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1.
J Proteome Res ; 23(1): 344-355, 2024 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-38113133

RESUMO

Diabetes mellitus hinders the process of bone regeneration by inhibiting the function of mesenchymal stem cells (MSCs) through elevated glucose levels, thereby impeding osteointegration. The stem cell niche (SCN) plays a crucial role in determining the fate of stem cells by integrating various signals. However, the precise mechanism by which high glucose levels affect the SCN and subsequently influence the function of MSCs remains unclear. In this study, we employed proteomic analysis to identify proteins with altered expression in the extracellular matrix (ECM), aiming to elucidate the underlying mechanism. Three cell supernatants were collected from bone marrow mesenchymal stem cells (BMSCs) or BMSCs stimulated with high glucose (BMSCs+Hg). A total of 590 differentially expressed proteins were identified, which were found to be associated with the ECM, including aging, autophagy, and osteogenic differentiation. The findings of our study indicate that elevated glucose levels exert an influence on the molecular aspects of the SCN, potentially contributing to a better comprehension of the underlying mechanism.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Osteogênese/genética , Proteômica , Diferenciação Celular , Células-Tronco Mesenquimais/metabolismo , Glucose/farmacologia , Glucose/metabolismo , Células da Medula Óssea , Células Cultivadas
2.
J Proteome Res ; 23(1): 3-15, 2024 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-38018860

RESUMO

The purpose of this study was to determine potential metabolic biomarkers and therapeutic drugs in the gingival tissue of individuals with periodontitis. Liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) were used to analyze the gingival tissue samples from 20 patients with severe periodontitis and 20 healthy controls. Differential metabolites were identified using variable important in projection (VIP) values from the orthogonal partial least squares discrimination analysis (OPLS-DA) model and then verified for significance between groups using a two-tailed Student's t test. In total, 65 metabolites were enriched in 33 metabolic pathways, with 40 showing a significant increase and 25 expressing a significant decrease. In addition, it was found that patients with severe periodontitis have abnormalities in metabolic pathways, such as glucose metabolism, purine metabolism, amino acid metabolism, and so on. Furthermore, based on a multidimensional analysis, 12 different metabolites may be the potential biomarkers of severe periodontitis. The experiment's raw data have been uploaded to the MetaboLights database, and the project number is MTBLS8357. Moreover, osteogenesis differentiation characteristics were detected in the selected metabolites. The findings may provide a basis for the study of diagnostic biomarkers and therapeutic metabolites in severe periodontitis.


Assuntos
Metabolômica , Periodontite , Humanos , Metabolômica/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Metaboloma , Biomarcadores
3.
Purinergic Signal ; 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39215950

RESUMO

Cardiovascular diseases (CVDs), including hypertension, atherosclerosis, myocardial ischemia, and myocardial infarction, constitute the primary cause of mortality worldwide. Transcription factors play critical roles in the development of CVDs and contribute to the pathophysiology of these diseases by coordinating the transcription of many genes involved in inflammation, oxidative stress, angiogenesis, and glycolytic metabolism. One important regulator of hemostasis in both healthy and pathological settings has been identified as a purinergic signalling pathway. Research has demonstrated that several signalling networks implicated in the pathophysiology of CVDs are formed by transcription factors that are regulated by purinergic substances. Here, we briefly summarize the roles and mechanisms of the transcription factors regulated by purinergic pathways in various types of CVD. This information will be essential for discovering novel approaches for CVD treatment and prevention.

4.
Eur J Clin Pharmacol ; 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39102039

RESUMO

PURPOSE: Based on the comparison of ramucirumab monoclonal antibody with control treatments in randomized controlled trials, this study aims to elucidate the role of ramucirumab monoclonal antibody in cancer therapy and its potential side effects, providing scientific evidence for clinical treatment. METHODS: PubMed, Embase, Cochrane, and Web of Science were searched systematically to obtain the trials on ramucirumab in the treatment of gastric or gastroesophageal junction (GEJ) adenocarcinoma up to April 13, 2023. We included randomized controlled trials (RCTs) evaluating the efficacy and safety of ramucirumab as monotherapy and in combination with other chemotherapy agents as interventions for treating gastric or gastroesophageal junction (GEJ) adenocarcinoma. RESULTS: After screening 2200 studies, we finally included 8 eligible studies (involving a total of 3,283 participants). Meta-analysis results showed that compared to the control group, ramucirumab monotherapy significantly improved overall survival (OS) (hazard ratio [HR] = 0.77, 95% confidence interval [CI] [0.67, 0.89]) and progression-free survival (PFS) (HR = 0.48, 95% CI [0.40, 0.58]). Similar results were obtained for ramucirumab combined with paclitaxel. In the treatment combining ramucirumab with paclitaxel, compared to monotherapy, three severe adverse reactions (grade ≥ 3) were observed with significantly increased risks (OR > 2). These include proteinuria (OR = 5.37, 95% CI [1.22, 23.54]), hypertension (OR = 4.02, 95% CI [2.63, 6.14]), and gastrointestinal perforation (OR = 4.64, 95% CI [1.00, 21.60]). Subgroup analysis further indicated that ramucirumab is effective in both non-East Asian and East Asian populations, with East Asian patients more prone to developing proteinuria, while having a lower incidence of hypertension. Additionally, ramucirumab demonstrated comparable efficacy between first-line and second-line treatments, with a higher incidence of proteinuria observed in second-line therapy. CONCLUSION: Ramucirumab significantly improves the prognosis of patients with gastric or gastroesophageal junction adenocarcinoma. When used in combination with paclitaxel, close monitoring of adverse reactions such as proteinuria (especially in East Asian populations), hypertension (especially in non-East Asian populations), and gastrointestinal perforation is essential.

5.
Ecotoxicol Environ Saf ; 275: 116252, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38547731

RESUMO

BACKGROUND: Phthalates are widely used plasticizers, which were identified as risk factors in the development of many human diseases. However, the effects of phthalates in the periodontitis are unknown. We aimed to investigated the relationship of periodontitis and phthalate exposure as well as the underlying mechanisms. MATERIALS AND METHODS: Univariate and multivariate logistic regressions were employed to evaluate the association between phthalate metabolites and periodontitis. The generalized additive model and piecewise logistic regression were conducted to investigate the dose-response relationship. Cell and animal models were used to explore the role and mechanism of DEHP in the development of periodontitis. Transcriptome sequencing, bioinformatics analysis, western blot, immunofluorescence and mice model of periodontitis were also employed. RESULTS: MEHP (OR 1.14, 95% CI 1.05-1.24), MCPP (OR 1.08, 95% CI 1.00-1.17), MEHHP (OR 1.18, 95% CI 1.08-1.29), MEOHP (OR 1.18, 95% CI 1.07-1.29), MiBP (OR 1.15, 95% CI 1.04-1.28), and MECPP (OR 1.20, 95% CI 1.09-1.32) were independent risk factors. And MEHHP, the metabolite of DEHP, showed the relative most important effects on periodontitis with the highest weight (0.34) among all risk factors assessed. And the increase of inflammation and the activation of NFκB pathway in the periodontitis model mice and cells were observed. CONCLUSION: Exposure to multiple phthalates was positively associated with periodontitis in US adults between 30 and 80 years old. And DEHP aggravated inflammation in periodontitis by activating NFκB pathway.


Assuntos
Dietilexilftalato , Poluentes Ambientais , Periodontite , Ácidos Ftálicos , Adulto , Humanos , Animais , Camundongos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Exposição Ambiental/análise , Dietilexilftalato/metabolismo , Ácidos Ftálicos/toxicidade , Ácidos Ftálicos/metabolismo , Periodontite/induzido quimicamente , Inflamação , Poluentes Ambientais/análise
6.
Hum Reprod ; 38(12): 2382-2390, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-37801294

RESUMO

STUDY QUESTION: Can blastocyst aneuploidy be predicted for patients with previous aneuploid pregnancy loss (PAPL) and receiving preimplantation genetic testing for aneuploidy (PGT-A)? SUMMARY ANSWER: Multivariable logistic regression models were established to predict high risk of blastocyst aneuploidy using four identified factors, presenting good predictive performance. WHAT IS KNOWN ALREADY: Aneuploidy is the most common embryonic chromosomal abnormality leading to pregnancy loss. Several studies have demonstrated a higher embryo aneuploidy rate in patients with PAPL, which has suggested that PGT-A should have benefits in PAPL patients intending to improve their pregnancy outcomes. However, recent studies have failed to demonstrate the efficacy of PGT-A for PAPL patients. One possible way to improve the efficacy is to predict the risk of blastocyst aneuploidy risk in order to identify the specific PAPL population who may benefit from PGT-A. STUDY DESIGN, SIZE, DURATION: We conducted a multicenter retrospective cohort study based on data analysis of 1119 patients receiving PGT-A in three reproductive medical centers of university affiliated teaching hospitals during January 2014 to June 2020. A cohort of 550 patients who had one to three PAPL(s) were included in the PAPL group. In addition, 569 patients with monogenic diseases without pregnancy loss were taken as the non-PAPL group. PARTICIPANTS/MATERIALS, SETTING, METHODS: PGT-A was conducted using single nucleotide polymorphism microarrays and next-generation sequencing. Aneuploidy rates in Day 5 blastocysts of each patient were calculated and high-risk aneuploidy was defined as a rate of ≥50%. Candidate risk factors for high-risk aneuploidy were selected using the Akaike information criterion and were subsequently included in multivariable logistic regression models. Overall predictive accuracy was assessed using the confusion matrix, discrimination by area under the receiver operating characteristic curve (AUC), and calibration by plotting the predicted probabilities versus the observed probabilities. Statistical significance was set at P < 0.05. MAIN RESULTS AND THE ROLE OF CHANCE: Blastocyst aneuploidy rates were 30 ± 25% and 21 ± 19% for PAPL and non-PAPL groups, respectively. Maternal age (odds ratio (OR) = 1.31, 95% CI 1.24-1.39, P < 0.001), number of PAPLs (OR = 1.40, 95% CI 1.05-1.86, P = 0.02), estradiol level on the ovulation trigger day (OR = 0.47, 95% CI 0.30-0.73, P < 0.001), and blastocyst formation rate (OR = 0.13, 95% CI 0.03-0.50, P = 0.003) were associated with high-risk of blastocyst aneuploidy. The predictive model based on the above four variables yielded AUCs of 0.80 using the training dataset and 0.83 using the test dataset, with average and maximal discrepancies of 2.89% and 12.76% for the training dataset, and 0.98% and 5.49% for the test dataset, respectively. LIMITATIONS, REASONS FOR CAUTION: Our conclusions might not be compatible with those having fewer than four biopsied blastocysts and diminished ovarian reserves, since all of the included patients had four or more biopsied blastocysts and had exhibited good ovarian reserves. WIDER IMPLICATIONS OF THE FINDINGS: The developed predictive model is critical for counseling PAPL patients before PGT-A by considering maternal age, number of PAPLs, estradiol levels on the ovulation trigger day, and the blastocyst formation rate. This prediction model achieves good risk stratification and so may be useful for identifying PAPL patients who may have higher risk of blastocyst aneuploidy and can therefore acquire better pregnancy outcomes by PGT-A. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China under Grant (81871159). No competing interest existed in the study. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Aborto Espontâneo , Diagnóstico Pré-Implantação , Gravidez , Humanos , Feminino , Diagnóstico Pré-Implantação/métodos , Estudos Retrospectivos , Blastocisto/patologia , Testes Genéticos/métodos , Resultado da Gravidez , Aborto Espontâneo/genética , Aborto Espontâneo/patologia , Aneuploidia , Estradiol
7.
Microvasc Res ; 149: 104554, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37236346

RESUMO

Intracranial aneurysm (IA) is a severe cerebrovascular disease characterized by abnormal bulging of cerebral vessels that may rupture and cause a stroke. The expansion of the aneurysm accompanies by the remodeling of vascular matrix. It is well-known that vascular remodeling is a process of synthesis and degradation of extracellular matrix (ECM), which is highly dependent on the phenotype of vascular smooth muscle cells (VSMCs). The phenotypic switching of VSMC is considered to be bidirectional, including the physiological contractile phenotype and alternative synthetic phenotype in response to injury. There is increasing evidence indicating that VSMCs have the ability to switch to various phenotypes, including pro-inflammatory, macrophagic, osteogenic, foamy and mesenchymal phenotypes. Although the mechanisms of VSMC phenotype switching are still being explored, it is becoming clear that phenotype switching of VSMCs plays an essential role in IA formation, progression, and rupture. This review summarized the various phenotypes and functions of VSMCs associated with IA pathology. The possible influencing factors and potential molecular mechanisms of the VSMC phenotype switching were further discussed. Understanding how phenotype switching of VSMC contributed to the pathogenesis of unruptured IAs can bring new preventative and therapeutic strategies for IA.


Assuntos
Aneurisma Intracraniano , Músculo Liso Vascular , Humanos , Músculo Liso Vascular/metabolismo , Aneurisma Intracraniano/genética , Aneurisma Intracraniano/metabolismo , Aneurisma Intracraniano/patologia , Transdução de Sinais , Miócitos de Músculo Liso/patologia , Fenótipo , Células Cultivadas , Proliferação de Células
8.
Nano Lett ; 22(1): 229-237, 2022 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-34928162

RESUMO

Oxidative stress induced by hyperglycemia or chronic inflammation can limit diabetic wound healing, resulting in diabetic foot ulcers. Hydrogen has the potential to act as an antioxidant and scavenge reactive oxygen species, thereby attenuating inflammation in these chronic wounds. However, most of the reported H2 delivery systems for wound healing, including hydrogen gas, hydrogen-rich water, and hydrogen-rich saline, are very short-lived for the low solubility of hydrogen gas. Here, we introduce a hydrogen-producing hydrogel made of living Chlorella and bacteria within a cell-impermeable casing that can continuously produce hydrogen for 60 h. This microbe-hydrogel system can selectively reduce highly toxic •OH and ONOO- species and reduce inflammation. Additional experiments indicated that the microbe-hydrogel dressing could promote cell proliferation and diabetic wound healing by almost 50% at day 3. The symbiotic algae-bacteria hydrogel has excellent biocompatibility and reactive oxygen species scavenging features, indicating it has great promise for clinical use.


Assuntos
Chlorella , Diabetes Mellitus , Pé Diabético , Bactérias , Bandagens , Pé Diabético/terapia , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Hidrogênio/farmacologia , Hidrogênio/uso terapêutico , Cicatrização
9.
Microb Pathog ; 164: 105443, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35150869

RESUMO

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease caused by PRRS virus (PRRSV), characterized by sow reproductive failure and respiratory symptoms in pigs of all ages. PRRSV mainly causes severe lung damage by invading alveolar macrophages. Visfatin is closely related to acute lung injury, immune response and inflammation along with virus invasion to the host. Therefore, the current study was performed to clarify the relationship between visfatin and PRRSV infection. We used ternary piglets to construct a piglet model to explore the expression of visfatin and tight junction protein in lung injury induced by PRRSV infection, and then further studied the inhibition effect of visfatin on PRRSV replication by PRRSV infection of Marc-145 cells. Our results indicated that both PRRSV attenuated and virulent infections could damage the lung tissues, which could not only lead to severe inflammatory reaction (such as increased expression of TNF-α, TGF-ß, IL-8 and IL-10) in lung tissues of piglets, but also brought about the sharp decrease of ZO-1 and Tricellulin expressions resulting in impaired alveolar epithelial barrier. Meanwhile, we found significantly up-regulated expression of visfatin in lungs and serum of pigs after PRRSV infection that were related to both the degree of lung injury and the virulence of PRRSV strain. Moreover, visfatin might inhibit the PRRSV infection to Marc-145 cells in time dependent fashion. Hence, the current investigation provides the novel information about the effect of visfatin and PRRSV co-culture on Marc-145 cells and the effect of visfatin on PRRSV proliferation at different time points.


Assuntos
Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Animais , Feminino , Pulmão , Macrófagos Alveolares , Nicotinamida Fosforribosiltransferase , Suínos , Replicação Viral
10.
PLoS Comput Biol ; 16(11): e1008342, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33141824

RESUMO

The brain makes flexible and adaptive responses in a complicated and ever-changing environment for an organism's survival. To achieve this, the brain needs to understand the contingencies between its sensory inputs, actions, and rewards. This is analogous to the statistical inference that has been extensively studied in the natural language processing field, where recent developments of recurrent neural networks have found many successes. We wonder whether these neural networks, the gated recurrent unit (GRU) networks in particular, reflect how the brain solves the contingency problem. Therefore, we build a GRU network framework inspired by the statistical learning approach of NLP and test it with four exemplar behavior tasks previously used in empirical studies. The network models are trained to predict future events based on past events, both comprising sensory, action, and reward events. We show the networks can successfully reproduce animal and human behavior. The networks generalize the training, perform Bayesian inference in novel conditions, and adapt their choices when event contingencies vary. Importantly, units in the network encode task variables and exhibit activity patterns that match previous neurophysiology findings. Our results suggest that the neural network approach based on statistical sequence learning may reflect the brain's computational principle underlying flexible and adaptive behaviors and serve as a useful approach to understand the brain.


Assuntos
Tomada de Decisões , Aprendizagem , Redes Neurais de Computação , Animais , Teorema de Bayes , Encéfalo/fisiologia , Biologia Computacional , Simulação por Computador , Humanos , Modelos Neurológicos , Modelos Estatísticos , Processamento de Linguagem Natural , Reforço Psicológico , Recompensa , Análise e Desempenho de Tarefas
11.
Environ Sci Technol ; 55(3): 1395-1418, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33314911

RESUMO

Hydrophobic membranes used in membrane distillation (MD) systems are often subject to wetting during long-term operation. Thus, it is of great importance to fully understand factors that influence the wettability of hydrophobic membranes and their impact on the overall separation efficiency that can be achieved in MD systems. This Critical Review summarizes both fundamental and applied aspects of membrane wetting with particular emphasis on interfacial interaction between the membrane and solutes in the feed solution. First, the theoretical background of surface wetting, including the relationship between wettability and interfacial interaction, definition and measurement of contact angle, surface tension, surface free energy, adhesion force, and liquid entry pressure, is described. Second, the nature of wettability, membrane wetting mechanisms, influence of membrane properties, feed characteristics and operating conditions on membrane wetting, and evolution of membrane wetting are reviewed in the context of an MD process. Third, specific membrane features that increase resistance to wetting (e.g., superhydrophobic, omniphobic, and Janus membranes) are discussed briefly followed by the comparison of various cleaning approaches to restore membrane hydrophobicity. Finally, challenges with the prevention of membrane wetting are summarized, and future work is proposed to improve the use of MD technology in a variety of applications.


Assuntos
Destilação , Purificação da Água , Interações Hidrofóbicas e Hidrofílicas , Membranas Artificiais , Molhabilidade
12.
Opt Express ; 28(24): 36466-36475, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33379739

RESUMO

In this paper, we propose and demonstrate a solution to the problem of coherence degradation and collapse caused by the back reflection of laser power into the laser resonator. The problem is most onerous in semiconductor lasers (SCLs), which are normally coupled to optical fibers, and results in the fact that practically every commercial SCL has appended to it a Faraday-effect isolator that blocks most of the reflected optical power preventing it from entering the laser resonator. The isolator assembly is many times greater in volume and cost than the SCL itself. This problem has resisted a practical and economic solution despite decades of effort and remains the main obstacle to the emergence of a CMOS-compatible photonic integrated circuit technology. A simple solution to the problem is thus of major economic and technological importance. We propose a strategy aimed at weaning semiconductor lasers from their dependence on external isolators. Lasers with large internal Q-factors can tolerate large reflections, limited only by the achievable Q values, without coherence collapse. A laser design is demonstrated on the heterogeneous Si/III-V platform that can withstand 25 dB higher reflected power compared to commercial DFB lasers. Larger values of internal Qs, achievable by employing resonator material of lower losses and improved optical design, should further increase the isolation margin and thus obviate the need for isolators altogether.

13.
Opt Lett ; 45(6): 1499-1502, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32164001

RESUMO

We experimentally demonstrate the use of a high-coherence hybrid silicon (Si)/III-V semiconductor laser as the light source for a transmitter generating 20 Gbaud 16- and 64- quadrature amplitude modulated (QAM) data signals over an 80 km single-mode fiber (SMF) link. The hybrid Si/III-V laser has a measured Schawlow-Townes linewidth of ${\sim}{10}\;{\rm kHz}$∼10kHz, which is achieved by storing modal optical energy in low-loss Si, rather than the relatively lossy III-V materials. We measure a received bit error rate (BER) of ${4.1} \times {{10}^{ - 3}}$4.1×10-3 when transmitting the 64-QAM data over an 80 km SMF using the hybrid Si/III-V laser. Furthermore, we measure a BER of $ {\lt} {1} \times {{10}^{ - 4}}$<1×10-4 with the Viterbi-Viterbi digital carrier phase recovery method when transmitting the 16-QAM data over an 80 km SMF using the hybrid Si/III-V laser. This performance is achieved at power penalties lower than those obtained with an exemplary distributed feedback laser and slightly higher than those with an exemplary narrow-linewidth external cavity laser.

14.
Minim Invasive Ther Allied Technol ; 29(5): 275-282, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31393746

RESUMO

Purpose: To evaluate the advantages and primary technical efficacy of an electromagnetic (EM) navigation system for computed tomography (CT)-guided thermal ablation of liver tumors.Material and methods: From August 2016 to January 2018, 40 patients scheduled for CT- guided thermal ablation were prospectively enrolled and divided into two groups. Twenty patients underwent CT-guided thermal ablation with an EM navigation system (navigation group), while the other 20 patients underwent conventional CT-guided thermal ablation (control group). Data on skin punctures, instrument adjustments, puncture time to target, CT scans, CT fluoroscopy time and dose-length-product (DLP) were compared between the two groups. Any postoperative complications were recorded and the primary technical efficacy was evaluated four to six weeks after the procedure.Results: All 20 patients in the navigation group successfully underwent EM navigation. Compared to the control group, there were fewer instrument adjustments (mean 2.40 vs. 4.95; p = .003), fewer CT scans (mean 7.10 vs. 10.30; p = .006), less CT fluoroscopy time (mean 40.47 vs. 59.98 s, p = .046), and less DLP (mean 807.39 vs. 1578.67 mGy × cm; p = .001). Although not statistically significant, EM navigation resulted in fewer skin punctures (mean 1.20 vs. 1.25; p = .803) and slightly longer puncture time to target (mean 16.50 vs. 15.20 min; p = .725). No patients experienced major complications and the primary efficacy rate was 90% and 84.21% in the navigation and control groups, respectively (p = .661).Conclusions: EM navigation system optimizes the thermal ablation process and reduces radiation exposure in patients. However, further studies are warranted to determine whether an EM navigation system can improve procedure time, complication rates, and primary technical efficiacy of thermal ablation.


Assuntos
Ablação por Cateter , Neoplasias Hepáticas , Exposição à Radiação , Fenômenos Eletromagnéticos , Fluoroscopia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Tomografia Computadorizada por Raios X
15.
PLoS Comput Biol ; 14(1): e1005925, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29300746

RESUMO

Reinforcement learning has been widely used in explaining animal behavior. In reinforcement learning, the agent learns the value of the states in the task, collectively constituting the task state space, and uses the knowledge to choose actions and acquire desired outcomes. It has been proposed that the orbitofrontal cortex (OFC) encodes the task state space during reinforcement learning. However, it is not well understood how the OFC acquires and stores task state information. Here, we propose a neural network model based on reservoir computing. Reservoir networks exhibit heterogeneous and dynamic activity patterns that are suitable to encode task states. The information can be extracted by a linear readout trained with reinforcement learning. We demonstrate how the network acquires and stores task structures. The network exhibits reinforcement learning behavior and its aspects resemble experimental findings of the OFC. Our study provides a theoretical explanation of how the OFC may contribute to reinforcement learning and a new approach to understanding the neural mechanism underlying reinforcement learning.


Assuntos
Tomada de Decisões , Aprendizagem , Rede Nervosa , Redes Neurais de Computação , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia , Reforço Psicológico , Aprendizagem Espacial/fisiologia , Animais , Cognição , Eletrofisiologia , Lobo Frontal , Humanos , Imageamento por Ressonância Magnética , Cadeias de Markov , Modelos Neurológicos , Probabilidade
16.
Urol Int ; 102(3): 348-355, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30844816

RESUMO

BACKGROUND: Renal ischemia-reperfusion injury (IRI) usually causes acute kidney injury. There is an urgent need to develop an effective agent to prevent renal IRI. This study aimed to examine the effect of butyrate on renal IRI in rats. MATERIALS AND METHODS: Rats were randomly assigned into 3 groups (10 rats in each group): the sham group, the IRI group, and the butyrate group. Rats were injected intravenously with 300 mg/kg of sodium butyrate in the butyrate group and with a saline solution in the sham group and IRI group 30 min before renal ischemia. After 24 h of reperfusion, renal function and histologic damage were examined. Myeloperoxidase (MPO) activity assay, in situ apoptosis examination, enzyme-linked immunosorbent assay, immunohistochemical assay, and Western blot were performed as well. RESULTS: Butyrate pretreatment significantly reduced renal dysfunction and histologic damage induced by renal IRI. Butyrate pretreatment caused a significant attenuation of neutrophil infiltration, which was reflected by the reduction of renal MPO activity. Butyrate also reduced apoptotic tubular cell death and improved caspase-3 activation. The expression of TNF-α was decreased following butyrate pretreatment. CONCLUSIONS: Butyrate pretreatment protects rats from renal IRI by inhibiting inflammation and apoptosis. Therefore, butyrate may be a potential therapeutic agent for preventing renal IRI.


Assuntos
Butiratos/farmacologia , Rim/efeitos dos fármacos , Rim/patologia , Traumatismo por Reperfusão/patologia , Injúria Renal Aguda/patologia , Animais , Anti-Inflamatórios/farmacologia , Apoptose , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Inflamação , Masculino , Neutrófilos/citologia , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
17.
Sensors (Basel) ; 19(15)2019 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-31382708

RESUMO

As restricted resources have seriously limited the computational performance of massive Internet of things (IoT) devices, better processing capability is urgently required. As an innovative technology, multi-access edge computing can provide cloudlet capabilities by offloading computation-intensive services from devices to a nearby edge server. This paper proposes an intelligent rapid adaptive offloading (IRAO) algorithm for a dynamic IoT system to increase overall computational performance and simultaneously keep the fairness of multiple participants, which can achieve agile centralized control and solve the joint optimization problems related to offloading policy and resource allocation. For reducing algorithm execution time, we apply machine learning methods and construct an adaptive learning-based framework consisting of offloading decision-making, radio resource slicing and algorithm parameters updating. In particular, the offloading policy can be rapidly derived from an estimation algorithm based on a deep neural network, which uses an experience replay training method to improve model accuracy and adopts an asynchronous sampling trick to enhance training convergence performance. Extensive simulations with different parameters are conducted to maintain the trade-off between accuracy and efficiency of the IRAO algorithm. Compared with other candidates, the results illustrate that the IRAO algorithm can achieve superior performance in terms of scalability, effectiveness and efficiency.

18.
BMC Urol ; 18(1): 44, 2018 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-29776405

RESUMO

BACKGROUND: Adjustable single-incision mini-sling (SIMS) is a new category of SIMS for stress urinary incontinence (SUI). The aim of this study was to compare the efficacy and safety of adjustable single-incision mini-sling with other slings. METHODS: Literature search in databases such as Pubmed, and Conchrane Library was performed up to December, 2015. The outcomes including cure rate, operation time, postoperative pain score and complications were reanalyzed. The pooled relative risk (RR) and mean difference (MD) with their 95% confidence interval (95% CI) were calculated by RevMan v5.0. RESULTS: Eight studies with 1093 SUI female patients were included. There was no significant difference between adjustable SIMS and other slings (transobturator slings and MiniArc) in patients subjective cure rate and objective cure rate. In addition, adjustable SIMS was associated with a significantly shorter operative time and lower postoperative pain score when comparing adjustable SIMS with transobturator tape (MD = - 1.35; 95%CI: -2.24 to - 0.46, P = 0.003). For the complications, there was also no significant difference between adjustable SIMS and transobturator slings. CONCLUSIONS: Adjustable SIMS had equally efficacy for SUI compared with transobturator slings and MiniArc. However, the significantly shorter operative time and lower postoperative pain score than transobturator tape supported the clinical application of adjustable SIMS.


Assuntos
Gerenciamento Clínico , Complicações Pós-Operatórias/epidemiologia , Implantação de Prótese/métodos , Slings Suburetrais/estatística & dados numéricos , Incontinência Urinária por Estresse/epidemiologia , Incontinência Urinária por Estresse/cirurgia , Feminino , Humanos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Resultado do Tratamento , Incontinência Urinária por Estresse/diagnóstico
19.
Tohoku J Exp Med ; 246(2): 87-96, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30333363

RESUMO

MicroRNAs (miRNAs) are small noncoding RNA molecules that participate in normal B cell lineage development through posttranscriptional gene regulation. Antibody-mediated renal allograft rejection (ABMR) is emerging as one of the most common serious threats to renal transplant patients. In this study, we explored the role of miRNAs in the pathogenesis of ABMR. The differentially expressed miRNAs were identified by Affymetrix miRNA microarray analysis using B lymphocytes from 5 recipients and 5 volunteers. Based on quantitative RT-PCR, the expression levels of miR-107 were lower in the B lymphocytes from recipients than in those from volunteers. Computational analysis predicted that 3'-untranslated region of the autophagy-related protein 12 (ATG12) mRNA was targeted by miR-107, and we identified ATG12 as a target of miR-107 by Luciferase assay. Importantly, the expression levels of ATG12 in B lymphocytes of recipients were higher than those in the volunteer group, and miR-107 mimic significantly decreased ATG12 expression and formation of autolysosomes in B lymphocytes of recipients. Furthermore, we observed that levels of autophagy in B lymphocytes of transplant recipients were higher than those in B cells from volunteers. These findings suggest that miR-107 may contribute to the regulation of autophagy via targeting ATG12. Lastly, treatment with an miR-107 mimic caused the decrease in the secretion of IgG and IgM antibodies from B lymphocytes of transplant recipients, indicating that deregulated miR-107 could be involved in the pathogenesis of ABMR. Taken together, we propose that decreased miR-107 expression is associated with autophagy activation in B lymphocytes from patients with ABMR.


Assuntos
Anticorpos/metabolismo , Linfócitos B/metabolismo , Rejeição de Enxerto/genética , Rejeição de Enxerto/imunologia , Transplante de Rim , MicroRNAs/genética , Adulto , Autofagia , Proteína 12 Relacionada à Autofagia/genética , Proteína 12 Relacionada à Autofagia/metabolismo , Linfócitos B/ultraestrutura , Sequência de Bases , Feminino , Perfilação da Expressão Gênica , Células HEK293 , Humanos , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Adulto Jovem
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