective prevention and intervention programs for exposure to domestic violence in childhood.