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l-Cysteine, distinguished by its possession of reactive sulfhydryl groups within its molecular structure, plays a significant role in both biological systems and the pharmaceutical industry. It stands not only as a natural component integral to the constitution of glutathione but also as the principal precursor for the synthesis of l-cystine through an oxidation reaction. This study endeavors to introduce a novel approach to l-cysteine analysis, capitalizing on its optical activity, whereby an optical rotation detection system grounded in the principles of quantum weak measurement is proffered. The optical rotation angle corresponding to the concentration of chiral solutions can be accurately ascertained through spectral analysis. In practical implementation, a chiral sensing system, boasting a sensitivity of 372 nm/rad, was meticulously constructed, leveraging the concept of weak value amplification. Then, the real-time monitoring of chemical reactions involving l-cysteine and dimethyl sulfoxide was performed. Under the specific experimental conditions outlined in this investigation, it was observed that the oxidation process culminated within approximately 12 h. The application of weak measurement-based chiral sensors holds immense potential, providing robust technical support for real-time monitoring in fields such as chiral analysis and the synthesis of chiral pharmaceutical compounds.
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The metal-semiconductor (M-S) contact is usually an Ohmic contact or a Schottky contact, which greatly affects the electronic properties of devices, and it remains a huge challenge to realize a low-resistance Ohmic contact in a metal-semiconductor junction (MSJ). Herein, we systematically studied the band structures, electrostatic potential, charge transfer, Schottky barrier height of carriers, effective carrier masses, and tunneling probability of carriers of a germanene (Ge)/GaAs MSJ. The transition from the Schottky to the Ohmic contact can be caused by applying certain biaxial strains or electric fields, which weakens the Fermi level pinning (FLP) effect and reduces contact resistance. Meanwhile, the electron injection efficiency of Ge/(GaAs)As MSJ (PTB > 27%) is far superior to that of other two-dimensional (2D) vdW MSJs. This work indicates that Ge/GaAs heterostructures are the most compatible for applying high-effective 2D electronic nanodevices under controllable conditions.
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The aim of this study was to investigate whether the protective effect of 2-deoxyglucose (2-DG) on lung ischemia/reperfusion (I/R) injury is mediated by inhibiting nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-mediated pyroptosis in rats. Male Sprague-Dawley rats were randomly divided into control group, 2-DG group, lung I/R injury group (I/R group) and 2-DG+I/R group. 2-DG (0.7 g/kg) was intraperitoneally injected 1 h prior to lung ischemia. The tissue structure was measured under light microscope. Lung injury parameters were detected. The contents of malondialdehyde (MDA), myeloperoxidase (MPO) and lactate were determined by commercially available kits. ELISA was used to detect the levels of IL-1ß and IL-18. Western blot, qRT-PCR and immunofluorescence staining were used to measure the expression changes of glycolysis and pyroptosis related indicators. The results showed that there was no significant difference in the parameters between the control group and the 2-DG group. However, the lung injury parameters, oxidative stress response, lactic acid content, IL-1ß, and IL-18 levels were significantly increased in the I/R group. The protein expression levels of glycolysis and pyroptosis related indicators including hexokinase 2 (HK2), pyruvate kinase 2 (PKM2), NLRP3, Gasdermin superfamily member GSDMD-N, cleaved-Caspase1, cleaved-IL-1ß and cleaved-IL-18, and the gene expression levels of HK2, PKM2 and NLRP3 were markedly up-regulated in the I/R group compared with those in the control group. The expression of HK2 and NLRP3 was also increased detected by immunofluorescence staining. Compared with the I/R group, the 2-DG+I/R group exhibited significantly improved alveolar structure and inflammatory infiltration, reduced lung injury parameters, and decreased expression of glycolysis and pyroptosis related indicators. These results suggest that 2-DG protects against lung I/R injury possibly by inhibiting NLRP3-mediated pyroptosis in rats.
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Desoxiglucose , Pulmão , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Ratos Sprague-Dawley , Traumatismo por Reperfusão , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Masculino , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Ratos , Pulmão/metabolismo , Pulmão/patologia , Desoxiglucose/farmacologia , Interleucina-1beta/metabolismo , Interleucina-18/metabolismo , Lesão Pulmonar/metabolismo , Lesão Pulmonar/prevenção & controle , Lesão Pulmonar/etiologia , Estresse OxidativoRESUMO
To achieve a better treatment regimen and follow-up assessment design for intensity-modulated radiotherapy (IMRT)-treated nasopharyngeal carcinoma (NPC) patients, an accurate progression-free survival (PFS) time prediction algorithm is needed. We propose developing a PFS prediction model of NPC patients after IMRT treatment using a deep learning method and comparing that with the traditional texture analysis method. One hundred and fifty-one NPC patients were included in this retrospective study. T1-weighted, proton density and dynamic contrast-enhanced magnetic resonance (MR) images were acquired. The expression level of five genes (HIF-1α, EGFR, PTEN, Ki-67, and VEGF) and infection of Epstein-Barr (EB) virus were tested. A residual network was trained to predict PFS from MR images. The output as well as patient characteristics were combined using a linear regression model to provide a final PFS prediction. The prediction accuracy was compared with that of the traditional texture analysis method. A regression model combining the deep learning output with HIF-1α expression and Epstein-Barr infection provides the best PFS prediction accuracy (Spearman correlation R2 = 0.53; Harrell's C-index = 0.82; receiver operative curve [ROC] analysis area under the curve [AUC] = 0.88; log-rank test hazard ratio [HR] = 8.45), higher than a regression model combining texture analysis with HIF-1α expression (Spearman correlation R2 = 0.14; Harrell's C-index =0.68; ROC analysis AUC = 0.76; log-rank test HR = 2.85). The deep learning method does not require a manually drawn tumor region of interest. MR image processing using deep learning combined with patient characteristics can provide accurate PFS prediction for nasopharyngeal carcinoma patients and does not rely on specific kernels or tumor regions of interest, which is needed for the texture analysis method.
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Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/radioterapia , Estudos Retrospectivos , Taxa de Sobrevida , Prognóstico , Imageamento por Ressonância Magnética/métodos , Herpesvirus Humano 4/genética , Redes Neurais de Computação , Expressão GênicaRESUMO
The La2LiSbO6: xCr3+ phosphors were synthesized by means of a high-temperature solid-phase method. Based on the differences in ionic radius, valence state, and formation energy, the substitution sites of Cr3+ ions are discussed in detail. The optimized doping concentration of Cr3+ is determined to be 0.01. Under 517 nm excitation, the La2LiSbO6: 0.01Cr3+ phosphor presents a wide emission band (from 700 to 1350 nm) with a peak centered at 952 nm. Additionally, its corresponding full width at half-maximum is 155 nm, and the internal quantum efficiency reaches 62.4%. Meanwhile, the emission intensity of the La2LiSbO6: 0.01Cr3+ phosphor at 373 K is about 63.7% of that at room temperature, exhibiting good thermal stability. Aiming to fabricate a near-infrared phosphor-converted light-emitting diode device, the La2LiSbO6: 0.01Cr3+ phosphor is mixed with epoxy adhesive and cured on a green light-emitting diode chip. Under the irradiation of the fabricated light-emitting diode device, fruits and writing in the dark environment can be captured by a near-infrared camera. Hence, the La2LiSbO6: 0.01Cr3+ phosphor is promising for night vision.
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Two-dimensional van der Waals heterostructures with multiple tunable approaches in electronic and optical properties are highly superior for photocatalysis and novel devices. By applying first-principles calculations, we systematically studied the electronic structure, optical absorption, carrier mobility and solar-to-hydrogen efficiency of PtSe2/GaN heterostructures, which are affected by different thicknesses, varying directions of polarization of the GaN nanosheets and applied mechanical strain of the whole system. The results indicate that these heterostructures exhibit thermodynamic stability at room-temperature (300 K), and most configurations have type-II band alignment, among which the heterostructure consisting of GaN trilayers and PtSe2 shows high visible-light absorption (1.71 × 105 cm-1) and ultra-wide range of pH values (pH = 0-14) for the photocatalytic water splitting reaction and exceedingly high overpotential for the hydrogen evolution reaction (3.375 eV). Simultaneously, being two of the most significant parameters of photocatalysis and devices, the carrier mobility and solar-to-hydrogen efficiency have also been calculated, respectively, reaching up to 1601 cm2 V-1 s-1 and 17.2%. Moreover, the photoelectrical properties can be highly tuned through further biaxial strain engineering; especially, the visible-light absorption can be enhanced to 2.85 × 105 cm-1 by applying 6% compression strain. Thus, the PtSe2/GaN heterostructure we proposed shows a broad prospect for photocatalytic water splitting.
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An optical phased array (OPA), especially a two-dimensional (2D) OPA, suffers from the trade-off among steering range, beam width, and the number of antennas. Aperiodic 2D array designs currently aimed to reduce the number of antennas and reduce grating lobes within a wide range fall short when an aperture approaches millimeter size. A circular OPA design is proposed to address this issue. The circular design substantially reduces the number of antennas while achieving the same wide steering range and narrow beam width of optimized aperiodic 2D OPA designs. Its efficient suppression of grating lobes, the key to a wide steering range with minimal number of antennas and large antenna spacing, is theoretically studied and validated by simulation. The novel, to the best of our knowledge, design allows less than 100 antennas, orders of magnitude reduction, for millimeter size aperture OPA designs. It paves the way for commercialization by significantly reducing control complexity and power consumption.
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Cadmium (Cd) exposure damages the reproductive system. Lipid droplets (LDs) play an important role in steroid-producing cells to provide raw material for steroid hormone. We have found that the LDs of Leydig cells exposed to Cd are bigger than those of normal cells, but the effects on steroidogenesis and its underlying mechanism remains unclear. Using Isobaric tag for relative and absolute quantitation (iTARQ) proteomics, phosphodiesterase beta-2 (PLCß2) was identified as the most significantly up-regulated protein in immature Leydig cells (ILCs) and adult Leydig cells (ALCs) derived from male rats exposed to maternal Cd. Consistent with high expression of PLCß2, the size of LDs was increased in Leydig cells exposed to Cd, accompanied by reduction in cholesterol and progesterone (P4) levels. However, the high PLCß2 did not result in high diacylglycerol (DAG) level, because Cd exposure up-regulated diacylglycerol kinases ε (DGKε) to promote the conversion from DAG to phosphatidic acid (PA). Exogenous PA, which was consistent with the intracellular PA concentration induced by Cd, facilitated the formation of large LDs in R2C cells, followed by reduced P4 level in the culture medium. When PLCß2 expression was knocked down, the increased DGKε caused by Cd was reversed, and then the PA level was decreased to normal. As results, large LDs returned to normal size, and the level of total cholesterol was improved to restore steroidogenesis. The accumulation of PA regulated by PLCß2-DAG-DGKε signal pathway is responsible for the formation of large LDs and insufficient steroid hormone synthesis in Leydig cells exposed to Cd. These data highlight that LD is an important target organelle for Cd-induced steroid hormone deficiency in males.
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Cádmio , Células Intersticiais do Testículo , Ratos , Masculino , Animais , Células Intersticiais do Testículo/metabolismo , Cádmio/toxicidade , Cádmio/metabolismo , Gotículas Lipídicas/metabolismo , Fosfolipase C beta/metabolismo , Ácidos Fosfatídicos/metabolismo , Diglicerídeos/metabolismo , Transdução de Sinais , Esteroides/metabolismo , Progesterona/metabolismo , Colesterol/metabolismoRESUMO
Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Many patients with osteosarcoma readily develop resistance to chemotherapy and have an extremely dismal prognosis. Dioscin, a saponin, is known to exhibit potent anticancer activities and induce cellular death of a variety of cancer types. However, the inhibitory effect of dioscin on osteosarcoma cells and its underlying mechanisms have not been fully elucidated. We investigated the responses of human U2-OS and MG63 osteosarcoma cells to dioscin with regard to proliferation, apoptosis, migration, and invasion, and studied the effect of dioscin on MAPK-related proteins by western blot analysis assays. Dioscin inhibited osteosarcoma cell proliferation, migration, and invasion. Moreover, it induced osteosarcoma cell apoptosis via reactive oxygen species (ROS)-dependent apoptotic signaling. N-acetylcysteine, a reactive oxygen species inhibitor, suppressed dioscin-induced apoptosis, indicating that ROS play an essential role in dioscin-induced apoptosis. Western blot analysis assays showed that p38 MAPK was upregulated after dioscin treatment, and that dioscin induced apoptosis by upregulating ROS-mediated p38 MAPK signaling. Our study suggests that dioscin possesses antitumor activities against human osteosarcoma cells, inhibits osteosarcoma cell proliferation, migration and invasion, and induces osteosarcoma cell apoptosis through upregulating ROS-mediated p38 MAPK signaling. This study may provide a new therapeutic strategy and potential clinical applications for the treatment of osteosarcoma.
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Antineoplásicos , Osteossarcoma , Adolescente , Criança , Humanos , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Proliferação de Células , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Osteossarcoma/tratamento farmacológico , Osteossarcoma/metabolismo , Osteossarcoma/patologiaRESUMO
BACKGROUND: Cerebral microbleeds (CMBs) have been recognized to play an important role in cognitive impairment of cerebral small vessel disease (CSVD) patients. However, the mechanism of this effect is still unclear. PURPOSE: Comparing the susceptibility values in the selected subcortical gray matter structures of CSVD patients without CMBs (CSVD-N) and with CMBs (CSVD-C) as well as healthy controls (HCs). STUDY TYPE: Prospective. SUBJECTS: Sixty-nine CSVD patients and 28 HCs were included; 24 CSVD patients (34.78%) had CMBs and 45 CSVD patients (65.22%) had no CMBs. FIELD STRENGTH/SEQUENCE: All subjects were imaged on a 3.0 T MR scanner. The protocol consisted of a three-dimensional (3D) T1-weighted sequence and a 3D multi-echo gradient echo (mGRE) sequence. Brain QSM maps were computed from mGRE data using the morphology-enabled dipole inversion with automatic uniform cerebrospinal fluid zero reference algorithm (MEDI+0). ASSESSMENT: The mean susceptibility value within each region of interest was recorded. All participants underwent the cognitive assessment. Brain iron deposition burden of CMB lesions of every CSVD-C patient was computed. STATISTICAL TESTS: One-way analysis of variance test followed by Tukey's honest significance test and Kruskal-Wallis test were used with significance level of 0.05. Stepwise multivariate linear analysis was used to explore the factors influencing cognitive scores. RESULTS: Montreal cognitive assessment (MoCA), trail-making test (TMT)-A and TMT-B scores in the three groups were significantly different (all P < 0.05). Stepwise multivariate linear regression analysis revealed that the factors influenced MoCA scores were having CMBs (P < 0.05), white matter hyperintensities (P < 0.05), lacunes (P < 0.05) in brain, and the brain iron deposition burden of CMB lesions (P < 0.05) and for TMT scores (TMT-A + TMT-B), the influencing factors were age (P < 0.05), education years (P < 0.05), and the brain iron deposition burden of CMB lesions (P < 0.05). DATA CONCLUSION: The higher iron deposition burden of CMB lesions in brain may be an imaging quantitative marker of cognitive decline in patients with CSVD-C. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.
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Doenças de Pequenos Vasos Cerebrais , Disfunção Cognitiva , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Hemorragia Cerebral/complicações , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/patologia , Disfunção Cognitiva/complicações , Humanos , Ferro , Imageamento por Ressonância Magnética/métodos , Estudos ProspectivosRESUMO
In the mammalian testis, two distinct populations of Sertoli cells (SCs), the immature SCs (ISCs) and adult SCs (ASCs), play significant roles in regulating the development and function of Leydig cells. However, the effect of different SC types on the function of Leydig cells is poorly understood. Here, our study showed that miR-145-5p expression was significantly different in SCs at different stages, with the highest expression observed in ISCs. Exosomes mediate the transfer of miR-145-5p from ISCs to Leydig cells. Overexpression of miR-145-5p in Leydig cells significantly downregulated steroidogenic gene expression and inhibited testosterone synthesis. Additionally, miR-145-5p functioned by directly targeted steroidogenic factor-1 (Sf-1) and downregulated the expression of SF-1, which further downregulated the expression of steroidogenic genes, induced accumulation of lipid droplets, and eventually suppressed testosterone production. These findings demonstrate that SC-derived miR-145-5p plays a significant role in regulating the functions of Leydig cells and may therefore serve as a diagnostic biomarker for male hypogonadism developmental abnormalities during puberty.
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Exossomos/metabolismo , Células Intersticiais do Testículo/metabolismo , MicroRNAs/genética , Células de Sertoli/metabolismo , Fator Esteroidogênico 1/antagonistas & inibidores , Esteroides/biossíntese , Testículo/metabolismo , Animais , Exossomos/genética , Células Intersticiais do Testículo/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células de Sertoli/patologia , Fator Esteroidogênico 1/genética , Fator Esteroidogênico 1/metabolismo , Testículo/patologiaRESUMO
Recently, the energy crisis and environmental pollution problems have become increasingly severe. There is an urgent need to develop a class of multifunctional materials that can both produce clean energy and detect harmful gases. Herein, we propose a g-GaN/SnS heterostructure and explored its dual-optimal performance in photocatalytic hydrogen production and gas detection. Our results demonstrated that the g-GaN/SnS heterostructure has a suitable type II band alignment and excellent absorption in the visible range, which both indicate its potential application in photocatalysis. Furthermore, when the g-GaN/SnS heterostructure acted as a gas detection material, it was consistently susceptible to NO2 gas molecules, according to charge transfer. Additionally, it has a very suitable material recovery time (â¼0.5 h) when used for NO2 detection, illustrating the recyclability of the material. Interestingly, the applied electric field of -0.4 V/Å can greatly increase the absorption coefficient in the visible range to 150% of the original. Also, the applied electric field of 0.6 V/Å can substantially enhance the gas detection sensitivity by 27% compared to the case without the electric field. Thus, the g-GaN/SnS heterostructure we proposed not only has the advantage of being bifunctional but also has the potential to be recycled.
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OBJECTIVES: The objective of this study was to compare oxygen extraction fraction (OEF) values in the deep gray matter (GM) of pre-eclampsia (PE) patients, pregnant healthy controls (PHCs), and non-pregnant healthy controls (NPHCs) to explore their brain oxygen metabolism differences in GM. METHODS: Forty-seven PE patients, forty NPHCs, and twenty-one PHCs were included. Brain OEF values were computed from quantitative susceptibility mapping (QSM) plus quantitative blood oxygen level-dependent magnitude (QSM + qBOLD = QQ)-based mapping. One-way ANOVA was used to compare mean OEF values in the three groups. The area under the curve of the mean OEF value in each region of interest was estimated using a receiver operating characteristic curve analysis. RESULTS: We found that the mean OEF values in the thalamus, putamen, caudate nucleus, pallidum, and substantia nigra were significantly different in these three groups (F = 5.867, p = 0.004; F = 5.142, p = 0007; F = 6.158, p = 0.003; F = 6.319, p = 0.003; F = 5.491, p = 0.005). The mean OEF values for these 5 regions were higher in PE patients than in NPHCs and in PHCs (p < 0.05). The AUC of these ROIs ranged from 0.673 to 0.692 (p < 0.01) and cutoff values varied from 35.1 to 36.6%, indicating that the OEF values could discriminate patients with and without PE. Stepwise multivariate analysis revealed that the OEF values correlated with hematocrit in pregnant women (r = 0.353, p = 0.003). CONCLUSION: OEF values in the brains of pregnant women can be measured in clinical practice using QQ-based OEF mapping for noninvasive assessment of hypertensive disorders. KEY POINTS: ⢠Pre-eclampsia is a hypertensive disorder associated with abnormalities in brain oxygen extraction. ⢠Oxygen extraction fraction (OEF) is an indicator of brain tissue viability and function. QQ-based mapping of OEF is a new MRI technique that can noninvasively quantify brain oxygen metabolism. ⢠OEF values in the brains of pregnant women can be measured for noninvasive assessment of hypertensive disorders in clinical practice.
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Hipertensão Induzida pela Gravidez , Pré-Eclâmpsia , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Mapeamento Encefálico/métodos , Circulação Cerebrovascular , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Hipertensão Induzida pela Gravidez/metabolismo , Imageamento por Ressonância Magnética/métodos , Oxigênio , Consumo de Oxigênio , Pré-Eclâmpsia/metabolismo , GravidezRESUMO
We report a two-dimensional Si photonic optical phased array (OPA) optimized for a large optical aperture with a minimal number of antennas while maintaining single-lobe far field. The OPA chip has an optical aperture of â¼200µm by 150 µm comprising a 9×9 antenna array. The two-dimensional spacings between these antennas are much larger than the wavelength and are highly non-uniform optimized by the genetic deep learning algorithm. The phase of each antenna is independently tunable by a thermo-optical phase shifter. The experimental results validate the design and exhibit a 0.39∘×0.41∘ beamwidth within the 3 dB steering range of 14∘×11∘ limited by the numerical aperture of the far-field camera system. The method can be easily extended to a larger aperture for narrower beamwidth and wider steering range.
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We present a method to design an optical phased array (OPA) simultaneously realizing both narrow beam width and aliasing-free 2D beam steering without the need to arrange the antennas at actual half-wavelength pitch. The method realizes an effective half-wavelength pitch in one direction formed by location projection of the antennas. The distances between the antennas in the other direction can be sufficiently large to form an effective large aperture realizing narrow beam width without needing a long grating. The presented method is proven by both theory and numerical simulations to achieve an equivalent grating-lobe-free far field of an ordinary half-wavelength pitch design. One design example exhibits 180° steering with a minimal beam width of 0.4° * 0.032° and a sidelobe suppression ratio of >13d B.
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Cadmium (Cd) is one of the most common environmental pollutants, which has a long biological half-life. Maternal Cd-exposure in the natural environment causes steroidogenesis defects resulting in spermatogenesis disorder in male offspring. For better understanding its underlying mechanism, we have employed iTRAQ to screen the differentially expressed protein and found that the expression of CORO1A and Cofilin 1 was up-regulated approximately 2 fold in Leydig cells of maternal Cd-exposure offspring. As the major source of steroid hormone, cholesterol is transported to cells via receptor-mediated endocytosis which relies on the remodel of cytoskeleton, then stores in lipid droplets (LDs). However, few studies have focused on the role of cytoskeleton in abnormal steroidogenesis. This study was performed to explore the role of CORO1A in androgen deficiency caused by Cd exposure and its involvement of low-density lipoprotein (LDL) uptake and effects on LDs. We found that Cd resulted in the up-regulation of CORO1A and Cofilin 1, and down-regulation of Profilin 1 in the testis of male offspring with maternal exposure. The structure of filamentous actin was broken, disordered and even crumpled up in Cd-treated R2C cells. F-actin disassembly led to a low uptake of LDL with a reduced number of LDs, followed by decreased total cholesterol and low progesterone production. When CORO1A was silenced, the expression of Cofilin 1 was down-regulated and Profilin 1 was up-regulated in Cd-treated R2C cells. The filamentous actin was rescued and the integrated cytoskeleton prompted LDL uptake, which resulted in the increased total cholesterol and high progesterone production. These findings highlight the crucial role of CORO1A as a cytoskeleton regulatory protein in steroidogenesis, which may help to better understand Cd-induced steroid hormone deficiency in children.
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Cádmio , Células Intersticiais do Testículo , Transporte Biológico , Cádmio/toxicidade , Feminino , Humanos , Lipoproteínas , Masculino , Exposição MaternaRESUMO
Self-renewal and differentiation of spermatogonial stem cell (SSC) are critical for male fertility and reproduction, both of which are highly regulated by testicular microenvironment. Exosomal miRNAs have emerged as new components in intercellular communication. However, their roles in the differentiation of SSC remain unclear. Here, we observed miR-486-5p enriched in Sertoli cell and Sertoli cell-derived exosomes. The exosomes mediate the transfer of miR-486-5p from Sertoli cells to SSCs. Exosomes release miR-486-5p, thus up-regulate expression of Stra8 (stimulated by retinoic acid 8) and promote differentiation of SSC. And PTEN was identified as a target of miR-486-5p. Overexpression of miR-486-5p in SSCs down-regulates PTEN expression, which up-regulates the expression of STRA8 and SYCP3, promotes SSCs differentiation. In addition, blocking the exosome-mediated transfer of miR-486-5p inhibits differentiation of SSC. Our findings demonstrate that miR-486-5p acts as a communication molecule between Sertoli cells and SSCs in modulating differentiation of SSCs. This provides a new insight on molecular mechanisms that regulates SSC differentiation and a basis for the diagnosis, treatment, and prevention of male infertility.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Diferenciação Celular , Exossomos/metabolismo , MicroRNAs/genética , PTEN Fosfo-Hidrolase/metabolismo , Células de Sertoli/citologia , Testículo/citologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Células Cultivadas , Exossomos/genética , Regulação da Expressão Gênica , Masculino , Camundongos , PTEN Fosfo-Hidrolase/genética , Células de Sertoli/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Testículo/metabolismoRESUMO
PURPOSE: Proof-of-concept study of mapping renal blood flow vector field according to the inverse solution to a mass transport model of time resolved tracer-labeled MRI data. THEORY AND METHODS: To determine tissue perfusion according to the underlying physics of spatiotemporal tracer concentration variation, the mass transport equation is integrated over a voxel with an approximate microvascular network for fitting time-resolved tracer imaging data. The inverse solution to the voxelized transport equation provides the blood flow vector field, which is referred to as quantitative transport mapping (QTM). A numerical microvascular network modeling the kidney with computational fluid dynamics reference was used to verify the accuracy of QTM and the current Kety's method that uses a global arterial input function. Multiple post-label delay arterial spin labeling (ASL) of the kidney on seven subjects was used to assess QTM in vivo feasibility. RESULTS: Against the ground truth in the numerical model, the error in flow estimated by QTM (18.6%) was smaller than that in Kety's method (45.7%, 2.5-fold reduction). The in vivo kidney perfusion quantification by QTM (cortex: 443 ± 58 mL/100 g/min and medulla: 190 ± 90 mL/100 g/min) was in the range of that by Kety's method (482 ± 51 mL/100 g/min in the cortex and 242 ± 73 mL/100 g/min in the medulla), and QTM provided better flow homogeneity in the cortex region. CONCLUSIONS: QTM flow velocity mapping is feasible from multi-delay ASL MRI data based on inverting the transport equation. In a numerical simulation, QTM with deconvolution in space and time provided more accurate perfusion quantification than Kety's method with deconvolution in time only.
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Rim , Circulação Renal , Humanos , Rim/diagnóstico por imagem , Imageamento por Ressonância Magnética , Microvasos/diagnóstico por imagem , Marcadores de SpinRESUMO
Periodontal disease is the main reason for tooth loss in adults. Tissue engineering and regenerative medicine are advanced technologies used to manage soft and hard tissue defects caused by periodontal disease. We developed a transforming growth factor-ß3/chitosan sponge (TGF-ß3/CS) to repair periodontal soft and hard tissue defects. We investigated the proliferation and osteogenic differentiation behaviors of primary human periodontal ligament stem cells (hPDLSCs) to determine the bioactivity and potential application of TGF-ß3 in periodontal disease. We employed calcein-AM/propidium iodide (PI) double labeling or cell membranes (CM)-Dil labeling coupled with fluorescence microscopy to trace the survival and function of cells after implantation in vitro and in vivo. The mineralization of osteogenically differentiated hPDLSCs was confirmed by measuring alkaline phosphatase (ALP) activity and calcium content. The levels of COL I, ALP, TGF-ßRI, TGF-ßRII, and Pp38/t-p38 were assessed by western blotting to explore the mechanism of bone repair prompted by TGF-ß3. When hPDLSCs were implanted with various concentrations of TGF-ß3/CS (62.5-500 ng/mL), ALP activity was the highest in the TGF-ß3 (250 ng/mL) group after 7 d (p < 0.05 vs. control). The calcium content in each group was increased significantly after 21 and 28 d (p < 0.001 vs. control). The optimal result was achieved by the TGF-ß3 (500 ng/mL) group. These results showed that TGF-ß3/CS promotes osteogenic differentiation of hPDLSCs, which may involve the p38 mitogen-activated protein kinase (MAPK) signaling pathway. TGF-ß3/CS has the potential for application in the repair of incomplete alveolar bone defects.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Quitosana , Osteogênese/efeitos dos fármacos , Ligamento Periodontal/citologia , Células-Tronco/efeitos dos fármacos , Fator de Crescimento Transformador beta3/farmacologia , Biomarcadores , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Quitosana/química , Humanos , Imuno-Histoquímica , Sistema de Sinalização das MAP Quinases , Células-Tronco/citologia , Fator de Crescimento Transformador beta3/químicaRESUMO
PURPOSE: The purpose of this study was to evaluate the effectiveness of conventional open surgery and percutaneous release with a specially designed needle for treating stenosing tenosynovitis in terms of cure, relapse and complication rates. METHODS: In this study 89 fingers from 76 patients were randomly assigned and allocated to one of the treatment groups. A total of 37 patients were treated with open surgery in group 1 and 39 patients with percutaneous release using a specially designed needle in group 2. A patient-based 4-inch visual analogue scale (VAS), Quinnell grading (QG), disability of arm shoulder and hand (DASH) score and finger total joint range of motion (FTROM) score were evaluated before treatment and after 7, 30 and 180 days. When finger QG scores were equal or greater than 2 points at follow-up at 180 days this was defined as recurrence.. RESULTS: There were no significant differences between the two groups (Pâ¯> 0.05) in terms of VAS, DASH and QG scores and the degree of FTROM. At 7 days all the data were significantly different (pâ¯< 0.05) compared with preoperative data, 30â¯days was significantly different (pâ¯< 0.05) compared with 7â¯days while at 180â¯days no significant differences could be found (pâ¯> 0.05) compared with 30â¯days. The recurrence rate in group 1 was 4.65% and 6.55% in group 2. CONCLUSION: The percutaneous release and open surgery methods displayed similar effectiveness regarding the cure and recurrence of trigger finger disorder. The use of a specially designed needle for release is a safe and reliable method.