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Hexavalent chromium (Cr(VI)) is a common pollutant in the marine environment, which impairs immunity and causes reproductive and heredity disorders in organisms. To clarify the immunotoxic effects of Cr (VI) on the marine worm Urechis unicinctus, we analyzed tissue damage and immune dysfunction caused by Cr (VI) in this organism at histopathologic, zymologic, apoptotic and molecular levels. The results indicated that the bioaccumulation of Cr (VI) bioaccumulation levels in coelomocytes was significantly higher than in the intestines and muscles. Pathological observation showed that Cr (VI) caused damage to the respiratory intestine, stomach and midgut. Cr (VI) also increased the replication of goblet cells and a reduction in the replication of epithelial cells. Meanwhile, Cr (VI) induced apoptosis of intestinal cells and coelomocytes, accompanied by an increase in the expression of Caspase-3, COX-2, and MyD88 in the intestine and coelomocytes. At the same time, Cr (VI) significantly affected the activities of antioxidant enzymes such as SOD, ACP, CAT, CAT, and GST, and increased H2O2 and MDA contents in U. unicinctus. Moreover, Cr (VI) exposure also up-regulated the transcription of hsc70, mt and jnk genes but decreased that of sod in the intestines. In contrast, Cr (VI) down-regulated the expression of sod, hsc70, mt, and jnk genes in coelomocytes. Collectively, Cr (VI) bioaccumulated in U. unicinctus cells and tissues, causing several histopathological changes, oxidative stress, and apoptosis of several cells in the organism, resulting in intestinal and coelomocyte damage and immune dysfunctioning.
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Polycystic ovary syndrome (PCOS) is the primary cause of female infertility with a lack of universal therapeutic regimen. Although osthole exhibits numerous pharmacological activities in treating various diseases, its therapeutic effect on PCOS is undiscovered. The present study found that application of osthole improved the symptoms of PCOS mice through preventing ovarian granulosa cells (GCs) production of more estrogen and alleviating the liberation of pro-inflammatory cytokine interleukin (IL)-1ß, IL-6, and tumor necrosis factor alpha. Meanwhile, osthole enhanced ovarian antioxidant capacity and alleviated intracellular reactive oxygen species (ROS) accumulation with a concurrent attenuation for oxidative stress, while intervention of antioxidant enzymic activity and glutathione (GSH) synthesis neutralized the salvation of osthole on GCs secretory disorder and chronic inflammation. Further analysis revealed that osthole restored the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and forkhead box O 1 (Foxo1) whose repression antagonized the amelioration of osthole on the insufficiency of antioxidant capacity and accumulation of ROS. Moreover, Nrf2 served as an intermedium to mediate the regulation of osthole on Foxo1. Additionally, osthole restricted the phosphorylation of IκBα and nuclear factor kappa B (NF-κB) subunit p65 by DHEA and weakened the transcriptional activity of NF-κB, but this effectiveness was abrogated by the obstruction of Nrf2 and Foxo1, whereas adjunction of GSH renewed the redemptive effect of osthole on NF-κB whose activation caused an invalidation of osthole in rescuing the aberration of GCs secretory function and inflammation response. Collectively, osthole might relieve the symptoms of PCOS mice via Nrf2-Foxo1-GSH-NF-κB pathway.
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Cumarinas , Proteína Forkhead Box O1 , Glutatión , Factor 2 Relacionado con NF-E2 , FN-kappa B , Estrés Oxidativo , Síndrome del Ovario Poliquístico , Especies Reactivas de Oxígeno , Transducción de Señal , Animales , Síndrome del Ovario Poliquístico/metabolismo , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Femenino , Factor 2 Relacionado con NF-E2/metabolismo , Ratones , Cumarinas/farmacología , Cumarinas/uso terapéutico , FN-kappa B/metabolismo , Proteína Forkhead Box O1/metabolismo , Transducción de Señal/efectos de los fármacos , Glutatión/metabolismo , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Antioxidantes/farmacología , Células de la Granulosa/metabolismo , Células de la Granulosa/efectos de los fármacos , Modelos Animales de EnfermedadRESUMEN
Based on a novel phenylacetylene capped polyimide (PI) with unique high-temperature resistance, its curing kinetics and thermal decomposition behavior were investigated. The curing mechanism and kinetics were studied by differential scanning calorimetry (DSC), and the activation energy (Ea) and pre-exponential factor (A) of the curing reaction were calculated based on the Kissinger equation, Ozawa equation, and Crane equation. According to the curve of conversion rate changing with temperature, the relationship between the dynamic reaction Ea and conversion rate (α) was calculated by the Friedman equation, Starink equation, and Ozawa-Flynn-Wall (O-F-W) equation, and the reaction Ea in different stages was compared with the results of molecular dynamics. Thermogravimetric analysis (TGA) and a scanning electron microscope (SEM) were used to analyze the thermal decomposition behavior of PI resins before and after curing. Temperatures at 5% and 20% mass loss (T5%, T20%), peak decomposition temperature (Tmax), residual carbon rate (RW), and integral process decomposition temperature (IPDT) were used to compare the thermal stability of PI resins and cured PI resins. The results display that the cured PI has excellent thermal stability. The Ea of the thermal decomposition reaction was calculated by the Coats-Redfern method, and the thermal decomposition behavior was analyzed. The thermal decomposition reaction of PI resins at different temperatures was simulated by molecular dynamics, the initial thermal decomposition reaction was studied, and the pyrolysis mechanism was analyzed more comprehensively and intuitively.
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Polycystic ovarian syndrome (PCOS) is the major cause of infertility in reproductive women, but no universal drug is feasible. Although puerarin clinically treats cerebrovascular and cardiovascular diseases, its curative effect on PCOS remains elusive. The present study discovered that administration of puerarin restored estrous cycle of PCOS mice and diminished the number of cystic follicles with the concomitant recovery for circulating testosterone, LH and FSH levels, and LH/FSH ratio, indicating the therapeutic role of puerarin in PCOS. KEGG analysis of differential genes between PCOS and control revealed the enrichment in MAPK and calcium signaling pathway. Application of puerarin restricted the phosphorylation of ERK1/2 and JNK, whose activation neutralized the improvement of puerarin on the secretory function and apoptosis of ovarian granulosa cells (GCs). Meanwhile, puerarin alleviated the accumulation of cytosolic Ca2+ through restricting the opening of Ryr and Itpr channels, but this effectiveness was counteracted by the activatory ERK1/2 and JNK. Attenuation of cytosolic Ca2+ counteracted the antagonistic effects of ERK1/2 and JNK activation on puerarin's role in rescuing the calcineurin and Nfatc. Further analysis manifested that Mcu had been authenticated as a direct downstream target of Nfatc to mediate the amelioration of puerarin on mitochondrial Ca2+ uptake. Moreover, puerarin prevented the disorder of ATP content, mitochondrial membrane potential, and mitochondrial permeability transition pore opening through maintaining mitochondrial Ca2+ homeostasis. Collectively, puerarin might ameliorate the symptoms of PCOS mice through preventing mitochondrial dysfunction that is dependent on the maintenance of intracellular Ca2+ homeostasis after inactivation of ERK1/2 and JNK.
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Isoflavonas , Enfermedades Mitocondriales , Síndrome del Ovario Poliquístico , Femenino , Humanos , Ratones , Animales , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/genética , Síndrome del Ovario Poliquístico/metabolismo , Calcio/metabolismo , Células de la Granulosa , Hormona Folículo Estimulante/metabolismo , Hormona Folículo Estimulante/farmacología , Hormona Folículo Estimulante/uso terapéutico , Enfermedades Mitocondriales/metabolismoRESUMEN
Great progress has been made in identifying positive regulators that activate adipocyte thermogenesis, but negative regulatory signaling of thermogenesis remains poorly understood. Here, we found that cardiotrophin-like cytokine factor 1 (CLCF1) signaling led to loss of brown fat identity, which impaired thermogenic capacity. CLCF1 levels decreased during thermogenic stimulation but were considerably increased in obesity. Adipocyte-specific CLCF1 transgenic (CLCF1-ATG) mice showed impaired energy expenditure and severe cold intolerance. Elevated CLCF1 triggered whitening of brown adipose tissue by suppressing mitochondrial biogenesis. Mechanistically, CLCF1 bound and activated ciliary neurotrophic factor receptor (CNTFR) and augmented signal transducer and activator of transcription 3 (STAT3) signaling. STAT3 transcriptionally inhibited both peroxisome proliferator-activated receptor-γ coactivator (PGC) 1α and 1ß, which thereafter restrained mitochondrial biogenesis in adipocytes. Inhibition of CNTFR or STAT3 could diminish the inhibitory effects of CLCF1 on mitochondrial biogenesis and thermogenesis. As a result, CLCF1-TG mice were predisposed to develop metabolic dysfunction even without external metabolic stress. Our findings revealed a brake signal on nonshivering thermogenesis and suggested that targeting this pathway could be used to restore brown fat activity and systemic metabolic homeostasis in obesity.
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Adipocitos Marrones , Biogénesis de Organelos , Animales , Ratones , Adipocitos Marrones/metabolismo , Tejido Adiposo Pardo/metabolismo , Homeostasis , Obesidad/genética , Obesidad/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Termogénesis/fisiologíaRESUMEN
Energy-dissipating adipocytes have the potential to improve metabolic health. Here, we identify hypoxia-induced gene domain protein-1a (HIGD1A), a mitochondrial inner membrane protein, as a positive regulator of adipose browning. HIGD1A is induced in thermogenic fats by cold exposure. Peroxisome proliferator-activated receptor gamma (PPARγ) transactivates HIGD1A expression synergistically with peroxisome proliferators-activated receptor γ coactivator α (PGC1α). HIGD1A knockdown inhibits adipocyte browning, whereas HIGD1A upregulation promotes the browning process. Mechanistically, HIGD1A deficiency impairs mitochondrial respiration to increase reactive oxygen species (ROS) level. This increases NAD+ consumption for DNA damage repair and curtails the NAD+/NADH ratio, which inhibits sirtuin1 (SIRT1) activity, thereby compromising adipocyte browning. Conversely, overexpression of HIGD1A blunts the above process to promote adaptive thermogenesis. Furthermore, mice with HIGD1A knockdown in inguinal and brown fat have impaired thermogenesis and are prone to diet-induced obesity (DIO). Overexpression of HIGD1A favors adipose tissue browning, ultimately preventing DIO and metabolic disorders. Thus, the mitochondrial protein HIGD1A links SIRT1 activity to adipocyte browning by inhibiting ROS levels.
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NAD , Sirtuina 1 , Animales , Ratones , Adipocitos Marrones/metabolismo , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Daño del ADN , Ratones Endogámicos C57BL , NAD/metabolismo , Obesidad/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sirtuina 1/genética , Sirtuina 1/metabolismo , Termogénesis/genéticaRESUMEN
The deleterious effects of aflatoxins, especially aflatoxin B1 (AFB1) which are widespread at all stages of food production, on the reproductive system have been widely reported in males. However, it is still far from fully understood about the toxic effect and molecular mechanism after exposure to AFB1 in various testicular cells, especially Sertoli cells (SCs) which provide various energy materials and support to the developing germ cells as nurse cells. In this work, we examined the effects of AFB1 in dairy goat SCs on lactate production and autophagy, and the role of autophagy on AFB1-induced reduction in lactate production. Mechanistically, AFB1 destroyed the energy balance and reduced the secretion of lactate in dairy goat SCs (P < 0.01), resulting in a reduced level of ATP (P < 0.01) and phosphorylation of AMPK (P < 0.01). Subsequently, activated AMPK triggers autophagy by directly phosphorylating ULK1 (P < 0.05). The enhancement of autophagy partially reversed the AFB1-induced decrease in lactate secretion by promoting glucose utilization (P < 0.01) and increasing the expression of proteins related to lactate secretion in dairy goat SCs (P < 0.05) such as GLUT1, GLUT3, LDHA, and MCT4. Collectively, our study suggests that AFB1 inhibits the secretion of lactate which supply for germ cell development by damaging the "Warburg-like" metabolism of dairy goat SCs. Moreover, autophagy contributes to the resistance of glucose metabolism damage induced by AFB1. DATA AVAILABILITY: All data generated or analyzed in this study are available from the corresponding authors upon request.
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Aflatoxina B1 , Células de Sertoli , Masculino , Animales , Células de Sertoli/metabolismo , Aflatoxina B1/toxicidad , Proteínas Quinasas Activadas por AMP/metabolismo , Autofagia , Ácido Láctico/metabolismo , Cabras/metabolismoRESUMEN
Background: The exact mechanism of glioblastoma multiforme (GBM) remains unclear. This study was to clarify the expression of P53 in glioma and its molecular mechanism, and to explore the possibility of P53 as a potential therapeutic target of glioma and its clinical application value, so as to provide a new theoretical basis for the treatment of glioma. Methods: Firstly, a dataset was established to analyze the expression of P53 in different stages of glioma and its relationship with prognosis by using The Cancer Genome Atlas (TCGA) database, RNA-seq data, and survival data of glioma and normal control samples in gene expression profiling and interactive analysis (GEPIA). The genes co-expressed with P53 were screened out, their differential expression between glioma and normal control group was analyzed, and their functions were analyzed by enrichment analysis. The TGGA database was used for data verification and analysis. The correlation between P53 expression and clinicopathological parameters was analyzed. Kaplan-Meier survival analysis was used to analyze the relationship between P53 expression and overall survival (OS) and progression-free survival (PFS) of glioma patients, and Cox regression analysis was used to analyze the independent factors affecting OS and PFS of glioma patients. Results: The results of TCGA data analysis were as follows: The expression level of P53 was different from that of different stages of glioma, namely, the expression level of P53 between grade II and grade III, grade III and grade IV, and grade II and grade IV were significantly different (P<0.05). The results of P53 gene-related survival analysis showed that KNL1 high expression and low expression were significantly different in OS, and the high expression group was associated with poor prognosis (P<0.05). Conclusions: The P53 expression can be an effective biological indicator of poor prognosis of glioma.
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Artificial intelligence and deep learning have attracted much attention from researchers in industry and academia. The volleyball movement standardization and recognition model involve the application of artificial intelligence and deep learning. In order to solve the problem that human action in volleyball video is continuous and effective spatial and temporal features need to be extracted from the video stream, the Inception module is decoupled and heterogeneous, replacing the original 5 × 5 convolutional structures with two 3 × 3 convolutional structures, as well as replacing the 3 × 3 convolutional structures with 1 × 3 and a 3 × 1 convolutional structure with internal parameter optimization to ensure the accuracy of recognition. The model uses the input motion video RGB map as the spatial input and the optical flow map as the temporal input, and the two are weighted 1 : 1 for feature fusion. Experiments are conducted on the volleyball action video and homemade dataset in UCF101, and the experimental data show that the accuracy of the DNet volleyball action standardization recognition model proposed in this paper is 94.12%, which proves that the method improves the recognition ability of the model while speeding up the training speed. The research presented in this paper provides important theoretical guidance for artificial intelligence and deep learning.
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Inteligencia Artificial , Voleibol , Humanos , Redes Neurales de la Computación , Movimiento , Movimiento (Física)RESUMEN
BACKGROUND: ICUs follow a restrictive companionship policy, especially after the COVID-19 outbreak. This strategy often limits the time families spend with patients, hinders their knowledge and skills in caregiving, and the sudden transfer of ICU patients to assist with disease monitoring and daily care can be very stressful for families. It is beneficial to use the transition period of transferring ICU patients to help families adjust to the role of caregiver. AIM: To develop and implement a patient- and family-centered transitional care intervention plan for patients transferred to the ICU. DESIGN: Prospective, pretest and posttest design. METHODS: The experimental group received an individualized family-centered transition plan led by the ICU liaison nurse that included 1) communication with health care professionals; distribution of a transfer booklet; 2) identification of nursing issues and communication with the ward nurse; invitation of family members to participate in the patient's rehabilitation; 3) follow-up instruction on bedside range of motion exercises; and provision of a patient rehabilitation diary. Patients in the control group received only routine care. Data were collected using the General Information Questionnaire, Family Satisfaction with ICU Patients (FS-ICU), the Family Relocation Stress Scale (FRSS), and the Stanford Acute Stress Response Questionnaire (SASRQR). RESULTS: After the intervention, the total family satisfaction score of ICU patients in the experimental group was significantly higher than that of the control group (87.18 ± 8.38 vs 78.74 ± 10.63, p<0.001), and the satisfaction with the care and information provided was significantly higher in the experimental group compared to the control group (p < 0.001), with no significant difference between the two groups in terms of satisfaction with decision making (p>0.001). The level of relocation stress of patients' families was significantly lower in the experimental group compared to the control group after the intervention (p < 0.001). And there was no statistically significant difference between the two groups in terms of patients' acute stress disorder scores (p>0.001). CONCLUSION: The implementation of a family-involved transition care programme significantly improved the satisfaction of ICU patients' families and reduced the stress of relocation for patients' families. RELEVANCE TO CLINICAL PRACTICE: Focusing on the transition of ICU patients to ensure continuity of critical care and improve the quality of care for ICU patient transfers can be accomplished through a family-centered transition care plan led by the ICU liaison nurse.
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COVID-19 , Rol de la Enfermera , Humanos , Adulto , Estudios Prospectivos , COVID-19/epidemiología , Comunicación , Unidades de Cuidados Intensivos , FamiliaRESUMEN
Cysteine dioxygenase 1 (Cdo1) is a key enzyme in taurine synthesis. Here we show that Cdo1 promotes lipolysis in adipose tissue. Adipose-specific knockout of Cdo1 in mice impairs energy expenditure, cold tolerance and lipolysis, exacerbates diet-induced obesity (DIO) and decreases adipose expression of the key lipolytic genes encoding ATGL and HSL, with little effect on adipose taurine levels. White-adipose-specific overexpression of ATGL and HSL blunts the role of adipose Cdo1 deficiency in promoting DIO. Mechanistically, Cdo1 interacts with PPARγ and facilitates the recruitment of Med24, the core subunit of mediator complex, to ATGL and HSL gene promoters, thereby transactivating their expression. Further, mice with transgenic overexpression of Cdo1 show better cold tolerance, ameliorated DIO and higher lipolysis capacity. Thus, we uncover an unexpected and important role of Cdo1 in regulating adipose lipolysis.
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Lipólisis , PPAR gamma , Masculino , Ratones , Animales , Lipólisis/fisiología , PPAR gamma/genética , PPAR gamma/metabolismo , Cisteína-Dioxigenasa/metabolismo , Esterol Esterasa/metabolismo , Lipasa/metabolismo , Tejido Adiposo/metabolismo , Obesidad/genética , Obesidad/metabolismo , Complejo Mediador/metabolismo , Taurina/metabolismoRESUMEN
OBJECTIVE: Due to the increasing prevalence of obesity and insulin resistance, there is an urgent need for better treatment of obesity and its related metabolic disorders. This study aimed to elucidate the role of SERPINA3C, an adipocyte secreted protein, in obesity and related metabolic disorders. METHODS: Male wild type (WT) and knockout (KO) mice were fed with high-fat diet (HFD) for 16 weeks, adiposity, insulin resistance, and inflammation were assessed. AAV-mediated overexpression of SERPINA3C was injected locally in inguinal white adipose tissue (iWAT) to examine the effect of SERPINA3C. In vitro analyses were conducted in 3T3-L1 adipocytes to explore the molecular pathways underlying the function of SERPINA3C. RESULTS: Functional exploration of the SERPINA3C knockout mice revealed that SERPINA3C deficiency led to an impaired metabolic phenotype (more severe obesity, lower metabolic rates, worse glucose intolerance and insulin insensitivity), which was associated with anabatic inflammation and apoptosis of white adipose tissues. Consistent with these results, overexpression of SERPINA3C in inguinal adipose tissue protected mice against diet-induced obesity and metabolic disorders with less inflammation and apoptosis in adipose tissue. Mechanistically, SERPINA3C inhibited Cathepsin G activity, acting as a serine protease inhibitor, which blocked Cathepsin G-mediated turnover of α5/ß1 Integrin protein. Then, the preserved integrity (increase) of α5/ß1 Integrin signaling activated AKT to decrease JNK phosphorylation, thereby inhibiting inflammation and promoting insulin sensitivity in adipocytes. CONCLUSIONS/INTERPRETATION: These findings demonstrate a previously unknown SERPINA3C/Cathepsin G/Integrin/AKT pathway in regulating adipose tissue inflammation, and suggest the therapeutic potential of targeting SERPINA3C/Cathepsin G axis in adipose tissue for the treatment of obesity and metabolic diseases.
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Tejido Adiposo , Catepsina G , Resistencia a la Insulina , Integrina alfa5beta1 , Obesidad , Serpinas , Adipocitos/metabolismo , Tejido Adiposo/metabolismo , Animales , Catepsina G/metabolismo , Catepsina G/farmacología , Dieta Alta en Grasa/efectos adversos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Resistencia a la Insulina/fisiología , Integrina alfa5beta1/metabolismo , Integrina beta1/metabolismo , Integrinas/metabolismo , Masculino , Ratones , Ratones Noqueados , Obesidad/etiología , Obesidad/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serpinas/deficiencia , Serpinas/metabolismoRESUMEN
Background: For breast cancer (BC) with sentinel lymph node micrometastases (SLNMs), there are limited data to guide the selection of postoperative adjuvant therapy. This study aimed to identify target populations who might benefit most from adjuvant therapy and examine prognostic factors among patients with T1-2N1miM0 BC with one or two SLNMs who underwent sentinel lymph node biopsy (SLNB) alone. Methods: There were 7,423 patients diagnosed with T1-2N1miM0 BC between 2010 and 2015, and patients with one or two SLNMs were extracted from the Surveillance, Epidemiology, and End Results database. All the patients underwent SLNB alone without further axillary lymph node dissection, and they were stratified according to adjuvant therapy. The statistical significance of categorical variables was analyzed using the χ 2 test. Univariable and multivariable Cox analyses were used to analyze characteristics predictive of Breast-cancer-specific survival and overall survival (OS). Kaplan-Meier methods with the log-rank test was analyzed to compare survival difference between the different treatments. Results: Adjuvant chemotherapy and radiotherapy improved 5-year OS rates. Multivariate analysis revealed that age ≥70 years, high grade, T2 stage, triple-negative subtype, and absence of radiotherapy were poor prognostic factors for OS. Patients who received breast-conserving surgery (BCS), and those with invasive ductal carcinoma (IDC), luminal A, luminal B, or basal-like subtype, and T1c or T2 stage benefited from adjuvant radiotherapy. Patients who received BCS, and those with IDC, luminal A subtype, and T1b, T1c, or T2 stage benefited from adjuvant chemotherapy. Conclusion: Our findings provide a clinical evaluation of treatment choice after surgery, which may help clinicians make individualized clinical decisions.
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Introduction: It has been believed that breast-conserving therapy (lumpectomy plus adjuvant radiation, Lum + RT) and mastectomy without radiation (Mast + NoRT) have equivalent survival outcomes. However, there is a need to re-evaluate the role of lumpectomy plus adjuvant radiation due to changed breast cancer management over time. This study aimed to conduct a population-based study that compare long-term oncologic survival outcomes after Lum + RT vs Mast + NoRT. Methods: The Surveillance, Epidemiology and End Results database was used to identify female breast cancer patients with a primary localized breast cancer diagnosis from 1988 to 2018. The standardized incidence/mortality ratio (SIR/SMR) for breast cancer recurrence (BCR) and breast cancer-specific death (BSD) was estimated by the SEER*Stat program. Cumulative incidences of BCR and BSD were assessed using Gray's method. We evaluated the effects of Lum + RT vs. Mast + NoRT on breast cancer recurrence-free survival (BRFS) and breast cancer-specific survival (BCSS). Fine-Gray competing risk model analyses, propensity score-adjusted Kaplan-Meier analyses and Cox proportional hazards model analyses were applied. Results: A total of 205,788 women were included in the study. Patients who underwent Lum + RT had higher SIR of BCR (4.14 [95% confidence interval, CI: 3.94-4.34] vs. 1.11 [95% CI: 1.07-1.14]) and lower SMR (9.89 [95% CI: 9.71-10.08] vs. 17.07 [95% CI: 16.82-17.33]) than patients who underwent Mast + NoRT. Lum + RT was associated with higher competing risk of BCR (adjusted hazard ratio [HR]: 1.996, 95% CI: 1.925-2.069, p < 0.001) and lower competing risk of BSD when compared to Mast + RT (adjusted HR: 0.584, 95% CI: 0.572-0.597, p < 0.001). Multivariate Cox regression analysis revealed similar results (adjusted HR after PSW for BRFS: 1.792, 95% CI 1.716-1.871, p < 0.001; adjusted HR after PSW for BCSS: 0.706, 95% CI 0.688-0.725, p < 0.001). These findings persisted in the sensitivity and subgroup analyses. Discussion: The present study further confirmed superior long-term survival with lumpectomy plus adjuvant radiation over mastectomy independent of patient characteristics including age, race, time period, historic subtype, tumor size, historic grade and stage, indicating that this benefit may result from the treatment itself.
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We present a coherent multi-band linear frequency modulated (LFM) signal generation and transmission system based on dual optical frequency combs (OFCs). In the proposed scheme, the two OFCs are phase-locked to ensure high coherence of the generated multi-band LFM signals. A round-trip phase correction is adopted to stabilize the time delay of the fiber transmission and enable the system to resist temperature variation. In the demonstration experiment, the generated multi-band LFM signals across L, S, and C frequency bands has a bandwidth of 200 MHz in each band. The root-mean-square (RMS) phase deviation of the multi-band signal is below 4×10-3rad after 1.2 km fiber transmission. During 1°C temperature variation, the RMS phase drift is suppressed from 1 rad to 0.1 rad. The high signal coherence between different bands and the capability of resisting temperature variation are highly desired for a multi-band distributed radar system.
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l-Theanine is a nonprotein amino acid with much beneficial efficacy. We found that intraperitoneal treatment of the mice with l-theanine (100 mg/kg/day) enhanced adaptive thermogenesis and induced the browning of inguinal white adipose tissue (iWAT) with elevated expression of Prdm16, Ucp1, and other thermogenic genes. Meanwhile, administration of the mice with l-theanine increased energy expenditure. In vitro studies indicated that l-theanine induced the development of brown-like features in adipocytes. The shRNA-mediated depletion of Prdm16 blunted the role of l-theanine in promoting the brown-like phenotypes in adipocytes and in the iWAT of mice. l-theanine treatment enhanced AMPKα phosphorylation both in adipocytes and iWAT. Knockdown of AMPKα abolished l-theanine-induced upregulation of Prdm16 and adipocyte browning. l-Theanine increased the α-ketoglutarate (α-KG) level in adipocytes, which may increase the transcription of Prdm16 by inducing active DNA demethylation on its promoter. AMPK activation was required for l-theanine-induced increase of α-KG and DNA demethylation on the Prdm16 promoter. Moreover, intraperitoneal administration with l-theanine ameliorated obesity, improved glucose tolerance and insulin sensitivity, and reduced plasma triglyceride, total cholesterol, and free fatty acids in the high-fat diet-fed mice. Our results suggest a potential role of l-theanine in combating diet-induced obesity in mice, which may involve l-theanine-induced browning of WAT.
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Proteínas Quinasas Activadas por AMP/fisiología , Tejido Adiposo Blanco/efectos de los fármacos , Proteínas de Unión al ADN/fisiología , Glutamatos/farmacología , Ácidos Cetoglutáricos/metabolismo , Reacción de Maillard/efectos de los fármacos , Obesidad/prevención & control , Factores de Transcripción/fisiología , Tejido Adiposo Blanco/metabolismo , Animales , Metilación de ADN , Proteínas de Unión al ADN/genética , Dieta Alta en Grasa , Masculino , Ratones Endogámicos C57BL , Factores de Transcripción/genéticaAsunto(s)
Adaptación Psicológica , Pueblo Asiatico , Humanos , Morbilidad , Investigación CualitativaRESUMEN
Hypertrophic olivary degeneration (HOD) is a rare phenomenon that occurs after various insults to the Guillain-mollaret triangle (GMT). HOD is unique because the degeneration of inferior olivary nucleus becomes hypertrophic rather than atrophic. In this study, a 31-year-old woman developed HOD after pontine cavernoma surgery had been performed. The clinical manifestation was involuntary intorsion of right lower extremity during walking, which has not been reported in the literature. The woman also presented with palatal tremor, the most classic symptom of HOD. HOD's imaging trait include olive hypertrophy with increased T2 signal intensity on MRI, which are corresponding to the pathological findings. HOD is a self-limiting disease and excessive treatments are unnecessary.
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Distonía/etiología , Pie/inervación , Pierna/inervación , Enfermedades Neurodegenerativas/etiología , Procedimientos Neuroquirúrgicos/efectos adversos , Núcleo Olivar/patología , Hueso Paladar/inervación , Temblor/etiología , Adulto , Distonía/fisiopatología , Femenino , Humanos , Hipertrofia , Degeneración Nerviosa , Enfermedades Neurodegenerativas/diagnóstico por imagen , Enfermedades Neurodegenerativas/patología , Enfermedades Neurodegenerativas/fisiopatología , Núcleo Olivar/diagnóstico por imagen , Núcleo Olivar/fisiopatología , Temblor/fisiopatologíaRESUMEN
BACKGROUND: The sharing of biomedical data is crucial to enable scientific discoveries across institutions and improve health care. For example, genome-wide association studies (GWAS) based on a large number of samples can identify disease-causing genetic variants. The privacy concern, however, has become a major hurdle for data management and utilization. Homomorphic encryption is one of the most powerful cryptographic primitives which can address the privacy and security issues. It supports the computation on encrypted data, so that we can aggregate data and perform an arbitrary computation on an untrusted cloud environment without the leakage of sensitive information. METHODS: This paper presents a secure outsourcing solution to assess logistic regression models for quantitative traits to test their associations with genotypes. We adapt the semi-parallel training method by Sikorska et al., which builds a logistic regression model for covariates, followed by one-step parallelizable regressions on all individual single nucleotide polymorphisms (SNPs). In addition, we modify our underlying approximate homomorphic encryption scheme for performance improvement. RESULTS: We evaluated the performance of our solution through experiments on real-world dataset. It achieves the best performance of homomorphic encryption system for GWAS analysis in terms of both complexity and accuracy. For example, given a dataset consisting of 245 samples, each of which has 10643 SNPs and 3 covariates, our algorithm takes about 43 seconds to perform logistic regression based genome wide association analysis over encryption. CONCLUSIONS: We demonstrate the feasibility and scalability of our solution.
Asunto(s)
Seguridad Computacional , Estudio de Asociación del Genoma Completo , Algoritmos , Estudios de Factibilidad , Humanos , Modelos Logísticos , Polimorfismo de Nucleótido Simple , PrivacidadRESUMEN
We propose a phase-stable high-efficiency down-conversion approach for broadband radio frequency signals transmitted from a remote site. A high power coherent optical local oscillator signal is used at the local site to increase the conversion gain and the spurious-free dynamic range (SFDR) at the same time. A sideband optical phase-locked loop ensures the suppression of the phase noise induced by the fiber transmission and the relative frequency drift of the remote and local lasers, which are essential for the signal transmission and the down-conversion. We first experimentally demonstrate the down-conversion of a single frequency signal at 16.45 GHz to a 250 MHz intermediate frequency (IF) signal with 3 dB gain and 103 dB/Hz2/3 SFDR after 10 km fiber transmission. Then we show the broadband down-conversion capability by down-converting a 1 GHz wide linear frequency modulated pulse signal centered at 11 GHz to 1 GHz with 3 dB gain. Along with a positive gain, the SFDR of the IF signal down-converted from 5 GHz to 40 GHz has reached 97.6 dB/Hz2/3 on average. This approach is suitable for weak broadband remote signal down-conversion with a simple-structured remote end.