RESUMEN

OBJECTIVE: Measurement of loop gain in patients with obstructive sleep apnea (OSA) is of great importance for determining the cause of OSA and realizing precision medicine. In this study, automatic measurement of loop gain is carried out during wakefulness based on the pseudorandom binary sequence (PRBS) CO2 stimulation method. METHODS: A respiratory data acquisition platform is designed and constructed to automate the processes of gas configuration, ventilatory stimulation with CO2 and data acquisition. The respiratory data are substituted into the model of the ventilatory control system for parameter identification, and the loop gain values are calculated and then compared with the apnea-hypopnea index (AHI) measured in a hypoxia chamber. RESULTS: A positive correlation is found between loop gain and AHI measured in the hypoxia chamber, with the linear correlation coefficient of approximately 0.65. CONCLUSION: The feasibility of automatic measurement of loop gain using the respiratory data acquisition platform based on the PRBS CO2 stimulation method is validated, and the measured loop gain values can be used to assess the stability of ventilatory control. SIGNIFICANCE: This study provides an automated, rapid, and instrumented solution for loop gain measurement, laying the foundation for wide-scale clinical application of the PRBS CO2 stimulation method.

RESUMEN

RATIONAL: Patients with gastric cancer show a relatively low incidence of developing secondary myelodysplastic syndrome (MDS). PATIENT CONCERNS: A 60-year-old man was admitted because of pain and discomfort in the upper abdomen and intermittent abdominal pain. DIAGNOSES: Ulcerative moderately poorly differentiated adenocarcinoma (pT2N2M0G3, stage IIB) and MDS. INTERVENTIONS: The patient underwent chemotherapy with oxaliplatin (OXP, intravenously guttae on day 1) plus capecitabine (CAP, bis in die orally on day 1-14). The patient developed degree III myelosuppression after OXP plus CAP chemotherapy and MDS was subsequently confirmed by diagnosis of the bone marrow biopsy. Temporary but significant hematological improvements were observed after the patient received corresponding treatment, which helped achieve remission and improve pancytopenia. OUTCOMES: The patient presented partial remission after corresponding treatment and no other complications have been recorded. LESSONS: Acute MDS is an unusual adverse effect induced by OXP plus CAP chemotherapy. It is urgent to suggest implementing a supplementary assessment or examination for patients receiving these therapies in future cases.

Asunto(s)

Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Síndromes Mielodisplásicos , Oxaliplatino , Neoplasias Gástricas , Humanos , Síndromes Mielodisplásicos/inducido químicamente , Síndromes Mielodisplásicos/tratamiento farmacológico , Capecitabina/efectos adversos , Capecitabina/administración & dosificación , Capecitabina/uso terapéutico , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/tratamiento farmacológico , Oxaliplatino/efectos adversos , Oxaliplatino/uso terapéutico , Oxaliplatino/administración & dosificación , Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Compuestos Organoplatinos/efectos adversos , Compuestos Organoplatinos/uso terapéutico , Compuestos Organoplatinos/administración & dosificación

RESUMEN

The mitochondrial citrate shuttle, which relies on the solute carrier family 25 member 1 (SLC25A1), plays a pivotal role in transporting citrate from the mitochondria to the cytoplasm. This shuttle supports glycolysis, lipid biosynthesis, and protein acetylation. Previous research has primarily focused on SLC25A1 in pathological models, particularly high-fat diet (HFD)-induced obesity. However, the impact of SLC25A1 inhibition on nutrient metabolism under HFD remains unclear. To address this gap, we used zebrafish (Danio rerio) and Nile tilapia (Oreochromis niloticus) to evaluate the effects of inhibiting Slc25a1. In zebrafish, we administered Slc25a1-specific inhibitors (CTPI-2) for 4 wk, whereas Nile tilapia received intraperitoneal injections of dsRNA to knock down slc25a1b for 7 days. Inhibition of the mitochondrial citrate shuttle effectively protected zebrafish from HFD-induced obesity, hepatic steatosis, and insulin resistance. Of note, glucose tolerance was unaffected. Inhibition of Slc25a1 altered hepatic protein acetylation patterns, with decreased cytoplasmic acetylation and increased mitochondrial acetylation. Under HFD conditions, Slc25a1 inhibition promoted fatty acid oxidation and reduced hepatic triglyceride (TAG) accumulation by deacetylating carnitine palmitoyltransferase 1a (Cpt1a). In addition, Slc25a1 inhibition triggered acetylation-induced inactivation of Pdhe1α, leading to a reduction in glucose oxidative catabolism. This was accompanied by enhanced glucose uptake and storage in zebrafish livers. Furthermore, Slc25a1 inhibition under HFD conditions activated the SIRT1/PGC1α pathway, promoting mitochondrial proliferation and enhancing oxidative phosphorylation for energy production. Our findings provide new insights into the role of nonhistone protein acetylation via the mitochondrial citrate shuttle in the development of hepatic lipid deposition and hyperglycemia caused by HFD.NEW & NOTEWORTHY The mitochondrial citrate shuttle is a crucial physiological process for maintaining metabolic homeostasis. In the present study, we found that inhibition of mitochondrial citrate shuttle (Slc25a1) could alleviate metabolic syndromes induced by high-fat diet (HFD) through remodeling hepatic protein acetylation modification. Briefly, Slc25a1 inhibition reduces hepatic triglyceride deposition by deacetylating Cpt1a and reduces glucose oxidative catabolism by acetylating Pdhe1α. Our study provides new insights into the treatment of diet-induced metabolic syndromes.

Asunto(s)

Ácido Cítrico , Dieta Alta en Grasa , Pez Cebra , Animales , Dieta Alta en Grasa/efectos adversos , Ácido Cítrico/metabolismo , Síndrome Metabólico/metabolismo , Síndrome Metabólico/prevención & control , Síndrome Metabólico/genética , Síndrome Metabólico/etiología , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Carnitina O-Palmitoiltransferasa/metabolismo , Carnitina O-Palmitoiltransferasa/genética , Obesidad/metabolismo , Obesidad/prevención & control , Obesidad/genética , Obesidad/etiología , Acetilación , Proteínas de Pez Cebra/metabolismo , Proteínas de Pez Cebra/genética , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Resistencia a la Insulina , Hígado Graso/metabolismo , Hígado Graso/prevención & control , Hígado Graso/patología , Hígado Graso/etiología , Metabolismo de los Lípidos/efectos de los fármacos

RESUMEN

Studying the implications and characterizations of the excited-state quantum phase transitions (ESQPTs) would enable us to understand various phenomena observed in quantum many-body systems. In this work, we delve into the affects and characterizations of the ESQPTs in the anharmonic Lipkin-Meshkov-Glick (LMG) model by means of the entropy of the quantum work distribution. The entropy of the work distribution measures the complexity of the work distribution and behaves as a valuable tool for analyzing nonequilibrium work statistics. We show that the entropy of the work distribution captures salient signatures of the underlying ESQPTs in the model. In particular, a detailed analysis of the scaling behavior of the entropy verifies that it not only acts as a witness of the ESQPTs but also reveals the difference between different types of ESQPTs. We further demonstrate that the work distribution entropy also behaves as a powerful tool for understanding the features and differences of ESQPTs in the energy space. Our results provide further evidence of the usefulness of the entropy of the work distribution for investigating various phase transitions in quantum many-body systems and open up a promising way for experimentally exploring the signatures of ESQPTs.

RESUMEN

Few reports exist on one-step enzymatic methods for the simultaneous production of biodiesel and eicosapentaenoic acid ethyl ester (EPA-EE), a high-value pharmaceutical compound. This study aimed to efficiently express Rhizomucor miehei lipase (pRML) in Pichia pastoris X-33 via propeptide mutation and high-copy strain screening. The mutated enzyme was then used to simultaneously catalyze the production of both biodiesel and EPA-EE. The P46N mutation in the propeptide (P46N-pRML) significantly boosted its production, with the four-copy strain increasing enzyme yield by 3.7-fold, reaching 3425 U/mL. Meanwhile, its optimal temperature increased to 45-50 °C, pH expanded to 7.0-8.0, specific activity doubled, Km reduced to one-third, and kcat/Km increased 7-fold. Notably, P46N-pRML efficiently converts Nannochloropsis gaditana oil's eicosapentaenoic acid (EPA). Under optimal conditions, it achieves up to 93% biodiesel and 92% EPA-EE yields in 9 h. Our study introduces a novel, efficient one-step green method to produce both biodiesel and EPA-EE using this advanced enzyme.

Asunto(s)

Biocombustibles , Ácido Eicosapentaenoico , Proteínas Fúngicas , Lipasa , Rhizomucor , Estramenopilos , Rhizomucor/enzimología , Rhizomucor/genética , Ácido Eicosapentaenoico/metabolismo , Ácido Eicosapentaenoico/química , Ácido Eicosapentaenoico/análogos & derivados , Lipasa/metabolismo , Lipasa/genética , Lipasa/química , Biocombustibles/análisis , Estramenopilos/genética , Estramenopilos/enzimología , Estramenopilos/metabolismo , Estramenopilos/química , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/química , Expresión Génica , Estabilidad de Enzimas , Cinética , Temperatura , Concentración de Iones de Hidrógeno , Saccharomycetales/genética , Saccharomycetales/metabolismo , Saccharomycetales/enzimología

RESUMEN

Chimeric antigen receptor (CAR)-modified immune cells have emerged as a promising approach for cancer treatment, but single-target CAR therapy in solid tumors is limited by immune escape caused by tumor antigen heterogeneity and shedding. Natural killer group 2D (NKG2D) is an activating receptor expressed in human NK cells, and its ligands, such as MICA and MICB (MICA/B), are widely expressed in malignant cells and typically absent from healthy tissue. NKG2D plays an important role in anti-tumor immunity, recognizing tumor cells and initiating an anti-tumor response. Therefore, NKG2D-based CAR is a promising CAR candidate. Nevertheless, the shedding of MICA/B hinders the therapeutic efficacy of NKG2D-CARs. Here, we designed a novel CAR by engineering an anti-MICA/B shedding antibody 1D5 into the CAR construct. The engineered NK cells exhibited significantly enhanced cytotoxicity against various MICA/B-expressing tumor cells and were not inhibited by NKG2D antibody or NKG2D-Fc fusion protein, indicating no interference with NKG2D-MICA/B binding. Therefore, the developed 1D5-CAR could be combined with NKG2D-CAR to further improve the obstacles caused by MICA/B shedding.

Asunto(s)

Neoplasias , Receptores Quiméricos de Antígenos , Humanos , Línea Celular Tumoral , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase I/metabolismo , Células Asesinas Naturales , Neoplasias/inmunología , Neoplasias/metabolismo , Subfamilia K de Receptores Similares a Lectina de Células NK/genética , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismo , Receptores Quiméricos de Antígenos/genética , Receptores Quiméricos de Antígenos/metabolismo , Inmunoterapia Adoptiva/métodos

RESUMEN

Background: Respiratory-triggered (RT) and breath-hold are the most common acquisition modalities for magnetic resonance cholangiopancreatography (MRCP). The present study compared the three different acquisition modalities for optimizing the use of MRCP in patients with diseases of the pancreatic and biliary systems. Materials and methods: Three MRCP acquisition modalities were used in this study: conventional respiratory-triggered sampling perfection with application-optimized contrasts using different flip evolutions (RT-SPACE), modified RT-SPACE, and breath-hold (BH)-SPACE. Fifty-eight patients with clinically suspected pancreatic and biliary system disease were included. All image data were acquired on a 1.5 T MR. Scan time and image quality were compared between the three acquisition modalities. Friedman test, which was followed by post-hoc analysis, was performed among triple-scan protocol. Results: There was a significant difference in the mean acquisition time among conventional RT-SPACE, modified RT-SPACE, and BH-SPACE (167.41±32.11 seconds vs 50.84±73.78 seconds vs 18.00 seconds, P <0.001). Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were also significantly different among the three groups (P <0.001). The SNR and CNR were higher in the RT-SPACE group than in the BH-SPACE group (P <0.05). However, there were no statistically significant differences (P >0.05) among the 3 groups regarding quality of overall image, image clarity, background inhibition, and visualization of the pancreatic and biliary system. Conclusions: MRCP acquisition with the modified RT-SPACE sequence greatly shortens the acquisition time with comparable quality images. The MRCP acquisition modality could be designed based on the patient's situation to improve the examination pass rate and obtain excellent images for diagnosis.

RESUMEN

Oxidative stress and intestinal inflammation are main pathological features of ulcerative colitis (UC). Ferroptosis, characterized by iron accumulation and lipid peroxidation, is closely related to the pathologic process of UC. 16S rRNA sequencing for intestinal microbiota analysis and gas chromatography-mass spectrometry (GC-MS) for short-chain fatty acid (SCFA) contents clearly demonstrated lower amounts of butyrate-producing bacteria and butyrate in colitis mice. However, the precise mechanisms of sodium butyrate (NaB) in treating UC remain largely unclear. We found that ferroptosis occurred in colitis models, as evidenced by the inflammatory response, intracellular iron level, mitochondria ultrastructural observations and associated protein expression. NaB inhibited ferroptosis in colitis, significantly rescued weight loss and colon shortening in mice and reduced inflammatory lesions and mitochondrial damage. Furthermore, NaB improved intestinal barrier integrity and markedly suppressed the expression of pro-ferroptosis proteins. Conversely, the protein expression of anti-ferroptosis markers including nuclear factor erythroid-related Factor 2 (Nrf2) and glutathione peroxidase 4 (GPX4), was significantly upregulated with NaB treatment. Moreover, the knockdown of Nrf2 reversed the anti-colitis effect of NaB. Taken together, NaB exhibited a protective effect by ameliorating ferroptosis in experimental colitis through Nrf2/GPX4 signaling and improving intestinal barrier integrity, which provides a novel mechanism for NaB prevention of UC.

Asunto(s)

Colitis Ulcerosa , Colitis , Ferroptosis , Animales , Ratones , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Factor 2 Relacionado con NF-E2/genética , ARN Ribosómico 16S , Ácido Butírico/farmacología , Ácido Butírico/uso terapéutico , Transducción de Señal , Hierro

RESUMEN

Science has long been viewed as a key driver of economic growth and rising standards of living. Knowledge about how scientific advances support marketplace inventions is therefore essential for understanding the role of science in propelling real-world applications and technological progress. The increasing availability of large-scale datasets tracing scientific publications and patented inventions and the complex interactions among them offers us new opportunities to explore the evolving dual frontiers of science and technology at an unprecedented level of scale and detail. However, we lack suitable visual analytics approaches to analyze such complex interactions effectively. Here we introduce InnovationInsights, an interactive visual analysis system for researchers, research institutions, and policymakers to explore the complex linkages between science and technology, and to identify critical innovations, inventors, and potential partners. The system first identifies important associations between scientific papers and patented inventions through a set of statistical measures introduced by our experts from the field of the Science of Science. A series of visualization views are then used to present these associations in the data context. In particular, we introduce the Interplay Graph to visualize patterns and insights derived from the data, helping users effectively navigate citation relationships between papers and patents. This visualization thereby helps them identify the origins of technical inventions and the impact of scientific research. We evaluate the system through two case studies with experts followed by expert interviews. We further engage a premier research institution to test-run the system, helping its institution leaders to extract new insights for innovation. Through both the case studies and the engagement project, we find that our system not only meets our original goals of design, allowing users to better identify the sources of technical inventions and to understand the broad impact of scientific research; it also goes beyond these purposes to enable an array of new applications for researchers and research institutions, ranging from identifying untapped innovation potential within an institution to forging new collaboration opportunities between science and industry.

RESUMEN

In omnivorous fish, the pyruvate dehydrogenase kinases (PDKs)-pyruvate dehydrogenase E1α subunit (PDHE1α) axis is essential in the regulation of carbohydrate oxidative catabolism. Among the existing research, the role of the PDKs-PDHE1α axis in carnivorous fish with poor glucose utilization is unclear. In the present study, we determined the effects of PDK inhibition on the liver glycolipid metabolism of largemouth bass (Micropterus salmoides). DCA is a PDK-specific inhibitor that inhibits PDK by binding the allosteric sites. A total of 160 juvenile largemouth bass were randomly divided into two groups, with four replicates of 20 fish each, fed a control diet and a control diet supplemented with dichloroacetate (DCA) for 8 weeks. The present results showed that DCA supplementation significantly decreased the hepatosomatic index, triglycerides in liver and serum, and total liver lipids of largemouth bass compared with the control group. In addition, compared with the control group, DCA treatment significantly down-regulated gene expression associated with lipogenesis. Furthermore, DCA supplementation significantly decreased the mRNA expression of pdk3a and increased PDHE1α activity. In addition, DCA supplementation improved glucose oxidative catabolism and pyruvate oxidative phosphorylation (OXPHOS) in the liver, as evidenced by low pyruvate content in the liver and up-regulated expressions of glycolysis-related and TCA cycle/OXPHOS-related genes. Moreover, DCA consumption decreased hepatic malondialdehyde (MDA) content, enhanced the activities of superoxide dismutase (SOD), and increased transforming growth factor beta (tgf-ß), glutathione S-transferase (gst), and superoxide dismutase 1 (sod1) gene expression compared with the control diet. This study demonstrated that inhibition of PDKs by DCA promoted glucose utilization, reduced hepatic lipid deposition, and improved oxidative stress in largemouth bass by increasing pyruvate OXPHOS. Our findings contribute to the understanding of the underlying mechanism of the PDKs-PDHE1α axis in glucose metabolism and improve the utilization of dietary carbohydrates in farmed carnivorous fish.

Asunto(s)

Lubina , Glucosa , Animales , Glucosa/metabolismo , Ácido Pirúvico/metabolismo , Ácido Pirúvico/farmacología , Fosforilación Oxidativa , Estrés Oxidativo , Hígado/metabolismo , Triglicéridos/metabolismo

RESUMEN

Purpose: Brain glymphatic dysfunction is involved in the pathologic process of acute ischemic stroke (IS). The relationship between brain glymphatic activity and dysfunction in subacute IS has not been fully elucidated. Diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was used in this study to explore whether glymphatic activity was related to motor dysfunction in subacute IS patients. Methods: Twenty-six subacute IS patients with a single lesion in the left subcortical region and 32 healthy controls (HCs) were recruited in this study. The DTI-ALPS index and DTI metrics (fractional anisotropy, FA, and mean diffusivity, MD) were compared within and between groups. Spearman's and Pearson's partial correlation analyses were performed to analyze the relationships of the DTI-ALPS index with Fugl-Meyer assessment (FMA) scores and with corticospinal tract (CST) integrity in the IS group, respectively. Results: Six IS patients and two HCs were excluded. The left DTI-ALPS index of the IS group was significantly lower than that of the HC group (t = -3.02, p = 0.004). In the IS group, a positive correlation between the left DTI-ALPS index and the simple Fugl-Meyer motor function score (ρ = 0.52, p = 0.019) and a significant negative correlation between the left DTI-ALPS index and the FA (R = -0.55, p = 0.023) and MD (R = -0.48, p = 0.032) values of the right CST were found. Conclusions: Glymphatic dysfunction is involved in subacute IS. DTI-ALPS could be a potential magnetic resonance (MR) biomarker of motor dysfunction in subacute IS patients. These findings contribute to a better understanding of the pathophysiological mechanisms of IS and provide a new target for alternative treatments for IS.

RESUMEN

Hormone-sensitive lipase (HSL) is one of the rate-determining enzymes in the hydrolysis of TAG, playing a crucial role in lipid metabolism. However, the role of HSL-mediated lipolysis in systemic nutrient homoeostasis has not been intensively understood. Therefore, we used CRISPR/Cas9 technique and Hsl inhibitor (HSL-IN-1) to establish hsla-deficient (hsla-/-) and Hsl-inhibited zebrafish models, respectively. As a result, the hsla-/- zebrafish showed retarded growth and reduced oxygen consumption rate, accompanied with higher mRNA expression of the genes related to inflammation and apoptosis in liver and muscle. Furthermore, hsla-/- and HSL-IN-1-treated zebrafish both exhibited severe fat deposition, whereas their expressions of the genes related to lipolysis and fatty acid oxidation were markedly reduced. The TLC results also showed that the dysfunction of Hsl changed the whole-body lipid profile, including increasing the content of TG and decreasing the proportion of phospholipids. In addition, the systemic metabolic pattern was remodelled in hsla-/- and HSL-IN-1-treated zebrafish. The dysfunction of Hsl lowered the glycogen content in liver and muscle and enhanced the utilisation of glucose plus the expressions of glucose transporter and glycolysis genes. Besides, the whole-body protein content had significantly decreased in the hsla-/- and HSL-IN-1-treated zebrafish, accompanied with the lower activation of the mTOR pathway and enhanced protein and amino acid catabolism. Taken together, Hsl plays an essential role in energy homoeostasis, and its dysfunction would cause the disturbance of lipid catabolism but enhanced breakdown of glycogen and protein for energy compensation.

Asunto(s)

Esterol Esterasa , Pez Cebra , Animales , Esterol Esterasa/genética , Esterol Esterasa/metabolismo , Pez Cebra/metabolismo , Lipasa/metabolismo , Lipólisis/genética , Metabolismo de los Lípidos/genética , Lípidos , Nutrientes

RESUMEN

Cinnamomum cassia (L.) Presl (cinnamon), an important folk medicine is widely used to prevent osteoporosis for long time in China. Our study aimed to investigate the anti-osteoporosis activity and mechanisms of cinnamon extracts obtained by supercritical CO2 extraction (SFE) and identify activity associated chemical components by gas chromatography-mass spectrometry. The cinnamon SFE exhibited superior anti-osteoporosis efficacy in an ovariectomised mice model to common alcohol extracts. It could induce calcified nodules and ALP activity, upregulate the mRNA expression of ALP, BMP-2, and RUNX2 in MC3T3-E1 cells. The major chemical classes of cinnamon extracts were alcohol esters (28.2%), and terpenes (16.1%). The spectrum-activity analysis indicated that the potential chemical-markers of extracts could be (E)-Cinnamaldehyde, γ-Sitosterol, and (Z, Z)-9,12-Octadecadienoic acid, which could induce the proliferation and ALP activity in MC3T3-E1 cells. Our study revealed the promising applications of the cinnamon SFE in prevention of osteoporosis, and identified its anti-osteoporosis associated compounds.

Asunto(s)

Cinnamomum aromaticum , Animales , Ratones , Cinnamomum aromaticum/química , Cinnamomum aromaticum/metabolismo , Cromatografía de Gases y Espectrometría de Masas , Cinnamomum zeylanicum/química , Medicina Tradicional , Análisis Espectral , Extractos Vegetales/química

RESUMEN

The regulation of cholesterol metabolism in fish is still unclear. Statins play important roles in promoting cholesterol metabolism development in mammals. However, studies on the role of statins in cholesterol metabolism in fish are currently limited. The present study evaluated the effects of statins on cholesterol metabolism in fish. Nile tilapia (Oreochromis niloticus) were fed on control diets supplemented with three atorvastatin levels (0, 12, and 24 mg/kg diet, ATV0, ATV12, and ATV24, respectively) for 4 wk. Intriguingly, the results showed that both atorvastatin treatments increased hepatic cholesterol and triglyceride contents mainly through inhibiting bile acid synthesis and efflux, and compensatorily enhancing cholesterol synthesis in fish liver (P < 0.05). Moreover, atorvastatin treatment significantly inhibited hepatic very-low-density lipoprotein (VLDL) assembly and thus decreased serum VLDL content (P < 0.05). However, fish treated with atorvastatin significantly reduced cholesterol and triglycerides contents in adipose tissue (P < 0.05). Further molecular analysis showed that atorvastatin treatment promoted cholesterol synthesis and lipogenesis pathways, but inhibited lipid catabolism and low-density lipoprotein (LDL) uptake in the adipose tissue of fish (P < 0.05). In general, atorvastatin induced the remodeling of lipid distribution between liver and adipose tissues through blocking VLDL efflux from the liver to adipose tissue of fish. Our results provide a novel regulatory pattern of cholesterol metabolism response caused by atorvastatin in fish, which is distinct from mammals: cholesterol inhibition by atorvastatin activates hepatic cholesterol synthesis and inhibits its efflux to maintain cholesterol homeostasis, consequently reduces cholesterol storage in fish adipose tissue.

Asunto(s)

Inhibidores de Hidroximetilglutaril-CoA Reductasas , Animales , Atorvastatina/farmacología , Atorvastatina/metabolismo , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/metabolismo , Lipoproteínas/metabolismo , Lipoproteínas/farmacología , Colesterol , Hígado/metabolismo , Triglicéridos , Lipoproteínas VLDL , Tejido Adiposo/metabolismo , Metabolismo de los Lípidos , Mamíferos/metabolismo

RESUMEN

A biochar (BC) harbored Ag3PO4/α-Fe2O3 type-Ⅰ heterojunction (Ag-Fe-BC) was prepared by a hydrothermal-impregnation method to transfer active center of heterojunctions. The electrochemical and spectroscopic tests demonstrated that BC enhanced the catalytic performance of the heterojunction by enhancing photocurrent, reducing fluorescence intensity, and facilitating separation of electron-hole pairs. The photocatalytic activity showed the Ag-Fe-BC (5:1:3) could degrade Rhodamine B (20 mg/L) by up to 92.7%, which was 3.35 times higher than Ag3PO4/α-Fe2O3. Tetracycline and ciprofloxacin (20 mg/L) were degraded efficiently by 58.3% and 79.4% within 2 h, respectively. Electron paramagnetic resonance and scavenging experiments confirmed the major reactive oxygen species (ROS) consisted of singlet oxygen (1O2) and superoxide (·O2-). Excellent RhB adsorption and electrons capturing capacity of BC facilitated electron-hole pairs separation and ROS transferring to target organics followed by elevated degradation. Thus, a facile method was proposed to synthesize a highly efficient visible-light responsive photocatalyst for degradation of various organics in water.

Asunto(s)

Contaminantes Ambientales , Catálisis , Carbón Orgánico , Especies Reactivas de Oxígeno

RESUMEN

We show that the classification performance of graph convolutional networks (GCNs) is related to the alignment between features, graph, and ground truth, which we quantify using a subspace alignment measure (SAM) corresponding to the Frobenius norm of the matrix of pairwise chordal distances between three subspaces associated with features, graph, and ground truth. The proposed measure is based on the principal angles between subspaces and has both spectral and geometrical interpretations. We showcase the relationship between the SAM and the classification performance through the study of limiting cases of GCNs and systematic randomizations of both features and graph structure applied to a constructive example and several examples of citation networks of different origins. The analysis also reveals the relative importance of the graph and features for classification purposes.

Asunto(s)

Aprendizaje Profundo , Redes Neurales de la Computación

RESUMEN

Since high-fat diet (HFD) intake elevates liver cholesterol and enhanced cholesterol-bile acid flux alleviates its lipid deposition, we assumed that the promoted cholesterol-bile acid flux is an adaptive metabolism in fish when fed an HFD. The present study investigated the characteristic of cholesterol and fatty acid metabolism in Nile tilapia (Oreochromis niloticus) after feeding an HFD (13% lipid level) for four and eight weeks. Visually healthy Nile tilapia fingerlings (average weight 3.50 ± 0.05 g) were randomly distributed into four treatments (4-week control diet or HFD and 8-week control diet or HFD). The liver lipid deposition and health statue, cholesterol/bile acid, and fatty acid metabolism were analyzed in fish after short-term and long-term HFD intake. The results showed that 4-week HFD feeding did not change serum alanine transaminase (ALT) and aspartate transferase (AST) enzyme activities, along with comparable liver malondialdehyde (MDA) content. But higher serum ALT and AST enzyme activities and liver MDA content were observed in fish fed 8-week HFD. Intriguingly, remarkably accumulated total cholesterol (mainly cholesterol ester, CE) was observed in the liver of fish fed 4-week HFD, along with slightly elevated free fatty acids (FFAs) and comparable TG contents. Further molecular analysis in the liver showed that obvious accumulation of CE and total bile acids (TBAs) in fish fed 4-week HFD was mainly attributed to the enhancement of cholesterol synthesis, esterification, and bile acid synthesis. Furthermore, the increased protein expressions of acyl-CoA oxidase 1/2 (Acox1 and Acox2), which serve as peroxisomal fatty acid ß-oxidation (FAO) rate-limiting enzymes and play key roles in the transformation of cholesterol into bile acids, were found in fish after 4-week HFD intake. Notably, 8-week HFD intake remarkably elevated FFA content (about 1.7-fold increase), and unaltered TBAs were found in fish liver, accompanied by suppressed Acox2 protein level and cholesterol/bile acid synthesis. Therefore, the robust cholesterol-bile acid flux serves as an adaptive metabolism in Nile tilapia when fed a short-term HFD and is possibly via stimulating peroxisomal FAO. This finding enlightens our understanding on the adaptive characteristics of cholesterol metabolism in fish fed an HFD and provides a new possible treatment strategy against metabolic disease induced by HFD in aquatic animals.

RESUMEN

PURPOSE: To determine the utility of short gamete coincubation in in vitro fertilization (IVF-S) combined with early rescue intracytoplasmic sperm injection (R-ICSI) and split IVF-ICSI in preventing low fertilization based on a retrospective cohort study. METHODS: Couples with a high risk of low IVF fertilization during the first ART cycle underwent IVF-S with R-ICSI or split IVF-ICSI. Fertilization rate, embryo quality, and clinical outcomes were measured. RESULTS: After propensity score matching, we included 188 couples in the IVF-S with R-ICSI group as Group 1 and 720 in the split IVF-ICSI group as Group 2. Normal fertilization rates were similar; however, Group 1 had a higher multiple pronuclei rate (10.42% vs. 4.50%, p < 0.001) but a higher embryo utilization rate (59.84% vs. 53.60%, p < 0.001). The groups were similar in the rates of high-quality embryos, embryo implantation, clinical pregnancy, and live birth. Low IVF fertilization rate was 4.79% and 9.03% in Group 1 and Group 2, respectively, with similar fertilization rate and embryo development. CONCLUSION: IVF-S with early R-ICSI and split IVF-ICSI were effective strategies in preventing low fertilization rate. IVF-S with early R-ICSI could become the preferred approach because of its advantages-higher embryo utilization rate, fewer ICSI procedures, similar clinical pregnancy rate, and live birth rate.

RESUMEN

BACKGROUND: Regional excessive iron overload is pernicious to motor functions and cognitive functioning of the brain. The aim of this research was to utilize quantitative susceptibility mapping (QSM) to inspect brain iron accumulation in patients with hypertension (HP), and to evaluate whether it is correlated with physiological parameters. METHODS: Thirty-one HP and 31 age- and sex-matched healthy controls (HC) were included. All participants underwent brain magnetic resonance imaging (MRI), and QSM data were obtained. Differences in brain iron deposition in deep gray matter nuclei of participants were compared between HP and HC. The correlations between iron deposition, body mass index (BMI), maximum systolic blood pressure (SBP), and diastolic blood pressure (DBP) were analyzed. RESULTS: The HP group showed increased susceptibility values in the caudate nucleus (CA), putamen (PU), globus pallidus (GP), and dorsal thalamus (TH), compared with the HC group. There was a significant positive correlation between BMI and the susceptibility values in the dentate nucleus (DN); the maximum SBP and DBP were positively correlated with magnetic susceptibility of the CA, PU, GP, and TH, respectively. CONCLUSIONS: These results are indicative of the role of overload brain iron in deep brain gray matter nuclei in HP and suggest that HP is associated with excess brain iron in certain deep gray matter regions.

RESUMEN

Traditional classification tasks learn to assign samples to given classes based solely on sample features. This paradigm is evolving to include other sources of information, such as known relations between samples. Here, we show that, even if additional relational information is not available in the dataset, one can improve classification by constructing geometric graphs from the features themselves, and using them within a Graph Convolutional Network. The improvement in classification accuracy is maximized by graphs that capture sample similarity with relatively low edge density. We show that such feature-derived graphs increase the alignment of the data to the ground truth while improving class separation. We also demonstrate that the graphs can be made more efficient using spectral sparsification, which reduces the number of edges while still improving classification performance. We illustrate our findings using synthetic and real-world datasets from various scientific domains.