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1.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(3): 331-348, 2024 Mar 28.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-38970507

RESUMEN

OBJECTIVES: Abnormal programmed cell death in immune cells is associated with autoimmune diseases, but the patterns of programmed cell death in systemic lupus erythematosus (SLE) and especially lupus nephritis (LN) remain unclear. This study aims to explore the association between SLE, LN, and immune cell death patterns. METHODS: Bulk RNA sequencing (bulk RNA-seq) and single-cell RNA sequencing (scRNA-seq) data were downloaded from the Gene Expression Omnibus (GEO) database. Bioinformatic analysis was conducted to explore the expression levels of genes related to 3 cell death patterns in peripheral blood mononuclear cells of SLE patients. Key cell subsets involved in the imbalance of cell death patterns were identified through scRNA-seq. Immunofluorescence was used to detect the expression levels of receptor interacting serine/threonine kinase 3 (RIPK3), mixed-lineage kinase domain-like protein (MLKL), phosphorylated MLKL (pMLKL), caspase 1 (CASP1), CD1c molecule (CD1C), C-type lectin domain containing 9A (CLEC9A), and X-C motif chemokine receptor 1 (XCR1) in dendritic cells (DC). scRNA-seq was performed on kidney tissues collected from LN patients and healthy controls (HC) at the Third Xiangya Hospital of Central South University, followed by bioinformatic analysis to identify key cell subsets involved in the imbalance of cell death patterns. Pseudotime analysis and ligand-receptor analysis were used to explore the differentiation direction and cell communication of different DC subsets. Transient transfection was used to transfect RAW264.7 cells with empty plasmid, empty plasmid+dsDNA (HSV-DNA), empty plasmid+200 µmol/L tert-butyl hydroperoxide (TBHP), stimulator of interferon genes (STING) shRNA plasmid, STING shRNA plasmid+dsDNA (HSV-DNA), and STING shRNA plasmid+200 µmol/L TBHP. Annexin V-mCherry and SYTOX Green staining were used to detect cell death in each group. Western blotting was used to detect the activation of CASP1, gasdermin D (GSDMD), RIPK3, and MLKL in each group. RESULTS: Bioinformatic analysis showed an imbalance in 3 cell death patterns in SLE and LN patients: Pro-inflammatory pyroptosis and necroptosis were activated, while anti-inflammatory apoptosis was inhibited. The key cell subsets involved were DC subsets, particularly focusing on CLEC9A+cDC1. Immunofluorescence results showed that the expression levels of RIPK3, MLKL, and CASP1 in DCs were higher in the SLE group compared to the HC group. pMLKL and CASP1 expression levels in renal cDC1 marked by CLEC9A and XCR1 were higher in the LN group than in the HC group. Pseudotime analysis and ligand-receptor analysis suggested that the CLEC9A+cDC1 subset in LN kidney tissues originated from peripheral circulation. Annexin V-mCherry and SYTOX Green staining results showed that the number of dead cells decreased in the STING shRNA transfection group compared to the empty plasmid group in RAW264.7 cells. Western blotting results showed that the activation of CASP1, GSDMD, RIPK3, and MLKL was decreased in the STING shRNA transfection group compared to the empty plasmid group. CONCLUSIONS: This study provides novel insights into the role of CLEC9A+cDC1 in the imbalance of cell death patterns in SLE and LN.


Asunto(s)
Células Dendríticas , Lupus Eritematoso Sistémico , Nefritis Lúpica , Proteína Serina-Treonina Quinasas de Interacción con Receptores , Humanos , Nefritis Lúpica/metabolismo , Nefritis Lúpica/genética , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/metabolismo , Células Dendríticas/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Apoptosis , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Biología Computacional , Leucocitos Mononucleares/metabolismo , Análisis de Secuencia de ARN
2.
Front Cell Infect Microbiol ; 14: 1382635, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39011516

RESUMEN

Objective: This study aimed to determine the sensitivity and specificity of metagenomic next-generation sequencing (mNGS) for detecting pathogens in spinal infections and to identify the differences in the diagnostic performance between mNGS and targeted next-generation sequencing (tNGS). Methods: A total of 76 consecutive patients with suspected spinal infections who underwent mNGS, culture, and histopathological examinations were retrospectively studied. The final diagnosis of the patient was determined by combining the clinical treatment results, pathological examinations, imaging changes and laboratory indicators. The sensitivity and specificity of mNGS and culture were determined. Results: The difference between the two detection rates was statistically significant (p < 0.001), with mNGS exhibiting a significantly higher detection rate (77.6% versus 18.4%). The average diagnosis time of mNGS was significantly shorter than that of bacterial culture (p < 0.001, 1.65 versus 3.07 days). The sensitivity and accuracy of mNGS were significantly higher than that of the culture group (p < 0.001, 82.3% versus 17.5%; 75% versus 27.6%), whereas the specificity of mNGS (42.9%) was lower than that of the culture group (p > 0.05, 42.9% versus 76.9%). The sensitivity, specificity, accuracy, and positive predictive value (PPV) of pus were higher than those of tissue samples for mNGS, whereas for culture, the sensitivity, specificity, accuracy, and PPV of tissue samples were higher than those of pus. tNGS demonstrated higher sensitivity and accuracy in diagnosing tuberculosis (TB) than mNGS (80% versus 50%; 87.5% versus 68.8%). Conclusion: mNGS for spinal infection demonstrated better diagnostic value in developing an antibiotic regimen earlier, and it is recommended to prioritize pus samples for testing through mNGS. Moreover, tNGS outperformed other methods for diagnosing spinal TB and identifying antibiotic-resistance genes in drug-resistant TB.


Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica , Sensibilidad y Especificidad , Humanos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Metagenómica/métodos , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , Adulto Joven , Técnicas de Diagnóstico Molecular/métodos , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/clasificación , Enfermedades de la Columna Vertebral/diagnóstico , Enfermedades de la Columna Vertebral/microbiología , Anciano de 80 o más Años , Adolescente
3.
Appl Opt ; 63(14): 3770-3778, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38856339

RESUMEN

In optical systems, diffraction limits significantly impact spot simulations. This study addresses this problem by applying the Fourier transform to calculate spots in imaging systems. Typically, a 1 mm image plane suffices; however, mosaic aperture telescopes with notable wavefront discontinuities require an approximately 10 mm simulation image plane. This necessitates high sampling rates for pupils, posing challenges for conventional methods. Our model overcomes this challenge by leveraging an interpolation technique to align multiwavelength spots on a uniform image plane grid, thus effectively analyzing spot translation and spreading in imaging systems with diffraction limits.

4.
Chemistry ; : e202401084, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38819870

RESUMEN

The link of an antenna dye with an electron spin converter, in this case naphthalenediimide and C60, produces a system with a rich photophysics including the detection of more than one triplet state on the long timescale (tens of µs). Beside the use of optical spectroscopies in the ns and in the fs time scale, we used time-resolved Electron Paramagnetic Resonance (TREPR) to study the system evolution following photoexcitation. TREPR keeps track of the formation path of the triplet states through specific spin polarization patterns observed in the spectra. The flexibility of the linker and solvent polarity play a role in favouring either electron transfer or energy transfer processes.

5.
Opt Express ; 32(7): 12601-12608, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38571078

RESUMEN

Silicon avalanche photodiode (APD) single-photon detectors in space are continuously affected by radiation, which gradually degrades their dark count performance. From August 2016 to June 2023, we conducted approximately seven years (2507 days) of in-orbit monitoring of the dark count performance of APD single-photon detectors on the Micius Quantum Science Experimental Satellite. The results showed that due to radiation effects, the dark count growth rate was approximately 6.79 cps/day @ -24 °C and 0.37 cps/day @ -55 °C, with a significant suppression effect on radiation-induced dark counts at lower operating temperature. Based on the proposed radiation damage induced dark count annealing model, simulations were conducted for the in-orbit dark counts of the detector, the simulation results are consistent with in-orbit test data. In May 2022, four of these detectors underwent a cumulative 5.7 hours high-temperature annealing test at 76 °C, dark count rate shows no measurable changes, consistent with annealing model. As of now, these ten APD single-photon detectors on the Micius Quantum Science Experimental Satellite have been in operation for approximately 2507 days and are still functioning properly, providing valuable experience for the future long-term space applications of silicon APD single-photon detectors.

6.
Opt Express ; 32(7): 12645-12655, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38571082

RESUMEN

The space time frequency transfer plays a crucial role in applications such as space optical clock networks, navigation, satellite ranging, and space quantum communication. Here, we propose a high-precision space time frequency transfer and time synchronization scheme based on a simple intensity modulation/direct detection (IM/DD) laser communication system, which occupies a communication bandwidth of approximately 0.2%. Furthermore, utilizing an optical-frequency comb time frequency transfer system as an out-of-loop reference, experimental verification was conducted on a 113 km horizontal atmospheric link, with a long-term stability approximately 8.3 × 10-16 over a duration of 7800 seconds. Over an 11-hour period, the peak-to-peak wander is approximately 100 ps. Our work establishes the foundation of the time frequency transfer, based on the space laser communication channel, for future ground-to-space and inter-satellite links.

7.
Regen Biomater ; 11: rbae029, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38638701

RESUMEN

Arteriovenous grafts (AVGs) have emerged as the preferred option for constructing hemodialysis access in numerous patients. Clinical trials have demonstrated that decellularized vascular graft exhibits superior patency and excellent biocompatibility compared to polymer materials; however, it still faces challenges such as intimal hyperplasia and luminal dilation. The absence of suitable animal models hinders our ability to describe and explain the pathological phenomena above and in vivo adaptation process of decellularized vascular graft at the molecular level. In this study, we first collected clinical samples from patients who underwent the construction of dialysis access using allogeneic decellularized vascular graft, and evaluated their histological features and immune cell infiltration status 5 years post-transplantation. Prior to the surgery, we assessed the patency and intimal hyperplasia of the decellularized vascular graft using non-invasive ultrasound. Subsequently, in order to investigate the in vivo adaptation of decellularized vascular grafts in an animal model, we attempted to construct an AVG model using decellularized vascular grafts in a small animal model. We employed a physical-chemical-biological approach to decellularize the rat carotid artery, and histological evaluation demonstrated the successful removal of cellular and antigenic components while preserving extracellular matrix constituents such as elastic fibers and collagen fibers. Based on these results, we designed and constructed the first allogeneic decellularized rat carotid artery AVG model, which exhibited excellent patency and closely resembled clinical characteristics. Using this animal model, we provided a preliminary description of the histological features and partial immune cell infiltration in decellularized vascular grafts at various time points, including Day 7, Day 21, Day 42, and up to one-year post-implantation. These findings establish a foundation for further investigation into the in vivo adaptation process of decellularized vascular grafts in small animal model.

8.
Comput Methods Programs Biomed ; 250: 108191, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38677079

RESUMEN

BACKGROUND AND OBJECTIVE: Enhanced external counterpulsation (EECP) is a mechanically assisted circulation technique widely used in the rehabilitation and management of ischemic cardiovascular diseases. It contributes to cardiovascular functions by regulating the afterload of ventricle to improve hemodynamic effects, including increased diastolic blood pressure at aortic root, increased cardiac output and enhanced blood perfusion to multiple organs including coronary circulation. However, the effects of EECP on the coupling of the ventricle and the arterial system, termed ventricular-arterial coupling (VAC), remain elusive. We aimed to investigate the acute effect of EECP on the dynamic interaction between the left ventricle and its afterload of the arterial system from the perspective of ventricular output work. METHODS: A neural network assisted optimization algorithm was proposed to identify the ordinary differential equation (ODE) relation between aortic root blood pressure and flow rate. Based on the optimized order of ODE, a lumped parameter model (LPM) under EECP was developed taking into consideration of the simultaneous action of cardiac and EECP pressure sources. The ventricular output work, in terms of aortic pressure and flow rate cooperated with the LPM, was used to characterize the VAC of ventricle and its afterload. The VAC subjected to the principle of minimal ventricular output work was validated by solving the Euler-Poisson equation of cost function, ultimately determining the waveforms of aortic pressure and flow rate. RESULTS: A third-order ODE can precisely describe the hemodynamic relationship between aortic pressure and flow rate. An optimized dual-source LPM with three energy-storage elements has been constructed, showing the potential in probing VAC under EECP. The LPM simulation results demonstrated that the VAC in terms of aortic pressure and flow rate yielded to the minimal ventricular output work under different EECP pressures. CONCLUSIONS: The ventricular-arterial coupling under EECP is subjected to the minimal ventricular output work, which can serve as a criterion for determining aortic pressure and flow rate. This study provides insight for the understanding of VAC and has the potential in characterizing the performance of the ventricular and arterial system under EECP.


Asunto(s)
Algoritmos , Contrapulsación , Ventrículos Cardíacos , Hemodinámica , Modelos Cardiovasculares , Humanos , Contrapulsación/métodos , Gasto Cardíaco , Arterias/fisiología , Presión Sanguínea , Simulación por Computador , Aorta/fisiología , Redes Neurales de la Computación
9.
Inorg Chem ; 63(12): 5689-5700, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38485494

RESUMEN

High-entropy oxides (HEOs) exhibit abundant structural diversity due to cationic and anionic sublattices with independence, rendering them superior in catalytic applications compared to monometallic oxides. Nevertheless, the conventional high-temperature calcination approach undermines the porosity and reduces the exposure of active sites (such as oxygen vacancies, OVs) in HEOs, leading to diminished catalytic efficiency. Herein, we fabricate a series of HEOs with a large surface area utilizing a microenvironment modulation strategy (m-NiMgCuZnCo: 86 m2/g, m-MnCuCoNiFe: 67 m2/g, and m-FeCrCoNiMn: 54 m2/g). The enhanced porosity in m-NiMgCuZnCo facilitates the presentation of numerous OVs, exhibiting an exceptional catalytic performance. This tactic creates inspiration for designing HEOs with rich porosity and active species with vast potential applications.

10.
Nat Commun ; 15(1): 1268, 2024 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-38341443

RESUMEN

The Li-S battery is a promising next-generation battery chemistry that offers high energy density and low cost. The Li-S battery has a unique chemistry with intermediate sulphur species readily solvated in electrolytes, and understanding their implications is important from both practical and fundamental perspectives. In this study, we utilise the solvation free energy of electrolytes as a metric to formulate solvation-property relationships in various electrolytes and investigate their impact on the solvated lithium polysulphides. We find that solvation free energy influences Li-S battery voltage profile, lithium polysulphide solubility, Li-S battery cyclability and the Li metal anode; weaker solvation leads to lower 1st plateau voltage, higher 2nd plateau voltage, lower lithium polysulphide solubility, and superior cyclability of Li-S full cells and Li metal anodes. We believe that relationships delineated in this study can guide the design of high-performance electrolytes for Li-S batteries.

11.
Opt Express ; 32(3): 3989-3996, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38297608

RESUMEN

With the rapid development of superconducting quantum computing and the implementation of surface code, large-scale quantum computing is emerging as an urgent demand. In a superconducting computing system, the qubit is maintained in a cryogenic environment to avoid thermal excitation. Thus, the transmission of control signals, which are generated at room temperature, is needed. Typically, the transmission of these signals to the qubit relies on a coaxial cable wiring approach. However, in a large-scale computing system with hundreds or even thousands of qubits, the coaxial cables will pose great space and heat load to the dilution refrigerator. Here, to tackle this problem, we propose and demonstrate a direct-modulation-based optical transmission line. In our experiment, the average single-qubit XEB error and control error are measured as 0.139% and 0.014% separately, demonstrating the feasibility of the optical wiring approach and paving the way for large-scale superconducting quantum computing.

12.
J Inflamm Res ; 17: 137-152, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38223424

RESUMEN

Purpose: Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis, but the low maturation rate is concerning. Immune cells' impact on AVF maturation lacks bioinformatics research. The study aims to investigate the potential predictive role of immune-related genes and immune cell infiltration characteristics in AVF maturation. Patients and Methods: We analyzed the high-throughput sequencing dataset to identify differentially expressed genes (DEGs). Then, we performed enrichment analyses (GO, KEGG, GSEA) on immune-related genes and pathways in mature AVF. We focused on differentially expressed immune-related genes (DEIRGs) and constructed a PPI network to identify hub genes. These hub genes were validated in other databases and experiments, including qPCR and immunohistochemistry (IHC). The immune cell infiltration characteristics in native veins, failed AVFs, and matured AVFs were analyzed by cibersortX. Partial experimental validation was conducted using clinical samples. Results: Our results showed that immune-related genes and signaling pathways are significantly enriched in mature AVF. We validated this in other databases and ultimately identified three hub genes (IL1B, IL6, CXCR4) in combination with experiments. Significant differences in immune cell infiltration characteristics were observed among native veins, failed AVFs, and matured AVFs. Immune cell infiltration analysis revealed that accumulation of CD4+ T cells, dendritic cells, mast cells and M2 macrophages contribute to AVF maturation. These immune-related genes and immune cells have the potential to serve as predictive factors for AVF maturation. We partially validated this experimentally. Conclusion: From a bioinformatics perspective, our results have identified, for the first time, a set of immune-related genes and immune cell infiltration features that can characterize the maturation of AVF and significantly impact AVF maturation. These features hold potential as predictive indicators for AVF maturation outcomes.

13.
Appl Opt ; 63(2): 406-414, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38227236

RESUMEN

Considering the conventional calibration restriction of the complicated calibration procedures, narrow dynamic range, and less correlation in the calibration data, a global optimization radiometric calibration method is proposed in this paper. First, a unified database is generated by integrating different gray-level images, neutral density attenuators, integration times, and target radiations under the deduced infrared physical model. Then, the calibration coefficients are automatically learned through the relative error backward propagation network. Finally, experiments are conducted on a large-aperture ground-based infrared system to evaluate the effectiveness of the proposed method. The results indicate the proposed method can solve the problem of learning imbalance with large fluctuations of infrared radiation, ensure global measurement precision with a simpler calibration procedure, and accurately measure the internal stray radiation of the optical system.

14.
J Phys Chem Lett ; 15(4): 959-968, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38252167

RESUMEN

To study the intersystem crossing (ISC) and the spatial confinement of the triplet excited states of organic chromophores, we prepared a series of Bodipy dimers. We found that the connection position of the two units has a significant effect on the absorption and fluorescence. Singlet oxygen quantum yields of 3.8-12.4% were observed for the dimers, which are independent of solvent polarity. Nanosecond transient absorption spectra indicate the population of long-lived triplet excited states with lifetimes (τT) of 45-454 µs. Pulsed laser-excited time-resolved electron paramagnetic resonance (TREPR) spectra show that the T1 triplet states are essentially delocalized, which is different from the case for the previously reported Bodipy dimers. The TREPR spectra of the triplet states imply that the delocalization over the whole dimer essentially depends on the electron density of the carbon atoms at the connection sites. This property may become a universal rule for controlling the T1 state confinement in multichromophore organic molecules.

15.
Eur Heart J Qual Care Clin Outcomes ; 10(2): 143-153, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-37296238

RESUMEN

BACKGROUND: The burden of elderly cardiovascular disease (CVD) has received increasing attention with population ageing worldwide. AIMS: We reported on the global CVD burden in elderly individuals over 70, 1990-2019. METHODS AND RESULTS: Based on the Global Burden of Disease Study 2019, elderly CVD burden data were analysed. Temporal burden trends were analysed with the joinpoint model. The slope index and concentration index were used to evaluate health inequality. From 1990 to 2019, the global elderly CVD incidence, prevalence, death, and disability-adjusted life year rates generally decreased. However, the current burden remains high. The rapid growth in burden in parts of sub-Saharan Africa and Asia is a cause for concern. Countries with a higher socio-demographic index (SDI) have generally seen a greater decrease in burden, while countries with a lower SDI have generally experienced increases or smaller declines in burden. Health inequality analysis confirmed that the burden was gradually concentrating towards countries with a low SDI. Among the different CVDs, ischaemic heart disease causes the greatest burden in elderly individuals. Most CVD burdens increase with age, but stroke and peripheral vascular disease show markedly different distributional characteristics. In addition, the burden of hypertensive heart disease shows an unusual shift towards high-SDI countries. High systolic blood pressure was consistently the leading risk factor for CVD among elderly individuals. CONCLUSION: The burden of CVD in older people remains severe and generally tends to shift to lower-SDI countries. Policymakers need to take targeted measures to reduce its harm.


Asunto(s)
Enfermedades Cardiovasculares , Cardiopatías , Hipertensión , Anciano , Humanos , Enfermedades Cardiovasculares/epidemiología , Carga Global de Enfermedades , Disparidades en el Estado de Salud
16.
Int Wound J ; 21(4): e14584, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38112035

RESUMEN

Varicose veins are the prevalent vascular disorder that has conventionally been managed via risky postoperative wound infections and conventional surgery. While ultrasound-guided microwave ablation (UMA) has gained attention as a minimally invasive alternative, there is still a lack of research examining its comparative effectiveness. A prospective comparative investigation was undertaken in the Zhejiang region of China from January to November 2023, involving 140 patients who had received the diagnosis of primary varicose veins. An equal number of 70 patients underwent UMA and conventional surgery. Exclusion criteria for the study encompassed adult patients aged 18-65, with the exception of those who had undergone prior venous surgery, deep vein thrombosis or peripheral arterial disease. The demographical characteristics, procedural details and complication profiles of patients who developed postoperative wound infections within 30 days were analysed statistically. The outcomes demonstrated that postoperative wound infections were significantly diminished (5.7%) with UMA in comparison to conventional surgery (17.1%). In addition, the average duration of procedures and length of hospital stay for UMA patients were both reduced, although neither of these differences was found to be statistically significant (p > 0.05). Infection management, age and gender distribution of varicose veins were comparable between the two groups (p > 0.05). A significant inverse correlation was observed between the severity of varicose veins and postoperative outcomes, as determined by the regression analysis (p < 0.05). Using UMA to treat varicose veins showed promise as an alternative to conventional surgery, specifically in minimizing the incidence of postoperative wound infections. Additional research and clinical consideration are needed regarding the potential transition toward minimally invasive techniques in treatment of varicose veins, as suggested by these results.


Asunto(s)
Ablación por Catéter , Terapia por Láser , Várices , Adulto , Humanos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/cirugía , Microondas/uso terapéutico , Estudios Prospectivos , Terapia por Láser/métodos , Ablación por Catéter/métodos , Vena Safena/diagnóstico por imagen , Vena Safena/cirugía , Várices/cirugía , Ultrasonografía Intervencional , Resultado del Tratamiento
17.
Nat Commun ; 14(1): 7435, 2023 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-37973913

RESUMEN

SND1 and MTDH are known to promote cancer and therapy resistance, but their mechanisms and interactions with other oncogenes remain unclear. Here, we show that oncoprotein ERG interacts with SND1/MTDH complex through SND1's Tudor domain. ERG, an ETS-domain transcription factor, is overexpressed in many prostate cancers. Knocking down SND1 in human prostate epithelial cells, especially those overexpressing ERG, negatively impacts cell proliferation. Transcriptional analysis shows substantial overlap in genes regulated by ERG and SND1. Mechanistically, we show that ERG promotes nuclear localization of SND1/MTDH. Forced nuclear localization of SND1 prominently increases its growth promoting function irrespective of ERG expression. In mice, prostate-specific Snd1 deletion reduces cancer growth and tumor burden in a prostate cancer model (PB-Cre/Ptenflox/flox/ERG mice), Moreover, we find a significant overlap between prostate transcriptional signatures of ERG and SND1. These findings highlight SND1's crucial role in prostate tumorigenesis, suggesting SND1 as a potential therapeutic target in prostate cancer.


Asunto(s)
Neoplasias de la Próstata , Animales , Humanos , Masculino , Ratones , Transformación Celular Neoplásica/genética , Endonucleasas/genética , Endonucleasas/metabolismo , Regulación Neoplásica de la Expresión Génica , Proteínas de la Membrana/metabolismo , Próstata/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Proteínas de Unión al ARN/metabolismo , Factores de Transcripción/metabolismo , Regulador Transcripcional ERG/genética , Regulador Transcripcional ERG/metabolismo , Dominio Tudor
18.
Inflammation ; 2023 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-37985573

RESUMEN

Ulcerative colitis, an inflammatory bowel disease, manifests with symptoms such as abdominal pain, diarrhea, and mucopurulent feces. The long non-coding RNA (lncRNA) ANRIL exhibits significantly reduced expression in UC, yet its specific mechanism is unknown. This study revealed that ANRIL is involved in the progression of UC by inhibiting IL-6 and TNF-α via miR-191-5P/SATB1 axis. We found that in patients with UC, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were significantly overexpressed in inflamed colon sites, whereas ANRIL was significantly under-expressed and associated with disease severity. The downregulation of ANRIL resulted in the increased expression of IL-6 and TNF-α in LPS-treated FHCs. ANRIL directly targeted miR-191-5p, thereby inhibiting its expression and augmenting SATB1 expression. Moreover, overexpression of miR-191-5p abolished ANRIL-mediated inhibition of IL-6 and TNF-α production. Dual luciferase reporter assays revealed the specific binding of miR-191-5p to ANRIL and SATB1. Furthermore, the downregulation of ANRIL promoted DSS-induced colitis in mice. Together, we provide evidence that ANRIL plays a critical role in regulating IL-6 and TNF-α expression in UC by modulating the miR-191-5p/SATB1 axis. Our study provides novel insights into progression and molecular therapeutic strategies in UC.

19.
Rev Sci Instrum ; 94(10)2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37796097

RESUMEN

Quantum key distribution (QKD) research has yielded highly fruitful results and is currently undergoing an industrialization transformation. In QKD systems, electro-optic modulators are typically employed to prepare the required quantum states. While various QKD systems operating at GHz repetition frequency have demonstrated exceptional performance, they predominantly rely on instruments or printed circuit boards to fulfill the driving circuit function of the electro-optic modulator. Consequently, these systems tend to be complex with low integration levels. To address this challenge, we have introduced a modulator driver integrated circuit in 0.18 µm SiGe BiCMOS technology. The circuit can generate multiple-level driving signals with a clock frequency of 1.25 GHz and a rising edge of ∼50 ps. Each voltage amplitude can be independently adjusted, ensuring the precise preparation of quantum states. The measured signal-to-noise ratio was more than 17 dB, resulting in a low quantum bit error rate of 0.24% in our polarization-encoding system. This work will contribute to the advancement of QKD system integration and promote the industrialization process in this field.

20.
Phys Rev Lett ; 131(10): 100802, 2023 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-37739363

RESUMEN

Measurement-device-independent quantum key distribution (MDI QKD) provides immunity against all attacks targeting measurement devices. It is essential to implement MDI QKD in the future global-scale quantum communication network. Toward this goal, we demonstrate a robust MDI QKD fully covering daytime, overcoming the high background noise that prevents BB84 protocol even when using a perfect single-photon source. Based on this, we establish a hybrid quantum communication network that integrates free-space and fiber channels through Hong-Ou-Mandle (HOM) interference. Additionally, we investigate the feasibility of implementing HOM interference with moving satellites. Our results serve as a significant cornerstone for future integrated space-ground quantum communication networks that incorporate measurement-device-independent security.

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