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BACKGROUND AND AIMS: Although the benefits of vertical sleeve gastrectomy (VSG) surgery are well known, the molecular mechanisms by which VSG alleviates obesity and its complications remain unclear. We aim to determine the role of CYP8B1 (cytochrome P450, family 8, subfamily B, polypeptide 1) in mediating the metabolic benefits of VSG. APPROACH AND RESULTS: We found that expression of CYP8B1, a key enzyme in controlling the 12α-hydroxylated (12α-OH) bile acid (BA) to non-12α-OH BA ratio, was strongly downregulated after VSG. Using genetic mouse models of CYP8B1 overexpression, knockdown, and knockout, we demonstrated that overexpression of CYP8B1 dampened the metabolic improvements associated with VSG. In contrast, short hairpin RNA-mediated CYP8B1 knockdown improved metabolism similar to those observed after VSG. Cyp8b1 deficiency diminished the metabolic effects of VSG. Further, VSG-induced alterations to the 12α-OH/non-12α-OH BA ratio in the BA pool depended on CYP8B1 expression level. Consequently, intestinal lipid absorption was restricted, and the gut microbiota (GM) profile was altered. Fecal microbiota transplantation from wild type-VSG mice (vs. fecal microbiota transplantation from wild-type-sham mice) improved metabolism in recipient mice, while there were no differences between mice that received fecal microbiota transplantation from knockout-sham and knockout-VSG mice. CONCLUSIONS: CYP8B1 is a critical downstream target of VSG. Modulation of BA composition and gut microbiota profile by targeting CYP8B1 may provide novel insight into the development of therapies that noninvasively mimic bariatric surgery to treat obesity and its complications.
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Cirurgia Bariátrica , Esteroide 12-alfa-Hidroxilase , Camundongos , Animais , Esteroide 12-alfa-Hidroxilase/metabolismo , Regulação para Baixo , Obesidade/metabolismo , Gastrectomia , Camundongos Endogâmicos C57BLRESUMO
Indigo is widely used in textile industries for denim garments dyeing and is mainly produced by chemical synthesis which, however, raises environmental sustainability issues. Bio-indigo may be produced by fermentation of metabolically engineering bacteria, but current methods are economically incompetent due to low titer and the need for an inducer. To address these problems, we first characterized several synthetic promoters in E. coli and demonstrated the feasibility of inducer-free indigo production from tryptophan using the inducer-free promoter. We next coupled the tryptophan-to-indigo and glucose-to-tryptophan pathways to generate a de novo glucose-to-indigo pathway. By rational design and combinatorial screening, we identified the optimal promoter-gene combinations, which underscored the importance of promoter choice and expression levels of pathway genes. We thus created a new E. coli strain that exploited an indole pathway to enhance the indigo titer to 123 mg/L. We further assessed a panel of heterologous tryptophan synthase homologs and identified a plant indole lyase (TaIGL), which along with modified pathway design, improved the indigo titer to 235 mg/L while reducing the tryptophan byproduct accumulation. The optimal E. coli strain expressed 8 genes essential for rewiring carbon flux from glucose to indole and then to indigo: mFMO, ppsA, tktA, trpD, trpC, TaIGL and feedback-resistant aroG and trpE. Fed-batch fermentation in a 3-L bioreactor with glucose feeding further increased the indigo titer (≈965 mg/L) and total quantity (≈2183 mg) at 72 h. This new synthetic glucose-to-indigo pathway enables high-titer indigo production without the need of inducer and holds promise for bio-indigo production.
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Vertical sleeve gastrectomy (VSG) is one of the most effective and durable therapies for morbid obesity and its related complications. Although bile acids (BAs) have been implicated as downstream mediators of VSG, the specific mechanisms through which BA changes contribute to the metabolic effects of VSG remain poorly understood. Here, we confirm that high fat diet-fed global farnesoid X receptor (Fxr) knockout mice are resistant to the beneficial metabolic effects of VSG. However, the beneficial effects of VSG were retained in high fat diet-fed intestine- or liver-specific Fxr knockouts, and VSG did not result in Fxr activation in the liver or intestine of control mice. Instead, VSG decreased expression of positive hepatic Fxr target genes, including the bile salt export pump (Bsep) that delivers BAs to the biliary pathway. This reduced small intestine BA levels in mice, leading to lower intestinal fat absorption. These findings were verified in sterol 27-hydroxylase (Cyp27a1) knockout mice, which exhibited low intestinal BAs and fat absorption and did not show metabolic improvements following VSG. In addition, restoring small intestinal BA levels by dietary supplementation with taurocholic acid (TCA) partially blocked the beneficial effects of VSG. Altogether, these findings suggest that reductions in intestinal BAs and lipid absorption contribute to the metabolic benefits of VSG.
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Colestanotriol 26-Mono-Oxigenase/genética , Gastrectomia/métodos , Obesidade Mórbida/cirurgia , Receptores Citoplasmáticos e Nucleares/genética , Animais , Ácidos e Sais Biliares/biossíntese , Ácidos e Sais Biliares/metabolismo , Dieta Hiperlipídica/efeitos adversos , Humanos , Metabolismo dos Lipídeos/genética , Lipídeos/genética , Camundongos , Camundongos Knockout , Obesidade Mórbida/metabolismo , Obesidade Mórbida/fisiopatologia , Redução de Peso/genéticaRESUMO
The present study compared the ipsilateral repeated bout effect (IL-RBE) and contralateral repeated bout effect (CL-RBE) of the elbow flexors (EF) and knee flexors (KF) for the same interval between bouts to shed light on their mechanisms. Fifty-two healthy sedentary young (20-28 years) men were randomly assigned to the IL-EF, IL-KF, CL-EF, and CL-KF groups (n = 13/group). Thirty maximal eccentric contractions of the EF were performed in IL-EF and CL-EF, and 60 maximal eccentric contractions of the KF were performed in IL-KF and CL-KF, with a 2-week interval between bouts. Changes in muscle damage markers such as maximal voluntary contraction (MVC) torque, muscle soreness, and plasma creatine kinase activity, and proprioception measures before to 5 days post-exercise were compared between groups. Changes in all variables were greater (p < 0.05) after the first than second bout for all groups, and the changes were greater (p < 0.05) for the EF than KF. The changes in all variables after the second bout were greater (p < 0.05) for the CL than IL condition for both EF and KF. The magnitude of the average protective effect was similar between CL-EF (33%) and CL-KF (32%), but slightly greater (p < 0.05) for IL-EF (67%) than IL-KF (61%). These demonstrate that the magnitude of CL-RBE relative to IL-RBE was similar between the EF and KF (approximately 50%), regardless of the greater muscle damage for the EF than KF. It appears that the CL-RBE is more associated with neural adaptations at cerebrum, cerebellum, interhemispheric inhibition, and coricospinal tract, but the IL-RBE is induced by additional adaptations at muscles.
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Cotovelo , Músculo Esquelético , Humanos , Masculino , Creatina Quinase , Cotovelo/fisiologia , Contração Isométrica/fisiologia , Músculo Esquelético/fisiologia , Mialgia/prevenção & controle , Adulto Jovem , AdultoRESUMO
Programmed -1 ribosomal frameshifting is an essential regulation mechanism of translation in viruses and bacteria. It is stimulated by mRNA structures inside the coding region. As the structure is unfolded repeatedly by consecutive translating ribosomes, whether it can refold properly each time is important in performing its function. By using single-molecule approaches and molecular dynamics simulations, we found that a frameshift-stimulating RNA pseudoknot folds sequentially through its upstream stem S1 and downstream stem S2. In this pathway, S2 folds from the downstream side and tends to be trapped in intermediates. By masking the last few nucleotides to mimic their gradual emergence from translating ribosomes, S2 can be directed to fold from the upstream region. The results show that the intermediates are greatly suppressed, suggesting that mRNA refolding may be modulated by ribosomes. Moreover, masking the first few nucleotides of S1 favors the folding from S2 and yields native pseudoknots, which are stable enough to retrieve the masked nucleotides. We hypothesize that translating ribosomes can remodel an intermediate mRNA structure into a stable conformation, which may in turn stimulate backward slippage of the ribosome. This supports an interactive model of ribosomal frameshifting and gives an insightful account addressing previous experimental observations.
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Mudança da Fase de Leitura do Gene Ribossômico , Dobramento de RNA , RNA Mensageiro/química , Sequência de Bases , Simulação de Dinâmica Molecular , Conformação de Ácido Nucleico , Pinças Ópticas , Ribossomos/metabolismoRESUMO
Diabetes remains one of the fastest growing chronic diseases and is a leading source of morbidity and accelerated mortality in the world. Loss of beta cell mass (BCM) and decreased sensitivity to insulin underlie diabetes pathogenesis. Yet, the ability to safely and directly assess BCM in individuals with diabetes does not exist. Measures such as blood glucose provide only a crude indirect picture of beta cell health. PET imaging could, in theory, allow for safe, direct, and precise characterization of BCM. However, identification of beta cell-specific radiolabeled tracers remains elusive. G-protein coupled receptor 44 (GPR44) is a transmembrane protein that was characterized in 2012 as highly beta cell-specific within the insulin-positive islets of Langerhans. Accordingly, radiolabeling of existing GPR44 antagonists could be a viable method to accelerate PET tracer development. The present study aims to evaluate and summarize published analogues of the GPR44 antagonist ramatroban to develop 18F-labeled PET tracers for BCM analysis. The 77 corresponding ramatroban analogues containing a fluorine nuclide were characterized for properties including binding affinity, selectivity, and pharmacokinetic and metabolic profile, and 32 compounds with favorable properties were identified. This review illustrates the potential of GPR44 analogues for the development of PET tracers.
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Carbazóis/química , Radioisótopos de Flúor/metabolismo , Células Secretoras de Insulina/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Traçadores Radioativos , Compostos Radiofarmacêuticos/metabolismo , Receptores Imunológicos/metabolismo , Receptores de Prostaglandina/metabolismo , Sulfonamidas/química , Humanos , Células Secretoras de Insulina/química , Células Secretoras de Insulina/citologia , Inibidores da Agregação Plaquetária/químicaRESUMO
The effect of low-impact dance on blood metabolites, the joint range of motion (ROM) of the lower extremities, knee extension torque, bone mass density (BMD), the number of falls, and the confidence to perform daily activities (Modified Falls Efficacy Scale [MFES]) was examined in older sedentary women (age: 59 ± 4 years) before and after a 16-week intervention. Results showed that the average score for the MFES, some parameters of blood chemistry, and joint ROM were significantly improved after low-impact intervention. In addition to improvements in blood lipids and body fat percentages, the increases shown in the parameters regarding the lower extremities may contribute to confidence in performing common daily activities in older women, although the number of falls did not significantly differ between the two groups during the 16-week period.
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Densidade Óssea/fisiologia , Dança/fisiologia , Extremidade Inferior/fisiologia , Amplitude de Movimento Articular/fisiologia , Acidentes por Quedas/estatística & dados numéricos , Atividades Cotidianas , Análise Química do Sangue , Composição Corporal , Feminino , Humanos , Lipídeos/sangue , Pessoa de Meia-Idade , Comportamento Sedentário , TorqueRESUMO
We investigated the roles of IFN regulatory factor (IRF)-3 and IRF-7 in innate antiviral immunity against dengue virus (DENV). Double-deficient Irf-3(-/-)7(-/-) mice infected with the DENV2 strain S221 possessed 1,000-150,000 fold higher levels of viral RNA than wild-type and single-deficient mice 24 h postinfection (hpi); however, they remained resistant to lethal infection. IFN-α/ß was induced similarly in wild-type and Irf-3(-/-) mice post-DENV infection, whereas in the Irf-7(-/-) and Irf-3(-/-)7(-/-) mice, significantly low levels of IFN-α/ß expression was observed within 24 hpi. IFN-stimulated gene induction was also delayed in Irf-3(-/-)7(-/-) mice relative to wild-type and single-deficient mice. In particular, Cxcl10 and Ifnα2 were rapidly induced independently of both IRF-3 and IRF-7 in the Irf-3(-/-)7(-/-) mice with DENV infection. Higher levels of serum IFN-γ, IL-6, CXCL10, IL-8, IL-12 p70, and TNF were also observed in Irf-3(-/-)7(-/-) mice 24 hpi, at which time point viral titers peaked and started to be cleared. Ab-mediated blockade experiments revealed that IFN-γ, CXCL10, and CXCR3 function to restrict DENV replication in Irf-3(-/-)7(-/-) mice. Additionally, the IFN-stimulated genes Cxcl10, Ifit1, Ifit3, and Mx2 can be induced via an IRF-3- and IRF-7-independent pathway that does not involve IFN-γ signaling for protection against DENV. Collectively, these results demonstrate that IRF-3 and IRF-7 are redundant, albeit IRF-7 plays a more important role than IRF-3 in inducing the initial IFN-α/ß response; only the combined actions of IRF-3 and IRF-7 are necessary for efficient control of early DENV infection; and the late, IRF-3- and IRF-7-independent pathway contributes to anti-DENV immunity.
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Vírus da Dengue/imunologia , Dengue/imunologia , Imunidade Inata , Fator Regulador 3 de Interferon/metabolismo , Fator Regulador 7 de Interferon/metabolismo , Interferon-alfa/sangue , Interferon beta/sangue , Proteínas Adaptadoras de Transdução de Sinal , Aedes , Animais , Proteínas de Transporte/metabolismo , Linhagem Celular , Quimiocina CXCL10/biossíntese , Quimiocina CXCL10/sangue , Quimiocina CXCL10/imunologia , Fator Regulador 3 de Interferon/deficiência , Fator Regulador 3 de Interferon/genética , Fator Regulador 7 de Interferon/deficiência , Fator Regulador 7 de Interferon/genética , Interferon gama/sangue , Interferon gama/imunologia , Interleucina-12/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas de Resistência a Myxovirus/metabolismo , Proteínas/metabolismo , RNA Viral/sangue , Proteínas de Ligação a RNA , Receptores CXCR3/imunologia , Transdução de Sinais , Fatores de Necrose Tumoral/sangue , Carga Viral , Replicação Viral/imunologiaRESUMO
In-group heterogeneity is often neglected during investigations of motor development patterns in children. Moreover, the variation in motor development patterns over time has seldom been examined. In this work, 1884 three-year-old preschoolers were selected from a panel study conducted in Taiwan called the National Longitudinal Study of Child Development and Care. A confirmatory factor analysis was applied to analyze the construct validity of the assessments of motor development used for these children. A latent profile analysis and latent transition analysis (LTA) were sequentially applied to clarify their motor development patterns at the ages of three and four years and their transitions between these two ages. The following findings were obtained: (1) The motor development assessment had good validity. (2) Considerable heterogeneity regarding motor development in preschoolers was observed, in which four and three subgroups displaying distinct levels of mastery with respect to their gross and fine motor skills were identified at the ages of three and four years, respectively. (3) From age three to age four, a large proportion of the preschoolers exhibited improvements or retentions in both gross and fine motor skills, whereas some of the preschoolers were classified into subgroups displaying "gross motor retention and fine motor progression," "gross motor progression and fine motor retention," "gross motor retention and fine motor regression," and "gross motor regression and fine motor progression." Few preschoolers exhibited "general motor regression." The present results suggest that there were considerable heterogeneous groups in the motor development in preschoolers in the middle of early childhood, and this phenomenon has rarely been addressed in former studies. The LTA results implied that effective interventions should be given sequentially to preschoolers in subgroups whose motor development presented regression and retention tendencies.
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Backpacks are commonly worn by many people for multiple purposes. This study investigated the effects of habitual wearing of backpacks on lower limb kinematics and kinetics. Fourteen participants were recruited for analysis. All participants performed four randomly assigned scenarios, including running and walking at speeds of 3.5 and 1.5 m/s, respectively, with and without load carriage. The motion analysis system and force plate were used to investigate the lower limb kinematics and kinetics. A paired sample t-test was performed for statistical measurement with a significance level of α = .05. The results indicated that active force, breaking force, impact peak, loading rate, active peak, maximum braking, hip flexion, and hip range of motion were substantially higher under load carriage conditions than under walking condition, however, time to peak was lower. Conversely, during load carriage running, active force, braking impulse, time to peak, ankle plantarflexion, and ankle range of motion were all higher than those during running. Carrying a backpack weighing 10% of the body weight induced different foot strike patterns at both speeds; during load carriage walking, the hip tended to flex more; whereas, during load carriage running, the ankle tended to flex more. In conclusion, human body seems to adopt different gait strategies during load carriage walking and running. That is, the hip strategy is used during walking, while the ankle strategy is used during running.
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Long non-coding RNAs (lncRNAs) are emerging important epigenetic regulators in metabolic processes. Whether they contribute to the metabolic effects of vertical sleeve gastrectomy (VSG), one of the most effective treatments for sustainable weight loss and metabolic improvement, is unknown. Herein, we identify a hepatic lncRNA Gm19619, which is strongly repressed by VSG but highly up-regulated by diet-induced obesity and overnight-fasting in mice. Forced transcription of Gm19619 in the mouse liver significantly promotes hepatic gluconeogenesis with the elevated expression of G6pc and Pck1. In contrast, AAV-CasRx mediated knockdown of Gm19619 in high-fat diet-fed mice significantly improves hepatic glucose and lipid metabolism. Mechanistically, Gm19619 is enriched along genomic regions encoding leptin receptor (Lepr) and transcription factor Foxo1, as revealed in chromatin isolation by RNA purification (ChIRP) assay and is confirmed to modulate their transcription in the mouse liver. In conclusion, Gm19619 may enhance gluconeogenesis and lipid accumulation in the liver.
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Lipogênese , RNA Longo não Codificante , Animais , Camundongos , Dieta Hiperlipídica , Regulação para Baixo , Gastrectomia , Gluconeogênese/genética , Lipogênese/genética , Fígado/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
Metabolic surgery, or bariatric surgery, is currently the most effective approach for treating obesity and its complications. Vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) are the top two types of commonly performed metabolic surgery now. The precise mechanisms of how the surgeries work are still unclear, therefore much research has been conducted in this area. Gut hormones such as GLP-1 and PYY have been studied extensively in the context of metabolic surgery because they both participate in satiety and glucose homeostasis. Bile acids, whose functions cover intestinal lipid absorption and various aspects of metabolic regulation via the action of FXR, TGR5, and other bile acid receptors, have also been actively investigated as potential mediators of metabolic surgery. Additionally, gut microbiota and their metabolites have also been studied because they can affect metabolic health. The current review summarizes and compares the recent scientific progress made on identifying the mechanisms of RYGB and VSG. One of the long-term goals of metabolic/bariatric surgery research is to develop new pharmacotherapeutic options for the treatment of obesity and diabetes. Because obesity is a growing health concern worldwide, there is a dire need in developing novel non-invasive treatment options.
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Cirurgia Bariátrica , Derivação Gástrica , Microbioma Gastrointestinal , Ácidos e Sais Biliares , Microbioma Gastrointestinal/fisiologia , Humanos , Obesidade/metabolismo , Obesidade/cirurgiaRESUMO
The demand for health care has increased with the development of global technology and the rise of public health awareness, and smart service systems have also been introduced to medical care to relieve the pressure on hospital staff. However, the survey found that patients' willingness to use smart services at the time of consultation has not improved. The main research purpose of this study was to understand the willingness of patients from various groups to use smart medical service systems and to explore the influencing factors on patients' use of smart service systems in hospitals through the technology acceptance model. This study distributed questionnaires in the outpatient area of National Taiwan University Hospital Yunlin Branch, and a total of 202 valid questionnaires were obtained. After related research and regression analysis, it was found that patients paid more attention to the benefits and convenience brought by smart services. If patients believed that smart services were trustworthy and beneficial to themselves, their usage intention and attitude would be positive. The results of this study are summarized by the following four points: (1) Designed according to the cultural conditions of different regions; (2) think about design from the patient's perspective; (3) strengthen the explanation and promotion of smart services; and (4) add humanized care and design. This study could be used as a reference for hospitals to improve their service quality and systems in the future.
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Hospitais , Intenção , Humanos , Saúde Pública , Inquéritos e Questionários , TecnologiaRESUMO
BACKGROUND & AIMS: Alcohol-associated liver disease (AALD) is one of the most common causes of liver injury and failure. Limited knowledge of the mechanisms underlying AALD impedes the development of efficacious therapies. Bile acid (BA) signaling was shown to participate in the progression of AALD. However, the mechanisms remain poorly understood. METHODS: C57BL/6J wild-type (WT), Takeda G-protein-coupled bile acid receptor 5 (TGR5) knockout (KO) and brown adipose tissue (BAT)-specific TGR5 knockdown mice were subjected to ethanol feeding-induced AALD. Liver samples from alcoholic hepatitis patients were used to examine the BA circulation signaling. Human Embryonic Kidney Cells 293 were used for the TGR5 reporter assay. 23(S)-methyl-lithocholic acid was used as a molecular tool to confirm the regulatory functions of BAT in the AALD mouse model. RESULTS: Ethanol feeding increased the expression of the thermogenesis genes downstream of TGR5 in BAT of WT, but not TGR5 KO, mice. TGR5 deficiency significantly blocked BAT activity and energy expenditure in mice after ethanol feeding. Alcohol increased serum BA levels in mice and human beings through altering BA transportation, and the altered BAs activated TGR5 signaling to regulate metabolism. Compared with ethanol-fed WT mice, ethanol-fed TGR5 KO mice showed less free fatty acid (FFA) ß-oxidation in BAT, leading to higher levels of FFA in the circulation, increased liver uptake of FFAs, and exacerbated AALD. BAT-specific TGR5 knockdown mice showed similar results with TGR5 KO mice in AALD. Agonist treatment significantly activated TGR5 signaling in BAT, increased thermogenesis, reduced serum FFA level, and ameliorated hepatic steatosis and injury in AALD mice, while these effects were lost in TGR5 KO mice. CONCLUSIONS: BA signaling plays a protective role in AALD by enhancing BAT thermogenesis. Targeting TGR5 in BAT may be a promising approach for the treatment of AALD.
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Tecido Adiposo Marrom , Ácidos e Sais Biliares , Animais , Ácidos e Sais Biliares/metabolismo , Etanol/toxicidade , Humanos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BLRESUMO
The energy-dissipating capacity of brown adipose tissue through thermogenesis can be targeted to improve energy balance. Mammalian 5'-AMP-activated protein kinase, a key nutrient sensor for maintaining cellular energy status, is a known therapeutic target in Type II diabetes. Despite its well-established roles in regulating glucose metabolism in various tissues, the functions of AMPK in the intestine remain largely unexplored. Here we show that AMPKα1 deficiency in the intestine results in weight gain and impaired glucose tolerance under high fat diet feeding, while metformin administration fails to ameliorate these metabolic disorders in intestinal AMPKα1 knockout mice. Further, AMPKα1 in the intestine communicates with brown adipose tissue to promote thermogenesis. Mechanistically, we uncover a link between intestinal AMPKα1 activation and BAT thermogenic regulation through modulating anti-microbial peptide-controlled gut microbiota and the metabolites. Our findings identify AMPKα1-mediated mechanisms of intestine-BAT communication that may partially underlie the therapeutic effects of metformin.
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Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Metformina , Proteínas Quinases Ativadas por AMP/metabolismo , Tecido Adiposo Marrom/metabolismo , Animais , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica , Metabolismo Energético , Microbioma Gastrointestinal/fisiologia , Intestinos , Mamíferos/metabolismo , Metformina/farmacologia , Camundongos , Termogênese/fisiologiaRESUMO
Cyanobacteria can convert CO2 to chemicals such as 2,3-butanediol (2,3-BDO), rendering them promising for renewable production and carbon neutralization, but their applications are limited by low titers. To enhance cyanobacterial 2,3-BDO production, we developed a combinatorial CRISPR interference (CRISPRi) library strategy. We integrated the 2,3-BDO pathway genes and a CRISPRi library into the cyanobacterium PCC7942 using the orthogonal CRISPR system to overexpress pathway genes and attenuate genes that inhibit 2,3-BDO formation. The combinatorial CRISPRi library strategy allowed us to inhibit fbp, pdh, ppc, and sps (which catalyzes the synthesis of fructose-6-phosphate, acetyl-coenzyme A, oxaloacetate, and sucrose, respectively) at different levels, thereby allowing for rapid screening of a strain that enhances 2,3-BDO production by almost 2-fold to 1583.8 mg/L. Coupled with a statistical model, we elucidated that differentially inhibiting all the four genes enhances 2,3-BDO synthesis to varying degrees. fbp and pdh suppression exerted more profound effects on 2,3-BDO production than ppc and sps suppression, and these four genes can be repressed simultaneously without mutual interference. The CRISPRi library approach paves a new avenue to combinatorial metabolic engineering of cyanobacteria.
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An acute bout of eccentric exercise affects insulin sensitivity and lipid profile, but how the magnitude of muscle damage affects them is not clear. We compared changes in blood insulin sensitivity and lipid markers after the first (EC1) and second (EC2) eccentric exercise bouts. Fifteen sedentary young men performed arm, leg and trunk muscle eccentric exercises, and repeated them 2 weeks later. Fasting blood samples were taken before, 2 h and 1-5 days after each exercise bout to analyze plasma creatine kinase (CK) activity, serum glucose (GLU), insulin, homeostasis model assessment (HOMA), triacylglycerols (TG), total (TC) and low- (LDLC) and high-density lipoprotein cholesterol (HDLC) concentrations as well as TC/HDLC ratio. Changes in these measures were compared between bouts and relationships to peak plasma CK activity were analyzed. Plasma CK activity increased (p < 0.05) after EC1 (peak: 101,668 ± 58,955 IU/L) but not after EC2. The magnitude of changes in GLU (peak after EC1: 26 ± 10% vs. EC2: 7 ± 6%), insulin (46 ± 27% vs. 15 ± 8%), HOMA (86 ± 48% vs. 24 ± 15%), TC (-20 ± 5% vs. -6 ± 4%), TG (-32 ± 11% vs. -6 ± 3%), LDHC (-47 ± 15% vs. -12 ± 9%), HDLC (35 ± 26% vs. 7 ± 4%), and TC/HDLC ratio (-139 ± 13% vs. -11 ± 7%) were significantly greater after EC1 than EC2. Peak plasma CK activity was significantly (p < 0.05) correlated with the peak changes in blood insulin sensitivity and lipid markers for the combined data of EC1 and EC2. These results suggest that the greater the magnitude of muscle damage, the greater the magnitude of changes in the insulin sensitivity to a negative direction and lipid markers to a positive direction.
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With rapid technology developments and the convenient and fast pace of life in recent years, many people are using disposable products, which cause environmental and ecological damages. A variety of eco-friendly menstrual products have been launched on the market, and "menstrual pads" now have a large market share in Taiwan's menstrual product industry. This study interviewed experts and collected questionnaires for qualitative and quantitative investigation and analysis. The results show that women have positive and open concepts regarding sustainability, as well as a good understanding of their body and are very interested in the performance and usage efficiency of products. The results also indicate that consumers purchase based on their lifestyles; most women collected enough product information before purchasing while overcoming the difficulties in dealing with the environment and learning to adapt them, and the majority of consumers attach importance to comfort, volume, and duration of blood absorption. The results suggest that the government and private enterprises should increase and improve sanitation education and sanitary facilities and guide the approach and serve as an important reference index for the promotion of eco-friendly menstrual products for environmental benefits.
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Produtos de Higiene Menstrual , Menstruação , Atitude , Cognição , Feminino , Humanos , Estilo de VidaRESUMO
The he purpose of this study is to examine the effects of ball velocity, court illumination, and volley type on the reaction time (RT) of a tennis athlete for a volley stroke. Eights cases with two different ball velocities (high and low), two volley types (forehand and backhand ) and two court illumination levels (dark and bright) were studied. The 30 participating subjects consisted of 18 male and 12 female college tennis athletes (age: 24 ± 3.2 yr), with a United States Tennis Association (USTA) ranking above 2.5. In order to ensure the validity of real-world correlations, the experiments were designed to simulate real competition situations. Reaction times were measured for volley strokes in response to different approaching ball velocities (high: 25.05 ± 0.37 m/s and low: 17.56 ± 0.92 m·s(-1)) for several volley types (forehand and backhand) and court illumination levels (55649 ± 4292 lux and 363.24 ± 6.53 lux on the court). During the tests, the signals from an electromyogram sensor and a 3-axis accelerometer (± 50 g) were recorded using an NI DAQ card (NI PXI-6251) and then analyzed to determine reaction time (RT), premotor reaction time (PRT), and motor reaction time (MRT) through the LabVIEW system. Subsequent 3-way ANOVA analysis indicated no RT, PRT, or MRT interaction between ball velocity, volley type and illumination. The ball velocity and illumination parameters did affect RT and PRT values significantly with p < 0.05, no significant variation in MRT was observed across any implemented experimental conditions. All experimental results indicate that ball velocity and illumination levels strongly affect the value of PRT, but have no significant effect on the value of MRT, the changes in RT were dominated by PRT. Key pointsRT can generally be divided into two components with the help of the electromyogram (EMG) signal - the premotor reaction time (PRT) and the motor reaction time (MRT).The purpose of this study is to examine the effects of ball velocity, court illumination level, and volley type on the reaction time (RT) of the tennis athlete for volley strokes.Results strongly suggest that changes in RT were dominated by PRT; in light of this correspondence, it is clear that the ability to sense visual stimuli may be enhanced by proper training and practice.
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Taiwan has actively promoted the concept of "successful aging" in recent years. The Executive Yuan drafted the White Paper for Aged Society, which set the primary goal to enable seniors to deal with daily life more independently. Although 'third places' enable seniors to live independently, the third places that Taiwanese seniors like are not well understood. Consequently, by investigating third places, this study will investigate the environment of achieving successful aging and happiness among seniors. This study uses the questionnaire survey, and the data of this study were collected from October to November 2018 in Taichung City Central District. A questionnaire survey was conducted in several administrative agencies and participants were selected by random sampling among the over-55-year-old citizens who were already retired. An estimate of 90% confidence limits with 5% marginal error gave us a sample size of 257. This study finally received 200 efficient samples. The women's top five choices of third places are the traditional market, supermarket, restaurant, daily necessities shop, and coffee shop. The men's top five choices of third places are the traditional market, supermarket, daily necessities shop, restaurant, and a friend's house. For seniors familiar with the concept of third places, the more often they go to third places, the higher happiness they achieve. This result investigates the importance of having awareness of third places for seniors. Therefore, we should encourage them to go to third places and engage in social activities frequently to achieve successful aging.