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Selenoprotein I (Selenoi) is highly expressed in liver and plays a key role in lipid metabolism as a phosphatidylethanolamine (PE) synthase. However, the precise function of Selenoi in the liver remains elusive. In the study, we generated hepatocyte-specific Selenoi conditional knockout (cKO) mice on a high-fat diet to identify the physiological function of Selenoi. The cKO group exhibited a significant increase in body weight, with a 15.6% and 13.7% increase in fat accumulation in white adipose tissue (WAT) and the liver, respectively. Downregulation of the lipolysis-related protein (p-Hsl) and upregulation of the adipogenesis-related protein (Fasn) were observed in the liver of cKO mice. The cKO group also showed decreased oxygen consumption (VO2), carbon dioxide production (VCO2), and energy expenditure (p < .05). Moreover, various metabolites of the steroid hormone synthesis pathway were affected in the liver of cKO mice. A potential cascade of Selenoi-phosphatidylethanolamine-steroid hormone synthesis might serve as a core mechanism that links hepatocyte-specific Selenoi cKO to biochemical and molecular reactions. In conclusion, we revealed that Selenoi inhibits body fat accumulation and hepatic steatosis and elevates energy consumption; this protein could also be considered a therapeutic target for such related diseases.
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Hígado Graso , Hepatocitos , Ratones Noqueados , Obesidad , Animales , Ratones , Obesidad/metabolismo , Obesidad/genética , Obesidad/etiología , Hepatocitos/metabolismo , Hígado Graso/metabolismo , Hígado Graso/etiología , Hígado Graso/genética , Hígado Graso/patología , Selenoproteínas/metabolismo , Selenoproteínas/genética , Dieta Alta en Grasa/efectos adversos , Masculino , Hígado/metabolismo , Metabolismo Energético , Metabolismo de los Lípidos , Ratones Endogámicos C57BL , Tejido Adiposo Blanco/metabolismoRESUMEN
BACKGROUND: The long reads of the third-generation sequencing significantly benefit the quality of the de novo genome assembly. However, its relatively high single-base error rate has been criticized. Currently, sequencing accuracy and throughput continue to improve, and many advanced tools are constantly emerging. PacBio HiFi sequencing and Oxford Nanopore Technologies (ONT) PromethION are two up-to-date platforms with low error rates and ultralong high-throughput reads. Therefore, it is urgently needed to select the appropriate sequencing platforms, depths and genome assembly tools for high-quality genomes in the era of explosive data production. METHODS: We performed 455 (7 assemblers with 4 polishing pipelines or without polishing on 13 subsets with different depths) and 88 (4 assemblers with or without polishing on 11 subsets with different depths) de novo assemblies of Yeast S288C on high-coverage ONT and HiFi datasets, respectively. The assembly quality was evaluated by Quality Assessment Tool (QUAST), Benchmarking Universal Single-Copy Orthologs (BUSCO) and the newly proposed Comprehensive_score (C_score). In addition, we applied four preferable pipelines to assemble the genome of nonreference yeast strains. RESULTS: The assembler plays an essential role in genome construction, especially for low-depth datasets. For ONT datasets, Flye is superior to other tools through C_score evaluation. Polishing by Pilon and Medaka improve accuracy and continuity of the preassemblies, respectively, and their combination pipeline worked well in most quality metrics. For HiFi datasets, Flye and NextDenovo performed better than other tools, and polishing is also necessary. Enough data depth is required for high-quality genome construction by ONT (>80X) and HiFi (>20X) datasets.
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Genoma Fúngico , Secuenciación de Nucleótidos de Alto Rendimiento , Saccharomyces cerevisiae , Genoma , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Saccharomyces cerevisiae/genética , Análisis de Secuencia de ADN/métodosRESUMEN
Zymomonas mobilis metabolizes sugar anaerobically through the Entner-Doudoroff pathway with less ATP generated for lower biomass accumulation to direct more sugar for product formation with improved yield, making it a suitable host to be engineered as microbial cell factories for producing bulk commodities with major costs from feedstock consumption. Self-flocculation of the bacterial cells presents many advantages, such as enhanced tolerance to environmental stresses, a prerequisite for achieving high product titers by using concentrated substrates. ZM401, a self-flocculating mutant developed from ZM4, the unicellular model strain of Z. mobilis, was employed in this work to explore the molecular mechanism underlying this self-flocculating phenotype. Comparative studies between ZM401 and ZM4 indicate that a frameshift caused by a single nucleotide deletion in the poly-T tract of ZMO1082 fused the putative gene with the open reading frame of ZMO1083, encoding the catalytic subunit BcsA of the bacterial cellulose synthase to catalyze cellulose biosynthesis. Furthermore, the single nucleotide polymorphism mutation in the open reading frame of ZMO1055, encoding a bifunctional GGDEF-EAL protein with apparent diguanylate cyclase/phosphodiesterase activities, resulted in the Ala526Val substitution, which consequently compromised in vivo specific phosphodiesterase activity for the degradation of cyclic diguanylic acid, leading to intracellular accumulation of the signaling molecule to activate cellulose biosynthesis. These discoveries are significant for engineering other unicellular strains from Z. mobilis with the self-flocculating phenotype for robust production. IMPORTANCE Stress tolerance is a prerequisite for microbial cell factories to be robust in production, particularly for biorefinery of lignocellulosic biomass to produce biofuels, bioenergy, and bio-based chemicals for sustainable socioeconomic development, since various inhibitors are released during the pretreatment to destroy the recalcitrant lignin-carbohydrate complex for sugar production through enzymatic hydrolysis of the cellulose component, and their detoxification is too costly for producing bulk commodities. Although tolerance to individual stress has been intensively studied, the progress seems less significant since microbial cells are inevitably suffering from multiple stresses simultaneously under production conditions. When self-flocculating, microbial cells are more tolerant to multiple stresses through the general stress response due to enhanced quorum sensing associated with the morphological change for physiological and metabolic advantages. Therefore, elucidation of the molecular mechanism underlying such a self-flocculating phenotype is significant for engineering microbial cells with the unique multicellular morphology through rational design to boost their production performance.
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Zymomonas , Celulosa/metabolismo , Floculación , Hidrolasas Diéster Fosfóricas/metabolismo , Azúcares/metabolismo , Zymomonas/genética , Zymomonas/metabolismoRESUMEN
Zymomonas mobilis is a gram-negative facultative anaerobic spore, which is generally recognized as a safe. As a promising ethanologenic organism for large-scale bio-ethanol production, Z. mobilis has also shown a good application prospect in food processing and food additive synthesis for its unique physiological characteristics and excellent industrial characteristics. It not only has obvious advantages in food processing and becomes the biorefinery chassis cell for food additives, but also has a certain healthcare effect on human health. Until to now, most of the research is still in theory and laboratory scale, and further research is also needed to achieve industrial production. This review summarized the physiological characteristics and advantages of Z. mobilis in food industry for the first time and further expounds its research status in food industry from three aspects of food additive synthesis, fermentation applications, and prebiotic efficacy, it will provide a theoretical basis for its development and applications in food industry. This review also discussed the shortcomings of its practical applications in the current food industry, and explored other ways to broaden the applications of Z. mobilis in the food industry, to promote its applications in food processing.
Potential applications of Zymomonas mobilis in food industry summarized for the first time.Research status of Z. mobilis in food additive synthesis, fermentation applications, and probiotics are discussed in details.Future research perspectives of Z. mobilis in food industry further proposed.
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Withanolides from six parts (flower, leaf, stem, root, seed, and peel) of Datura metel L. (D metel L.) obtained from ten production areas in China were identified and quantified by UPLC-MS/MS. A total of 85 withanolides were characterized for the first time using the UPLC-Q-TOF-MS/MS system. Additionally, a simultaneous, rapid and accurate measurement method was developed for the determination of 22 bioactive withanolides from ten production areas with the UPLC-Q-TRAP-MS/MS system. The results show the total withanolide content is highest in the leaves (155640.0 ng/g) and lowest in the roots (14839.8 ng/g). Compared with other production areas, the total content of plants from Dujiangyan was the highest at 82013.9 ng/g (value range of ten areas: 82013.9-42278.5 ng/g). The results also show significant differences in the distribution of withanolides in the different plant parts, as well as across different production areas. This is a breakthrough report providing a simultaneous qualitative and quantitative analysis of 22 withanolides in D. metel L. It could be the basis for the more rational use of various parts of D. metel L., and the expansion of medicinal resources. This work also lays a solid foundation for research on the quality control of D. metel L.
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Factores Biológicos/aislamiento & purificación , Datura metel/química , Extractos Vegetales/normas , Witanólidos/aislamiento & purificación , Factores Biológicos/química , Factores Biológicos/clasificación , China , Flores/química , Frutas/química , Humanos , Extractos Vegetales/química , Hojas de la Planta/química , Raíces de Plantas/química , Tallos de la Planta/química , Plantas Medicinales , Control de Calidad , Semillas/química , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/normas , Witanólidos/química , Witanólidos/clasificaciónRESUMEN
PURPOSE: Higher neutrophil-lymphocyte ratio (NLRs) indicate a pro-inflammatory state and are associated with poor survival. Conversely, higher albumin-globulin ratio (AGRs) may be associated with improved prognosis. We aimed to investigate the association between NLR and AGR and prognosis and survival in patients with breast cancer. METHODS: This retrospective study included all patients with stage I-III breast cancer between 2011 and 2017 in Singapore General Hospital and National Cancer Center Singapore. Multivariate logistic regression analysis of NLR, AGR, age, stage, grade, and subtype was performed. Survival data between groups were compared using Cox regression analysis and log-rank tests. RESULTS: A total of 1,188 patients were included, of whom 323 received neoadjuvant chemotherapy (NACT) and 865 underwent upfront surgery. In patients who underwent NACT, a higher AGR was significantly associated with a higher pCR rate (cut-off > 1.28; odds ratio [OR], 2.03; 95% confidence interval [CI], 1.13-3.74; p = 0.020), better DFS (cut off > 1.55; hazard ratio [HR], 0.37; 95% CI, 0.16-0.85; p = 0.019), and better CSS (cut off > 1.46; HR, 0.39; 95% CI, 0.17-0.92; p = 0.031). Higher NLR was significantly associated with worse DFS (cut off > 4.09; HR, 1.77; 95% CI, 1.07-2.91; p = 0.026) and worse CSS (cut off > 4.09; HR, 1.98; 95% CI, 1.11-3.53; p = 0.021). In patients who underwent upfront surgery, higher AGR correlated with significantly better OS (cut off > 1.17; HR, 0.54; 95% CI, 0.36-0.82; p = 0.004) and higher NLR correlated with worse OS (cut off > 2.38; HR, 1.63; 95% CI, 1.09-2.44; p = 0.018). CONCLUSION: NLR and AGR are useful in predicting the response to NACT as well as prognosis of patients with breast cancer. Further studies are needed to explore their value in clinical decision making.
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Zymomonas mobilis is a potential alternative of Saccharomyces cerevisiae to produce cellulosic ethanol with strengths in cofactor balance, but its lower tolerance to inhibitors in the lignocellulosic hydrolysate restricts the application. Although biofilm can improve bacteria stress tolerance, regulating biofilm formation in Z. mobilis is still a challenge. In this work, we constructed a pathway by heterologous expressing pfs and luxS from Escherichia coli in Z. mobilis to produce AI-2 (autoinducer 2), a universal quorum-sensing signal molecule, to control cell morphology for enhancing stress tolerance. Unexpectedly, the results suggested that neither endogenous AI-2 nor exogenous AI-2 promoted biofilm formation, while heterologous expression of pfs can significantly raise biofilm. Therefore, we proposed that the main factor in assisting biofilm formation was the product accumulated due to heterologous expression of pfs, like methylated DNA. Consequently, ZM4::pfs produced more biofilm, which presented an enhanced tolerance to acetic acid. All these findings provide a novel strategy to improve the stress tolerance of Z. mobilis by enhancing biofilm formation for efficient production of lignocellulosic ethanol and other value-added chemical products.
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BiobraneTM is a popular biosynthetic semi-permeable skin substitute conventionally applied onto non-excised partial thickness burn wounds to facilitate healing. The use of BiobraneTM for definitive coverage after excision of partial-thickness thermal burns has not been reported. We highlighted our experience of immediate BiobraneTM application for definitive coverage of tangentially-excised partial thickness thermal burn wounds in four patients. This technique is safe and efficient, minimizes painful and costly dressing changes, avoids the complications associated with autologous skin grafting, and eliminates the unpredictability of burns wound conversion. We believe this method expands the indications for BiobraneTM usage, accelerates wound healing, and provides better aesthetic outcomes.
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Healthy mothers and children are essential to maintaining and expanding national prosperity. This article reviews maternal and child health policies in several countries, including the United States, Canada, United Kingdom, Norway, Denmark, Japan, Singapore, and Republic of Korea. Comparing and considering the policy experiences of different countries can provide references for designing and revising women's and children's health care policies in Taiwan. Secondary data used in this study were retrieved from a variety of resources including websites of the World Health Organization and various national governments, official publications, and articles related to women's and children's health. The life cycles of women and children embraces differing needs at different stages (e.g., preconception, pregnancy, postpartum, newborn, infant, and young adulthood). To meet these needs, a broad spectrum of policies offers different levels of coverage. Strengthened cooperation among agencies and with nongovernmental organizations is needed to achieve goals. This review showed that countries with greater achievements in women's and children's health focus on families and manage effective cooperation between departments to execute policies. The successes of such policies may be referenced by Taiwanese policymakers and government officials.
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Protección a la Infancia , Política de Salud , Bienestar Materno , Niño , Femenino , Humanos , EmbarazoRESUMEN
BACKGROUND: In this case study, a minimally invasive transalveolar approach using platelet-rich fibrin and bone substitute with simultaneous implantation was carried out in an elderly patient. We analyzed the cone-beam computed tomography (CBCT) findings to evaluate bone regeneration. CASE SUMMARY: A 65-year-old female with no contraindications for dental implants and loss of maxillary bilateral molars is described. Examination by CBCT showed the available vertical bone height in the bilateral posterior maxilla was 0.5-6.8 mm in the left and 2.8-6.5 mm in the right. The patient underwent a transalveolar approach using platelet-rich fibrin and bone substitute with simulataneous placement of an implant 10 mm in length. Six months post-surgery, the implant showed excellent osseointegration with the bone graft. Thereafter, full-ceramic crowns were fitted. Follow-up at 2 years demonstrated satisfactory prognosis. CONCLUSION: Platelet-rich fibrin and bone substitute can be used to augment the maxillary sinus with a vertical bone height less than 4 mm.
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Nine new (1-9) and three known (10-12) sesquiterpenoids were isolated from the ethanol-water (7:3, v/v) extract of the Datura metel L. leaves. The structures of 1-9 were elucidated by detailed spectroscopic analyses, including 1D and 2D NMR, HR-ESI-MS. All isolates (1-12) were evaluated for anti-inflammatory activity against the production of nitrogen oxide in lipopolysaccharide-induced RAW264.7 cells and compound 5 possessed the best inhibitory effect among them, with the IC50 value reaching 9.33-11.67 µM, which was lower than positive control, L-NMMA, with IC50 range from 13.64 to 17.02 µM.
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Antiinflamatorios/aislamiento & purificación , Datura metel/química , Sesquiterpenos/aislamiento & purificación , Animales , Antiinflamatorios/química , Ratones , Células RAW 264.7 , Sesquiterpenos/químicaRESUMEN
Breast cancer is the most common diagnosed malignancy in women. This study genotyped blood samples from 236 Han Chinese women with breast cancer and 128 healthy controls for single nucleotide polymorphisms (SNPs) rs2977537, rs2929970, rs2929973, rs2977530, and rs62514004, to determine whether these WNT1-inducible signaling pathway protein 1 (WISP-1) genetic polymorphisms increase the risk of developing breast cancer. Compared with wild-type (AA) carriers, those carrying the WISP1 rs62514004 AG or AGâ+âGG genetic variants had a greater risk of developing breast cancer. In an evaluation of the association between clinicopathological aspects and the WISP1 SNP rs62514004 in the breast cancer cohort, patients with the GG genotype were less likely than those with the AA genotype to develop stage III/IV disease. Patients carrying the WISP1 rs2929973 GGâ+âTT variant were almost twice as likely as those carrying the GT genotype to have estrogen receptor (ER)- and progesterone receptor (PR)-positive tumors, while those with the WISP1 rs62514004 AGâ+âGG genetic variants were around twice as likely as those with the AA genotype to have HER2-positive tumors. This study details risk associations between WISP1 SNPs and breast cancer susceptibility in women of Han Chinese ethnicity.
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Pueblo Asiatico/genética , Neoplasias de la Mama/genética , Proteínas CCN de Señalización Intercelular/genética , Polimorfismo de Nucleótido Simple , Proteínas Proto-Oncogénicas/genética , Adulto , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Persona de Mediana Edad , Receptor ErbB-2/análisis , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Factores de Riesgo , Transducción de SeñalRESUMEN
INTRODUCTION: Although an uncommon form of admission to a burns centre, the deep, penetrating nature of noxious currents mean that electrical burns have the most catastrophic consequences of all burn injuries. Understanding the physics of electricity is crucial to explaining the mechanisms of tissue damage and organ failure in electrical injuries which necessitate special management above and beyond that of regular thermal burns. PRESENTATION OF CASE: We present a young man who suffered significant occupation-related electrical burns that was complicated by compartment syndrome, rhabdomyolysis and acute kidney injury. He required multiple surgeries (including fasciotomy as well as soft tissue reconstruction), critical care and lengthy rehabilitation. DISCUSSION: Rhabdomyolysis is common sequela of electrical burns and may result in severe and permanent metabolic and renal impairment. High cut-off dialysis membranes have shown great promise in myoglobin removal but further studies are required to determine whether this improves clinical outcomes. Debridement and decompression are the cornerstones of initial surgical intervention and are crucial to minimising infectious complications and preserving vital structures. Free tissue transfer has become increasingly popular, but the ideal timing of microsurgery is still uncertain. Nonetheless, pedicled flaps remain widely used and still have an important role in reconstruction of electrical burns. CONCLUSION: Patients with electrical injuries have several unique acute manifestations that differ from other burns. Prognosticating outcomes is difficult, as the full scale of damage is seldom immediately evident. Multiple organ systems are often affected, which makes the treatment of such patients exceptionally challenging, multi-disciplinary and resource-intensive.
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OBJECTIVE: To evaluate the efficacy of ropivacaine injection at the acupoints Hegu and Sanyinjiao for labor analgesia and its effects on cortisol level in parturients. METHODS: A total of 120 ASA class I-II nulliparous women undergoing spontaneous term labor (37 to 41 weeks of gestation) with a live, singleton fetus in the occiput anterior position and requiring labor analgesia with acupuncture were enrolled in this study. These women were randomized into study group and control group and received injections of 1 mL of 0.2% ropivacaine and normal saline, respectively, at each of the acupoints of bilateral Sanyinjiao and Hegu in the first stage of labor. The Visual Analogue Scale (VAS) before and at 30, 60 and 120 min after analgesia, the time of labor, delivery outcome and cortisol levels were compared between the two groups. RESULTS: The VAS was significantly lower in the study group than in the control group (P<0.05). At 120 min after injections of ropivacaine or saline, serum cortisol level was significantly higher in the control group than in the study group (P<0.05). The rates of cesarean section and instrumental delivery and the time of labor were all similar between the two groups (P>0.05). CONCLUSION: Ropivacaine injection at Hegu and Sanyinjiao is effective for labor analgesia and does not prolong the process of labor or increase the rates of cesarean section or instrumental delivery.
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Puntos de Acupuntura , Analgesia Obstétrica , Anestésicos Locales/administración & dosificación , Hidrocortisona/sangre , Ropivacaína/administración & dosificación , Cesárea/estadística & datos numéricos , Femenino , Humanos , EmbarazoRESUMEN
OBJECTIVE: To observe the anesthetic effect and safety of different doses of dexmedetomidine combined with ropivacaine for brachial plexus nerve block in children undergoing polydactyly surgery. METHODS: Eighty children undergoing polydactyly surgery were randomized into 4 groups to receive brachial plexus nerve block with dexmedetomidine at 0.25, 0.50 or 0.75 µg/kg combined with 0.25% ropivacaine (0.20 mL/kg) (D1, D2, and D3 groups, respectively) or with 0.25% ropivacaine (0.20 mL/kg) only (control group). The onset time, duration of brachial plexus nerve block, awakening time, success rate, and incidence of complications were compared among the groups. Results In D2 and D3 groups, the onset time and awakening time were shorter and anesthesia lasted longer than those in the control group. The onset time and awakening time were shorter and anesthesia maintenance time was longer in D3 group than in D1 group. The success rates of brachial plexus nerve block were significantly higher in D1-3 groups than in the control group (P<0.05). Hematoma was found in one of the patients. In each of the 4 groups, laryngeal nerve block occurred in 1 child and respiratory depression in another; 2 or 3 patients had Horner syndrome, and 1 patient in D3 group experienced an episode of lowered heart beat to below 70 min-1. All the complications were managed properly and the patients all recovered uneventfully. CONCLUSION: Brachial plexus nerve block with 0.5 µg/kg dexmedetomidine combined with 0.25% ropivacaine (0.20 mL/kg) is safe for effective anesthesia in children undergoing surgery for polydactyly.
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Amidas/administración & dosificación , Anestésicos Locales/administración & dosificación , Plexo Braquial/efectos de los fármacos , Dexmedetomidina/administración & dosificación , Bloqueo Nervioso , Polidactilia/cirugía , Niño , Método Doble Ciego , Humanos , RopivacaínaRESUMEN
Several observations of the Nb long-lived Mossbauer phenomena are presented, in consequence of an irradiation increased by an order of magnitude compared with previous work. These are 1) two ß decays of 182Ta and 92mNb are enhanced, i.e., 182Ta is now 200 times faster than in previous results while 92mNb is twice as fast as normal; 2) γs emitted from two ß decays compete to eject electrons in a winner-takes-all rule, rather than by superposition; 3) abrupt spectral changes reveal three decay phases of 182Ta; 4) the biphoton γγ of 93mNb is released from the sample for the first time; 5) the γγ distribution is narrow, in contrast to the broad γγ spectrum obtained from independent nuclei; 6) Nb K-lines super-radiate along the long sample axis; 7) collective scattering of multipolar MeV γs. The manipulation of nuclear decay speeds demonstrated here highlights a potential application of this work in cleaning up the nuclear wastes.