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Herein we demonstrate an "in-ring establishing" strategy for assembling interlocked molecules through dynamic imine formation, "establishing" the host recognition sites in situ. Using Zn2+ ions to template the assembly of a pyridine-containing macrocycle with semidumbbell-shaped triazole-containing aldehyde and amine derivatives, we obtained the corresponding [2]rotaxane in high yield (85%) after subsequent imine reduction (NaBH4) and amine protonation (NH4PF6). We performed the same three steps (assembly, reduction, protonation) to prepare a stable and highly symmetrical [5]molecular necklace ([5]MN) from 12 components (two almost-90°-oriented dialdehydes, two almost-90°-oriented diamines, four macrocycles, four Zn2+ ions) in an overall yield of 69%.
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Mitochondria (MITO) and peroxisomes (PEXO) are the major organelles involved in the oxidative metabolism of cells, but detailed examination of their dynamics and functional adaptations during skeletal muscle (SKM) development (myogenesis) is still lacking. In this study, we found that during myogenesis, MITO DNA, ROS level, and redox ratio increased in myotubes, but the membrane potential (Δψm) and ATP content reduced, implying that the MITO efficiency might reduce during myogenesis. The PEXO number and density both increased during myogenesis, which probably resulted from the accumulation and increased biogenesis of PEXO. The expression of PEXO biogenesis factors was induced during myogenesis in vitro and in utero, and their promoters were also activated by MyoD. Knockdown of the biogenesis factors Pex3 repressed not only the PEXO density and functions but also the levels of MITO genes and functions, suggesting a close coupling between PEXO biogenesis and MITO functions. Surprisingly, Pex3 knockdown by the CRISPRi system repressed myogenic differentiation, indicating critical involvement of PEXO biogenesis in myogenesis. Taken together, these observations suggest that the dynamics and functions of both MITO and PEXO are coupled with each other and with the metabolic changes that occur during myogenesis, and these metabolic couplings are critical to myogenesis.
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Fibras Musculares Esqueléticas , Peroxissomos , Peroxissomos/metabolismo , Diferenciação Celular/genética , Fibras Musculares Esqueléticas/metabolismo , Mitocôndrias/metabolismo , Desenvolvimento Muscular/genética , Músculo Esquelético/metabolismoRESUMO
BACKGROUND: The albumin-bilirubin (ALBI) grade has been validated as a significant prognostic predictor for hepatocellular carcinoma (HCC). However, there is little information about the ALBI grade in patients with non-B non-C HCC (NBNC-HCC) receiving surgery. AIM: This study aimed to evaluate the prognostic significance of the ALBI grade in patients with NBNC-HCC after primary curative resection. METHOD: From January 2010 to April 2016, 2137 patients with HCC who received hepatectomy were screened for study eligibility. Finally, a total of 168 NBNC-HCC patients who received primary curative resection were analyzed. The impacts of the ALBI grade on disease-free survival (DFS) and overall survival (OS) were analyzed by multivariate analysis. RESULTS: There were 66 (39.3%), 98 (58.3%), and 4 (2.4%) patients with an ALBI grade of I, II, and III, respectively. Patients with an ALBI grade II/III were older (p = 0.002), more likely to have hypoalbuminemia (p < 0.001), and more commonly had Child-Pugh class B (p = 0.009) than patients with an ALBI grade I. After a median follow-up of 76 months, 74 (44%) patients experienced recurrence, and 72 (42.9%) patients died. Multivariate analysis revealed that alpha-fetoprotein (AFP) > 200 ng/mL (p = 0.021), number of tumors (p = 0.001), and tumor stage (p = 0.007) were independent prognostic factors for DFS. Additionally, AFP > 200 ng/mL (p = 0.002), ALBI grade II/III (p = 0.002), and tumor stage (p < 0.001) were independent risk factors for poor OS. CONCLUSION: The preoperative ALBI grade can be used to predict mortality in patients with NBNC-HCC after primary curative resection.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Bilirrubina , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos , Albumina Sérica/análiseRESUMO
Background and Objectives: Protease activated receptor-2 (PAR2) is elevated in a variety of cancers and has been promoted as a potential therapeutic target. However, the clinical and prognostic values of PAR2 in hepatocellular carcinoma (HCC) are poorly characterized. This study aimed to evaluate the expression of PAR2 in HCC tissues and examine the prognostic value of PAR2 after resection in HCC. Materials and Methods: Two hundred and eight resected specimens were collected from HCC patients at Kaohsiung Chang Gung Memorial Hospital. PAR2 protein expression was assessed by western blotting in HCC tissues and matched normal tissues. The correlation between PAR2 expression and clinicopathological parameters was analyzed. Disease-free survival (DFS) and overall survival (OS) were compared using the log-rank test. A Cox regression model was used to identify independent prognostic factors. Results: PAR2 was expressed at higher levels in HCC tissues than the paired adjacent nontumor tissues. High expression of PAR2 was associated with advanced tumor, node, metastasis (TNM )stage and histological grade. Kaplan-Meier analysis indicated high PAR2 expression was associated with poorer DFS and OS compared to low PAR2 expression. Multivariate analyses indicated high PAR2 expression [hazard ratio (HR), 1.779, p = 0.006), α-fetoprotein (AFP) (HR, 1.696, p = 0.003), liver cirrhosis (HR, 1.735, p = 0.002), and advanced TNM stage (HR, 2.061, p < 0.001) were prognostic factors for DFS, and advanced TNM stage (HR, 2.741, p < 0.001) and histological grade (HR, 2.675, p = 0.002) and high PAR2 expression (HR, 1.832, p = 0.012) were significant risk factors for OS. In subgroup analyses, the combination of PAR2 expression and serum AFP provided improved prognostic ability for OS and DFS. Conclusion: Combination PAR2 and AFP predict HCC outcomes after resection. PAR2 represents a potentially clinically relevant biomarker for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/cirurgia , Prognóstico , Receptor PAR-2 , Estudos RetrospectivosRESUMO
Inadvertent recurrent laryngeal nerve (RLN) injury is a major complication of thyroidectomy. This study aimed to investigate the association between preoperative clinical parameters and RLN size prediction. Total thyroidectomy and thyroid lobectomy data were collected between January 2014 and April 2017. Routine identification of the recurrent laryngeal nerves was performed, while intraoperative findings (nerve diameter, thyroid gland weight, intraoperative neuromonitoring (IONM) use, and signal recording) and demographic data were collected for analysis. A total of 848 patients with 1357 RLNs at risk were enrolled in this study. RLN diameter was thinner in females, those with body height <160 cm, and those with a BMI <25 (all p < 0.001). RLN diameter was directly proportional to age, body weight, height, and BMI. RLN diameter was thinner (1.71 mm vs. 1.55 mm, p = 0.039) and branched nerve incidence was higher (18.5% vs. 29.7%, p = 0.09) in the postoperative RLN injury group. Branched nerves were more frequently encountered in female patients (female vs. male: 28.8% vs. 18.7%, p = 0.004). The risk of RLN palsy in intraoperative IONM loss patients was 27 times higher compared to that in IONM normal patients (1.55% vs. 30%, p < 0.001). Thinner nerves did not yield a higher rate of IONM signal loss. Thinner nerves and higher palsy rates could be anticipated in females, younger age groups, those with shorter stature, and those with low BMI. RLN diameter was not associated with the rate of IONM signal loss.
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Traumatismos do Nervo Laríngeo Recorrente/prevenção & controle , Nervo Laríngeo Recorrente/anatomia & histologia , Glândula Tireoide/cirurgia , Tireoidectomia/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Período Pré-Operatório , Traumatismos do Nervo Laríngeo Recorrente/diagnóstico , Traumatismos do Nervo Laríngeo Recorrente/epidemiologia , Traumatismos do Nervo Laríngeo Recorrente/etiologia , Glândula Tireoide/inervação , Adulto JovemRESUMO
Hepatitis B virus (HBV) is an aetiological factor for liver cirrhosis and hepatocellular carcinoma (HCC). Despite current antiviral therapies that successfully reduce the viral load in patients with chronic hepatitis B, persistent hepatitis B surface antigen (HBsAg) remains a risk factor for HCC. To explore whether intrahepatic viral antigens contribute directly to hepatocarcinogenesis, we monitored the mitotic progression of HBV-positive cells. Cytokinesis failure was increased in HBV-positive HepG2.2.15 and 1.3ES2 cells, as well as in HuH-7 cells transfected with a wild-type or X-deficient HBV construct, but not in cells transfected with an HBsAg-deficient construct. We show that expression of viral large surface antigen (LHBS) was sufficient to induce cytokinesis failure of immortalized hepatocytes. Premitotic defects with DNA damage and G2 /M checkpoint attenuation preceded cytokinesis in LHBS-positive cells, and ultimately resulted in hyperploidy. Inhibition of polo-like kinase-1 (Plk1) not only restored the G2 /M checkpoint in these cells, but also suppressed LHBS-mediated in vivo tumourigenesis. Finally, a positive correlation between intrahepatic LHBS expression and hepatocyte hyperploidy was detected in >70% of patients with chronic hepatitis B. We conclude that HBV LHBS provokes hyperploidy by inducing DNA damage and upregulation of Plk1; the former results in atypical chromatin structures, and the latter attenuates the function of the G2 /M DNA damage checkpoint. Our data uncover a mechanism by which genomic integrity of hepatocytes is disrupted by viral LHBS. These findings highlight the role of intrahepatic surface antigen as an oncogenic risk factor in the development of HCC. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Carcinoma Hepatocelular/virologia , Citocinese , Antígenos de Superfície da Hepatite B/metabolismo , Vírus da Hepatite B/metabolismo , Hepatite B Crônica/virologia , Hepatócitos/virologia , Neoplasias Hepáticas/virologia , Ploidias , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Proteínas de Ciclo Celular/metabolismo , Transformação Celular Viral , Dano ao DNA , Modelos Animais de Doenças , Pontos de Checagem da Fase G2 do Ciclo Celular , Células Hep G2 , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B da Marmota/genética , Vírus da Hepatite B da Marmota/metabolismo , Vírus da Hepatite B/genética , Hepatite B Crônica/genética , Hepatite B Crônica/metabolismo , Hepatite B Crônica/patologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Hepatócitos/transplante , Interações Hospedeiro-Patógeno , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Marmota , Camundongos Transgênicos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Quinase 1 Polo-LikeRESUMO
Folding messenger RNA into specific structures is a common regulatory mechanism involved in translation. In Escherichia coli, the operator of the rpsO gene transcript folds into a pseudoknot or double-hairpin conformation. S15, the gene product, binds only to the pseudoknot, thereby repressing its own synthesis when it is present in excess in the cell. The two RNA conformations have been proposed to exist in equilibrium. However, it remained unclear how structural changes can be achieved between these two topologically distinct conformations. We used optical tweezers to study the structural dynamics and rearrangements of the rpsO operator RNA at the single-molecule level. We discovered that the two RNA structures can be interchanged spontaneously and the pseudoknot can exist in conformations that exhibit various levels of stability. Conversion from the double hairpin to a pseudoknot through potential hairpin-hairpin interactions favoured the high-stability conformation. By contrast, mutations that blocked the formation of a hairpin typically resulted in alternative low-stability pseudoknots. These results demonstrate that specific tertiary interactions of RNA can be established and modulated based on the interactions and rearrangements between secondary structural components. Our findings provide new insight into the RNA folding pathway that leads to a regulatory conformation for target protein binding.
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Dobramento de RNA , RNA Mensageiro/química , Escherichia coli/genética , Mutação , Conformação de Ácido Nucleico , Regiões Operadoras GenéticasRESUMO
The relationship of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) in sediment, water, and fish was studied for 55 fish farms near a contaminated site in Tainan, Taiwan. Samples were collected from the farms and analyzed for seventeen 2,3,7,8-substituted PCDD/Fs congeners. High correlations were found between PCDD/Fs in water and sediment in regard to both concentration and toxicity (R(2) = 0.933 for concentration and R(2) = 0.832 for toxicity). The congener profiles of the 17 PCDD/Fs in water were similar to those in the sediment. However, the PCDD/Fs congener composition in the fish and fish belly samples were different from those in the sediment and water samples obtained from the same fish farm and were also different among the fish samples. It is thus suggested that the biotic PCDD/Fs distribution is more complex than the abiotic PCDD/Fs distribution. Among the seven factors analyzed, only the lipid percentage presented a relationship with the PCDD/Fs congener composition in the fish and fish bellies. A multiple linear regression of the concentration of each congener in the fish was conducted using the concentration of each congener in the site-matched sediment and the lipid content of the fish as independent variables. The results showed that only seven PCDD/Fs congeners with a lower degree of chlorination, which were 4-6 chlorine substitutes, in the fish presented a significant correlation with the lipid content in the fish and their concentration in sediment (r > 0.65, P < 0.005 for both independent variables). In addition, the octanol-water partition coefficients were not significantly related to this distribution behavior.
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Benzofuranos/química , Dioxinas/química , Sedimentos Geológicos/química , Poluentes do Solo/análise , Poluentes Químicos da Água/química , Animais , Dibenzofuranos Policlorados , Monitoramento Ambiental , Poluição Ambiental , Peixes , Alimentos Marinhos/análise , Poluentes do Solo/metabolismo , Estereoisomerismo , TaiwanRESUMO
This study investigated methanogenic communities involved in degradation of tetramethylammonium hydroxide (TMAH) in three full-scale bioreactors treating TMAH-containing wastewater. Based on the results of terminal-restriction fragment-length polymorphism (T-RFLP) and quantitative PCR analyses targeting the methyl-coenzyme M reductase alpha subunit (mcrA) genes retrieved from three bioreactors, Methanomethylovorans and Methanosarcina were the dominant methanogens involved in the methanogenic degradation of TMAH in the bioreactors. Furthermore, batch experiments were conducted to evaluate mcrA messenger RNA (mRNA) expression during methanogenic TMAH degradation, and the results indicated that a higher level of TMAH favored mcrA mRNA expression by Methansarcina, while Methanomethylovorans could only express considerable amount of mcrA mRNA at a lower level of TMAH. These results suggest that Methansarcina is responsible for methanogenic TMAH degradation at higher TMAH concentrations, while Methanomethylovorans may be important at a lower TMAH condition.
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Bactérias/metabolismo , Reatores Biológicos/microbiologia , Metano/metabolismo , Compostos de Amônio Quaternário/metabolismo , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Polimorfismo de Fragmento de Restrição , Esgotos/microbiologiaRESUMO
BACKGROUND: This study aimed to evaluate the efficacy of vascular intervention in percutaneous transluminal angioplasty (PTA) for the treatment of hepatic artery and hepatic vein stenosis after liver transplantation (LT), including thrombotic total occluded lesions. METHODS: Percutaneous transluminal angioplasty after orthotopic liver transplantation was performed to re-open hepatic vessel lesions. We daily used routine Doppler ultrasound during admission for early detection of graft hepatic vessel lesions, including hepatic artery and vein lesions. In outpatients, Doppler ultrasound was performed every month. Urokinase was delivered with a dose of 150,000-300,000 IU by catheter before PTA for thrombotic total occlusion of the graft for hepatic artery patients. Laboratory data were collected to evaluate the effects of the PTA procedure. RESULTS: The study involved a total of seven patients, six of whom were successfully treated by a first PTA procedure. Thrombolysis use of urokinase in totally occluded donor hepatic arteries post-LT following stenting was successful in three patients. One complication occurred, an arterial dissection and perforation, finalizing the success rate at ~86% and the complication rate at ~14%. Therefore, our study has a primary patency rate of 100% at 1 and 3 months. Also, the graft survival rate was 100 % and 86 % in the first and third months, respectively. CONCLUSIONS: PTA with stenting is an effective treatment for hepatic vessel stenosis, including hepatic arteries and hepatic veins, after a liver transplantation without an increase in the complication rate. In addition, thrombolysis using urokinase intra-artery infusion in graft thrombotic total occluded patients is a good treatment strategy as well. KEY WORDS: Angioplasty; Complication; Liver transplantation.
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BACKGROUND: Total parathyroidectomy for secondary hyperparathyroidism has low morbidity and mortality rates and requires a special workup in the preoperative period. METHODS: Neck echography and technetium-99m-sestamibi scintigraphy were performed preoperatively. Cardiac echography, a thallium-201 myocardial perfusion scan, and cardiac catheterization were performed if necessary. During surgery, we removed all the parathyroid glands and the upper thymus and autotransplanted 100 mg of the smallest gland into the subcutaneous tissue of the forearm. RESULTS: The success rate in three months after total parathyroidectomy was 91.7% without mortality. In the elderly (age ≤65 years, n = 35), bone pain, skin itching, general weakness, and insomnia improved three months after surgery, and grip strength increased significantly. One year after parathyroidectomy, the serum levels of Ca, P, alkaline phosphatase, and intact parathyroid hormone were all within the normal ranges. Except for the bone mineral density (BMD) of the radial distal one-third, the BMD of the lumbar spine (L2 to L4), femoral neck, femoral global, and radial global increased significantly. Furthermore, the bone density T-scores of the lumbar spine (L2 to L4), femoral neck, femoral global, radial distal one-third, and radial global improved significantly. CONCLUSIONS: After a meticulous preoperative workup, parathyroidectomy plus autotransplantation can be performed safely for the treatment of symptomatic secondary hyperparathyroidism in the elderly to improve their quality of life and decrease their incidence of bone fractures.
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Hiperparatireoidismo Secundário , Paratireoidectomia , Humanos , Idoso , Qualidade de Vida , Hiperparatireoidismo Secundário/cirurgia , Glândulas Paratireoides/transplante , Hormônio ParatireóideoRESUMO
Manufacturing processes in semiconductor and photonics industries involve the use of a significant amount of organic solvents. Recycle and reuse of these solvents produce distillate residues and require treatment before being discharged. This study aimed to evaluate the performance of the biological treatment system in a full-scale wastewater treatment plant that treats wastewater containing distillate residues from the recycling of electronic chemicals. Batch experiments were conducted to investigate the optimal operational conditions for the full-scale wastewater treatment plant. To achieve good nitrogen removal efficiency with effluent ammonia and nitrate concentrations below 20 mg N/L and 50 mg N/L, respectively, it was suggested to control the ammonia concentration and pH of the influent below 500 mg N/L and 8.0, respectively. In addition, the biodegradability of N-methylpyrrolidone, diethylene glycol monobutyl ether, and cyclopentanone distillate residues from the electronic chemicals manufacturing process were evaluated under aerobic, anoxic, and anaerobic conditions. N-methylpyrrolidone and cyclopentanone distillate residues were suggested to be treated under anoxic condition. However, substrate inhibition occurred when using cyclopentanone distillate residue as a carbon source with chemical oxygen demand (COD) levels higher than 866 mg/L and nitrate levels higher than 415 mg N/L. Under aerobic condition, the COD from both N-methylpyrrolidone and cyclopentanone distillate residues could be easily degraded. Nevertheless, a negative effect on nitrification was observed, with a prolonged lag time for ammonia oxidation as the initial COD concentration increased. The specific ammonia oxidation rate and nitrate production rate decreased under high COD concentration contributed by N-methylpyrrolidone and cyclopentanone distillate residues. Furthermore, the biodegradability of diethylene glycol monobutyl ether distillate residue was found to be low under aerobic, anoxic, and anaerobic conditions. With respect to the abundance of nitrogen removal microorganisms in the wastewater treatment plant, results showed that Comammox may have an advantage over ammonia oxidizing bacteria under high pH conditions. In addition, Comammox may have higher resistance to environmental changes. Dominance of Comammox over ammonia oxidizing bacteria under high ammonia condition was first reported in this study.
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Biodegradação Ambiental , Ciclopentanos , Etilenoglicóis , Nitrogênio , Pirrolidinonas , Eliminação de Resíduos Líquidos , Águas Residuárias , Poluentes Químicos da Água , Águas Residuárias/química , Eliminação de Resíduos Líquidos/métodos , Ciclopentanos/química , Pirrolidinonas/química , Etilenoglicóis/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química , Amônia/química , Amônia/análise , Solventes/químicaRESUMO
Anammox process offers reduced operational cost and energy requirement compared to nitrification-denitrification methods due to lower biomass generation and no need for external carbon sources and aeration. High ammonia concetration and low biodegradable anaerobic digester of swaine wastewater provided an advantage for the growth of anammox microorangism. An anoxic/oxic (A/O) SBR and an anammox SBR were implemented parallelly to treat the same swine wastewater with partial nitrification/denitrification and partial nitrification/anammox process, respectively, and to compare their nitrogen removal efficiency. The nitrogen removal rates (NRRs) of the A/O SBR and anammox SBR were 0.054 and 0.26 kg-N/m3/day, respectively. The lower NRR of the A/O SBR could be attributed to insufficient biodegradable organic carbon sources in the denitrification process. The kinetic parameters obtained from the two SBRs were applied to estimate the time required for using the A/O process and partial nitrification/anammox process to treat the same amount of ammonia with the same reaction volume. Results showed that the A/O process required 3.3 times the reaction time of the partial nitrification/anammox process, suggesting that the partial nitrification/anammox process is a more efficient and economic nitrogen removal process for swine wastewater treatment. The next generation sequencing results revealed that Candidatus Brocadia, ranging from 10 to 23%, was the predominant anammox bacteria in the anammox SBR. More than 78.2 % of nitrite in the anammox SBR was removed through the anammox reaction.
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This study investigated the performance of the full-scale unit over a two-year period to enhance nitrification efficiency and provide operational strategies. Results indicated that raw water quality from Donggan River was notably influenced by seasonal variations, particularly during dry and wet seasons, impacting the nitrification efficiency of the biological pretreatment process. Factors such as influent concentrations of ammonia and total Kjeldahl nitrogen were found to have significant effects on nitrification, with temperature and conductivity also showing correlations. The specific rate of ammonia removal was calculated to be approximately 0.1 kg-N/m3/d under the existing operational setup. Moreover, elevating dissolved oxygen levels above 4 mg/L was proposed to potentially boost ammonia oxidation based on findings from experiments conducted in lab-scale bioreactors. In times of increased influent ammonia levels, the elimination of about 1-3 mg-N/L of total nitrogen signified the activation of denitrification processes. This observation was corroborated by results from next-generation sequencing techniques, verifying the existence of denitrifying microorganisms. The real-time PCR analysis results indicated that the abundance of comammox amoA gene was comparable with the abundance of the AOB amoA gene, indicating the presence of comammox Nitrospira and their potential role on nitrification in the system.
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Amônia , Reatores Biológicos , Água Potável , Nitrificação , Nitrogênio , Estações do Ano , Purificação da Água , Água Potável/química , Água Potável/microbiologia , Nitrogênio/análise , Reatores Biológicos/microbiologia , Amônia/análise , Amônia/metabolismo , Purificação da Água/métodos , Desnitrificação , Microbiota , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/metabolismo , Bactérias/metabolismo , Bactérias/genética , Bactérias/classificação , Rios/química , Rios/microbiologiaRESUMO
This study examined the hypothesis that different inorganic carbon (IC) conditions enrich different ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) populations by operating two laboratory-scale continuous-flow bioreactors fed with 15 and 100 mg IC/L, respectively. During this study, both bioreactors maintained satisfactory nitrification performance and stably oxidized 250 mg N/L of influent ammonium without nitrite accumulation. Based on results of cloning/sequencing and terminal restriction fragment length polymorphism targeting on the ammonia monooxygenase subunit A (amoA) gene, Nitrosomonas nitrosa lineage was identified as the dominant AOB population in the high-IC bioreactor, while Nitrosomonas europaea and Nitrosomonas nitrosa lineage AOB were dominant in the low-IC bioreactor. Results of real-time polymerase chain reactions for Nitrobacter and Nitrospira 16S rRNA genes indicated that Nitrospira was the predominant NOB population in the high-IC bioreactor, while Nitrobacter was the dominant NOB in the low-IC bioreactor. Furthermore, batch experiment results suggest that N. europaea and Nitrobacter populations are proliferated in the low-IC bioreactor due to their higher rates under low IC conditions despite the fact that these two populations have been identified as weak competitors, compared with N. nitrosa and Nitrospira, under low ammonium/nitrite environments. This study revealed that in addition to ammonium/nitrite concentrations, limited IC conditions may also be important in selecting dominant AOB/NOB communities of nitrifying bioreactors.
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Amônia/metabolismo , Bactérias/isolamento & purificação , Bactérias/metabolismo , Carbono/metabolismo , Nitritos/metabolismo , Bactérias/classificação , Bactérias/genética , Reatores Biológicos/microbiologia , Dados de Sequência Molecular , Nitrificação , Oxirredução , Filogenia , Esgotos/microbiologiaRESUMO
Although the success rates of non-surgical treatments for Graves' disease such as antithyroid medication and radioiodine ablation were good, there were still failure of treatments or intolerance for some patients. Traditional thyroid surgery could treat these patients but result in unaesthetic neck scars. Herein, we report the preliminary results of our combination of treatments with the transoral endoscopic thyroidectomy vestibular approach for Graves' disease. A retrospective review of patients who underwent the transoral endoscopic thyroidectomy vestibular approach for the treatment of different sizes of goiters between January 2019 and December 2020 was performed. The demographic and clinical data of patients were collected. All patients were followed up for > 12 months. Each patient's goiter size was determined using four grades-from 0 to 3. In total, 14 female patients receiving the combination treatment with > 1 year of follow-up and a median (range) age of 35 (20-48) years at surgery were included. There were two, three, four, and five patients with grade 0, 1, 2, and 3 goiters, respectively. The median (range) intraoperative blood loss was higher in grade 3 patients (100 [20-850] mL) than in grade 2 patients (20 [10-200] mL) and grade 1 and 0 patients (both < 10 mL) (p = 0.033). All patients had normal-looking necks with a euthyroid or hypothyroid status within 1 year. There were no complications, including re-operation for bleeding, hypoparathyroidism, vocal cord palsy, or infections. The designed combination treatment with the transoral endoscopic thyroidectomy vestibular approach for Graves' disease provides optimal cosmetic results with a high success rate.
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Bócio , Doença de Graves , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Tireoidectomia/efeitos adversos , Tireoidectomia/métodos , Radioisótopos do Iodo , Doença de Graves/cirurgia , Doença de Graves/etiologia , Endoscopia/métodos , Bócio/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: Chronic mTORC1 activation in skeletal muscle is linked with age-associated loss of muscle mass and strength, known as sarcopenia. Genetic activation of mTORC1 by conditionally ablating mTORC1 upstream inhibitor TSC1 in skeletal muscle accelerates sarcopenia development in adult mice. Conversely, genetic suppression of mTORC1 downstream effectors of protein synthesis delays sarcopenia in natural aging mice. mTORC1 promotes protein synthesis by activating ribosomal protein S6 kinases (S6Ks) and inhibiting eIF4E-binding proteins (4EBPs). Whole-body knockout of S6K1 or muscle-specific over-expression of a 4EBP1 mutant transgene (4EBP1mt), which is resistant to mTORC1-mediated inhibition, ameliorates muscle loss with age and preserves muscle function by enhancing mitochondria activities, despite both transgenic mice showing retarded muscle growth at a young age. Why repression of mTORC1-mediated protein synthesis can mitigate progressive muscle atrophy and dysfunction with age remains unclear. METHODS: Mice with myofiber-specific knockout of TSC1 (TSC1mKO), in which mTORC1 is hyperactivated in fully differentiated myofibers, were used as a mouse model of sarcopenia. To elucidate the role of mTORC1-mediated protein synthesis in regulating muscle mass and physiology, we bred the 4EBP1mt transgene or S6k1 floxed mice into the TSC1mKO mouse background to generate 4EBP1mt-TSC1mKO or S6K1-TSC1mKO mice, respectively. Functional and molecular analyses were performed to assess their role in sarcopenia development. RESULTS: Here, we show that 4EBP1mt-TSC1mKO, but not S6K1-TSC1mKO, preserved muscle mass (36.7% increase compared with TSC1mKO, P < 0.001) and strength (36.8% increase compared with TSC1mKO, P < 0.01) at the level of control mice. Mechanistically, 4EBP1 activation suppressed aberrant protein synthesis (two-fold reduction compared with TSC1mKO, P < 0.05) and restored autophagy flux without relieving mTORC1-mediated inhibition of ULK1, an upstream activator of autophagosome initiation. We discovered a previously unidentified phenotype of lysosomal failure in TSC1mKO mouse muscle, in which the lysosomal defect was also conserved in the naturally aged mouse muscle, whereas 4EBP1 activation enhanced lysosomal protease activities to compensate for impaired autophagy induced by mTORC1 hyperactivity. Consequently, 4EBP1 activation relieved oxidative stress to prevent toxic aggregate accumulation (0.5-fold reduction compared with TSC1mKO, P < 0.05) in muscle and restored mitochondrial homeostasis and function. CONCLUSIONS: We identify 4EBP1 as a communication hub coordinating protein synthesis and degradation to protect proteostasis, revealing therapeutic potential for activating lysosomal degradation to mitigate sarcopenia.
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Alvo Mecanístico do Complexo 1 de Rapamicina , Sarcopenia , Animais , Camundongos , Modelos Animais de Doenças , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos Knockout , Camundongos Transgênicos , Sarcopenia/genética , Sarcopenia/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismoRESUMO
BACKGROUND Thyroid incidentalomas are typically nonpalpable thyroid nodules discovered during radiographic evaluation for a non-thyroid issue. Thyroid incidentalomas visualized by computed tomography (CT) and ¹8F-flurodeoxyglucose (FDG) positron emission tomography (PET) before living donor liver transplantation (LDLT) are rare. The aim of the study was to analyze the clinical impact of thyroid incidentalomas discovered prior to transplantation. MATERIAL AND METHODS This retrospective study recruited 1010 patients undergoing LDLT between 2010 and 2019. CT was performed on each patient, whereas PET was performed on randomized patients (n=498). RESULTS The prevalence and malignant risk of thyroid incidentaloma on CT was 2.3% (23/1010) and 13.0% (3/23), respectively. The prevalence of thyroid incidentaloma on PET was 3.0% (15/498). Approximately half of the FDG uptake on PET was diffuse uptake (n=7), whereas the other half was focal uptake (n=8). The malignant risk of PET incidentaloma with focal FDG uptake was 37.5% (3/8). Four asymptomatic thyroid cancers were identified incidentally. After total thyroidectomy followed by LDLT, these patients maintained cancer-free status. CONCLUSIONS Thyroid incidentalomas occurred at a rate of 2-3% in LDLT candidates. The malignant risk was 13.0% on CT incidentaloma, and 37.5% on PET incidentaloma with focal FDG uptake. Curative treatment of incidental thyroid cancer followed by LDLT without delay can achieve a favorable prognosis.
Assuntos
Transplante de Fígado , Neoplasias da Glândula Tireoide , Fluordesoxiglucose F18 , Humanos , Achados Incidentais , Doadores Vivos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To find changes in voice quality, airway invasion during swallowing, pharyngeal residue after swallowing, acoustic and aerodynamic measurements and pulmonary function tests after total parathyroidectomy plus auto-transplantation for secondary hyperparathyroidism. METHODS: We recruited 38 patients who underwent successful surgery for secondary hyperparathyroidism in this study. Voice quality was evaluated using voice handicap index (VHI-10), eating assessment tool (EAT-10), voice impairment, and the grade, roughness, breathiness, asthenia, strain (GRBAS) scale. Acoustic and aerodynamic measurements included fundamental frequency (F0), maximal phonation time, high pitch, jitter, s/z, shimmer and noise-to-harmonic ratio. Vocal cord mobility, vocal cord closure, premature spillage, the penetration-aspiration scale and the Yale pharyngeal residue severity rating scale (PRSRS) after swallowing were examined using fiber-optic endoscopy. Pulmonary function tests included forced vital capacity, forced expiratory volume in 1 s, bronchodilator test, total lung capacity, diffusion capacity of the lung for carbon monoxide, alveolar volume, and distance and O2 desaturation of the 6 min walking test (6MWT). RESULTS: Four months after successful parathyroidectomy, VHI-10 improved significantly (p < 0.01); incomplete vocal cord closure decreased significantly (p < 0.01); the Yale PRSRS for vallecula and pyriform sinus improved significantly (p = 0.02 and p = 0.02); F0 and high pitch increased significantly (p < 0.01 and p = 0.01); O2 desaturation (<4%) of 6MWT improved significantly (p = 0.04). CONCLUSIONS: Parathyroidectomy for secondary hyperparathyroidism can improve the voice quality, vocal cord closure, the Yale PRSRS for vallecular and pyriform sinus and O2 desaturation of 6MWT, and increase F0 and high pitch.
Assuntos
Hiperparatireoidismo Secundário , Qualidade da Voz , Broncodilatadores , Monóxido de Carbono , Deglutição , Humanos , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/cirurgia , Pulmão , ParatireoidectomiaRESUMO
This study investigated biological treatment for two kinds of volatile organic compounds (VOCs)-containing wastewaters collected from wet scrubbers in a semiconductor industry. Batch test results indicated that one wastewater containing highly volatile organic compounds was not suitable for aerated treatment conditions while the other containing much lower volatile organic compounds was suitable for aerobic treatment. Accordingly, two moving bed bioreactors, by adding commercial biocarrier BioNET, were operated under aerobic and anoxic conditions for treating low volatility wastewater (LVW) and high volatility wastewater (HVW), respectively. During 280 days of operation, the aerobic LVW bioreactor attained the highest chemical oxygen demand (COD) removal rate of 98.9 mg-COD/L/h with 81% of COD removal efficiency at hydraulic retention time (HRT) of 1 day. The anoxic HVW bioreactor performed above 80% of COD removal efficiency with the highest COD removal rate of 16.5 mg-COD/L/h at HRT of 2 days after 380 days of operation. The specific COD removal rates at different initial substrate-to-biomass (S0/X0) ratios, using either suspended sludge or microorganisms attached onto BioNET from both bioreactors, followed the Monod-type kinetics, while the half-saturation coefficients were generally higher for the microorganisms onto BioNET due presumably to relatively poor mass transfer efficiency. Based on the results of microbial community analysis using the next generation sequencing technique, the dominant communities of suspended sludge and BioNET, including nitrifiers, denitrifiers, and degraders for polycyclic aromatic hydrocarbons, were similar in the corresponded bioreactors, but microbial community shifts were observed with increased organic loadings.