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Our nervous system contains billions of neurons that form precise connections with each other through interactions between cell surface proteins. In Drosophila, the Dpr and DIP immunoglobulin protein subfamilies form homophilic or heterophilic interactions to instruct synaptic connectivity, synaptic growth, and cell survival. However, the upstream regulatory mechanisms of Dprs and DIPs are not clear. On the other hand, while transcription factors have been implicated in target recognition, their downstream cell surface proteins remain mostly unknown. We conduct an F1 dominant modifier genetic screen to identify regulators of Dprs and DIPs. We identify huckebein (hkb), a transcription factor previously implicated in target recognition of the dorsal Is motor neuron. We show that hkb genetically interacts with DIP-α and loss of hkb leads to complete removal of DIP-α expression specifically in dorsal Is motor neurons. We then confirm that this specificity is through the dorsal Is motor neuron specific transcription factor, even-skipped (eve), which acts downstream of hkb. Analysis of the genetic interaction between hkb and eve reveals that they act in the same pathway to regulate dorsal Is motor neuron connectivity. Our study provides insight into the transcriptional regulation of DIP-α and suggests that distinct regulatory mechanisms exist for the same CSP in different neurons.
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Proteínas de Drosophila , Fatores de Transcrição , Animais , Drosophila/genética , Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Neurônios Motores/metabolismo , Junção Neuromuscular/metabolismo , Junção Neuromuscular/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genéticaRESUMO
Conjugated polymers (CPs) with low crystallinity are promising candidates for application in organic thermoelectrics (OTEs), particularly in flexible devices, because the disordered structures of these CPs can effectively accommodate dopants and ensure robust resistance to bending. However, n-doped CPs usually exhibit poor thermoelectric performance, which hinders the development of high-performance thermoelectric generators. Herein, we report an n-type CP (ThDPP-CNBTz) comprising two acceptor units: a thiophene-flanked diketopyrrolopyrrole and a cyano-functionalized benzothiadiazole. ThDPP-CNBTz shows a low LUMO energy level of below -4.20â eV and features low crystallinity, enabling high doping efficiency. Moreover, the dual-acceptor design enhances polaron delocalization, resulting in good thermoelectric performance. After n-doping, ThDPP-CNBTz exhibits an average electrical conductivity (σ) of 50.6â S cm-1 and a maximum power factor (PF) of 126.8â µW m-1 K-2, which is among the highest values reported for solution-processed n-type CPs to date. Additionally, a solution-processed flexible OTE device based on doped ThDPP-CNBTz exhibits a maximum PF of 70â µW m-1 K-2; the flexible device also shows remarkable resistance to bending strain, with only a marginal change in σ after 600 bending cycles. The findings presented in this work will advance the development of n-type CPs for OTE devices, and flexible devices in particular.
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BACKGROUND: Severe peripheral nerve injury (PNI) often leads to significant movement disorders and intractable pain. Therefore, promoting nerve regeneration while avoiding neuropathic pain is crucial for the clinical treatment of PNI patients. However, established animal models for peripheral neuropathy fail to accurately recapitulate the clinical features of PNI. Additionally, researchers usually investigate neuropathic pain and axonal regeneration separately, leaving the intrinsic relationship between the development of neuropathic pain and nerve regeneration after PNI unclear. To explore the underlying connections between pain and regeneration after PNI and provide potential molecular targets, we performed single-cell RNA sequencing and functional verification in an established rat model, allowing simultaneous study of the neuropathic pain and axonal regeneration after PNI. RESULTS: First, a novel rat model named spared nerve crush (SNC) was created. In this model, two branches of the sciatic nerve were crushed, but the epineurium remained unsevered. This model successfully recapitulated both neuropathic pain and axonal regeneration after PNI, allowing for the study of the intrinsic link between these two crucial biological processes. Dorsal root ganglions (DRGs) from SNC and naïve rats at various time points after SNC were collected for single-cell RNA sequencing (scRNA-seq). After matching all scRNA-seq data to the 7 known DRG types, we discovered that the PEP1 and PEP3 DRG neuron subtypes increased in crushed and uncrushed DRG separately after SNC. Using experimental design scRNA-seq processing (EDSSP), we identified Adcyap1 as a potential gene contributing to both pain and nerve regeneration. Indeed, repeated intrathecal administration of PACAP38 mitigated pain and facilitated axonal regeneration, while Adcyap1 siRNA or PACAP6-38, an antagonist of PAC1R (a receptor of PACAP38) led to both mechanical hyperalgesia and delayed DRG axon regeneration in SNC rats. Moreover, these effects can be reversed by repeated intrathecal administration of PACAP38 in the acute phase but not the late phase after PNI, resulting in alleviated pain and promoted axonal regeneration. CONCLUSIONS: Our study reveals that Adcyap1 is an intrinsic protective factor linking neuropathic pain and axonal regeneration following PNI. This finding provides new potential targets and strategies for early therapeutic intervention of PNI.
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Axônios , Neuralgia , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Animais , Ratos , Axônios/fisiologia , Gânglios Espinais/fisiologia , Regeneração Nervosa/genética , Neuralgia/genética , Neurônios , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , Fatores de Proteção , Ratos Sprague-Dawley , Análise de Sequência de RNARESUMO
The layer bonding performance of hydraulic engineered cementitious composites (HECCs) plays an important role in their application in hydraulic buildings. This performance encompasses the bonding between layers of HECCs, as well as between HECCs and normal mortar (NM) layers. The influence of various factors on the layer bonding performance of HECCs was investigated. These factors included different pouring intervals (0 min, 20 min, 40 min, 60 min, 2.5 h, 7 days, 14 days, and 28 days), pouring directions (horizontal and vertical), degree of saturation (100%, 70%, 50%, 30%, and 0%), and surface roughness (varying sand-pour roughness). It was found that longer pouring interval times led to a decrease in the layer bonding performance, and the strength of the layer bonding fell below 50% compared to concrete without layers, with the lowest recorded strength being only 1.12 MPa. The layer's horizontal flexural strength surpassed the vertical flexural strength, but the horizontal compressive strength fell below the vertical compressive strength. Additionally, the bonding performance of the substrate at 0% saturation was 15-20% lower compared to other saturation levels. Notably, roughness significantly enhanced the performance of HECC layers, with improvements reaching a maximum of 180-200%. Furthermore, the layer performance of HECCs and NM experienced an improvement of 20.5-37.5%.
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Our nervous system contains billions of neurons that form precise connections with each other through interactions between cell surface proteins (CSPs). In Drosophila, the Dpr and DIP immunoglobulin protein subfamilies form homophilic or heterophilic interactions to instruct synaptic connectivity, synaptic growth and cell survival. However, the upstream regulation and downstream signaling mechanisms of Dprs and DIPs are not clear. In the Drosophila larval neuromuscular system, DIP-α is expressed in the dorsal and ventral type-Is motor neurons (MNs). We conducted an F1 dominant modifier genetic screen to identify regulators of Dprs and DIPs. We found that the transcription factor, huckebein (hkb), genetically interacts with DIP-α and is important for target recognition specifically in the dorsal Is MN, but not the ventral Is MN. Loss of hkb led to complete removal of DIP-α expression. We then confirmed that this specificity is through the dorsal Is MN specific transcription factor, even-skipped (eve), which acts downstream of hkb. Genetic interaction between hkb and eve revealed that they act in the same pathway to regulate dorsal Is MN connectivity. Our study provides insight into the transcriptional regulation of DIP-α and suggests that distinct regulatory mechanisms exist for the same CSP in different neurons.
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Neuronal cell death and subsequent brain dysfunction are hallmarks of aging and neurodegeneration, but how the nearby healthy neurons (bystanders) respond to the death of their neighbors is not fully understood. In the Drosophila larval neuromuscular system, bystander motor neurons can structurally and functionally compensate for the loss of their neighbors by increasing their terminal bouton number and activity. We term this compensation as cross-neuron plasticity, and in this study, we demonstrate that the Drosophila engulfment receptor, Draper, and the associated kinase, Shark, are required for cross-neuron plasticity. Overexpression of the Draper-I isoform boosts cross-neuron plasticity, implying that the strength of plasticity correlates with Draper signaling. In addition, we find that functional cross-neuron plasticity can be induced at different developmental stages. Our work uncovers a role for Draper signaling in cross-neuron plasticity and provides insights into how healthy bystander neurons respond to the loss of their neighboring neurons.
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Drosophila , Neuroglia , Animais , Neurônios Motores , Morte Celular , Neurônios EferentesRESUMO
Chemical reduction in oxides plays a crucial role in engineering the material properties through structural transformation and electron filling. Controlling the reduction at nanoscale forms a promising pathway to harvest functionalities, which however is of great challenge for conventional methods (e.g., thermal treatment and chemical reaction). Here, we demonstrate a convenient pathway to achieve nanoscale chemical reduction for vanadium dioxide through the electron-beam illumination. The electron beam induces both surface oxygen desorption through radiolytic process and positively charged background through secondary electrons, which contribute cooperatively to facilitate the vacancy migration from the surface toward the sample bulk. Consequently, the VO2 transforms into a reduced V2O3 phase, which is associated with a distinct insulator to metal transition at room temperature. Furthermore, this process shows an interesting facet-dependence with the pronounced transformation observed for the c-facet VO2 as compared with the a-facet, which is attributed to the intrinsically different oxygen vacancy formation energy between these facets. Remarkably, we readily achieve a lateral resolution of tens nanometer for the controlled structural transformation with a commercial scanning electron microscope. This work provides a feasible strategy to manipulate the nanoscale chemical reduction in complex oxides for exploiting functionalities.
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Elétrons , Iluminação , Engenharia , Óxidos , OxigênioRESUMO
Neuronal cell death and subsequent brain dysfunction are hallmarks of aging and neurodegeneration, but how the nearby healthy neurons (bystanders) respond to the cell death of their neighbors is not fully understood. In the Drosophila larval neuromuscular system, bystander motor neurons can structurally and functionally compensate for the loss of their neighbors by increasing their axon terminal size and activity. We termed this compensation as cross-neuron plasticity, and in this study, we demonstrated that the Drosophila engulfment receptor, Draper, and the associated kinase, Shark, are required in glial cells. Surprisingly, overexpression of the Draper-I isoform boosts cross-neuron plasticity, implying that the strength of plasticity correlates with Draper signaling. Synaptic plasticity normally declines as animals age, but in our system, functional cross-neuron plasticity can be induced at different time points, whereas structural cross-neuron plasticity can only be induced at early stages. Our work uncovers a novel role for glial Draper signaling in cross-neuron plasticity that may enhance nervous system function during neurodegeneration and provides insights into how healthy bystander neurons respond to the loss of their neighboring neurons.
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With the exponentially rapid development of solar-driven interfacial evaporation, evaporators with both high evaporation efficiency and recyclability are highly desirable to alleviate resource waste and environmental problems but remain challenging. Here, a monolithic evaporator was developed based on a dynamic disulfide vitrimer (a covalently cross-linked polymer network with associative exchangeable covalent bonds). Two types of solar absorbers, carbon nanotubes and oligoanilines, were simultaneously introduced to enhance the optical absorption. A high evaporation efficiency of 89.2% was achieved at 1 sun (1 kW m-2). When the evaporator was applied to solar desalination, it shows self-cleaning performance with long-term stability. Drinkable water with low ion concentrations satisfying the drinkable water levels of the World Health Organization and a high output (8.66 kg m-2, 8 h per day) was obtained, revealing great potential for practical seawater desalination. Moreover, a high-performance film material was obtained from the used evaporator via simple hot-pressing, indicating excellent fully closed-loop recyclability of the evaporator. This work provides a promising platform for high-efficiency and recyclable solar-driven interfacial evaporators.
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Electroacupuncture may play a role in treatment of learning and memory impairment after ischemic stroke by regulating phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA)/cAMP response element binding protein (CREB) signaling pathway, nerve growth factor (NGF)/tyrosine kinase-A (TrkA) signaling pathway, Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway, Notch signaling pathway, erythropoietin-producing hepatocyte (Eph)/ephrin signaling pathway. The interactions among these pathways should be further explored in treatment of learning and memory impairment after ischemic stroke.
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Eletroacupuntura , AVC Isquêmico , Humanos , Aprendizagem , Transdução de Sinais/fisiologiaRESUMO
OBJECTIVE: This study aimed to determine the incidence and clinicopathological patterns of metastatic carcinoma of the parotid gland. METHOD: Ninety patients with parotid gland metastases admitted to our hospital between January 2003 and December 2018 were included in this study. Clinical and pathological data were obtained from the medical records and follow-ups. Kaplan-Meier analysis was used to assess overall survival of patients. RESULTS: Among the 90 patients, parotid gland metastases originated from the head and neck in 86 (95.6%), from non-head and neck in 4 (4.4%), from the oral cavity in 30(33.3%), and from the eyelid in 21 (23.3%). Among the 85 cases with parotid gland lymph node metastasis, 45 (52.9%) were diagnosed with extra-lymph node metastasis. The capsule of the parotid lymph nodes was thinner than that of the cervical lymph nodes (P < 0.05). Hematogenous metastases to the parotid gland (only five cases) were rare, mainly from the non-head and neck malignancies. Patients with oral squamous cell carcinoma and meibomian adenocarcinoma with parotid metastatic disease had poorer overall survival (P < 0.05). CONCLUSION: Eastern China population analysis showed that parotid gland metastases usually arise from oral squamous cell carcinoma and eyelid, but rarely from cutaneous squamous cell carcinoma. Most cases metastasize to the parotid lymph nodes via the lymphatic system and are prone to extranodal extension with little or no facial nerve involvement. These findings have important implications for the treatment of metastatic parotid malignancies.
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Neoplasias Bucais , Neoplasias Parotídeas , Neoplasias Cutâneas , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , População do Leste Asiático , Metástase Linfática , Neoplasias Bucais/patologia , Glândula Parótida/patologia , Neoplasias Parotídeas/epidemiologia , Neoplasias Parotídeas/secundário , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
The paths axons travel to reach their targets and the subsequent synaptic connections they form are highly stereotyped. How cell surface proteins (CSPs) mediate these processes is not completely understood. The Drosophila neuromuscular junction (NMJ) is an ideal system to study how pathfinding and target specificity are accomplished, as the axon trajectories and innervation patterns are known and easily visualized. Dpr10 is a CSP required for synaptic partner choice in the neuromuscular and visual circuits and for axon pathfinding in olfactory neuron organization. In this study, we show that Dpr10 is also required for motor axon pathfinding. To uncover how Dpr10 mediates this process, we used immunoprecipitation followed by mass spectrometry to identify Dpr10 associated proteins. One of these, Nocte, is an unstructured, intracellular protein implicated in circadian rhythm entrainment. We mapped nocte expression in larvae and found it widely expressed in neurons, muscles, and glia. Cell-specific knockdown suggests nocte is required presynaptically to mediate motor axon pathfinding. Additionally, we found that nocte and dpr10 genetically interact to control NMJ assembly, suggesting that they function in the same molecular pathway. Overall, these data reveal novel roles for Dpr10 and its newly identified interactor, Nocte, in motor axon pathfinding and provide insight into how CSPs regulate circuit assembly.
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Proteínas de Drosophila , Drosophila , Animais , Orientação de Axônios , Neurônios Motores/fisiologia , Axônios/fisiologia , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismoRESUMO
Ultrathin organic solar cells (OSCs) with both high power conversion efficiency (PCE) and operational stability are of great significance for the industrial applications but still challenging. Here, a polyimide (PI) substrate for high-performance and stable ultrathin OSCs, which is physically crosslinked via strong hydrogen bonds (denoted as HB-PI) to enhance the mechanical, thermal, solvent-resistant, and UV filtering properties (with a cut-off wavelength of 376 nm), is synthesized. An ultrathin flexible transparent composite electrode (FTCE, ≈7 µm) is fabricated via semi-embedding AgNWs in the HB-PI substrate. The FTCE possesses excellent optoelectronic property, smooth surface, and high mechanical stability simultaneously. Based on this FTCE, an ultrathin OSC is constructed with a PCE of 13.52% (average of 13.22%). Moreover, the ultrathin OSC shows outstanding mechanical stability (PCE decreased by less than 4% after 1000 bending cycles at a small bending radius of 0.5 mm) and superior UV light stability (no evident PCE degradation after irradiation under UV light for 10 h). This work will provide a new avenue for fabricating high-performance and stable ultrathin OSCs.
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BACKGROUND: This study aimed to investigate the potential role of nidogen 1 (NID1), a basement membrane component, in the growth and metastasis of salivary gland adenoid cystic carcinoma (SACC) and the underlying molecular mechanism. METHODS: High-throughput next-generation sequencing was used to compare the gene expression profiles of SACC with and without lung metastasis. Luciferase gene reporter assays were used to measure the NID1 promoter activity. BALB/c nude mice were used to establish a lung metastasis model of SACC to evaluate the prometastatic activity of NID1. ChIP and dual-luciferase reporter assays were performed to confirm the HIF-1α-binding site in the NID1 promoter. RESULTS: NID1 expression in SACC was significantly increased and associated with lung metastasis (P = 0.011). The elevated NID1 expression was a predictor of poor outcomes in patients with SACC (P < 0.05). Overexpression of NID1 promoted cancer cell migration and invasion through PI3K/AKT pathway activation and subsequent epithelial-mesenchymal transition (EMT), as indicated by the upregulation of N-cadherin and vimentin. Furthermore, in vivo live monitoring of a mouse model of lung cancer demonstrated the pro-metastatic role of NID1 in SACC cell lung metastasis. Hypoxia-inducible factor 1α (HIF-1α) upregulation via transfection of an HIF-1α-overexpressing plasmid enhanced HIF-1α binding to the NID1 promoter and the subsequent transcriptional activity and expression of NID1. CONCLUSION: HIF-1α-activated NID1 overexpression promotes SACC cell metastasis via PI3K/AKT pathway activation and EMT. Thus, NID1 could be a novel biomarker and therapeutic target for preventing metastasis and treating patients with SACC in future.
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Carcinoma Adenoide Cístico , Neoplasias Pulmonares , Neoplasias das Glândulas Salivares , Animais , Carcinoma Adenoide Cístico/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Transição Epitelial-Mesenquimal/fisiologia , Regulação Neoplásica da Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia/farmacologia , Neoplasias Pulmonares/secundário , Glicoproteínas de Membrana , Camundongos , Camundongos Nus , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/metabolismo , Transdução de SinaisRESUMO
In complex nervous systems, neurons must identify their correct partners to form synaptic connections. The prevailing model to ensure correct recognition posits that cell-surface proteins (CSPs) in individual neurons act as identification tags. Thus, knowing what cells express which CSPs would provide insights into neural development, synaptic connectivity, and nervous system evolution. Here, we investigated expression of Dpr and DIP genes, two CSP subfamilies belonging to the immunoglobulin superfamily, in Drosophila larval motor neurons (MNs), muscles, glia and sensory neurons (SNs) using a collection of GAL4 driver lines. We found that Dpr genes are more broadly expressed than DIP genes in MNs and SNs, and each examined neuron expresses a unique combination of Dpr and DIP genes. Interestingly, many Dpr and DIP genes are not robustly expressed, but are found instead in gradient and temporal expression patterns. In addition, the unique expression patterns of Dpr and DIP genes revealed three uncharacterized MNs. This study sets the stage for exploring the functions of Dpr and DIP genes in Drosophila MNs and SNs and provides genetic access to subsets of neurons.
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Proteínas de Drosophila , Drosophila , Animais , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Larva/genética , Larva/metabolismo , Proteínas de Membrana/metabolismo , Células Receptoras Sensoriais/metabolismo , Sinapses/metabolismoRESUMO
The optimization of mix proportions based on the targeted fresh and hardened performances of self-compacting concrete (SCC) is a foundation for its transition from laboratory research to industrial production. In this paper, the mix proportions of various SCC mixtures were designed by the absolute volume method with changes in the content of river sand and manufactured sand, the content of fly ash and granulated ground blast furnace slag (GGBS) and the maximum particle sizes of coarse aggregates. This experimental study was carried out to verify the workability, density and cubic compressive strength of SCC. The results show that SCC demonstrated good performance with appropriate mix proportions of manufactured sand and river sand. A hybrid effect of fly ash and GGBS appeared on the fresh performance of SCC with a constant strength, and the coarse aggregate with a smaller maximum particle size was beneficial to the workability but detrimental to the compressive strength of SCC. Finally, the optimization of the mix proportion of SCC was evaluated by grey relational analysis, in which the weight of the indicators was determined by the entropy method to improve the evaluation credibility. As a result, the optimal mix proportions of SCC were selected.
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Epigenetic modifications are involved in the onset, development, and maintenance of pain; however, the precise epigenetic mechanism underlying pain regulation remains elusive. Here it is reported that the epigenetic factor chromodomain Y-like (CDYL) is crucial for pain processing. Selective knockout of CDYL in sensory neurons results in decreased neuronal excitability and nociception. Moreover, CDYL facilitates histone 3 lysine 27 trimethylation (H3K27me3) deposition at the Kcnb1 intron region thus silencing voltage-gated potassium channel (Kv ) subfamily member Kv 2.1 transcription. Loss function of CDYL enhances total Kv and Kv 2.1 current density in dorsal root ganglia and knockdown of Kv 2.1 reverses the pain-related phenotypes of Cdyl deficiency mice. Furthermore, focal administration of a novel potent CDYL antagonist blunts nociception and attenuates neuropathic pain. These findings reveal that CDYL is a critical regulator of pain sensation and shed light on the development of novel analgesics targeting epigenetic mechanisms.
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Proteínas Correpressoras , Hidroliases , Nociceptividade , Canais de Potássio Shab , Animais , Proteínas Correpressoras/genética , Proteínas Correpressoras/metabolismo , Histonas/genética , Hidroliases/genética , Hidroliases/metabolismo , Camundongos , Células Receptoras Sensoriais/metabolismo , Canais de Potássio Shab/genéticaRESUMO
The stress of a coal seam increases with an increase in the mining depth, which makes the failure mechanism of a coal mass more complex. To reveal the deformation and failure law of deep coal, a series of triaxial experiments was carried out via laboratory experiments and numerical simulation experiments to analyze the influence of the confining stress on the nonlinear failure characteristics of coal. Based on the crack-propagation model, the values for the inelastic flexibility S1 and the damage variable D were calculated. The results showed that the value of S1 decreased with an increase in the confining stress, which indicated that the increase in the confining pressure could inhibit the crack propagation and that the inhibitory effect was more obvious when the confining pressure increased in a small range of 4 to 12 MPa. The damage variable decreased with an increase in the confining pressure at the yield point; moreover, with an increase in the initial confining pressure, the damage rate gradually decreased. The coal body changed from the compression state to the expansion state when moving from the yield point to the peak point, and the compression value of the yield point and the dilation value of the peak point increased with the increase in the confining pressure. After the coal body entered the yield stage, the change in the confining pressure had a more significant effect on the damage to the coal body.
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Carvão Mineral , Mineração , Pressão , LaboratóriosRESUMO
OBJECTIVES: To study and analyze the clinical patterns of lower-level lymph node (â £ and â ¤) metastasis in primary tongue squamous cell carcinoma, and establish a reference for the decision-making of the lower-level neck dissection in tongue squamous cell carcinoma. METHODS: A total of 203 patients with primary tongue squamous cell carcinoma were recruited. These patients underwent simultaneous/secondary comprehensive neck (level â -â ¤) dissection in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2010 to December 2015. Their clinicopathological and follow-up data were obtained and analyzed to reveal the prognosis and risk factors of primary tongue squamous cell carcinoma with lower-level lymph node metastasis. RESULTS: Among the 203 patients, the metastasis rates of levels â £ and â ¤ are 14.78% and 4.93%, respectively. Level â £ metastasis is more prevalent in males than females (P=0.04); non-smokers are more likely to have level â ¤ metastasis than smokers (P=0.046). Lymph node status in levels â ¢ and â £ are significantly associated with the risk of metastasis in level â ¤ (P=0.001). Patients with extracapsular invasion in level â ¢ have a significantly increased risk of metastasis in levels â £ (P=0.014) and â ¤ (P=0.026). The 5-year survival rate of patients with lower lymph node (â £/â ¤) metastasis is only 14.70%, which is an independent poor prognostic factor for patients with primary tongue squamous cell carcinoma (P<0.000 1). CONCLUSIONS: Most primary tongue squamous cell carcinoma metastases occur in levels â -â ¢. However, the rate of lower-level lymph node metastasis is rather low. For the cN0 and cN+ patients with levels â -â ¡ lymph node metastases without extracapsular invasion, the strategy for level â ¤ management may be observation rather than dissection.