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1.
iScience ; 27(7): 110276, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39109172

RESUMEN

Understanding the mechanism of cancer immune surveillance is crucial for precision medicine and effective immunotherapy. We report here that ZNF408, encoded by a gene linked to familial exudative vitreoretinopathy (FEVR) and autosomal recessive retinitis pigmentosa (RP), is physically associated with the SETD1A/COMPASS complex mediating histone H3 lysine 4 (H3K4) methylation in breast cancer cells. Integrative epigenomic and transcriptomic analyses reveal that ZNF408 and SETD1A share overlapped chromatin landscape and coordinately activate a cohort of genes, among which STING1 is critical in innate immune responses. ZNF408-SETD1A complex enhances STING1 expression and promotes STING-mediated anti-tumor immune responses both in vitro and in vivo. Importantly, ZNF408 expression is positively correlated with that of STING1 and negatively correlated with the histological grade of breast cancer. Our study uncovers a role for ZNF408 in cancer immune surveillance, supporting further investigations for therapeutic targeting of ZNF408-SETD1A-STING1 axis in breast carcinogenesis and other ZNF408-associated diseases including FEVR and RP.

2.
J Alzheimers Dis Rep ; 8(1): 935-944, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39114552

RESUMEN

Background: Excessive daytime sleepiness (EDS) and caudate nucleus volume alterations have been linked to Alzheimer's disease (AD), but their relationship remains unclear under the context of subjective cognitive decline (SCD). Objective: This study aimed to investigate the relationship between EDS and caudate nucleus volume in patients with SCD. Methods: The volume of entire brain was measured in 170 patients with SCD, including 37 patients with EDS and 133 non-EDS, from the Sino Longitudinal Study on Cognitive Decline (SILCODE). Participants underwent a comprehensive assessment battery, including neuropsychological and clinical evaluations, blood tests, genetic analysis for APOE ɛ4, and structural MRI scans analyzed using the fully automated segmentation tool, volBrain. Results: Patients with EDS had significantly increased volume in the total and left caudate nucleus compared to non-EDS. The most significant cognitive behavioral factor associated with caudate nucleus volume in the EDS was the Auditory Verbal Learning Test-recognition. Conclusions: These findings suggest that EDS may be associated with alterations in caudate nucleus volume, particularly in the left hemisphere, in the context of SCD. Further research is necessary to understand the underlying mechanisms of this relationship and its implications for clinical management.

3.
J Neurosurg ; : 1-10, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39126717

RESUMEN

OBJECTIVE: The aim of this study was to noninvasively explore the glymphatic system (GS) in glioma and its association with glioma characteristics and prognosis by using diffusion tensor image analysis along the perivascular space (ALPS). METHODS: In the period from April 2015 to November 2021, all patients with pathologically confirmed unihemispheric glioma who had not undergone surgery, chemotherapy, radiotherapy, or stereotactic biopsy; who did not have severe brain deformation; who had undergone preoperative conventional and advanced whole-brain diffusion-weighted imaging; and whose data were available and uncompromised were included in this study. Age- and sex-matched healthy controls (HCs) who had undergone diffusion-weighted imaging were also included. The ALPS index was calculated based on diffusivity maps, allowing noninvasive analysis of the GS. The contralateral ALPS index was measured in all glioma patients, and the ipsilateral ALPS index was measured in glioma patients without severe deformation of the ipsilateral hemisphere. The ALPS index was compared between glioma patients and HCs according to tumor grade, IDH genotype, tumor and edema volume, and tumor location. The association between the bilateral ALPS index of gliomas and tumor characteristics was further analyzed. Survival analysis was conducted using Kaplan-Meier survival curves with the log-rank test and univariable and multivariable Cox regressions. RESULTS: Ninety-one patients with unihemispheric glioma (33 female, mean age 46 ± 13 years) and 59 age- and sex-matched HCs were included in this study. The ipsilateral ALPS index decreased in the glioma group versus the HC group, regardless of tumor grade, IDH genotype, tumor and edema volume, or tumor location (p ≤ 0.048), whereas the contralateral ALPS index decreased in gliomas with a high grade, IDH wildtype, larger edema volume, different tumor volumes and locations (p ≤ 0.009). The ipsilateral versus contralateral ALPS index was lower regardless of tumor grade, IDH genotype, tumor and edema volume, or tumor location (p ≤ 0.044). Univariable linear regression revealed age (ß = -0.004, p = 0.026), tumor grade (ß = -0.114, p = 0.011), and IDH genotype (ß = 0.120, p = 0.008) were associated with the ipsilateral ALPS index in glioma. Age (ß = -0.005, p < 0.001), tumor grade (ß = -0.144, p < 0.001), IDH genotype (ß = 0.154, p < 0.001), tumor volume (ß = -0.002, p = 0.001), and peritumoral edema volume (ß = -0.002, p < 0.001) were correlated with the contralateral ALPS index in glioma. Multivariable linear regression revealed that tumor grade (ß = -0.125, p = 0.005) was independently associated with the ipsilateral ALPS index. Age (ß = -0.003, p = 0.022), IDH status (ß = 0.132, p = 0.001), and tumor volume (ß = -0.002, p < 0.001) were independently associated with the contralateral ALPS index. Kaplan-Meier analysis showed different survival times between low and high contralateral ALPS groups (log-rank = 10.574, p = 0.001). Univariable Cox regression analysis demonstrated that the lower contralateral ALPS index was related to a shorter survival time (HR 0.095, p = 0.005). Multivariable Cox regression analysis revealed IDH status as the only independent factor for survival (HR 0.138, p < 0.001). CONCLUSIONS: GS function was impaired in glioma and correlated with tumor characteristics, and worse contralateral GS function was associated with a shorter survival time.

4.
Parkinsonism Relat Disord ; 126: 107050, 2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38986305

RESUMEN

INTRODUCTION: Parkinson's disease (PD) is often accompanied by sleep disturbances, impacting patients' quality of life. While repetitive transcranial magnetic stimulation (rTMS) shows promise in improving self-reported sleep quality, its effects on objective sleep architecture in PD remain understudied. Sleep disturbances, including rapid eye movement (REM) and slow-wave sleep disturbances, correlate with cognitive decline and motor symptoms. This study investigated the effect of low-frequency rTMS targeting the right dorsolateral prefrontal cortex (DLPFC) modifying objective sleep architecture and explored symptom improvement mechanisms in PD patients. METHODS: In this randomized, double-blind, sham-controlled trial, 67 PD patients received 10 consecutive days of 1-Hz rTMS over the right DLPFC. Polysomnography assessed sleep microstructure, while electroencephalogram recordings evaluated power spectral density and sleep spindle activity. Clinical scales measured sleep quality, motor symptoms, and cognition at baseline, post-treatment, and 3 months post-rTMS. RESULTS: The rTMS group exhibited improvements in sleep quality, motor symptoms, and cognition post-treatment, persisting at the 3-month follow-up. There was a notable increase in the REM sleep proportion post-rTMS. The rTMS group exhibited elevated low-frequency (0.5-2 Hz) slow-wave electroencephalogram spectral density during non-REM sleep. Cognitive enhancement correlated with increased lower delta power, while motor symptom progression correlated with spindle frequency and slow-wave sleep percentage changes. CONCLUSION: Low-frequency rTMS targeting the right DLPFC holds promise for improving clinical symptoms and modulating sleep architecture in PD. These findings suggest a link between symptom improvement and sleep structure enhancement, highlighting the need for further investigation into the therapeutic potential of rTMS in PD management.

5.
Angew Chem Int Ed Engl ; : e202407074, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38978178

RESUMEN

Designing and synthesizing multifunctional hybrid copper halides with near ultraviolet (NUV) light-excited high-energy emission (< 500 nm) remains challenging. Here, a pair of broadband-excited high-energy emitting isomers, namely, α-/ß-(MePh3P)2CuI3 (MePh3P = methyltriphenylphosphonium), were synthesized. α-(MePh3P)2CuI3 with blue emission peaking at 475 nm is firstly discovered wherein its structure contains regular [CuI3]2‒ triangles and crystallizes in centrosymmetric space group P21/c. While ß-(MePh3P)2CuI3 featuring distorted [CuI3]2‒ planar triangles shows inversion symmetry breaking and crystallizes in the noncentrosymmetric space group P21, which exhibits cyan emission peaking at 495 nm with prominent near-unity photoluminescence quantum yield and the excitation band ranging from 200 to 450 nm. Intriguingly, ß-(MePh3P)2CuI3 exhibits phase-matchable second-harmonic generation response of 0.54 × KDP and a suitable birefringence of 0.06@1064 nm. Furthermore, ß-(MePh3P)2CuI3 also can be excited by X-ray radioluminescence with a high scintillation light yield of 16193 photon/MeV and an ultra-low detection limit of 47.97 nGy/s, which is only 0.87% of the standard medical diagnosis (5.5 µGy/s). This work not only promotes the development of solid-state lighting, laser frequency conversion and X-ray imaging, but also provides a reference for constructing multifunctional hybrid metal halides.

6.
J Dairy Sci ; 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39004137

RESUMEN

The lack of fat in yogurt can lead to alterations in taste and whey separation, reducing consumer acceptance. In this study, the feasibility of enhancing the quality of skim milk yogurt through a combination of transglutaminase (TG) and protein-glutaminase (PG) was investigated. The combination of TG and PG resulted in simultaneous cross-linking and deamidated of casein micelles, with PG deamidation taking priority over TG cross-linking, leading to higher solubility and lower turbidity of milk proteins compared with TG alone. When 0.06 U/mL TG and 0.03 U/mL PG were added, firmness and viscosity indexes significantly increased by 38.26 and 78.59%, respectively as compared with the control. Microscopic images revealed increased cross-linking with casein and filling of cavities by smaller sub-micelles in the combination of TG and PG treatment. Furthermore, the combination of TG and PG resolved issues of rough taste and whey separation, leading to improved overall liking. This study highlights the benefits of using both enzymes in dairy production and has important implication for future research.

7.
Inorg Chem ; 63(27): 12409-12416, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38905324

RESUMEN

The potential application of stimuli-responsive hybrid copper halides in information storage and switch devices has generated significant interest. However, their transformation mechanism needs to be further studied deeply. Herein, two zero-dimensional (0D) organic-inorganic hybrids, namely, (TBA)CuBr2 (1) with linear [CuBr2]- units and (TBA)2Cu4Br6 (2) with [Cu4Br6]2- clusters (TBA+ = (C4H9)4N+), are synthesized using simple solvent evaporation approaches. Interestingly, upon exposure to distinct protic solvents, such as methanol, ethanol, ethylene glycol, or hot water, 1 undergoes a transformation into 2 with varying degrees of transition, accompanied by a change in luminescence color from cyan to orange (or mixed color) under high-energy emission (e.g., 254 nm) excitation. Hot water can trigger 1 to completely transform into 2 because of its large contact angle difference in the solvents. Furthermore, 2 can be converted back to 1 through a simple solid-state mechanochemical reaction. Additionally, the structure of 2 remains unchanged even after immersion in 80 °C H2O for 168 h due to the dense organic framework. This study provides valuable insights for exploring reversible structural transformation materials in the 0D metal halide system.

9.
Front Neurosci ; 18: 1329718, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38660224

RESUMEN

Purpose: To develop deep learning models based on four-dimensional computed tomography angiography (4D-CTA) images for automatic detection of large vessel occlusion (LVO) in the anterior circulation that cause acute ischemic stroke. Methods: This retrospective study included 104 LVO patients and 105 non-LVO patients for deep learning models development. Another 30 LVO patients and 31 non-LVO patients formed the time-independent validation set. Four phases of 4D-CTA (arterial phase P1, arterial-venous phase P2, venous phase P3 and late venous phase P4) were arranged and combined and two input methods was used: combined input and superimposed input. Totally 26 models were constructed using a modified HRNet network. Assessment metrics included the areas under the curve (AUC), accuracy, sensitivity, specificity and F1 score. Kappa analysis was performed to assess inter-rater agreement between the best model and radiologists of different seniority. Results: The P1 + P2 model (combined input) had the best diagnostic performance. In the internal validation set, the AUC was 0.975 (95%CI: 0.878-0.999), accuracy was 0.911, sensitivity was 0.889, specificity was 0.944, and the F1 score was 0.909. In the time-independent validation set, the model demonstrated consistently high performance with an AUC of 0.942 (95%CI: 0.851-0.986), accuracy of 0.902, sensitivity of 0.867, specificity of 0.935, and an F1 score of 0.901. The best model showed strong consistency with the diagnostic efficacy of three radiologists of different seniority (k = 0.84, 0.80, 0.70, respectively). Conclusion: The deep learning model, using combined arterial and arterial-venous phase, was highly effective in detecting LVO, alerting radiologists to speed up the diagnosis.

10.
Nanoscale ; 16(17): 8345-8351, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38606457

RESUMEN

2D WSe2-based electronic devices have received much research interest. However, it is still a challenge to achieve high electronic performance in WSe2-based devices. In this work, we report greatly enhanced performances of different thickness WSe2 ambipolar transistors and demonstrate homogeneous WSe2 inverter devices, which are obtained by using a semiconductor processing-compatible layer removal technique via chemical removal of the surface top WOx layer formed by O2 plasma treatment. Importantly, monolayer WSe2 was realised after several consecutive removal processes, demonstrating that the single layer removal is accurate and reliable. After subsequent removal of the top layer WOx by KOH, the fabricated WSe2 field-effect transistors exhibit greatly enhanced electronic performance along with the high electron and hole mobilities of 40 and 85 cm2 V-1 s-1, respectively. Our work demonstrates that the layer removal technique is an efficient route to fabricate high performance 2D material-based electronic devices.

11.
Front Microbiol ; 15: 1372069, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38577684

RESUMEN

Introduction: Hepatitis E virus (HEV), with heightened virulence in immunocompromised individuals and pregnant women, is a pervasive threat in developing countries. A globaly available vaccine against HEV is currently lacking. Methods: We designed a multi-epitope vaccine based on protein ORF2 and ORF3 of HEV using immunoinformatics. Results: The vaccine comprised 23 nontoxic, nonallergenic, soluble peptides. The stability of the docked peptide vaccine-TLR3 complex was validated by molecular dynamic simulations. The induction of effective cellular and humoral immune responses by the multi-peptide vaccine was verified by simulated immunization. Discussion: These findings provide a foundation for future HEV vaccine studies.

12.
Food Chem X ; 22: 101312, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38559444

RESUMEN

Protein glutaminase (PG), originating from Chryseobacterium proteolyticum, can catalyze the deamidation of glutamine residues in plant proteins into glutamic acid, thus enhancing its functional properties. However, the low yield of PG limits its industrial production. In this study, the yield of PG in C. proteolyticum TM1040 increased by 121 %, up to 7.30 U/mL in a 15 L fermenter after medium optimization. Subsequently, purified PG was obtained by cation exchange chromatography (CEX) coupled with hydrophobic interaction chromatography (HIC). The degree of deamidation (DD) of wheat gluten after purified PG deamidation was 87.11 %, which is superior to chemical deamidation in safety and DD. The emulsifying and foaming properties of deamidated wheat gluten were 2.67 and 18.86 times higher, and the water- and oil-holding properties were 4.23 and 18.77 times higher, respectively. The deamidated wheat gluten with enhanced functional properties was used to improve the flavor and texture in baking cakes.

13.
MedComm (2020) ; 5(4): e517, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38525106

RESUMEN

Regarding the extensive global attention to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that constitutes an international public health emergency, pseudovirus neutralization assays have been widely applied due to their advantages of being able to be conducted in biosafety level 2 laboratories and having a high safety factor. In this study, by adding a blue fluorescent protein (AmCyan) gene to the HIV system pSG3-△env backbone plasmid HpaI and truncating the C-terminal 21 amino acids of the SARS-CoV-2 spike protein (S), high-titer SARS-CoV-2-Sdel21-AmCyan fluorescent pseudovirus was successfully packaged. The fluorescent pseudovirus was used to establish a neutralization assay in a 96-well plate using 293T cells stably transfected with the AF cells. Then, parameters such as the ratio of backbone and membrane plasmid, sensitive cells, inoculation of cells and virus, as well as incubation and detection time were optimized. The pseudovirus neutralization assay demonstrated high accuracy, sensitivity, repeatability, and a strong correlation with the luminescent pseudovirus neutralization assay. Additionally, we scaled up the neutralizing antibody determination method by increasing the plate size from 96 wells to 384 wells. We have established a robust fluorescent pseudotyped virus neutralization assay for SARS-CoV-2 using the HIV system, providing a foundation for serum neutralization antibody detection, monoclonal antibody screening, and vaccine development.

14.
Int J Biol Macromol ; 262(Pt 2): 130092, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38354920

RESUMEN

Protein glutaminase (PG; EC 3.5.1.44) is a novel deamidase that helps to improve functional properties of food proteins. Currently, the highest activated PG enzyme activity was 26 U/mg when recombinantly expressed via the twin-arginine translocation (Tat) pathway in Corynebacterium glutamicum. In this study, superfolder green fluorescent protein (sfGFP) was used to replace traditional signal peptides to facilitate efficient heterologous expression and secretion of Propeptide-Protein glutaminase (PP) in Bacillus subtilis. The fusion protein, sfGFP-PP, was secreted from 12 h of fermentation and reached its highest extracellular expression at 28 h, with a secretion efficiency of about 93 %. Moreover, when fusing sfGFP with PP at the N-terminus, it significantly enhances PG expression up to 26 U/mL by approximately 2.2-fold compared to conventional signal-peptides- guided PP with 11.9 U/mL. Finally, the PG enzyme activity increased from 26 U/mL to 36.9 U/mL after promoter and RBS optimization. This strategy not only provides a new approach to increase PG production as well as extracellular secretion but also offers sfGFP as an effective N-terminal tag for increased secreted production of difficult-to-express proteins.


Asunto(s)
Bacillus subtilis , Glutaminasa , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/química , Glutaminasa/genética , Glutaminasa/metabolismo , Transporte de Proteínas , Señales de Clasificación de Proteína , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo
15.
J Med Virol ; 96(1): e29314, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38163276

RESUMEN

SARS-CoV-2 breakthrough infections in vaccinated individuals underscore the threat posed by continuous mutating variants, such as Omicron, to vaccine-induced immunity. This necessitates the search for broad-spectrum immunogens capable of countering infections from such variants. This study evaluates the immunogenicity relationship among SARS-CoV-2 variants, from D614G to XBB, through Guinea pig vaccination, covering D614G, Alpha, Beta, Gamma, Delta, BA.1, BA.2, BA.2.75, BA.2.75.2, BA.5, BF.7, BQ.1.1, and XBB, employing three immunization strategies: three-dose monovalent immunogens, three-dose bivalent immunogens, and a two-dose vaccination with D614G followed by a booster immunization with a variant strain immunogen. Three distinct immunogenicity clusters were identified: D614G, Alpha, Beta, Gamma, and Delta as cluster 1, BA.1, BA.2, and BA.2.75 as cluster 2, BA.2.75.2, BA.5, BF.7, BQ.1.1, and XBB as cluster 3. Broad-spectrum protection could be achieved through a combined immunization strategy using bivalent immunogens or D614G and XBB, or two initial D614G vaccinations followed by two XBB boosters. A comparison of neutralizing antibody levels induced by XBB boosting and equivalent dosing of D614G and XBB revealed that the XBB booster produced higher antibody levels. The study suggests that vaccine antigen selection should focus on the antigenic alterations among variants, eliminating the need for updating vaccine components for each variant.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Animales , Cobayas , SARS-CoV-2/genética , COVID-19/prevención & control , Anticuerpos Neutralizantes , Análisis por Conglomerados , Vacunas Combinadas , Anticuerpos Antivirales
16.
Inorg Chem ; 63(1): 73-77, 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-38153229

RESUMEN

Chiral organic-inorganic hybrid metal halides are a promising class of nonlinear-optical materials with unique optical properties and flexible crystal structures. However, the structures and properties of chiral hybrid tellurium halides, especially second harmonic generation (SHG), have not been reported. Here, by introducing chiral organic molecule (R/S)-methylbenzylammonium (R/S-MBA), we synthesized a pair of novel zero-dimensional (0D) chiral tellurium-based hybrid halides with noncentrosymmetric space group C2, (R/S-MBA)2TeCl6 (R/S-Cl). Single-crystal X-ray diffraction analysis and solid-state circular dichroism (CD) spectra confirm that R/S-Cl shows obvious enantiomer enrichment. Moreover, the resulting chiral products present an efficient SHG response. Interestingly, through manipulation of halogen atoms, two pairs of achiral tellurium halides, (R/S-MBA)2TeBr6 (R/S-Br) and (R/S-MBA)2TeI6 (R/S-I), were obtained, both of which crystallize in the centrosymmetric space group R3̅. It is noteworthy that R/S-I has a narrow band gap of 1.55 eV, which is smaller than that of most 0D metal halides and comparable to that of three-dimensional lead halide, showing its potential as a highly efficient light absorber.

17.
Inorg Chem ; 62(46): 18825-18829, 2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-37934934

RESUMEN

Herein, we successfully synthesized a stable copper iodide hybrid with a 0D structure, (C20H20P)2Cu2I4, in which [Cu2I4]2- dimers with a short Cu-Cu distance (2.64 Å) are isolated and surrounded by [C20H20P]+ organic cations. Bright broadband yellow emission (576 nm) featuring a wide excitation range from 240 to 450 nm was achieved, along with a large Stokes shift (211 nm), long-lived lifetime (1.99 µs), and zero self-absorption. The results combined with crystal structure, spectroscopy analysis, and theoretical studies reveal that a cluster-centered excited state is responsible for this yellow emission. Importantly, the structure of (C20H20P)2Cu2I4 remains unchanged even after soaking in water for 30 days or heating at 80 °C for 240 h due to the intermolecular interaction. Furthermore, a stable white LED showing a naturally correlated color temperature (CCT) of 6573 K and CIE color coordinate of (0.31, 0.37) was also demonstrated. This work demonstrates efficient light emitters based on lead-free and stable metal halides for lighting, providing an important reference for the development of stable, high-performance metal halide phosphors.

18.
Sci Adv ; 9(44): eadk3860, 2023 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-37922355

RESUMEN

Imaging and identifying target signatures and biomedical markers in the ultraviolet (UV) spectrum is broadly important to medical imaging, military target tracking, remote sensing, and industrial automation. However, current silicon-based imaging sensors are fundamentally limited because of the rapid absorption and attenuation of UV light, hindering their ability to resolve UV spectral signatures. Here, we present a bioinspired imaging sensor capable of wavelength-resolved imaging in the UV range. Inspired by the UV-sensitive visual system of the Papilio xuthus butterfly, the sensor monolithically combines vertically stacked photodiodes and perovskite nanocrystals. This imaging design combines two complementary UV detection mechanisms: The nanocrystal layer converts a portion of UV signals into visible fluorescence, detected by the photodiode array, while the remaining UV light is detected by the top photodiode. Our label-free UV fluorescence imaging data from aromatic amino acids and cancer/normal cells enables real-time differentiation of these biomedical materials with 99% confidence.


Asunto(s)
Mariposas Diurnas , Luz , Animales , Rayos Ultravioleta , Óxidos , Imagen Óptica
19.
Oncogene ; 42(50): 3684-3697, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37903896

RESUMEN

Regulator of chromosome condensation domain-containing protein 1 (RCCD1), previously reported as a partner of histone H3K36 demethylase KDM8 involved in chromosome segregation, has been identified as a potential driver for breast cancer in a recent transcriptome-wide association study. We report here that, unexpectedly, RCCD1 is also localized in mitochondria. We show that RCCD1 resides in the mitochondrial matrix, where it interacts with the mitochondrial contact site/cristae organizing system (MICOS) and mitochondrial DNA (mtDNA) to regulate mtDNA transcription, oxidative phosphorylation, and the production of reactive oxygen species. Interestingly, RCCD1 is upregulated under hypoxic conditions, leading to decreased generation of reactive oxygen species and alleviated apoptosis favoring cancer cell survival. We show that RCCD1 promotes breast cancer cell proliferation in vitro and accelerates breast tumor growth in vivo. Indeed, RCCD1 is overexpressed in breast carcinomas, and its level of expression is associated with aggressive breast cancer phenotypes and poor patient survival. Our study reveals an additional dimension of RCCD1 functionality in regulating mitochondrial homeostasis, whose dysregulation inflicts pathologic states such as breast cancer.


Asunto(s)
Neoplasias de la Mama , Mitocondrias , Humanos , Femenino , Especies Reactivas de Oxígeno/metabolismo , Mitocondrias/metabolismo , ADN Mitocondrial/genética , Neoplasias de la Mama/patología , Hipoxia/metabolismo , Carcinogénesis/patología , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Proteínas Portadoras/metabolismo , Proteínas de la Membrana/genética , Histona Demetilasas/metabolismo
20.
Quant Imaging Med Surg ; 13(9): 6026-6036, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37711776

RESUMEN

Background: Identifying cardioembolic stroke is important for the decision-making of endovascular treatment and anticoagulation therapy. We aimed to explore the features of cardioembolic stroke on 4-dimensional (4D) computed tomography angiography (4D-CTA) and assess whether these features can assist in classifying stroke etiology. Methods: In this retrospective study, we analyzed the images of 294 patients with acute ischemic stroke (AIS) from July 2020 to February 2022 at the First Affiliated Hospital of Chongqing Medical University, which had been consecutively collected. The data of 110 patients with occlusion of the M1/M2 segment of the middle cerebral artery (MCA) with/without intracranial internal carotid artery (ICA) occlusion were analyzed to calculate the clot burden score (CBS) and collateral score (CS), and the data of 88 patients with a clear origin and distal part were analyzed to measure clot length. Maximum intensity projection (MIP) and time MIP (tMIP) post-processing were used to assess the clot features. The Mann-Whitney U test was used to compare the clot characteristics between the 2 groups. Binary logistic regression was performed to assess the association between the image characteristics and cardioembolic stroke. Moreover, the receiver operating characteristic (ROC) curve was used to test the diagnostic efficacy of MIP/tMIP clot features in classifying cardioembolic stroke. Results: Age, high-risk factors for cerebrovascular disease, high/medium-risk sources of cardioembolic stroke, clot length, CBS, and CS were significantly different between the cardioembolic stroke group and non-cardioembolic stroke group (P<0.05). In the cardioembolic stroke group, the median MIP and tMIP clot length was 12 mm [interquartile range (IQR), 8.3-17.4 mm] and 9.3 mm (IQR, 6.8-14.3 mm), respectively. In the non-cardioembolic stroke group, the median MIP and tMIP clot length was 6.5 mm (IQR, 4.7-11.5 mm) and 5.8 mm (IQR, 3.9-10.6 mm), respectively. Binary logistic regression showed that cardioembolic stroke was significantly associated with MIP-clot length [odds ratio (OR), 1.15; 95% confidence interval (CI): 1.02-1.29; P<0.05], tMIP-clot length (OR, 1.18; 95% CI: 1.02-1.36; P<0.05), and tMIP-CBS (OR, 3.96; 95% CI: 1.08-14.58; P<0.05). The area under the ROC curve (AUC) values of MIP clot length for identifying cardioembolic stroke were 0.75 (95% CI: 0.65-0.84, P<0.05), with a cut-off value of >7.4 mm [sensitivity: 84.62% (95% CI: 69.50-94.10%); specificity: 59.18% (95% CI: 44.20-73.00%)]. The AUC value of tMIP clot length was 0.72 (95% CI: 0.61-0.81, P<0.05), with a cut-off value of >5.4 mm [sensitivity: 92.31% (95% CI: 79.10-98.40%); specificity: 48.98% (95% CI: 34.40-63.70%)]. Conclusions: Clot length and CBS were overestimated on MIP images. Among the clot characteristics, clot length could identify cardioembolic stroke.

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