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Surfactant-free microemulsions (SFMEs) have been explored extensively to avoid the residual surfactant problem caused by traditional surfactant microemulsions. Many researchers focused on the SFMEs with tertiary amine, which exhibited the typical CO2 response behavior. In this study, the phase diagram of the SFMEs consisting of tripropylamine (TPA), ethanol, and water was readily prepared via the measurements of electrical conductivity. The CO2 response behavior of SFME was confirmed by determination of conductivity and measurement of the average diameter of SFME, which was mainly dependent on the protonation of TPA induced by the additional CO2. The transition of protonated TPA to a more hydrophilic nature from lipophilicity to hydrophilicity should be responsible for the variation of SFME average diameter. In addition, the SFMEs exhibited remarkable solubilizing capacity of crude oil, and three types of SFMEs achieved more than 80% oil removal rate in the washing process of oil sands. It was noted that both oil-in-water and bicontinuous SFMEs could be circularly utilized at least three times with a relatively high oil removal rate (%). Our work provided the insight perspective on the mechanism of SFMEs with a CO2 response behavior.
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Hydrate-based CO2 storage in the ocean is considered a potential method for mitigating the greenhouse effect. Numerous studies demonstrated that NaCl exhibited the dual effects of promotion and inhibition in the nucleation and growth processes of CO2 hydrate, whose mechanisms remain unclear. In this study, the effects of NaCl at various concentrations on the CO2 hydrate growth and crystal are investigated. The independent gradient model based on Hirshfeld partition, electrostatic potential, and binding energy is conducted to study the interaction between ions and water molecules. The motion trajectories of ions are observed at the molecular level to reflect the impact of ion motion on hydrate growth. The results show that the influence of NaCl on hydrate growth depends on a delicate balance of dual promotion-inhibition effects. NaCl can combine more water molecules and provide a transport channel of CO2 to promote hydrate growth at low concentrations. Meanwhile, the promoting effects shift toward inhibition with increasing NaCl concentrations. In a word, this paper proposes a novel mechanism for the dual promotion-inhibition effects of NaCl on hydrate growth, which is significant for further research on hydrate-based CO2 storage in the ocean.
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Although the Three Gorges Dam (TGD) is the world's largest hydroelectric dam, little is known about the spatial-temporal patterns and community assembly mechanisms of meio- and micro-eukaryotes and its two subtaxa (zooplankton and zoobenthos). This knowledge gap is particularly evident across various habitats and during different water-level periods, primarily arising from the annual regular dam regulation. To address this inquiry, we employed mitochondrial cytochrome c oxidase I (COI) gene-based environmental DNA (eDNA) metabarcoding technology to systematically analyze the biogeographic pattern of the three communities within the Three Gorges Reservoir (TGR). Our findings reveal distinct spatiotemporal characteristics and complementary patterns in the distribution of meio- and micro-eukaryotes. The three communities showed similar biogeographic patterns and assembly processes. Notably, the diversity of these three taxa gradually decreased along the river. Their communities were less shaped by stochastic processes, which gradually decreased along the longitudinal riverine-transition-lacustrine gradient. Hence, deterministic factors, such as seasonality, environmental, and spatial variables, along with species interactions, likely play a pivotal role in shaping these communities. Environmental factors primarily drive seasonal variations in these communities, while hydrological conditions, represented as spatial distance, predominantly influence spatial variations. These three communities followed the distance-decay pattern. In winter, compared to summer, both the decay and species interrelationships are more pronounced. Taken together, this study offers fresh insights into the composition and diversity patterns of meio- and micro-eukaryotes at the spatial-temporal level. It also uncovers the mechanisms behind community assembly in various environmental niches within the dam-induced river-reservoir systems. KEY POINTS: ⢠Distribution and diversity of meio- and micro-eukaryotes exhibit distinct spatiotemporal patterns in the TGR. ⢠Contribution of stochastic processes in community assembly gradually decreases along the river. ⢠Deterministic factors and species interactions shape meio- and micro-eukaryotic community.
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Monitoramento Ambiental , Rios , Animais , Ecossistema , Zooplâncton , Estações do Ano , ChinaRESUMO
In order to solve the star identification problem in the lost space mode for scientific cameras with small fields of view and higher instruction magnitudes, this paper proposes a star identification algorithm based on a hybrid grid pattern. The application of a hybrid pattern generated by multi-calibration stars in the initial matching enables the position distribution features of neighboring stars around the main star to be more comprehensively described and avoids the interference of position noise and magnitude noise as much as possible. Moreover, calibration star filtering is adopted to eliminate incorrect candidates and pick the true matched navigation star from candidate stars in the initial match. Then, the reference star image is utilized to efficiently verify and determine the final identification results of the algorithm via the nearest principle. The performance of the proposed algorithm in simulation experiments shows that, when the position noise is 2 pixels, the identification rate of the algorithm is 96.43%, which is higher than that of the optimized grid algorithm by 2.21% and the grid algorithm by 4.05%; when the magnitude noise is 0.3 mag, the star identification rate of the algorithm is 96.45%, which is superior to the optimized grid algorithm by 2.03% and to the grid algorithm by 3.82%. In addition, in the actual star image test, star magnitude values of ≤12 mag can be successfully identified using the proposed algorithm.
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Spin obit torque (SOT) driven magnetization switching has been used widely for encoding consumption-efficient memory and logic. However, symmetry breaking under a magnetic field is required to realize the deterministic switching in synthetic antiferromagnets with perpendicular magnetic anisotropy (PMA), which limits their potential applications. Herein, we report all electric-controlled magnetization switching in the antiferromagnetic Co/Ir/Co trilayers with vertical magnetic imbalance. Besides, the switching polarity could be reversed by optimizing the Ir thickness. By using the polarized neutron reflection (PNR) measurements, the canted noncollinear spin configuration was observed in Co/Ir/Co trilayers, which results from the competition of magnetic inhomogeneity. In addition, the asymmetric domain walls demonstrated by micromagnetic simulations result from introducing imbalance magnetism, leading to the deterministic magnetization switching in Co/Ir/Co trilayers. Our findings highlight a promising route to electric-controlled magnetism via tunable spin configuration, improve our understanding of physical mechanisms, and significantly promote industrial applications in spintronic devices.
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Wastewater containing organic dyes has become one of the important challenges in water treatment due to its high salt content and resistance to natural degradation. In this work, a novelty adsorbent, PEI-SMA, was prepared by grafting polyethyleneimine (PEI) onto styrene-maleic anhydride copolymer (SMA) through an amidation reaction. The various factors, such as pH, adsorbent dosage, contact time, dye concentration, and temperature, which may affect the adsorption of PEI-SMA for Reactive Black 5 (RB5), were systematically investigated by static adsorption experiments. The adsorption process of PEI-SMA for RB5 was more consistent with the Langmuir isotherm model and the pseudo-second-order model, suggesting a single-layer chemisorption. PEI-SMA exhibits excellent adsorption performance for RB5 dye, with a maximum adsorption capacity of 1749.19 mg g-1 at pH = 2. Additionally, PEI-SMA exhibited highly efficient RB5 competitive adsorption against coexisting Cl- and SO42- ions and cationic dyes. The adsorption mechanism was explored, and it can be explained as the synergistic effect of electrostatic interaction, hydrogen bonding and π-π interaction. This study demonstrates that PEI-SMA could act as a high performance and promising candidate for the effective adsorption of anionic dyes from aqueous solutions.
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BACKGROUND: Recently, PET/CT imaging with radiolabelled FAP inhibitors (FAPIs) has been widely evaluated in diverse diseases. However, rare report has been published using SPECT/CT, a more available imaging method, with [99mTc]Tc-labelled FAPI. In this study, we evaluated the potential effect of [99mTc]Tc-HFAPi in clinical analysis for digestive system tumours. METHODS: This is a single-centre prospective diagnostic efficiency study (Ethic approved No.: XJTU1AF2021LSK-021 of the First Affiliated Hospital of Xi'an Jiaotong University and ChiCTR2100048093 of the Chinese Clinical Trial Register). Forty patients with suspected or confirmed digestive system tumours underwent [99mTc]Tc-HFAPi SPECT/CT between January and June 2021. For dynamic biodistribution and dosimetry estimation, whole-body planar scintigraphy was performed at 10, 30, 90, 150, and 240 min post-injection in four representative patients. Optimal acquisition time was considered in all the patients at 60-90 min post-injection, then quantified or semi-quantified using SUVmax and T/B ratio was done. The diagnostic performance of [99mTc]Tc-HFAPi was calculated and compared with those of contrast-enhanced CT (ceCT) using McNemar test, and the changes of tumour stage and oncologic management were recorded. RESULTS: Physiological distribution of [99mTc]Tc-HFAPi was observed in the liver, pancreas, gallbladder, and to a lesser extent in the kidneys, spleen and thyroid. Totally, 40 patients with 115 lesions were analysed. The diagnostic sensitivity of [99mTc]Tc-HFAPi for non-operative primary lesions was similar to that of ceCT (94.29% [33/35] vs 100% [35/35], respectively; P = 0.5); in local relapse detection, [99mTc]Tc-HFAPi was successfully detected in 100% (n = 3) of patients. In the diagnosis of suspected metastatic lesions, [99mTc]Tc-HFAPi exhibited higher sensitivity (89.66% [26/29] vs 68.97% [20/29], respectively, P = 0.03) and specificity (97.9% [47/48] vs 85.4% [41/48], respectively, P = 0.03) than ceCT, especially with 100% (24/24) specificity in the diagnosis of liver metastases, resulting in 20.0% (8/40) changes in TNM stage and 15.0% (6/40) changes in oncologic management. CONCLUSION: [99mTc]Tc-HFAPi demonstrates a greater diagnostic efficiency than ceCT in the detection of distant metastasis, especially in identifying liver metastases.
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Neoplasias Hepáticas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Sistema Digestório , Recidiva Local de Neoplasia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Prospectivos , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Chemoresistance poses a significant impediment to effective treatment strategies for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Our previous study unveiled that oncogene TWIST1 interacted with DNA methyltransferase 3a (DNMT3a) to regulate the decitabine (DAC) resistance in MDS/AML. However, the underlying mechanism of TWIST1 dysregulation in DAC resistance remained enigmatic. Here, we found that O-GlcNAc modification was upregulated in CD34+ cells from MDS/AML patients who do not respond to DAC treatment. Functional study revealed that O-GlcNAcylation could stabilize TWIST1 by impeding its interaction with ubiquitin E3 ligase CBLC. In addition, as one typical transcription factor, TWIST1 could bind to the promoter of O-GlcNAc transferase (OGT) gene and activate its transcription. Collectively, we highlighted the crucial role of the O-GlcNAcylated TWIST1 in the chemoresistance capacity of MDS/AML clonal cells, which may pave the way for the development of a new therapeutic strategy targeting O-GlcNAcylated proteins and reducing the ratio of MDS/AML relapse. Video Abstract.
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Síndromes Mielodisplásicas , Oncogenes , Humanos , Decitabina/farmacologia , N-Acetilglucosaminiltransferases , Síndromes Mielodisplásicas/tratamento farmacológico , Proteínas Nucleares , Proteína 1 Relacionada a TwistRESUMO
Dysregulation of clusterin (CLU) has been demonstrated in many cancers and has been proposed as a regulator of carcinogenesis. However, the roles of CLU in gliomas remain unclear. The expression of CLU was assessed using TIMER2.0, GEPIA2, and R package 4.2.1 software, leveraging data from TCGA and/or GTEx databases. Survival analysis and Cox regression were employed to investigate the prognostic significance of CLU. Immune infiltration was evaluated utilizing TIMER2.0, ESTIMATE, and CIBERSORT. The findings reveal the dysregulated expression of CLU in many cancers, with a marked increase observed in glioblastoma and lower-grade glioma (LGG). High CLU expression indicated worse survival outcomes and was an independent risk factor for the prognosis in LGG patients. CLU was involved in immune status as evidenced by its strong correlations with immune and stromal scores and the infiltration levels of multiple immune cells. Additionally, CLU was co-expressed with multiple immune-related genes, and high CLU expression was associated with the activation of immune-related pathways, such as binding to the antigen/immunoglobulin receptor and aiding the cytokine and cytokine receptor interaction. In conclusion, CLU appears to play crucial roles in tumor immunity within gliomas, highlighting its potential as a biomarker or target in glioma immunotherapy.
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Glioblastoma , Glioma , Humanos , Carcinogênese , Clusterina/genética , Glioma/genética , PrognósticoRESUMO
BACKGROUND: Thyroglobulin measurement in fine-needle aspiration (FNA-Tg) is an additional diagnostic tool of lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC). However, its performance as a preoperative indicator of lateral neck LNM in PTC is unclear. We evaluated the use of FNA cytology and FNA-Tg to detect neck LNM presurgery using a simple methodology, and established a cut-off value for diagnosing LNM in PTC. METHODS: We performed a retrospective cohort study based on hospital records, including 299 FNA-Tg measurements from 228 patients with PTC. The cut-off value for FNA-Tg was obtained through a receiver operating characteristic (ROC) curve analysis. The relationships between various parameters and FNA-Tg were analyzed using Spearman's correlation. RESULTS: Of 299 lymph nodes (LNs) from 228 patients following surgery, 151 were malignant and 148 were benign. The median FNA-Tg levels were 414.40 ng/mL and 6.36 ng/mL in the metastatic and benign LNs, respectively. An FNA-Tg cut-off value of 28.3 ng/mL had the best diagnostic performance (93.38% sensitivity, 70.27% specificity, area under the ROC curve [AUC] 0.868) in the whole cohort. The diagnostic value performed better in the lateral neck group (level II-V, n = 163) than in the central neck group (level VI, n = 136); in the lateral neck group, the sensitivity and specificity of the FNA-Tg cut-off (16.8 ng/mL) were 96.25% and 96.36%, respectively. CONCLUSIONS: FNA-Tg is a useful technique for the diagnosis of LNM before surgery, especially in lateral neck dissection. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR1900028547.
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Tireoglobulina , Neoplasias da Glândula Tireoide , Biópsia por Agulha Fina , Dissecação , Humanos , Esvaziamento Cervical , Estudos Retrospectivos , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
Professional skill is required to reproduce ultrasound images of the kidney as an optimal cross-section is easily lost with slight deviation in scanning location or angle of the probe. We developed a motion-capture technique-based interface screen that displays the real-time probe position and angle to overlap those provided beforehand. When a professional operator captured the approximate kidney image, our system recorded the relative spatial relationship between the subject and the probe. Next, an amateur operator who had no experience of clinical practice manipulated the probe only with the aid of the interface until the probe position and angle coincided with the professional ones. Eventually, amateur operators could place the probe with a deviation of distance of (x = 2.7 ± 1.2 mm, y = 3.0 ± 1.7 mm, z = 6.6 ± 1.8 mm) and angle of (Rx = 1.5 ± 0.3 degrees, Ry = 2.6 ± 1.1 degrees, Rz = 1.1 ± 0.3 degrees) from the professional goal to produce very similar cross-sectional kidney images (N = 8). Also, motion-capture technique-based evaluation of relative locations of the probe and subject body revealed difficulty in reproducing those without the interface screen navigation. In summary, our motion-capture technique-based ultrasound guide system provides operators with the opportunity to handle the probe just as another operator would beforehand. This could help in medical procedures wherein the same cross-sectional image should be repeatedly obtained. Moreover, it requires no conventional probe training for beginners and could even shift the paradigm for ultrasound probe handling.
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Rim , Humanos , Rim/diagnóstico por imagem , Ultrassonografia/métodosRESUMO
Ptosis is one of the common diseases of plastic surgery, which is caused by various causes of levator palpebrae superioris dysfunction or Müller muscle insufficiency, which is manifested by the upper eyelid margin being lower than normal when level viewed. Ptosis can be divided into congenital and acquired, and the main cause of congenital ptosis is due to congenital levator palpebrae superioris dysplasia or the motor nerve innervation that innervates it is caused by abnormal oculomotor neurodevelopment and dysfunction. Acquired ptosis can be divided into traumatic, neurogenic, myogenic, senile, mechanical, and false ptosis. At present, there are few reports of ptosis due to the degeneration of the aponeurosis of the upper eyelid muscle. We received a case of ptosis caused by degeneration of the levator palpebrae superioris aponeurotic membrane, we use the method of the levator palpebrae superioris high advancement. The levator palpebrae superioris-Miller muscle was folded to form a stable composite structure by the levator palpebrae superioris high advancement. During the operation, the levator palpebrae superioris was separated along the gap, and the surrounding tissues were less damaged. Therefore, postoperative adhesion was less, and the main complications of severe blepharoptosis after the operation, such as upper eyelid hysteresis and incomplete closure, almost did not occur, and after surgery, the results were good.
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Blefaroptose , Cirurgia Plástica , Humanos , Blefaroptose/cirurgia , Blefaroptose/congênito , Músculos Oculomotores/cirurgia , Aponeurose/cirurgia , Pálpebras/cirurgiaRESUMO
This study established the EA.hy926 cell myocardial ischemia model to compare the effects of two Kaixin Powder prescriptions, Buxin Decoction(BXD) and Dingzhi Pills(DZP), at three dosages(500, 200, and 100 µg·mL~(-1)) on the cell viability. Further, the public databases(TCMSP, TCMID, SYMMAP, and STRING) and the network pharmacology methods such as KEGG pathway enrichment were employed to decipher the possible molecular mechanism of BXD in exerting the cardioprotective effect. The pharmacological effect of BXD was evaluated with the rat model of isoprenaline(ISO)-induced myocardial ischemia. The expression levels of proteins involved in the phosphatidylinositol-3-kinase/protein kinase B(PI3 K/AKT) signaling pathway were measured by Western blot. BXD significantly increased the viability of EA.hy926 cells, showing the performance superior to DZP. The network pharmacology analysis predicted that BXD might exert cardiac protection through the PI3 K/AKT signaling pathway. The in vivo experiment on rats showed that BXD treatment significantly increased the cardiac ejection fraction(EF), fractional shortening(FS), diastolic left ventricular anterior wall(LVAWd), systolic left ventricular anterior wall(LVAWs), and diastolic left ventricular posterior wall(LVPWd), significantly decreased the beat per minute(BPM) and diastolic left ventricular internal diameter(LVIDd), and significantly improved the ST segment in the electrocardiogram. The pathological results(Masson staining) showed that BXD restored the myocardial thickness, decreased the collagen fiber, increased the muscle fiber, and reduced the infarct area to alleviate myocardial ischemia. Furthermore, BXD lowered the serum levels of inflammatory cytokines [tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6)] and myocardial enzymes [creatine kinase(CK) and lactate dehydrogenase(LDH)], increased the p-AKT/AKT ratio, up-regulated the protein levels of PI3 K, NF-κB, IKK-α, and Bcl-xl, and down-regulated that of the apoptotic protein Bax. In conclusion, BXD may exert cardiac protection effect by regulating the PI3 K/AKT signaling pathway.
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Isquemia Miocárdica , Proteínas Proto-Oncogênicas c-akt , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Pós , Farmacologia em Rede , Transdução de Sinais , Miocárdio/patologia , Creatina Quinase , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , PrescriçõesRESUMO
In this study, a series of novel 2H-imidazo [1, 2-c] pyrazolo [3, 4-e] pyrimidine derivatives were designed, synthesized, and evaluated for their cytotoxic activities. The in vitro cell growth inhibition assay of the target compounds indicated their selectivity in inhibiting the proliferation of blood tumor cells (K562, U937) and solid tumor cells (HCT116, HT-29). Compound 9b exhibited the highest antiproliferative activities against K562 (IC50 = 5.597 µM) and U937 (IC50 = 3.512 µM). Based on the flow cytometry assays, compound 9b caused obvious induction of cell apoptosis and cell arrest at the S phase. Furthermore, western blot analysis revealed that compound 9b upregulated the expression of Bax, downregulated the levels of Bcl-2, and further activated caspase-3 in K562 cells. Therefore, compound 9b may be a potential anticancer agent that deserves further investigation.
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Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Desenho de Fármacos , Pirimidinas/síntese química , Pirimidinas/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Concentração Inibidora 50 , Células K562 , Pirimidinas/química , Células U937RESUMO
Environmental exposure to lead (Pb) can damage to the central nervous system (CNS) in humans. High-fat diet (HFD) also has been suggested to impair neurocognitive function. Blood-brain barrier (BBB) is a rigorous permeability barrier for maintaining homeostasis of CNS. The damage of BBB caused by tight junctions (TJs) disruption is central to the etiology of various CNS disorders. This study aimed to investigate whether HFD could exacerbate Pb exposure induced the destruction of BBB integrity by TJs disruption. To this end, we measured cell viability assay, trans-endothelial electrical resistance assay, horseradish peroxidase flux measurement, Western blot analysis, and immunofluorescence experiments. The results showed that palmitic acid (PA), the most common saturated fatty acid found in the human body, can increase the permeability of the BBB in vitro which formed in bEnd.3 cells induced by Pb exposure, and decrease the expression of TJs, such as zonula occludins-1 (ZO-1) and occludin. Besides, we found that PA could promote the up-regulation of matrix metalloproteinase (MMP)-9 expression and activate the c-Jun N-terminal kinase (JNK) pathway induced by Pb. MMP-9 inhibitor or JNK inhibitor could increase BBB integrity and up-regulate the expressions of ZO-1 and occludin after treatment, respectively. Moreover, the JNK inhibitor could down-regulate the expression of MMP-9. In conclusion, these results suggested that HFD exacerbates Pb-induced BBB disruption by disrupting TJs integrity. This may be because PA promotes the activation of JNK pathway and then up-regulated the expression of MMP-9 after Pb-exposure. It is suggested that people with HFD exposed to environmental Pb may cause more serious damage to the CNS.
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Barreira Hematoencefálica , Junções Íntimas , Barreira Hematoencefálica/metabolismo , Dieta Hiperlipídica/efeitos adversos , Humanos , Chumbo/toxicidade , Ocludina/metabolismo , Junções Íntimas/metabolismoRESUMO
BACKGROUND: It has always been a great challenge for clinical doctors to reconstruct total and near-total lower lip defects. Compared with elderly patients, the repair operation in young patients is more difficult where free flaps are usually used for transfer. In order to obtain better postoperative results, the authors combined two kinds of local skin flaps for operation purpose, and evaluated their postoperative clinical effects. METHODS: From April 2011 to May 2019, a total of 5 young patients with lower lip tumor or trauma were included in this study, with an average age of 30.4 years old. The lesion was all resected and resulted in a defect of 87% to total area of the lower lip, accompanied by a partial defect of the chin each. To repair the defect of the lower lip, the authors firstly used the modified Bernard flap. Then the authors designed the double Abbe flap to perform the operation according to the recovery of the patient 3 months later than the first operation. Finally, the outcomes of either operation were compared upon slit width, mouth opening height, aesthetics, and function of the patients, and statistically analyzed the results. RESULTS: All patients underwent the repair of modified Bernard flaps and double Abbe flaps of with no hemodynamic disorder of the flaps and well-recovery. At 3 months after the operation, the average gap width of lip was 4.34â±â0.24âcm, the average opening height was 3.18â±â0.28âcm, the average aesthetic score was 7.98â±â0.51 (full score of 10), and the average functional score was 11.4â±â0.55 (full score of 12). The 5 patients showed no obvious scar but a good shape on the lower lip. The function of eating, pronunciation, expression of feelings and smiling change were close to normal. Three patients had mild numbness in the lower lip, while the other two had normal sensory function. CONCLUSION: Combined modified Bernard flap and double Abbe flaps can bring out promising reparative outcomes of near-total or total lower lip defects in lower lip in young patients with good aesthetic and functional recovery, which is recommended while considering surgical alternatives.
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Retalhos de Tecido Biológico , Neoplasias Labiais , Procedimentos de Cirurgia Plástica , Adulto , Idoso , Estética Dentária , Humanos , Lábio/cirurgia , Neoplasias Labiais/cirurgia , Transplante de Pele , Resultado do TratamentoRESUMO
Maximization of phototoxic damage on tumor with minimized side effect on normal tissue is essential for effective anticancer photodynamic therapy (PDT). This requires highly cancer-cell-specific or even cancer-cell-organelle-specific synthesis or delivery of efficient photosensitizers (PSs) in vitro and in vivo, which is difficult to achieve. Herein, we report a strategy of cancer-cell-activated PS synthesis, by which an efficient mitochondria-targeting photosensitizer with aggregation-induced-emission (AIE) feature can be selectively synthesized as an efficient image-guided PDT agent inside cancer cells. MOF-199, a CuII -based metal-organic framework, was selected as an inert carrier to load the PS precursors for efficient delivery and served as a CuI catalyst source for in situ click reaction to form PSs exclusively in cancer cells. The in situ synthesized PS showed mitochondria-targeting capability, allowing potent cancer-cell-specific ablation under light irradiation. The high specificity of PSs produced in cancer cells also makes it safer post-treatment.
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Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Cobre/farmacologia , Mitocôndrias/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Células 3T3 , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Cobre/química , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Camundongos , Neoplasias/metabolismo , Neoplasias/patologia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/químicaRESUMO
The Lyot coronagraph is a widely known astronomical instrument used to realize direct imaging of exoplanets, and designing transmittance of an apodizer and Lyot stop is the key to obtaining high-contrast imaging. In this paper a new (to the best of our knowledge) optimization procedure used to design the apodizer and Lyot stop in the Lyot coronagraph is proposed. A two-step optimization program is established to obtain the optimum transmittance of an apodizer and Lyot stop in a sequential way. By using the optimized apodizer and Lyot stop obtained through the proposed optimization procedure, both the stellar light and its diffraction light could be strongly suppressed. Numerical results indicate that such an optimized Lyot coronagraph can produce a 1e-10 extinction of the stellar light near the diffraction limit (1.59λ/D), and a high contrast imaging of 1e-07 could still be obtained even with the influence of light intensity of planets themselves. In addition, the two-step optimization procedure brings in two benefits. First, the two-step optimization is approximately 1000 times faster than the joint optimization method [J. Astron. Telesc. Instrum. Syst.2, 011012 (2016)2329-412410.1117/1.JATIS.2.1.011012]. Second, the optimum transmittance of the Lyot stop is binary, and therefore, the requirements of the production process are reduced, resulting in a greatly reduced cost. At the same time, the performance of the optimized Lyot coronagraph is also analyzed in the case of a monochromatic light incident and bandwidth light incident, and the effect of the diameter of the Lyot stop on the results is also discussed in this paper, which makes sense when designing a coronagraph.
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Previous studies have shown that κ-opioid receptor activation possesses cardioprotection against myocardial ischemia and reperfusion (MI/R) injury. The current study was designed to investigate whether mitochondrial dysfunction after MI/R is regulated by the κ-opioid receptor and to further explore the underlying mechanisms involved. MI/R rat model was established in vivo, and a hypoxia and reoxygenation cardiomyocytes model was used in vitro. Mitochondrial morphology and function as well as myocardial apoptosis were determined. Our data indicated that treatment with U50,488H (a selective κ-opioid receptor agonist) not only reduced apoptosis but also significantly improved mitochondrial morphology and function. These effects were blocked by nor-binaltorphimine (nor-BNI, a selective κ-opioid receptor antagonist), Compound C (an AMPK inhibitor), and AR-A014418 (a GSK3ß inhibitor). Moreover, in cardiomyocytes, treatment with U50,488H significantly increased the expression in phosphorylation of AMPK and the phosphorylation of GSK3ß. Treatment of cardiomyocytes with AMPKα siRNA decreased the phosphorylation of AMPK and GSK3ß. Moreover, AMPK activation resulted in the phosphorylation of GSK3ß. Our findings suggested that U50,488H exerted cardioprotective effects by improving mitochondrial morphology and function against MI/R injury through activation of the κ-opioid receptor-mediated AMPK/GSK3ß pathway.
Assuntos
(trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Apoptose/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/metabolismo , Mitocôndrias Cardíacas/efeitos dos fármacos , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Receptores Opioides kappa/agonistas , Proteínas Quinases Ativadas por AMP/genética , Animais , Linhagem Celular , Modelos Animais de Doenças , Masculino , Mitocôndrias Cardíacas/enzimologia , Mitocôndrias Cardíacas/ultraestrutura , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/enzimologia , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/ultraestrutura , Fosforilação , Ratos Sprague-Dawley , Receptores Opioides kappa/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: This study was designed to test the hypothesis that κ-opioid receptor (κ-OR) stimulation reduces palmitate-induced HUVECs apoptosis and to investigate its mechanisms. METHODS: HUVECs were subjected to sodium palmitate, apoptosis and cell viability were determined, HUVECs were treated with specific inhibitors to PI3K, Akt, eNOS and siRNAs targeting κ-OR and Akt. Groups were divided as follows: the control group, the sodium palmitate group, the sodium palmitate+U50,488H (a selective κ-OR agonist) group and the sodium palmitate+U50,488H + nor-BNI (a selective κ-OR antagonist) group. RESULTS: Treatment with sodium palmitate significantly reduced cell viability and increased apoptosis rate which were significantly alleviated by pretreatment with U50,488H, the effect of U50,488H was abolished by nor-BNI. Phosphorylation of Akt and eNOS, as well as NO production were attenuated and accompanied by an increased expression of caspase 3 when HUVECs were subjected to sodium palmitate, and all these changes were restored by pretreatment with U50,488H, the effects of U50,488H were abolished by nor-BNI, and specific inhibitors to PI3K, Akt, eNOS, respectively. SiRNAs targeting κ-OR or Akt abolished the effects of U50,488H on phosphorylation of Akt and eNOS as well as the expressions of caspase 3, Bax and Bcl-2. SiRNAs targeting Akt elicited no effect on the expression of κ-OR. CONCLUSION: This study provides the evidence for the first time that κ-OR stimulation possesses anti-palmitate-induced apoptosis effect, which is mediated by PI3K/Akt/eNOS signaling pathway.