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1.
Medicine (Baltimore) ; 103(43): e40298, 2024 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-39470538

RESUMEN

This retrospective study aimed to investigate the clinical efficacy of single-channel percutaneous endoscopic nucleotomy combined with annulus fibrosus suturing for treating lumbar disc herniation (LDH). The study included 86 patients with LDH treated in our spinal department from August 2020 to January 2022. The suture group consisted of 26 males and 18 females, while the control group (nucleotomy alone) included 25 males and 17 females. All patients were followed for at least 1 year, with follow-up points at 3 days, 3 months, and 12 months postoperatively. Various clinical and radiological indicators were used to evaluate and compare the efficacy and safety of the 2 procedures. No statistically significant differences were observed in age, sex, BMI, surgical segments, degree of disc degeneration, or postoperative length of hospital stay. However, the suture group had a longer operative time (63.28 ±â€…4.17 minutes vs 54.71 ±â€…4.89 minutes, t = 8.759, P < .05). At 12 months postoperatively, neither group showed aggravated disc degeneration. There was also no significant difference in excellent rates between the 2 groups (95.45% vs 92.86%, X2=0.265, P = .607). However, the suture group had a lower intervertebral disc height loss rate compared to the control group (22.3% ±â€…4.6% vs 29.8% ±â€…6.2%, X2=6.390, P < .001). In conclusion, single-channel percutaneous endoscopic nucleotomy combined with annulus fibrosus suturing is a safe and reliable treatment for LDH. It effectively reduces the recurrence rate, slows disc degeneration and loss of disc height, and achieves excellent early outcomes.


Asunto(s)
Anillo Fibroso , Endoscopía , Desplazamiento del Disco Intervertebral , Vértebras Lumbares , Humanos , Masculino , Femenino , Desplazamiento del Disco Intervertebral/cirugía , Estudios Retrospectivos , Persona de Mediana Edad , Vértebras Lumbares/cirugía , Adulto , Endoscopía/métodos , Anillo Fibroso/cirugía , Resultado del Tratamiento , Discectomía Percutánea/métodos , Técnicas de Sutura , Tempo Operativo
2.
ISA Trans ; 154: 57-72, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39152079

RESUMEN

Aiming to address the multiscale characteristics and noise corruption problems in the vibration signals of aviation hydraulic pumps, this article develops a novel Multiscale Dynamically Parallel Shrinkage Network (MDPSN) to learn complementary and rich fault-related multiscale features, with the ultimate goal of yielding higher diagnostic accuracy. One significant property is the development of a novel dynamically parallel shrinking module (DPSM) that adaptively generates independent soft thresholds for different scales, effectively shrinking noise-related features to zeros. On one hand, DPSM aggregates and interacts with features at all scales to construct a global feature representation containing richer fault-related information, which is served as the foundation for soft thresholding generation, significantly improving the accuracy and rationality of the generated thresholds. On the other hand, DPSM can adaptively generate individual soft threshold for each scale, allowing each scale to use an independent threshold tailored to its own characteristic to eliminate noise-related information. This avoids the issues of over-denoising or under-denoising caused by the uniform application of thresholds across all scales. Finally, the effectiveness of MDPSN is validated by a series of experiment comparisons on an aviation hydraulic pump dataset and two bearing datasets with various types of noise. The experimental results demonstrate that MDPSN achieves superior diagnostic accuracy compared to five other comparison methods.

3.
Br J Cancer ; 130(11): 1819-1827, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38594370

RESUMEN

BACKGROUND: Although DHFR gene amplification has long been known as a major mechanism for methotrexate (MTX) resistance in cancer, the early changes and detailed development of the resistance are not yet fully understood. METHODS: We performed genomic, transcriptional and proteomic analyses of human colon cancer cells with sequentially increasing levels of MTX-resistance. RESULTS: The genomic amplification evolved in three phases (pre-amplification, homogenously staining region (HSR) and extrachromosomal DNA (ecDNA)). We confirm that genomic amplification and increased expression of DHFR, with formation of HSRs and especially ecDNAs, is the major driver of resistance. However, DHFR did not play a detectable role in the early phase. In the late phase (ecDNA), increase in FAM151B protein level may also have an important role by decreasing sensitivity to MTX. In addition, although MSH3 and ZFYVE16 may be subject to different posttranscriptional regulations and therefore protein expressions are decreased in ecDNA stages compared to HSR stages, they still play important roles in MTX resistance. CONCLUSION: The study provides a detailed evolutionary trajectory of MTX-resistance and identifies new targets, especially ecDNAs, which could help to prevent drug resistance. It also presents a proof-of-principal approach which could be applied to other cancer drug resistance studies.


Asunto(s)
Resistencia a Antineoplásicos , Amplificación de Genes , Metotrexato , Tetrahidrofolato Deshidrogenasa , Humanos , Metotrexato/farmacología , Resistencia a Antineoplásicos/genética , Tetrahidrofolato Deshidrogenasa/genética , Tetrahidrofolato Deshidrogenasa/metabolismo , Línea Celular Tumoral , Neoplasias del Colon/genética , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Antimetabolitos Antineoplásicos/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Genómica/métodos
4.
Sci Total Environ ; 922: 171357, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38431167

RESUMEN

Nitrous oxide (N2O) represents a significant environmental challenge as a harmful, long-lived greenhouse gas that contributes to the depletion of stratospheric ozone and exacerbates global anthropogenic greenhouse warming. Composting is considered a promising and economically feasible strategy for the treatment of organic waste. However, recent research indicates that composting is a source of N2O, contributing to atmospheric pollution and greenhouse effect. Consequently, there is a need for the development of effective, cost-efficient methodologies to quantify N2O emissions accurately. In this study, we employed the model-agnostic meta-learning (MAML) method to improve the performance of N2O emissions prediction during manure composting. The highest R2 and lowest root mean squared error (RMSE) values achieved were 0.939 and 18.42 mg d-1, respectively. Five machine learning methods including the backpropagation neural network, extreme learning machine, integrated machine learning method based on ELM and random forest, gradient boosting decision tree, and extreme gradient boosting were adopted for comparison to further demonstrate the effectiveness of the MAML prediction model. Feature analysis showed that moisture content of structure material and ammonium concentration during composting process were the two most significant features affecting N2O emissions. This study serves as proof of the application of MAML during N2O emissions prediction, further giving new insights into the effects of manure material properties and composting process data on N2O emissions. This approach helps determining the strategies for mitigating N2O emissions.

5.
Curr Med Sci ; 44(1): 93-101, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38393524

RESUMEN

OBJECTIVE: Keshan disease (KD) is a myocardial mitochondrial disease closely related to insufficient selenium (Se) and protein intake. PTEN induced putative kinase 1 (PINK1)/Parkin mediated mitochondrial autophagy regulates various physiological and pathological processes in the body. This study aimed to elucidate the relationship between PINK1/Parkin-regulated mitochondrial autophagy and KD-related myocardial injury. METHODS: A low Se and low protein animal model was established. One hundred Wistar rats were randomly divided into 5 groups (control group, low Se group, low protein group, low Se + low protein group, and corn from KD area group). The JC-1 method was used to detect the mitochondrial membrane potential (MMP). ELISA was used to detect serum creatine kinase MB (CK-MB), cardiac troponin I (cTnI), and mitochondrial-glutamicoxalacetic transaminase (M-GOT) levels. RT-PCR and Western blot analysis were used to detect the expression of PINK1, Parkin, sequestome 1 (P62), and microtubule-associated proteins1A/1B light chain 3B (MAP1LC3B). RESULTS: The MMP was significantly decreased and the activity of CK-MB, cTnI, and M-GOT significantly increased in each experimental group (low Se group, low protein group, low Se + low protein group and corn from KD area group) compared with the control group (P<0.05 for all). The mRNA and protein expression levels of PINK1, Parkin and MAP1LC3B were profoundly increased, and those of P62 markedly decreased in the experimental groups compared with the control group (P<0.05 for all). CONCLUSION: Low Se and low protein levels exacerbate myocardial damage in KD by affecting the PINK1/Parkin-mediated mitochondrial autophagy pathway.


Asunto(s)
Cardiomiopatías , Infecciones por Enterovirus , Proteínas Quinasas , Selenio , Ubiquitina-Proteína Ligasas , Animales , Ratas , Autofagia/genética , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Ratas Wistar , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo
6.
BMC Musculoskelet Disord ; 25(1): 187, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38424521

RESUMEN

BACKGROUND: Osteoporotic fractures are a growing problem in an aging society. The association between body mass index (BMI) and osteoporotic fractures varies by fracture site and ethnicity. Limited knowledge exists regarding this association in native Chinese, particularly utilizing local databases as reference sources. OBJECTIVE: To investigate the association between BMI and osteoporotic fractures at different sites in Chinese women. METHODS: Three thousand ninety-eight female patients with radiographic fractures and 3098 age- and sex-matched healthy controls without fractures were included in the study. Both of them underwent assessment using dual-energy X-ray absorptiometry (DXA), with BMD measurements calculated using our own BMD reference database. Participants were classified into underweight (BMI < 18.5 kg/m2), normal weight (18.5 ≤ BMI < 24.0 kg/m2), overweight (24 ≤ BMI < 28 kg/m2) and obese (BMI ≥ 28 kg/m2) according to the Chinese BMI classification standard. RESULTS: There were 2296 (74.1%) vertebral fractures, 374 (12.1%) femoral neck fractures, and 428 (13.8%) other types of fractures in the case group. Bone mineral density (BMD) was almost lower in the fracture groups compared to the control groups (p = 0.048 to < 0.001). Compared with normal weight, underweight had a protective effect on total [odds ratio (OR) = 0.61; 95% confidence interval (CI), 0.49 -0.75; P< 0.001], and lumbar fractures (OR = 0.52; 95% CI, 0.41 - 0.67; P < 0.001), while obesity was associated with an increased risk for total (OR = 2.26; 95% CI, 1.85 - 2.76; P < 0.001), lumbar (OR = 2.17; 95% CI, 1.72 - 2.73; P < 0.001), and femoral neck fractures (OR = 4.08; 95% CI, 2.18 - 7.63; P < 0.001). Non-linear associations were observed between BMI and fractures: A J-curve for total, lumbar, and femoral neck fractures, and no statistical change for other types of fractures. Underweight was found to be a risk factor for other types of fracturess after adjusting for BMD (OR = 2.29; 95% CI, 1.09 - 4.80; P < 0.001). Osteoporosis and osteopenia were identified as risk factors for almost all sites of fracture when compared to normal bone mass. CONCLUSIONS: Underweight has a protective effect on total and lumbar spine fractures in Chinese women, while obesity poses a risk factor for total, lumbar, and femoral neck fractures. The effect of BMI on fractures may be mainly mediated by BMD.


Asunto(s)
Fracturas del Cuello Femoral , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Humanos , Femenino , Fracturas Osteoporóticas/diagnóstico por imagen , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/complicaciones , Índice de Masa Corporal , Estudios Retrospectivos , Delgadez/complicaciones , Delgadez/epidemiología , Densidad Ósea , Absorciometría de Fotón , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/epidemiología , Fracturas de la Columna Vertebral/complicaciones , Fracturas del Cuello Femoral/diagnóstico por imagen , Fracturas del Cuello Femoral/epidemiología , Fracturas del Cuello Femoral/complicaciones , Obesidad/complicaciones , Obesidad/epidemiología , Estudios de Casos y Controles , Vértebras Lumbares/diagnóstico por imagen , China/epidemiología
7.
Mol Biol Rep ; 51(1): 309, 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38372835

RESUMEN

OBJECTIVE: The aim of this study is to examine and evaluate the impact of benzene poisoning on the relative content of the mitochondrial MT-ND1 gene and telomere length in individuals with occupational chronic benzene poisoning (CBP) compared to a control group. The study will analyze and gather data on the mitochondrial gene content and telomere length in cases of benzene poisoning, and investigate the relationship with blood routine parameters in order to contribute scientific experimental data for the prevention and treatment of CBP. METHOD: The case group comprised 30 individuals diagnosed with occupational chronic benzene poisoning, whereas the control group consisted of 60 healthy individuals who underwent physical examinations at our hospital concurrently. Blood routine indicators were detected and analyzed, and the PCR method was employed to measure changes in mitochondrial MT-ND1 content and telomere length. Subsequently, a comparison and analysis of the aforementioned indicators was conducted. RESULT: The case group exhibited a higher mitochondrial gene content (median 366.2, IQR 90.0 rate) compared to the control group (median 101.5, IQR 12.0 rate), with a statistically significant difference between the two groups (P < 0.05). Additionally, the case group demonstrated lower white blood cell levels (3.78 ± 1.387 × 109/L) compared to the control group (5.74 ± 1.41 × 109/L), with a significant difference between the two groups (P < 0.05). Furthermore, the case group displayed lower red blood cell levels (3.86 ± 0.65 × 1012/L) compared to the control group (4.89 ± 0.65 × 1012/L), with a significant difference between the two groups (P < 0.05). The hemoglobin level in the case group (113.33 ± 16.34 g/L) was lower than that in the control group (138.22 ± 13.22 g/L). There was a significant difference between the two groups (P < 0.05). Platelet levels in the case group (153.80 ± 58.31 × 109/L) is smaller than the control group (244.92 ± 51.99 × 109/L), there was a significant difference between the two groups (P < 0.05). The average telomere length of the normal control group was 1.451 ± 0.475 (rate); The mean telomere length of individuals in the case group diagnosed with benzene poisoning was determined to be 1.237 ± 0.457 (rate). No significant correlation was observed between telomere length and three blood routine parameters, namely white blood cells (WBC), hemoglobin (HB), and platelets (PLT). However, a significant correlation was found between telomere length and red blood cell count (RBC). Additionally, a negative correlation was observed between mitochondrial gene content and white blood cell count (r = - 0.314, P = 0.026), as well as between mitochondrial gene content and red blood cell count (r = - 0.226, P = 0.032). Furthermore, a negative correlation was identified between mitochondrial gene content and hemoglobin (r = - 0.314, P = 0.028), and platelets (r = - 0.445, P = 0.001). CONCLUSION: Individuals diagnosed with occupational chronic benzene poisoning exhibit a reduction in telomere length and an elevation in the relative content of the mitochondrial MT-ND1 gene. Moreover, a negative correlation is observed between the content of the mitochondrial MT-ND1 gene and four blood routine parameters, namely white blood cells (WBC), red blood cells (RBC), hemoglobin (HB), and platelets (PLT). Consequently, benzene exposure may potentially contribute to the onset of premature aging.


Asunto(s)
Benceno , ADN Mitocondrial , Humanos , ADN Mitocondrial/genética , Variaciones en el Número de Copia de ADN/genética , Leucocitos , Hemoglobinas , Telómero/genética
8.
Mol Cell Endocrinol ; 581: 112113, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37989409

RESUMEN

Although disorders of primary cilia (PCs) were first reported in human papillary thyroid cancer (PTC) tissues in 1987, their precise role in PTC remains unclear. PCs sense the thyroid follicle colloid environment and act as a cell signaling hub. The present study investigated whether PCs are needed for BRAFV600E-driven PTC. We assessed whether BRAFV600E protein expression correlates with papillary histological architecture and clinicopathological features of PTC. We found that expression of ciliary intraflagellar transport 88 (IFT88) and PC formation were reduced in BRAFV600E-driven PTCs and that loss of cilia may be associated with lymph node metastasis. In PTC cells, the BRAFV600E mutation maintained the aggressiveness of PTC, which was partially related to loss of PCs. Our work confirms that BRAFV600E mutation-driven PC downregulation contributes to maintaining the aggressiveness of PTCs and that manipulating PC can potentially reduce the adverse incidence of PTC in a range of conditions.


Asunto(s)
Carcinoma Papilar , Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/patología , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas B-raf/metabolismo , Cilios/metabolismo , Regulación hacia Abajo/genética , Carcinoma Papilar/genética , Carcinoma Papilar/patología , Mutación/genética
9.
Gastroenterol Res Pract ; 2023: 7838601, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38035162

RESUMEN

Background: Washed microbiota transplantation (WMT) as the improved methods of fecal microbiota transplantation has been employed as a therapeutic approach for ameliorating symptoms associated with autism spectrum disorder (ASD). In this context, colonic transendoscopic enteral tubing (TET) has been utilized as a novel procedure for administering WMT. Methods: Data of children with ASD who received WMT by TET were retrospectively reviewed, including bowel preparation methods, TET operation time, success rate, tube retention time, the comfort of children, adverse events, and parent satisfaction. Results: A total of 38 participants underwent 124 colonic TET catheterization procedures. The average time of TET operation was 15 minutes, and the success rate was 100% (124/124). There was no significant difference in TET operation time between high-seniority physicians and low-seniority physicians. In 123 procedures (99%), the TET tube allowed the completion of WMT treatment for 6 consecutive days. In 118 procedures (95.2%), the tube was detached spontaneously after the end of the treatment course, and the average TET tube retention time was 8 days. There was no incidence of tube blockage during the treatment course. No severe adverse events occurred during follow-up. Parents of all participants reported a high level of satisfaction with TET. Conclusion: Colonic TET is a safe and feasible method for WMT in children with ASD.

10.
Nat Commun ; 14(1): 6866, 2023 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-37891189

RESUMEN

Mars lacks a global magnetic field, and instead possesses small-scale crustal magnetic fields, making its magnetic environment fundamentally different from intrinsic magnetospheres like those of Earth or Saturn. Here we report the discovery of magnetospheric ion drift patterns, typical of intrinsic magnetospheres, at Mars using measurements from Mars Atmosphere and Volatile EvolutioN mission. Specifically, we observe wedge-like dispersion structures of hydrogen ions exhibiting butterfly-shaped distributions (pitch angle peaks at 22.5°-45° and 135°-157.5°) within the Martian crustal fields, a feature previously observed only in planetary-scale intrinsic magnetospheres. These dispersed structures are the results of drift motions that fundamentally resemble those observed in intrinsic magnetospheres. Our findings indicate that the Martian magnetosphere embodies an intermediate case where both the unmagnetized and magnetized ion behaviors could be observed because of the wide range of strengths and spatial scales of the crustal magnetic fields around Mars.

11.
Sensors (Basel) ; 23(13)2023 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-37448071

RESUMEN

The landing gear structure suffers from large loads during aircraft takeoff and landing, and an accurate prediction of landing gear performance is beneficial to ensure flight safety. Nevertheless, the landing gear performance prediction method based on machine learning has a strong reliance on the dataset, in which the feature dimension and data distribution will have a great impact on the prediction accuracy. To address these issues, a novel MCA-MLPSA is developed. First, an MCA (multiple correlation analysis) method is proposed to select key features. Second, a heterogeneous multilearner integration framework is proposed, which makes use of different base learners. Third, an MLPSA (multilayer perceptron with self-attention) model is proposed to adaptively capture the data distribution and adjust the weights of each base learner. Finally, the excellent prediction performance of the proposed MCA-MLPSA is validated by a series of experiments on the landing gear data.


Asunto(s)
Aeronaves , Aprendizaje Automático , Redes Neurales de la Computación
12.
EMBO J ; 42(13): e113033, 2023 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-36896912

RESUMEN

Mitophagy is a fundamental quality control mechanism of mitochondria. Its regulatory mechanisms and pathological implications remain poorly understood. Here, via a mitochondria-targeted genetic screen, we found that knockout (KO) of FBXL4, a mitochondrial disease gene, hyperactivates mitophagy at basal conditions. Subsequent counter screen revealed that FBXL4-KO hyperactivates mitophagy via two mitophagy receptors BNIP3 and NIX. We determined that FBXL4 functions as an integral outer-membrane protein that forms an SCF-FBXL4 ubiquitin E3 ligase complex. SCF-FBXL4 ubiquitinates BNIP3 and NIX to target them for degradation. Pathogenic FBXL4 mutations disrupt SCF-FBXL4 assembly and impair substrate degradation. Fbxl4-/- mice exhibit elevated BNIP3 and NIX proteins, hyperactive mitophagy, and perinatal lethality. Importantly, knockout of either Bnip3 or Nix rescues metabolic derangements and viability of the Fbxl4-/- mice. Together, beyond identifying SCF-FBXL4 as a novel mitochondrial ubiquitin E3 ligase restraining basal mitophagy, our results reveal hyperactivated mitophagy as a cause of mitochondrial disease and suggest therapeutic strategies.


Asunto(s)
Enfermedades Mitocondriales , Mitofagia , Ratones , Animales , Mitofagia/fisiología , Mitocondrias/metabolismo , Enfermedades Mitocondriales/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinas/metabolismo , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo
13.
Front Public Health ; 11: 990051, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36817889

RESUMEN

Benzene is used as an industrial solvent, which may result in chronic benzene poisoning (CBP). Several studies suggested that CBP was associated with mitochondrial epigenetic regulation. This study aimed to explore the potential relation between CBP and mitochondrial DNA (mtDNA) methylation. This prospective observational study enrolled CBP patients admitted to Shenzhen Prevention and Treatment Center for Occupational Diseases hospital and healthy individuals between 2018 and 2021. The white blood cell (WBC), red blood cell (RBC), hemoglobin (HB), and platelet (PLT) counts and mtDNA methylation levels were measured using blood flow cytometry and targeted bisulfite sequencing, respectively. A total of 90 participants were recruited, including 30 cases of CBP (20 females, mean age 43.0 ± 8.0 years) and 60 healthy individuals (42 females, mean age 43.5 ± 11.5 years). This study detected 168 mitochondrial methylation sites >0 in all study subjects. The mtDNA methylation levels in the CBP cases were lower than the healthy individuals [median ± interquartile-range (IQR), 25th percentile, 75th percentile: (1.140 ± 0.570, 0.965, 1.535)% vs. median ± IQR, 25th percentile, 75th percentile: (1.705 ± 0.205,1.240,2.445)%, P < 0.05]. Additionally, the spearman correlation analysis showed that the mtDNA methylation levels were positively correlated with the counts of circulating leukocytes [WBC (r = 0.048, P = 0.036)] and platelets [PLT (r = 0.129, P < 0.01)]. We provided solid evidence of association between CBP and aberrant mtDNA methylation.


Asunto(s)
Benceno , Epigénesis Genética , Femenino , Humanos , Adulto , Persona de Mediana Edad , Mitocondrias , ADN Mitocondrial , Metilación de ADN
14.
Cell Rep ; 41(10): 111774, 2022 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-36476853

RESUMEN

Mitochondrial damage causes mitochondrial DNA (mtDNA) release to activate the type I interferon (IFN-I) response via the cGAS-STING pathway. mtDNA-induced inflammation promotes autoimmune- and aging-related degenerative disorders. However, the global picture of inflammation-inducing mitochondrial damages remains obscure. Here, we have performed a mitochondria-targeted CRISPR knockout screen for regulators of the IFN-I response. Strikingly, our screen reveals dozens of hits enriched with key regulators of cristae architecture, including phospholipid cardiolipin and protein complexes such as OPA1, mitochondrial contact site and cristae organization (MICOS), sorting and assembly machinery (SAM), mitochondrial intermembrane space bridging (MIB), prohibitin (PHB), and the F1Fo-ATP synthase. Disrupting these cristae organizers consistently induces mtDNA release and the STING-dependent IFN-I response. Furthermore, knocking out MTX2, a subunit of the SAM complex whose null mutations cause progeria in humans, induces a robust STING-dependent IFN-I response in mouse liver. Taken together, beyond revealing the central role of cristae architecture to prevent mtDNA release and inflammation, our results mechanistically link mitochondrial cristae disorganization and inflammation, two emerging hallmarks of aging and aging-related degenerative diseases.


Asunto(s)
ADN Mitocondrial , Humanos , Animales , Ratones , ADN Mitocondrial/genética
15.
Materials (Basel) ; 15(21)2022 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-36363115

RESUMEN

In this study, low-iron Zn-Fe alloy coatings and pure Zn coatings, with or without trivalent chromium passivation treatment, were electrodeposited onto a sintered NdFeB magnet from a weak acid chloride bath. The surface morphology and structure of the coatings were then examined using the X-ray diffraction, a scanning electron microscope and 3D white-light interfering surface analysis. Meanwhile, the electrodeposition behavior and anti-corrosive properties of the coatings were investigated using cyclic voltammetry, potentiodynamic polarization, electrochemical impedance spectroscopy, and natural salt spray tests. The results indicate that a passivated Zn-Fe alloy coating with a 0.9 wt.% Fe content provided much better corrosion resistance than a pure Zn coating and could provide both anodic protection and physical barrier function in the NdFeB substrates. The Fe element in Zn-Fe alloy coating was predominantly in solid solution in η-phase and small amounts in elemental form, which was beneficial to acquire a compact coating and passivation film. Finally, the passivated Zn-Fe alloy coating withstood 210 h against a neutral 3.5 wt.% NaCl salt spray without any white rust, which was 3-4 times longer than the pure Zn coating.

16.
Cardiovasc Diabetol ; 21(1): 74, 2022 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-35568946

RESUMEN

Cardiovascular diseases (CVDs) are the main cause of death among patients with type 2 diabetes mellitus (T2DM), particularly in low- and middle-income countries. To effectively prevent the development of CVDs in T2DM, considerable effort has been made to explore novel preventive approaches, individualized glycemic control and cardiovascular risk management (strict blood pressure and lipid control), together with recently developed glucose-lowering agents and lipid-lowering drugs. This review mainly addresses the important issues affecting the choice of antidiabetic agents and lipid, blood pressure and antiplatelet treatments considering the cardiovascular status of the patient. Finally, we also discuss the changes in therapy principles underlying CVDs in T2DM.


Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Glucemia , Presión Sanguínea , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Hipoglucemiantes/efectos adversos , Lípidos
18.
Cancer Med ; 11(4): 1136-1144, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35032114

RESUMEN

BACKGROUND: The prevalence of obesity and an increased incidence of thyroid carcinoma (TC) threaten public health in parallel on a global scale. Sufficient evidence supports excess body fatness in thyroid carcinogenesis, and the role and anthropometric markers of obesity have been causally associated with the rising risk of TC. METHODS: A literature search was conducted in PubMed. Studies focused on the effect of obesity in TC. RESULTS: This review mainly discusses the global incidence and prevalence of obesity-related TC. We also review the role of obesity in TC and potential clinical strategies for obesity-related TC. CONCLUSIONS: Excess body fatness in early life and TC survival initiate adverse effects later in life.


Asunto(s)
Obesidad , Neoplasias de la Tiroides , Humanos , Incidencia , Obesidad/complicaciones , Obesidad/epidemiología , Prevalencia , Factores de Riesgo , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/etiología
19.
J Inherit Metab Dis ; 45(2): 264-277, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34873722

RESUMEN

Pyruvate, the end product of glycolysis, is a key metabolic molecule enabling mitochondrial adenosine triphosphate synthesis and takes part in multiple biosynthetic pathways within mitochondria. The mitochondrial pyruvate carrier (MPC) plays a vital role in transporting pyruvate from the cytosol into the organelle. In humans, MPC is a hetero-oligomeric complex formed by the MPC1 and MPC2 paralogs that are both necessary to stabilize each other and form a functional MPC. MPC deficiency (OMIM#614741) due to pathogenic MPC1 variants is a rare autosomal recessive disease involving developmental delay, microcephaly, growth failure, and increased serum lactate and pyruvate. To date, two MPC1 variants in four cases have been reported, though only one with a detailed clinical description. Herein, we report three novel pathogenic MPC1 variants in six patients from three unrelated families, identified within European, Kuwaiti, and Chinese mitochondrial disease patient cohorts, one of whom presented as a Leigh-like syndrome. Functional analysis in primary fibroblasts from the patients revealed decreased expression of MPC1 and MPC2. We rescued pyruvate-driven oxygen consumption rate in patient's fibroblasts by reconstituting with wild-type MPC1. Complementing homozygous MPC1 mutant cDNA with CRISPR-deleted MPC1 C2C12 cells verified the mechanism of variants: unstable MPC complex or ablated pyruvate uptake activity. Furthermore, we showed that glutamine and beta-hydroxybutyrate were alternative substrates to maintain mitochondrial respiration when cells lack pyruvate. In conclusion, we expand the clinical phenotypes and genotypes associated with MPC deficiency, with our studies revealing glutamine as a potential therapy for MPC deficiency.


Asunto(s)
Proteínas de Transporte de Membrana Mitocondrial , Transportadores de Ácidos Monocarboxílicos , Glutamina/metabolismo , Humanos , Mitocondrias/genética , Mitocondrias/metabolismo , Proteínas de Transporte de Membrana Mitocondrial/genética , Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/metabolismo , Ácido Pirúvico/metabolismo
20.
IEEE Trans Neural Netw Learn Syst ; 33(12): 7114-7125, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-34152990

RESUMEN

One of the significant tasks in remaining useful life (RUL) prediction is to find a good health indicator (HI) that can effectively represent the degradation process of a system. However, it is difficult for traditional data-driven methods to construct accurate HIs due to their incomprehensive consideration of temporal dependencies within the monitoring data, especially for aeroengines working under nonstationary operating conditions (OCs). Aiming at this problem, this article develops a novel unsupervised deep neural network, the so-called times series memory auto-encoder with sequentially updated reconstructions (SUR-TSMAE) to improve the accuracy of extracted HIs, which directly takes the multidimensional time series as input to simultaneously achieve feature extraction from both feature-dimension and time-dimension. Further, to make full use of the temporal dependencies, a novel long-short time memory with sequentially updated reconstructions (SUR-LSTM), which uses the errors not only from the current memory cell but also from subsequent memory cells to update the output layer's weight of the current memory cell, is developed to act as the reconstructed layer in the SUR-TSMAE. The use of SUR-LSTM can help the SUR-TSMAE rapidly reconstruct the input time series with higher precision. Experimental results on a public dataset demonstrate the outstanding performance of SUR-TSMAE in comparison with some existing methods.


Asunto(s)
Redes Neurales de la Computación , Factores de Tiempo
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