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The aim of the study was to investigate whether the biomarkers for bone turnover could rapidly recover during the period of diabetic ketoacidosis (DKA). Bone turnover biomarkers, including 25-hydroxyvitamin D3, N-terminal middle molecular fragment of osteocalcin (NMID), and ß-C terminal cross-linking telopeptide of type 1 collagen were evaluated using in-patient data (n=627) from Shanghai Pudong Hospital from 2018-2022. The comparison was performed between type 2 diabetes (T2D only) (n=602) and DKA (n=25), in which we checked the bone turnover markers at pre-treatment and recovery. After matching by body mass index (BMI), we found that except for 25-OH-VitD3, the age difference, indices of glucose metabolism, and bone turnover were significant between the 2 groups (p<0.05). We found only a significant restoration of NMID (p<0.001). NMID and ß-CTX, when compared with T2D, showed overt distinction between recovery and T2D (p<0.05). In addition, the investigations demonstrated a substantial difference between 25-OH-VitD3 in males and NMID in females, regardless of age (p<0.05). Multilinear regression analysis revealed that 2 hours postprandial plasma C-peptide was an independent predictor of the NMID in both pre-treatment (ß=0.58, p=0.003) and recovery (ß=0.447, p=0.025), although sex was significant in pre-treatment (ß=-0.444, p=0.020). Finally, we found that only age variation affected DKA's fasting plasma glucose level (p<0.05). The study revealed that the bone turnover of DKA is significantly different in pre-treatment and recovery; however, NMID might recover quickly if the patients received appropriate treatment. Importantly, pancreatic function plays a critical role in changing bone turnover biomarkers.
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Biomarcadores , Remodelação Óssea , Diabetes Mellitus Tipo 2 , Cetoacidose Diabética , Humanos , Feminino , Masculino , Biomarcadores/sangue , Pessoa de Meia-Idade , Adulto , Cetoacidose Diabética/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Osteocalcina/sangue , Idoso , Colágeno Tipo I/sangueRESUMO
Pulmonary Fibrosis (PF) is a fatal disease in the interstitial lung associated with high mortality, morbidity, and poor prognosis. Transforming growth factor-ß1 (TGF-ß1) is a fibroblast-activating protein that promotes fibrous diseases. Herein, an inhalable system was first developed using milk exosomes (M-Exos) encapsulating siRNA against TGF-ß1 (MsiTGF-ß1), and their therapeutic potential for bleomycin (BLM)-induced PF was investigated. M-siTGF-ß1 was introduced into the lungs of mice with PF through nebulization. The collagen penetration effect and lysosomal escape ability were verified in vitro. Inhaled MsiTGF-ß1 notably alleviated inflammatory infiltration, attenuated extracellular matrix (ECM) deposition, and increased the survival rate of PF mice by 4.7-fold. M-siTGF-ß1 protected lung tissue from BLM toxicity by efficiently delivering specific siRNA to the lungs, leading to TGF-ß1 mRNA silencing and epithelial mesenchymal transition pathway inhibition. Therefore, M-siTGF-ß1 offers a promising avenue for therapeutic intervention in fibrosis-related disorders.
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Bleomicina , Colágeno , Transição Epitelial-Mesenquimal , Exossomos , Pulmão , Leite , Fibrose Pulmonar , RNA Interferente Pequeno , Fator de Crescimento Transformador beta1 , Animais , Exossomos/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fibrose Pulmonar/tratamento farmacológico , Camundongos , Colágeno/metabolismo , Bleomicina/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Pulmão/efeitos dos fármacos , Leite/química , Camundongos Endogâmicos C57BL , Humanos , Permeabilidade , Masculino , Nebulizadores e VaporizadoresRESUMO
Prostate cancer is a male malignant tumor disease with high incidence and mortality. This study was designed to explore the effects of ulinastatin (UTI) on the malignant progression of prostate cancer and its relevant mechanism of action. Human prostate cancer cell line PC-3 was applied to investigate the anticancer activity of UTI. PC-3 cells were treated with increasing concentrations (400, 800, and 1600 U/ml) of UTI. Cell proliferation, migration, invasion, and apoptosis were determined by cell counting kit-8 (CCK-8), colony formation, wound-healing, Transwell assay, and flow cytometry analysis, respectively. The expression level of corresponding proteins was detected by western blot. In addition, PC-3 cells were pretreated with RhoA agonist CN03 (1 µg/ml) or NLRP3 agonist nigericin (10 µM) before UTI treatment, and the cellular behaviors above were detected again. It was demonstrated that UTI significantly suppressed cell proliferation, migration, and invasion but promoted apoptosis in PC-3 cells in a concentration-dependent manner. Meanwhile, UTI could block RhoA/ROCK/NLRP3 inflammasome pathway in PC-3 cells, and the activation of RhoA or NLRP3 inflammasome partly weakened the impacts of UTI on cell proliferation, migration, and apoptosis in PC-3 cells, respectively. In summary, our study demonstrated the antitumor activity of UTI against prostate cancer by regulating RhoA/NLRP3 inflammasome pathway, providing a promising candidate drug for the therapeutic treatment of prostate cancer.
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Inflamassomos , Neoplasias da Próstata , Masculino , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Transdução de Sinais , Movimento Celular , Neoplasias da Próstata/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Proteína rhoA de Ligação ao GTP/metabolismo , Proteína rhoA de Ligação ao GTP/farmacologia , Proteína rhoA de Ligação ao GTP/uso terapêuticoRESUMO
BACKGROUND: Non-alcoholic fatty liver (NAFLD) is a complex metabolic disease characterized by fatty degeneration of hepatocytes. Circular RNAs (circRNAs) have been reported to be essential for (NAFLD progression. The potential mechanism of circRNA low-density lipoprotein receptor (circLDLR) in the NAFLD was investigated in this study. METHODS: Hepatocyte (Hepa1-6) cells treated with oleic acid/palmitic acid (OA/PA) were used as the in vitro NAFLD model, and C57BL/6 mice fed with high-fat diet (HFD) were used as the in vivo NAFLD model. The circLDLR, LDLR, and miR-667-5p expression were measured by quantitative real-time polymerase chain reaction (qRT-PCR), while the protein levels of Light Chain Microtubule-Associated Protein 3 (LC3) and Sequestosome-1(p62) was examined by western blot. The circLDLR location was confirmed using RNA fluorescence in situ hybridization. Oil red O staining was carried out to measure lipid deposition in cells. The secreted levels of triglyceride (TG) and total cholesterol (TC) were detected through Enzymatic. The existence of the circLDLR/miR-667-5p/sirtuin 1 (SIRT1) regulatory axis was validated by applying the dual-luciferase reporter assay. RESULTS: The circLDLR expression showed a prominent down-regulation in OA/PA-treated Hepa1-6 cells, whereas the LDLR expression was up-regulated. Overexpression of circLDLR significantly attenuated lipid droplet accumulation in NAFLD models in vitro/vivo, reduced TG, TC, and p62 levels, and increased LC3-II levels and the amount of the green fluorescent protein (GFP)-LC3 puncta in cells. CircLDLR and SIRT1 are common targets of miR-667-5p to inhibit the TG and TC and promote the autophagy pathway. SIRT1 knockdown reversed the effects of circLDLR overexpression. CONCLUSIONS: CircLDLR alleviated the development of NAFLD by inducing autophagic flux while modulating the miR-667-5p/SIRT1 axis reversed its effects, suggesting that targeting circLDLR/miR-667-5p/SIRT1 axis may be a promising therapeutic strategy for NAFLD.
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MicroRNAs , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Camundongos Endogâmicos C57BL , Sirtuína 1/genética , Hepatopatia Gordurosa não Alcoólica/genética , Hibridização in Situ Fluorescente , Camundongos Endogâmicos , Ácido Palmítico , Triglicerídeos , Ácido Oleico , MicroRNAs/genéticaRESUMO
BACKGROUND: This study aimed to investigate the expression level of the GATA6 gene in different oral cancer cells. METHODS: In this study, we sub-cultured normal oral epithelial cell lines HOK, human tongue squamous cell carcinoma cell lines CAL-27 and SCC-4, and human salivary gland adenoid cystic carcinoma cell lines SACC-LM and SACC-83. Subsequently, we used reverse transcription-polymerase chain reaction RT-PCR and Western blot methods to detect the mRNA and the protein expressions of GATA6 in normal oral epithelial cells, human tongue squamous cell carcinoma cells, and human salivary gland adenoid cystic carcinoma cells. RESULTS: The results of this study showed that the mRNA expression levels of GATA6 in CAL-27, SCC-4, and SACC-LM cells were significantly increased when compared with the HOK cells. However, the mRNA expression level of GATA6 in the SACC-83 cells had no significant difference compared with the HOK cells. The protein expression levels of GATA6 in the SCC-4 and SACC-LM cells were, however, significantly increased whereas the protein expression levels of GATA6 in the CAL-27 and SACC-83 cells had no significant difference when compared with the HOK cells. CONCLUSION: The GATA6 gene may be related to the occurrence and progression of certain oral cancers.
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Carcinoma Adenoide Cístico , Carcinoma de Células Escamosas , Neoplasias das Glândulas Salivares , Neoplasias da Língua , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Fator de Transcrição GATA6/genética , Humanos , Prognóstico , Neoplasias da Língua/genéticaRESUMO
Currently, a paucity of targeted dust suppressants exists for the management of laterite dust, and most of them lack sufficient resistance to the harsh conditions in the plateau areas, such as high temperatures, low rainfall, and wind erosion. To solve the problem, a new type of dust suppressant must be developed. Initially, xanthan gum was employed to enhance the viscosity and stability of guar gum. Subsequently, the synergistic mechanism between the reagents was considered, and the composition of the composite dust suppressant was selected as poly(acrylic acid), sodium dodecyl sulfate, guar gum, and xanthan gum by one- and two-factor methods. The dosage of each component was then determined via orthogonal experiments. To increase the suitability of the dust suppressant in high-temperature and low-humidity environments, hydroxypropyl methylcellulose was added to enhance the "film" effect. Both intuitive and polar analysis methods demonstrated that the composite dust suppressant was the optimal choice for controlling laterite dust emissions. The performance test experimental results show that the dust suppressant can fill the gap between particles well after spraying, the solidified layer formed is flat and smooth, and the moisture content of the sample was still above 9% after 72 h. The hardness of the consolidation layer can reach 42 HA, which can resist the destructive ability of external force; when the wind speed is 7 m/s, the mass loss rate stays below 0.63%, and the emission concentrations of PM2.5 and PM10 are 32 µg/m3 and 43 µg/m3, respectively, which is in line with the requirements of the emission standards. The dust suppressant components are all less toxic to plants, and the degradation rate can reach 57.84% in the sixth cycle, ensuring degradability and biocompatibility. The composite dust suppressant demonstrated superior performance to that of the two commercially available dust suppressants. It exhibited remarkable adaptability to harsh environments, effectively regulating construction site dust emissions and reducing particulate matter in the air.
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Objective: To investigate the implications of elevated myoglobin (MYO) in acute diabetic conditions of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). Materials and methods: This study integrates in-patient data from Shanghai Pudong Hospital from 2019 to 2023. Laboratory data were compared between stable T2D patients (without acute diabetic complications), DKA, and HHS patients. The multilinear regression explored variables relevant to the elevated MYO in DKA and HHS. The dynamics of MYO, the survival rate, and associated risk factors in HHS were determined. Results: Except for triglyceride, procalcitonin, low-density lipoprotein, islet cell autoimmune antibodies, N-terminal Pro-brain natriuretic peptide (NT-ProBNP), and brain natriuretic peptide (BNP), there were significant differences in age, gender distribution, duration of diabetes, type of diabetes, and other referred laboratory data (p<0.05). The age, gender, creatine kinase (CK), estimated glomerular filtration rate (eGFR), and free triiodothyronine (FT3) in DKA, whereas osmolar, uric acid (UA), and cardiac troponin I (cTNI) in the HHS, were significant determinants of elevated MYO, respectively (p<0.05). The dynamic of MYO in HHS was in line with the survival trend, where the percentage of death was 29.73%, and aging with higher procalcitonin levels was a key risk factor. Besides, the cumulative survival rates between patients with or without bone fracture or muscle injury were substantially different. Conclusion: This real-world study demonstrated DKA and HHS potentially have unique causes for increased MYO. By utilizing the appropriate regression parameters, we could forecast the progression of increased MYO in groups of DKA and HHS, while based on risk factors of aging, severity of infection, and different MYO sources, we could predict the prognosis of HHS.
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Objectives: To investigate the variation in bone turnover biomarkers among patients with type 2 diabetes (T2D) and low triiodothyronine levels (Low T3 syndrome). Materials and Methods: This retrospective analytic study included 418 inpatient records from Shanghai Pudong Hospital covering the years 2021 to 2023. Laboratory data related to metabolic and bone turnover biomarkers in patients were analyzed with T2D and the low T3 syndrome. Results: The results indicated that patients with reduced serum T3 levels exhibited statistically significant variations in thyroid function, age, fasting plasma glucose (FPG), glycated hemoglobin A1c (HbA1c), and the proportion of medication history associated with diabetes in comparison to euthyroid patients. In addition to parathyroid hormones, bone turnover biomarkers including N-terminal middle molecular fragment of osteocalcin (NMID), plasma calcium (Ca2+), ß C-terminal cross-linking telopeptide of type 1 collagen (ß-CTX), and 25-hydroxyvitamin D3 (25 OH VitD3) exhibited significant changes in patients with decreased T3 levels. Evident irregularities were observed in patients with a decreased T3 level, including elevated serum creatinine (SCr), decreased concentrations of albumin and total protein, and a decreased estimated glomerular filtration rate (eGFR), as assessed through hepatic and renal testing, respectively. Significant associations between bone turnover biomarkers and the subsequent variables (gender, adiposity, hepatic, renal, and thyroid function) were revealed through the correlational analysis. Further investigation utilized multivariate linear regression to determine that, in addition to thyroid function, several other factors such as age, gender, bodyweight, pancreatic, hepatic, and renal function, affected the variability in bone turnover biomarkers among patients demonstrating a low serum T3 level. Conclusions: This comparative study demonstrated that despite age, gender, bodyweight, hepatic, renal function, thyroid hormone and pancreatic function were significant factors associated with bone metabolism in patients with T2D and Low T3 syndrome, which may increase the risk of osteoporosis.
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University accidents in China are frequent, and to find out the relationship pattern of factors influencing accidents, 248 university accidents occurring within 2017-2021 were studied using difference analysis (Independent-samples T-test, Mann-Whitney U test), logistic regression analysis, and diagnostic analysis of receiver operating characteristic curves. The results show: The variability in time, space, and qualifications was statistically significant (p < 0.05), and when the number of university safety policies ≥77 would significantly reduce the frequency of university accidents, with an influence strength value of 0.884 and a diagnostic accuracy of 79.8 %. In addition, the perpetrators, the time and the location of the accidents were usually undergraduate students, first semester of university, and economically developed and educationally rich provinces, respectively, with influence strength value and diagnostic accuracy of greater than 1 and 70%, respectively. Finally, specific suggestions are offered for the future prevention and reduction of accidents at the University based on the findings of the studies.
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Supervised neural speech enhancement methods always require a large scale of paired noisy and clean speech data. Since collecting adequate paired data from real-world applications is infeasible, simulated data is always adopted in supervised learning methods. However, the mismatch between the simulated data and in-the-wild data always causes performance inconsistency when the system is deployed in real-world applications. Unsupervised speech enhancement methods are studied to address the mismatch problem by directly using the in-the-wild noisy data without access to the corresponding clean speech. Therefore, the simulated paired data is not necessary. However, the performance of the unsupervised speech enhancement method is not on par with the supervised learning method. To address the aforementioned problems, this work proposes an unsupervised pre-training and mixture training algorithm by leveraging the advantages of supervised and unsupervised learning methods. Specifically, the proposed speech enhancement approach employs large volumes of unpaired noisy and clean speech to conduct unsupervised pre-training. The noisy data and a small amount of simulated paired data are then used for mixture training to optimize the pre-trained model. Experimental results show that the proposed method achieves better performances than other state-of-the-art supervised and unsupervised learning methods.
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Algoritmos , FalaRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Therapeutic options for advanced HCC are limited, which is due to a lack of full understanding of pathogenesis. Cellular senescence is a state of cell cycle arrest, which plays important roles in the pathogenesis of HCC. Mechanisms underlying hepatocellular senescence are not fully understood. LncRNA NEAT1 acts as an oncogene and contributes to the development of HCC. Whether NEAT1 modulates hepatocellular senescence in HCC is unknown. METHODS: The role of NEAT1 and KIF11 in cellular senescence and tumor growth in HCC was assessed both in vitro and in vivo. RNA pulldown, mass spectrometry, Chromatin immunoprecipitation (ChIP), luciferase reporter assays, RNA FISH and immunofluorescence (IF) staining were used to explore the detailed molecular mechanism of NEAT1 and KIF11 in cellular senescence of HCC. RESULTS: We found that NEAT1 was upregulated in tumor tissues and hepatoma cells, which negatively correlated with a senescence biomarker CDKN2A encoding p16INK4a and p14ARF proteins. NEAT1 was reduced in senescent hepatoma cells induced by doxorubicin (DOXO) or serum starvation. Furthermore, NEAT1 deficiency caused senescence in cultured hepatoma cells, and protected against the progression of HCC in a mouse model. During senescence, NEAT1 translocated into cytosol and interacted with a motor protein KIF11, resulting in KIF11 protein degradation and subsequent increased expression of CDKN2A in cultured hepatoma cells. Furthermore, KIF11 knockdown caused senescence in cultured hepatoma cells. Genetic deletion of Kif11 in hepatocytes inhibited the development of HCC in a mouse model. CONCLUSIONS: Conclusively, NEAT1 overexpression reduces senescence and promotes tumor progression in HCC tissues and hepatoma cells, whereas NEAT1 deficiency causes senescence and inhibits tumor progression in HCC. This is associated with KIF11-dependent repression of CDKN2A. These findings lay the foundation to develop potential therapies for HCC by inhibiting NEAT1 and KIF11 or inducing senescence.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante , Animais , Camundongos , Carcinoma Hepatocelular/genética , Linhagem Celular , Senescência Celular/genética , Proteínas Inibidoras de Quinase Dependente de Ciclina , Modelos Animais de Doenças , Neoplasias Hepáticas/genética , RNA Longo não Codificante/genéticaRESUMO
PURPOSE: Despite the fact that diabetes individuals are often associated with a higher risk of bone fracture, our previous research demonstrated that Diabetic ketosis (DK) or ketoacidosis (DKA) induced significant alterations in bone biomarkers. It is unknown whether there is a difference in bone metabolism between obese and non-obese diabetic populations while they are in DK or DKA; hence the current study will investigate this further to aid in the prognosis and prediction of bone fracture risk in patients with different BMIs. METHODS: We categorized patients into four groups based on their BMI utilizing data from our hospital's medical record system from 2018 to 2020 in the Department of Endocrinology: obese DK or DKA patients (OB+DK/DKA, n = 41), non-obese DK or DKA patients (DK/DKA, n = 201), obese type 2 diabetes patients without DK or DKA (OB+T2D, n = 93), and patients with type 2 diabetes only (T2D only, n = 304). The comparisons were made on glycosylated hemoglobin (HbA1c), body mass index (BMI), fasting plasma C-peptide (FPCP), and plasma lipids, in addition to bone metabolism indicators such as total 25-OH-VitD3 (25-OH-VitD3), N-terminal middle molecular fragment of osteocalcin (NMID), -C terminal cross-linking telopeptide of type 1 collagen (-CTX), parathyroid hormone (PTH), and blood calcium (Ca2+). RESULTS: The OB+DK/DKA group had a lower average age (p < 0.05) than the DK/DKA group, while the DK/DKA group had a significantly lower FPCP (p < 0.05). The 25-OH-VitD3 levels of DK/DKA patients were considerably lower than those of the T2D-only group (p < 0.05). In contrast, NMID and Ca2+ levels were significantly lower than those of non-ketosis or acidosis patients (p < 0.05), and PTH levels in the DK/DKA group were significantly lower than those of OB+ T2D patients (p < 0.05). In contrast, the ß-CTX of the DK or DKA group (OB+DK/DKA and DK+DKA) was significantly greater than that of the non-DK or DKA group (p < 0.05), although there was no significant difference in blood phosphorus between OB+DK/DKA and DK/ DKA (p > 0.05). The levels of thyroid-stimulating hormone (TSH) and free T4 (FT4) did not differ significantly among the four groups (p > 0.05); however, the levels of total T3 (TT3), T4 (TT4), and free T3 (FT3) were significantly lower in the DK/DKA group (p < 0.05); the ratio of TT3 to TT4 (TT3/TT4) was significantly decreased in the DK/DKA group, whereas the ratio of FT3/FT4 was significantly lower (p < 0.05). CONCLUSION: Obese patients with DK or DKA have a younger onset age, superior pancreatic function, and better blood glucose management than non-obese patients with DK/DKA. Despite having higher bone absorption signals than non-DK/DKA patients, OB+DK/DKA patients have stronger bone formation markers than non-obese DK/DKA patients, according to a recent study. Changes in markers of bone metabolism may be linked to non-thyroidal illness syndrome in cases of DK or DKA.
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PURPOSES: The primary aim of this clinical study is to identify the factors associated with rapid glycemic, bodyweight, and lipid profile remission in young obese patients following bariatric surgery. MATERIALS AND METHODS: In a total of 131 Chinese in-patients at Shanghai Pudong Hospital, China, we retrospectively analyzed in-patient data of metabolic parameters, including BMI, waist circumference, blood pressure (BP), and blood laboratory tests, such as plasma lipids and lipoprotein, hemoglobulin A1c (HbA1c), and oral glucose tolerance tests (OGTT) before bariatric surgery. We followed up these indices at the first month, third months, half-year, and one year later. RESULTS: The results showed that bodyweight, BP, fasting plasma glucose (FPG), HbA1c, and triglyceride (TG) levels decreased significantly in one to three months following surgery in both male and female patients (p<0.05). We demonstrated that age (male: ß=-0.181; female: ß=-0.292) and the pre-operation HbA1c levels (male: ß=0.935; female: ß=0.919) were independent predictors of HbA1c reduction in both young obese male and female patients in three months after surgery. For body weight loss, age (ß=-0.229) and pre-operation bodyweight (ß=0.735) are the predictors in females, but only pre-operation body weight (ß=0.798) is the independent predictor in obese young male patients. CONCLUSION: This study discovered that changes in bodyweight were determined by age, pre-operation status of bodyweight, and HbA1C in obese young Chinese.
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This paper presents an improved method for selecting a specific location in the development of convenience stores in municipal areas. This method solves the problem of self-service store location from the perspective of sustainability and uncertainty and adequately considers the characteristics of individual locations with the proposition of an improved grey wolf optimization algorithm. The example presented shows that the improved algorithm has obvious advantages in facilitating the selection of convenience stores with respect to the search precision, stability, and convergence. Based on the macroenvironment, income, and cost, this work establishes a relatively complex, complete, and targeted mathematical model. Finally, taking the Xiaonanzhuang area of Suzhou Street in Beijing as an example, the scientificity, feasibility, and sustainability of the location model are verified.
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Algoritmos , Modelos Teóricos , IncertezaRESUMO
Spiking neural networks (SNNs) have shown clear advantages over traditional artificial neural networks (ANNs) for low latency and high computational efficiency, due to their event-driven nature and sparse communication. However, the training of deep SNNs is not straightforward. In this paper, we propose a novel ANN-to-SNN conversion and layer-wise learning framework for rapid and efficient pattern recognition, which is referred to as progressive tandem learning. By studying the equivalence between ANNs and SNNs in the discrete representation space, a primitive network conversion method is introduced that takes full advantage of spike count to approximate the activation value of ANN neurons. To compensate for the approximation errors arising from the primitive network conversion, we further introduce a layer-wise learning method with an adaptive training scheduler to fine-tune the network weights. The progressive tandem learning framework also allows hardware constraints, such as limited weight precision and fan-in connections, to be progressively imposed during training. The SNNs thus trained have demonstrated remarkable classification and regression capabilities on large-scale object recognition, image reconstruction, and speech separation tasks, while requiring at least an order of magnitude reduced inference time and synaptic operations than other state-of-the-art SNN implementations. It, therefore, opens up a myriad of opportunities for pervasive mobile and embedded devices with a limited power budget.
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Algoritmos , Redes Neurais de Computação , Aprendizagem , Aprendizado de Máquina , NeurôniosRESUMO
Purpose: This study aims to identify changes in bone turnover markers and thyroid function in diabetic ketosis (DK) and diabetic ketoacidosis (DKA). Materials and Methods: We compared data from the Department of Endocrinology at Shanghai Pudong Hospital from 2018 to 2020 on the pancreatic status and previous glucose control, bone transformation, calcium homeostasis, and thyroid function in groups with diabetes (DM alone, n=602), DK (n=232), and DKA (n=60). Similar comparisons were made in recurrent DK (A) (n=17) and single DK (A) (n=272). Results: The fasting C-peptide level decreased significantly, but hemoglobin A1c (HbA1c) levels were higher in DK or DKA (p<0.05). Blood calcium and 25-hydroxyvitamin D3 (25-OH-VitD3) levels were significantly lower in DKA (p<0.05), but parathyroid hormone (PTH) levels remained constant across all three groups. The N-terminal middle molecular fragment of osteocalcin (N-MID) and ß-C terminal cross-linking telopeptide of type 1 collagen (ß-CTX) showed significant inverse alterations in DKA, regardless of gender or age (p<0.05). Otherwise, DKA significantly inhibited thyroid function (p<0.05). Furthermore, Spearman correlation analyses revealed a relationship between N-MID and HbA1c in DM alone (r=-0.27, p<0.01), while total triiodothyronine (TT3, r=0.62, p<0.01) or free T3 (FT3, r=0.61, p<0.01) in DK, and DKA (TT3, r=0.45, p<0.01; FT3, r=0.43, p<0.01). Multilinear regression analyses revealed that ß-CTX (ß=0.564), HbA1c (ß=-0.196), TT3 (ß=0.183), and 25-OH-VitD3 (ß=-0.120) were the only independent determinants of N-MID in DM, whereas FT3 (ß=0.491), ß-CTX (ß=0.315) in DK, and FT3 (ß=0.420), ß-CTX (ß=0.367), TG (ß=-0.278) in DKA. Only 25-OH-VitD3 was found to be significantly lower in recurrent DK (A) than in single onset DK (A) (p<0.05), and ß-CTX (ß=0.745) was found to be significantly independently associated with N-MID. Conclusion: Our preliminary findings show a dramatic change in bone turnover markers in DM patients with DK and DKA, and this change may be related to thyroid function.
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As an important promising biomarker, high frequency oscillations (HFOs) can be used to track epileptic activity and localize epileptogenic zones. However, visual marking of HFOs from a large amount of intracranial electroencephalogram (iEEG) data requires a great deal of time and effort from researchers, and is also very dependent on visual features and easily influenced by subjective factors. Therefore, we proposed an automatic epileptic HFO detection method based on visual features and non-intuitive multi-domain features. To eliminate the interference of continuous oscillatory activity in detected sporadic short HFO events, the iEEG signals adjacent to the detected events were set as the neighboring environmental range while the number of oscillations and the peak-valley differences were calculated as the environmental reference features. The proposed method was developed as a MatLab-based HFO detector to automatically detect HFOs in multi-channel, long-distance iEEG signals. The performance of our detector was evaluated on iEEG recordings from epileptic mice and patients with intractable epilepsy. More than 90% of the HFO events detected by this method were confirmed by experts, while the average missed-detection rate was < 10%. Compared with recent related research, the proposed method achieved a synchronous improvement of sensitivity and specificity, and a balance between low false-alarm rate and high detection rate. Detection results demonstrated that the proposed method performs well in sensitivity, specificity, and precision. As an auxiliary tool, our detector can greatly improve the efficiency of clinical experts in inspecting HFO events during the diagnosis and treatment of epilepsy.
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Epilepsia Resistente a Medicamentos , Epilepsia , Animais , Biomarcadores , Eletroencefalografia , Epilepsia/diagnóstico , Humanos , Camundongos , Sensibilidade e EspecificidadeRESUMO
Metformin, the first-line drug to treat type 2 diabetes, inhibits mitochondrial glycerolphosphate dehydrogenase in the liver to suppress gluconeogenesis. The major adverse effects caused by metformin were lactic acidosis and gastrointestinal discomfort. Therefore, there is need to develop a strategy with excellent permeability and appropriate retention effects.In this study, we synthesized a simple and biocompatible PolyMetformin (denoted as PolyMet) through conjugation of PEI1.8K with dicyandiamide, and then formed PolyMet-hyaluronic acid (HA) nanocomplexs by electrostatic self-assembly of the polycationic PolyMet and polyanionic hyaluronic acid (HA). Similar to metformin, the PolyMet-HA nanocomplexs could reduce the catalytic activity of the recombinant SHIP2 phosphatase domain in vitro. In SHIP2-overexpressing myotubes, PolyMet-HA nanocomplexes ameliorated glucose uptake by downregulating glucose transporter 4 endocytosis. PolyMet-HA nanocomplexes also could restore Akt signaling and protect the podocyte from apoptosis induced by SHIP2 overexpression. In essence, the PolyMet-HA nanocomplexes act similarly to metformin and increase glucose uptake, and maybe have a potential role in the treatment of type 2 diabetes.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucose/metabolismo , Metformina/farmacologia , Nanomedicina/métodos , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/antagonistas & inibidores , Animais , Apoptose , Transporte Biológico , Catálise , Cátions , Sobrevivência Celular , Células Cultivadas/citologia , Colorimetria , Diabetes Mellitus Tipo 2/metabolismo , Regulação para Baixo , Endocitose , Transportador de Glucose Tipo 4/metabolismo , Humanos , Ácido Hialurônico/farmacologia , Fibras Musculares Esqueléticas/metabolismo , Mioblastos/citologia , Podócitos/citologia , Domínios Proteicos , Ratos , Proteínas Recombinantes/química , Transdução de SinaisRESUMO
An optical device scheme that serves simultaneously as a power combiner for upstream and wavelength demultiplexer for downstream signals is presented. The design concept is validated experimentally by an optical module based on off-the-shelf discrete optical components. An integrated device based on planar lightwave circuit (PLC) is proposed and analyzed in which a multi-mode interference (MMI) device is utilized to separate the upstream 1310 nm signal from the downstream 155x nm signals. The dense WDM function is realized through an arrayed-waveguide-grating (AWG). Design guidelines and optimization procedure for the device are discussed by way of examples.
RESUMO
Design optimization of a novel integrated bi-directional (BiDi) triplexer filter based on planar lightwave circuit (PLC) for fiber-to-the premise (FTTP) applications is described. A multi-mode interference (MMI) device is used to filter the up-stream 1310nm signal from the down-stream 1490nm and 1555nm signals. An array waveguide grating (AWG) device performs the dense WDM function by further separating the two down-stream signals. The MMI and AWG are built on the same substrate with monolithic integration. The design is validated by simulation, which shows excellent performance in terms of filter spectral characteristics (e.g., bandwidth, cross-talk, etc.) as well as insertion loss.