RESUMO
The deep learning method faces the challenges of small sample data and high dimensional shield operational parameters in predicting the longitudinal surface settlement caused by shield excavation. In this study, various optimization algorithms were compared, and the slime mould algorithm (SMA) was optimally chosen to optimize the hyperparameters of random forest (RF), and SMA-RF was used for dimensionality reduction and feature contribution analysis. A double-input deep neural network (D-DNN) framework was proposed for the prediction of surface settlement, which considers the influence of twin tunnels and effectively increases the high-fidelity data in the database. The results show that SMA performs best among various optimization algorithms; employing features that have a cumulative contribution value exceeding 90% as input can result in high prediction accuracy; there is significant uncertainty in the feature contribution analysis for small sample data; the reduced shield running parameters show a strong nonlinear relationship with surface settlement; compared with S-DNN, D-DNN takes into account the excavation of twin tunnels and expands the database capacity by more than 1.5 times, with an average increase of 27.85% in the R2 and an average decrease of 53.2% in the MAE.
RESUMO
INTRODUCTION: Women living with HIV (WLWH) are more likely to develop cervical cancer. Screening and available healthcare can effectively reduce its incidence and mortality rates. We aimed to summarize the lifetime prevalence and adherence rate of cervical cancer screening among WLWH across low- and middle-income countries (LMICs), and high-income countries (HICs). METHODS: We systematically searched PubMed, Web of Science and Embase for studies published between database inception and 2 September 2022, without language or geographical restrictions. Those reporting the lifetime prevalence and/or adherence rate of cervical cancer screening among WLWH were included. Pooled estimates across LMICs and HICs were obtained using DerSimonian-Laird random-effects models. When the number of eligible studies was greater than 10, we further conducted stratified analyses by the World Health Organization (WHO) region, setting (rural vs. urban), investigation year, screening method, type of cervical cancer screening programme, age and education level. RESULTS: Among the 63 included articles, 26 provided data on lifetime prevalence, 24 on adherence rate and 13 on both. The pooled lifetime prevalence in LMICs was 30.2% (95% confidence interval [CI]: 21.0-41.3), compared to 92.4% in HICs (95% CI: 89.6-94.6). The pooled adherence rate was 20.1% in LMICs (95% CI: 16.4-24.3) and 59.5% in HICs (95% CI: 51.2-67.2). DISCUSSION: There was a large gap in cervical cancer screening among WLWH between LMICs and HICs. Further analysis found that those in LMICs had higher lifetime prevalence in subgroups with urban settings, with older age and with higher education levels; and those in HICs had higher adherence in subgroups with younger age and with higher education levels. CONCLUSIONS: Cervical cancer screening among WLWH falls considerably short of the WHO's goal. There should be continuous efforts to further increase screening among these women, especially those residing in the rural areas of LMICs and with lower education levels.
Assuntos
Detecção Precoce de Câncer , Infecções por HIV , Neoplasias do Colo do Útero , Humanos , Feminino , Infecções por HIV/complicações , Infecções por HIV/patologia , Países em Desenvolvimento , Detecção Precoce de Câncer/métodos , Neoplasias do Colo do Útero/diagnóstico , Países Desenvolvidos , Cooperação e Adesão ao Tratamento , Escolaridade , População Rural , Teste de PapanicolaouRESUMO
Osteocytes are the terminally differentiated bone cells resulted from bone formation. Although there are two distinct processes of bone formation, intramembranous and endochondral ossifications contributing to the formation of calvarial and long bones, it is not clear whether the distinct pathways determine the differences between calvaria and femoral cortical bone derived osteocytes. In the present study, we employed confocal structured illumination microscopy and mRNA-sequencing analysis to characterize the morphologic and transcriptomic expression of osteocytes from murine calvaria and mid-shaft femoral cortical bone. Structured illumination microscopy and geometric modelling showed round shaped and irregularly scattered calvarial osteocytes compared to spindle shaped and orderly arrayed cortical osteocytes. mRNA-sequencing analysis indicated different transcriptomic profiles between calvarial and cortical osteocytes and provided evidence that mechanical response of osteocytes may contribute to geometrical differences. Furthermore, transcriptomic analysis showed that these two groups of osteocytes come from distinct pathways with 121 ossification-related genes differentially expressed. Analysis of correlation between ossification and osteocyte geometries via a Venn diagram showed that several genes related to ossification, cytoskeleton organization and dendrite development were differentially expressed between calvarial and cortical osteocytes. Finally, we demonstrated that aging disrupted the organization of dendrites and cortical osteocytes but had no significant effects on calvarial osteocytes. Together, we conclude that calvarial and cortical osteocytes are different in various aspects, which is probably the consequence of their distinct pathways of ossification.
Assuntos
Osteócitos , Crânio , Animais , Camundongos , Osteócitos/metabolismo , Expressão Gênica , RNA Mensageiro/metabolismo , Envelhecimento/genéticaRESUMO
Evidence regarding associations of general and abdominal obesity with the risk of conventional adenomas (ADs) and serrated polyps (SPs) from Asian population is scarce. Our study aimed to investigate the independent and joint associations of general obesity assessed by body mass index (BMI) and abdominal obesity assessed by waist circumference (WC) or waist-to-hip ratio (WHR) with the risk of ADs and SPs among 25 222 participants recruited by a population-based screening program. Compared to participants with normal BMI, those with a BMI ≥28 kg/m2 had increased risk of ADs (odds ratio [OR] 1.52, 95% confidence interval [CI]: 1.36-1.70) and SPs (OR 1.69, 95% CI: 1.38-2.07). For participants with a WC ≥102 cm (≥88 cm for females), the risk of ADs (OR 1.37, 95% CI: 1.25-1.51) and SPs (OR 1.81, 95% CI: 1.52-2.16) was higher than that of the reference group. For participants with a WHR ≥0.95 (≥0.90 for females), the risk of ADs (OR 1.26, 95% CI: 1.16-1.36) and SPs (OR 1.46, 95% CI: 1.26-1.69) was higher than that of the reference group. Moreover, participants with both BMI ≥28 kg/m2 and WC ≥102 cm (≥88 cm for females) had 61% and 119% higher risk of ADs (OR 1.61, 95% CI: 1.39-1.85) and SPs (OR 2.19, 95% CI: 1.70-2.82) compared to those with both normal BMI and WC. These findings indicate that both general and abdominal obesity are associated with SPs and ADs, presenting stronger association with SPs than ADs. Moreover, the association is more evident when both obesities exist.
Assuntos
Adenoma , Obesidade Abdominal , Feminino , Humanos , Obesidade Abdominal/complicações , Obesidade Abdominal/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Relação Cintura-Quadril , Circunferência da Cintura , Índice de Massa Corporal , Ásia Oriental , Adenoma/epidemiologia , Adenoma/etiologia , Fatores de RiscoRESUMO
BACKGROUND: circRNA hsa_circ_0018289-mediated growth and metastasis of CC cells were investigated, as well as the mechanistic pathway. METHODS: Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was carried out to examine the expression of hsa_circ_0018289, microRNA (miR)-1294, and isoprenylcysteine carboxyl methyltransferase (ICMT). CC cell proliferation, migration, and invasion were evaluated by 5-ethynyl-2'-deoxyuridine (EdU) incorporation, colony formation, transwell assays, Western blot analysis of ICMT, and glycolysis-associated proteins. Dual-luciferase reporter or RNA pull-down analysis of the target interaction between miR-1294 and hsa_hsa_circ_0018289 or ICMT. Xenograft model assay was implemented to assess the role of hsa_circ_0018289 in vivo. Immunofluorescence (IHC) was employed to detect the level of Ki-67. RESULTS: Hsa_circ_0018289 was elevated in CC tissues and cells, its deficiency could repress growth, metastasis, and glycolysis of CC cells in vitro, as well as hamper tumor growth in vivo. Hsa_circ_0018289 sponged miR-1294 while miR-1294 bound with ICMT, and the inhibition of miR-1294 or addition of ICMT could partially relieve the effect caused by hsa_circ_0018289 depletion. CONCLUSION: Hsa_circ_0018289 contributes to malignant development by regulating the miR-1294/ICMT axis, affording novel insight into CC therapy.
Assuntos
MicroRNAs , Proteínas Metiltransferases , RNA Circular , Neoplasias do Colo do Útero , Carcinogênese , Proliferação de Células/genética , Feminino , Humanos , MicroRNAs/genética , Proteínas Metiltransferases/genética , RNA Circular/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologiaRESUMO
Latent Epstein-Barr virus (EBV) is reactivated by 12-O-tetradecanoylphorbol-13-acetate (TPA) in EBV-infected cells. In this study, we found that TPA up-regulated phosphorylation of p38, a mitogen-activated protein kinase, and activated c-myc mRNA in EBV-positive epithelial GT38 cells. The EBV immediate-early gene BZLF1 mRNA and its product ZEBRA protein were induced following TPA treatment. Protein kinase C inhibitors, 1-(5-isoquinolinesulphonyl)-2, 5-dimethylpiperazine (H7) and staurosporine, inhibited the induction of p38 phosphorylation and the activation of c-Myc by TPA. The p38 inhibitor SB203580 blocked both p38 phosphorylation and ZEBRA expression by TPA. Pretreatment of GT38 cells with the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine inhibited p38 phosphorylation and c-Myc activation by TPA, suggesting that NO may inhibit EBV reactivation via both p38 and c-Myc. By using short interfering RNA (siRNA) targeting either p38 or c-myc, we found that p38 or c-myc siRNA specifically inhibited expression of the respective gene and also suppressed the induction of ZEBRA and EBV early antigen. The interferon (IFN)-responsive gene expression tests ruled out the possibility that the antiviral effect of siRNA is dependent on IFN. Our present study demonstrates for the first time that either p38 or c-myc siRNA can efficiently inhibit TPA-induced EBV reactivation in GT38 cells, indicating that p38- and/or c-myc-associated signaling pathways may play critical roles in the disruption of EBV latency by TPA.
Assuntos
Herpesvirus Humano 4/fisiologia , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Penicilamina/análogos & derivados , Proteínas Proto-Oncogênicas c-myc/antagonistas & inibidores , Interferência de RNA , Ativação Viral , Linhagem Celular , Humanos , Proteínas Imediatamente Precoces/genética , Proteínas Quinases Ativadas por Mitógeno/genética , Penicilamina/farmacologia , Fosforilação , Proteína Quinase C/antagonistas & inibidores , Acetato de Tetradecanoilforbol/farmacologia , Transativadores/genética , Proteínas Virais , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
M5 muscarinic receptors are coexpressed with D2 dopamine receptors in the ventral tegmentum and striatum, and are important for reward in rodents. Previously, we reported that disruption of the M5 receptor gene in mice reduced dopamine release in the nucleus accumbens. In this study, we established a polymerase chain reaction (PCR) genotyping method for M5 mutant mice, and, using RT-PCR, found that M5 mRNA expression was highest in the ventral tegmentum, striatum, and thalamus in wild-type mice. In the M5 mutant mice, D2 mRNA expression was increased in several brain structures, including the striatum. Genome mapping studies showed the M5 gene is localized to chromosome 2E4 in mice, and to 15q13 in humans in the region that has been linked to schizophrenia. Amphetamine-induced locomotion, but not baseline locomotion or motor functions, decreased in M5 mutant mice, consistent with lower accumbal dopamine release. Previous reports found latent inhibition improvement in rats following nucleus accumbens lesions, or blockade of dopamine D2 receptors with neuroleptic drugs. Here, latent inhibition was significantly increased in M5 mutant mice as compared with controls, consistent with reduced dopamine function in the nucleus accumbens. In summary, our results showed that M5 gene disruption in mice decreased amphetamine-induced locomotion and increased latent inhibition, suggesting that increased M5 mesolimbic function may be relevant to schizophrenia.
Assuntos
Anfetamina/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Cromossomos Humanos Par 15 , Inibição Psicológica , Locomoção/efeitos dos fármacos , Receptor Muscarínico M5/genética , Estimulação Acústica/métodos , Animais , Comportamento Animal , Southern Blotting/métodos , Encéfalo/anatomia & histologia , Encéfalo/metabolismo , Mapeamento Cromossômico/métodos , Relação Dose-Resposta a Droga , Genótipo , Humanos , Camundongos , Camundongos Mutantes , Medição da Dor/efeitos dos fármacos , Desempenho Psicomotor/efeitos dos fármacos , RNA Mensageiro/biossíntese , Receptor Muscarínico M5/metabolismo , Receptor Muscarínico M5/fisiologia , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/imunologia , Reflexo de Sobressalto/efeitos dos fármacos , Reflexo de Sobressalto/efeitos da radiação , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Fatores de TempoRESUMO
The central feature of drug addiction is compulsive drug use--loss of control over apparently voluntary acts of drug seeking and drug taking. Drug addiction, as a chronic brain disease, may result from abnormal engagement of long-term associative memory. Addiction and memory are likely to share much in common in the aspects of neural adaptations, synaptic plasticity, and related molecular mechanisms. This paper reviews the possible roles of learning mechanisms in the development of relapse, sensitization, and drug addiction, abnormal associative learning and compulsive behavior, addiction memory and addiction, multiple memory systems and the development of addiction, and emphasize the importance of synaptic plasticity and addiction memory in drug addiction. Addiction is characterized by the involvement of specific learning patterns of information. Addiction is closely related to the disorder of associate learning that depends on dopamine. Hippocampus may play a key role in addiction. At last, we put forward the future directions for research.
Assuntos
Comportamento Aditivo , Memória/fisiologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adaptação Fisiológica , Animais , Comportamento Compulsivo , Dopamina/metabolismo , Hipocampo/fisiopatologia , Humanos , Aprendizagem/fisiologia , Plasticidade Neuronal , Reforço Psicológico , Transtornos Relacionados ao Uso de Substâncias/fisiopatologiaRESUMO
DNA chips and proteomics are two of the recently developed high-throughput technologies that allow us to simultaneously analyze the expression levels of multiple genes and the interactions of their products in the brain. Their applications in neuroscience provide us with the unprecedented opportunities for understanding of the brain. A typical gene chip experiment contains a series of steps, including preparations (or purchase) of DNA chips, target DNA and probes, hybridization of chips with target DNA, chip scanning, and imaging analysis. The technologies in proteomics are more complicated, which comprise of three main aspects of technologies: protein isolation, identification and bioinformatic analysis of data. If protein isolation is based on 2-D, it includes the preparation of protein sample, 2-D, staining gels, spot excision, proteolysis, mass spectrometry of purified protein and finally undergoing bioinformatic analysis. Here we review the two technologies with emphasis on their applications in neurosciences. The challenges, advantages and disadvantages of the two techniques, and perspectives for their developments are discussed.