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Industrial water saving is an objective requirement for the high-quality development of the Yellow River Basin, as water resource is the largest rigid constraint. In this study, water resources input-output model, structural decomposition analysis (SDA) and structural path analysis (SPA) were constructed to decompose the driving factors of total water use in typical water-deficient provinces (Ningxia, Shanxi, and Henan) in China's Yellow River Basin, to calculate their water use at each production stage and identify their key water-saving pathways. The results were as follows: (i) Water intensity had the most obvious impact on total water saving, resulting in efficiency improvements of 81.39%, 9.21%, and 78.45% for each province, respectively. The next factor was the final demand structure, which suppressed total water-saving efforts by 24.23%, 11.52%, and 113.12% in the respective provinces. (ii) The key water-saving paths in the typical water-deficient provinces of the Yellow River Basin were primarily centered around Sector 1. (iii) Water intensity had a strong water-saving effect on the key paths in the three provinces, with contribution rates of 100.42%, 59.02%, and 42.34% for Ningxia, Henan, and Shanxi, respectively. Final demand also contributed to water-saving in the key paths of Shanxi and Henan, with contribution rates of 35.06% and 28.23%, respectively. However, it inhibited water-saving efforts in the key paths of Ningxia, reducing it by 8.64%. Policy measures should be tailored to local conditions.
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Conservación de los Recursos Hídricos , Ríos , Abastecimiento de Agua , China , Conservación de los Recursos Hídricos/métodos , Modelos Teóricos , Conservación de los Recursos Naturales/métodosRESUMEN
The brominated flame retardant 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE) widely used in manufacturing is inevitably released into the environment, resulting in the exposure of organisms to BTBPE. Therefore, it is particularly important to explore its toxic mechanism. The liver is one of the main accumulating organs of BTBPE, but the mechanism underlying BTBPE hepatotoxicity has not been thoroughly investigated. In our study, BTBPE was administered to Sprague-Dawley (SD) rats and rat hepatocytes (BRL cells) in vivo and in vitro, respectively, and HE staining, AO/EB staining, fluorescent probes, qPCR, immunofluorescence, and dual-luciferase reporter assays were performed. We investigated the mechanism of action of growth arrest-specific 5 (GAS5), miR-743a-5p, and NUAK family kinase 1 (NUAK1) in BTBPE-induced necroptosis from the perspective of competing endogenous RNAs (ceRNAs) using NUAK1 inhibitors, siRNAs, mimics, and overexpression plasmids. Our study showed that exposure to BTBPE caused necroptosis in the liver and BRL cells, accompanied by an oxidation-reduction imbalance and an inflammatory response. It is worth noting that NUAK1 is a newly discovered upstream regulatory target for necroptosis. In addition, miR-743a-5p was shown to inhibit necroptosis by targeting NUAK1 and down-regulating NUAK1. GAS5 upregulates NUAK1 expression by competitively binding to miR-743a-5p, thereby inducing necroptosis. This study demonstrated, for the first time, that the GAS5-miR-743a-5p-NUAK1 axis is involved in the regulation of necroptosis via ceRNAs. Thus, GAS5 and NUAK1 induce necroptosis by competitively binding to miR-743a-5p.
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Circular RNA (circRNA) has emerged as potential therapeutic targets for cardiovascular diseases. Given the central role of the TGFß signaling pathway in cardiac remodeling and its potential as a therapeutic target, we hypothesized that a circRNA from this pathway could modulate cardiac remodeling and serve as a heart failure treatment. Therefore, we identified a circRNA, named circSMAD3, that was significantly reduced in murine heart failure models. Functionally, circSMAD3 mitigated cardiomyocyte hypertrophy and inhibited cardiac fibroblast activation in vitro. Mechanistically, circSMAD3 interacts with YBX1, stabilizing it and facilitating its binding to SMAD3 in the nucleus, disrupting the TGFß/SMAD3 signaling pathway, and ultimately restoring cardiac remodeling. This study highlights circSMAD3 as a promising therapeutic target for heart failure treatment.
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This study explored the effects of 1, 2-bis (2,4, 6-tribromophenoxy) ethane (BTBPE) and bis (2-ethylhexyl) tetrabromophthalate (TBPH) on serum metabolites and lipids in male Sprague-Dawley (SD) rats. Rats were orally gavaged 250 mg/kg bw of BTBPE and 500 mg/kg bw of TBPH for 28 consecutive days. Serum samples were collected for metabolomics and lipidomics analysis. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to explore changes in rat metabolic patterns. Least absolute shrinkage and selection operator (LASSO) regression models were established using serum levels of total thyroxine (TT4), free thyroxine (FT4), and rats' grouping information as variables to screen for robust differential substances. SuperPred was the database to obtain potential targets. The metabolomics and lipidomics results showed that BTBPE and TBPH had an impact on rat metabolic patterns, affecting pathways such as vitamin B6 synthesis. For BTBPE treatment, pyridoxal and ceramide (Cer) 24:0;4O were selected as differential substances related to thyroid hormones. For TBPH treatment, dehydroascorbic acid, acylcarnitine (CAR) 19:0, and diglyceride (DG) 38:4 were selected as differential substances related to thyroid hormones. Serotonin 2c receptor and cyclooxygenase-2 were chosen as potential targets of BTBPE and TBPH, respectively. In conclusion, this study found that BTBPE and TBPH impacted the metabolism of rats, and this effect may be related to changes in thyroid function.
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Metabolómica , Ácidos Ftálicos , Ratas Sprague-Dawley , Animales , Masculino , Ratas , Ácidos Ftálicos/toxicidad , Tiroxina/sangre , Lipidómica , Lípidos/sangre , Metabolismo de los Lípidos/efectos de los fármacosRESUMEN
Ferroptosis hallmarked by lipid peroxidation and iron homeostasis imbalance is involved in the occurrence and development of various diseases. The plant growth regulator chlormequat chloride (CCC) can contribute to the causality and exacerbation of reproductive disorders. However, the mechanism by which CCC may cause Leydig cell attenuation remains poorly understood. In this study, TM3 Leydig cells were used to investigate the inhibitory effect of CCC on cell growth and its possible mechanism. The results showed that CCC caused apoptosis, pyroptosis, ferroptosis and necroinflammation in TM3 cells. By comparing the effects of ferroptosis inhibitor Ferrostatin-1 (Fer-1) and pan-Caspase inhibitor Z-VAD-FMK (ZVF) on lipid peroxidation and Caspase-mediated regulated cell death (RCD), we found that Fer-1 was better at rescuing the growth of TM3 cells than ZVF. Although ZVF reduced mitochondrial ROS level and inhibited the activation of Caspase3 and Caspase1, it could not significantly ameliorate lipid peroxidation and the levels of IL-1ß and HMGB1 like Fer-1. Therefore, ferroptosis might be a key non apoptotic RCD mode responsible for CCC-driven inflammation, leading to weakened viability and proliferation of TM3 cells. In addition, overexpression of ferritin light chain (FTL) promoted the resistance of TM3 cells to CCC-induced ferroptosis-mediated inflammation and to some extent improved the inhibition of viability and proliferation. Altogether, ferroptosis-initiated inflammation might play a key role in CCC-impaired TM3 cell growth.
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Proliferación Celular , Ferroptosis , Inflamación , Células Intersticiales del Testículo , Ferroptosis/efectos de los fármacos , Animales , Masculino , Ratones , Células Intersticiales del Testículo/efectos de los fármacos , Células Intersticiales del Testículo/metabolismo , Células Intersticiales del Testículo/patología , Inflamación/patología , Inflamación/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Línea Celular , Apoptosis/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Clorometilcetonas de Aminoácidos/farmacología , Ciclohexilaminas , FenilendiaminasRESUMEN
The one-year survival rate for patients experiencing a relapse of B-cell acute lymphocytic leukemia (B-ALL) following hematopoietic stem cell transplantation (HSCT) is approximately 30%. Patients experiencing a relapse after allogeneic HSCT frequently encounter difficulties in obtaining autologous CAR-T products. We conducted a study involving 14 patients who received donor-derived CAR-T therapy for relapsed B-ALL following HSCT between August 2019 and May 2023 in our center. The results revealed a CR/CRi rate of 78.6% (11/14), a GVHD rate of 21.4% (3/14), and a 1-year overall survival (OS) rate of 56%. Decreased bone marrow donor cell chimerism in 9 patients recovered after CAR-T therapy. The main causes of death were disease progression and infection. Further analysis showed that GVHD (HR 7.224, 95% CI 1.42-36.82, P = 0.017) and platelet recovery at 30 days (HR 6.807, 95% CI 1.61-28.83, P = 0.009) are significantly associated with OS after CAR-T therapy. Based on the findings, we conclude that donor-derived CAR-T cells are effective in treating relapsed B-ALL patients following HSCT. Additionally, GVHD and poor platelet recovery impact OS, but further verification with a larger sample size is needed.
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Chlormequat chloride (CCC), a widely used plant growth regulator, is a choline analogue that has been shown to have endocrine-disrupting effects. Previous studies have shown that maternal exposure to CCC could induce hyperlipidemia and growth disruption in rat offspring. This study aims to further investigate the effects of peripubertal exposure to CCC on pubertal development and lipid homeostasis, as well as the underlying mechanisms. In vivo, male weanling rats were exposed to CCC (0, 20, 75 and 200 mg/kg bw/day) from post-natal day 21-60 via daily oral gavage. The results in rats showed that 75 mg/kg CCC treatment induced hepatic steatosis, predominantly microvesicular steatosis with a small amount of macrovesicular steatosis, in rat livers and 200 mg/kg CCC treatment induced liver damage including inflammatory infiltration, hepatic sinusoidal dilation and necrosis. In vitro, HepG2 cells were treated with CCC (0, 30, 60, 120, 240 and 480 µg/mL) for 24 h. And the results showed that CCC above 120 µg/mL induced an increase in triglyceride and neutral lipid levels of HepG2 cells. Mechanism exploration revealed that CCC treatment promoted the activation of mTOR/SREBP1 signalling pathway and inhibited activation of AMPK in both in vivo rat livers and in vitro HepG2 cells. Treatment with AMPK activator Acadesine (AICAR) could alleviate the lipid accumulation in HepG2 cells induced by CCC. Collectively, the present results indicate that CCC might induce hepatic steatosis by promoting mTOR/SREBP1 mediated lipogenesis via AMPK inhibition.
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Proteínas Quinasas Activadas por AMP , Clormequat , Hígado Graso , Lipogénesis , Proteína 1 de Unión a los Elementos Reguladores de Esteroles , Serina-Treonina Quinasas TOR , Animales , Serina-Treonina Quinasas TOR/metabolismo , Masculino , Hígado Graso/inducido químicamente , Hígado Graso/metabolismo , Lipogénesis/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Humanos , Células Hep G2 , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Ratas , Clormequat/toxicidad , Ratas Sprague-Dawley , Hígado/efectos de los fármacos , Hígado/metabolismoRESUMEN
The APOA1/C3/A4/A5 cluster is an essential component in regulating lipoprotein metabolism and maintaining plasma lipid homeostasis. A genome-wide association analysis and Mendelian randomization have revealed potential associations between genetic variants within this cluster and lipid metabolism disorders, including hyperlipidemia and cardiovascular events. An enhanced understanding of the complexity of gene regulation has led to growing recognition regarding the role of epigenetic variation in modulating APOA1/C3/A4/A5 gene expression. Intensive research into the epigenetic regulatory patterns of the APOA1/C3/A4/A5 cluster will help increase our understanding of the pathogenesis of lipid metabolism disorders and facilitate the development of new therapeutic approaches. This review discusses the biology of how the APOA1/C3/A4/A5 cluster affects circulating lipoproteins and the current progress in the epigenetic regulation of the APOA1/C3/A4/A5 cluster.
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Caramel color is a widely used food pigment, and 2-Acetyl-4-tetrahydroxybutylimidazole (THI) is a by-products of Class III caramel color. Some studies have shown that THI can reduce the number of peripheral blood lymphocytes. However, the comprehensive mechanism of THI immunotoxicity requires further study. In this study, the effects of THI on lymphocyte count, humoral immunity, cellular immunity and nonspecific immunity were determined and the effect of the nutritional status of VB6 on THI immunotoxicity was evaluated. Female BALB/c mice were divided into 3 groups and fed chow containing different doses of VB6: VB6-normal (6â¯mg/kg VB6), VB6-deprived (0.5â¯mg/kg VB6) or VB6-enhanced (12â¯mg/kg VB6) feed. Each group was further divided into 4 subgroups and treated with THI (0.5, 2.5 or 12.5â¯mg/kg bw) or the solvent control by gavage for 30 days. The thymic cortical thickness was measured with ViewPoint; the proportions of major immune cells and T cells in peripheral blood and tissues were detected via flow cytometry; the transformation and proliferation abilities of T and B cells were detected via T and B lymphocyte proliferation assays; NK cell activity was assessed via lactate dehydrogenase assays; humoral immune function was assessed via plaque-forming cell assays; and the immune function of T lymphocytes was assessed via delayed type hypersensitivity assays. The results showed that compared with those in the corresponding control group, the white blood cell count and lymphocyte count decreased significantly in all the VB6-deprived groups, in the 2.5 and 12.5â¯mg/kg VB6 groups, and in the 12.5â¯mg/kg VB6-enhanced group. With increasing THI dose, the thymic cortical layer became thinner. In the thymus, THI increased the proportions of CD3+ T cells and mature CD8+ T cells and decreased the proportions of immature double-positive, double-negative T cells and CD69-expressing lymphocytes. The proportions of naïve T cells and Tcm (central memory T) cells related to homing decreased. The proportion of mature T cells in the spleen decreased significantly. The proliferation of T cells stimulated by ConA decreased after THI exposure. VB6-deficient mice were more sensitive to THI immunotoxicity, and supplementation with VB6 had a certain protective effect on these mice. The results of the PFC and NK cell activity assays indicated that THI exposure might not affect humoral immune or innate immune function.
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Imidazoles , Inmunidad Humoral , Ratones Endogámicos BALB C , Vitamina B 6 , Animales , Femenino , Ratones , Imidazoles/toxicidad , Imidazoles/farmacología , Inmunidad Humoral/efectos de los fármacos , Vitamina B 6/farmacología , Vitamina B 6/administración & dosificación , Recuento de Linfocitos , Estado Nutricional/efectos de los fármacos , Timo/efectos de los fármacos , Timo/inmunología , Inmunidad Celular/efectos de los fármacos , Bazo/efectos de los fármacos , Bazo/inmunología , Colorantes de Alimentos/toxicidad , Proliferación Celular/efectos de los fármacos , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunologíaRESUMEN
Chlorocholine chloride (CCC) is a plant growth regulator used worldwide that is detectable in cereals, fruits and animal products. The health effects of CCC exposure have raised public concern. Our previous research showed that CCC exposure decreased testosterone synthesis in pubertal rats. However, little is known about whether and how pubertal CCC exposure impacts spermatogenesis. In this study, we used BALB/c mice and spermatogonia-derived GC-1 cells to examine CCC-induced spermatogenic dysfunction. In vivo, pubertal CCC exposure led to decreased testicular weight, decreased testicular germ cells and poor sperm quality. This effect worsened after cessation of CCC exposure for the next 30 days. RNA-seq and western blot analysis revealed that CCC induced aryl hydrocarbon receptor (AhR) signaling, endoplasmic reticulum stress (ERS) and ferritinophagy. Increased iron content and lipid peroxidation levels were also observed in CCC-treated testes. In vitro, it was identified that iron overload mediated by enhanced ferritinophagy occurred in CCC-treated GC-1 cells, which might be attributed to the PERK pathway in ERS. Further, for the first time, our study elucidated the involvement of AhR in CCC-induced iron overload, which aggravated testicular oxidative damage via lipid peroxidation. Considering the adverse impact of CCC exposure on rodents, supportive evidence from GC-1 cells, and the critical importance of spermatogenesis on male development, the effects of CCC on the male reproduction warrant increased attention.
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Acetatos , Clormequat , Sobrecarga de Hierro , Fenoles , Espermatogénesis , Animales , Masculino , Ratones , Ratas , Clormequat/metabolismo , Clormequat/toxicidad , Sobrecarga de Hierro/metabolismo , Receptores de Hidrocarburo de Aril/genética , Receptores de Hidrocarburo de Aril/metabolismo , Semillas , Espermatogénesis/efectos de los fármacos , Testículo , eIF-2 Quinasa/efectos de los fármacos , eIF-2 Quinasa/metabolismoRESUMEN
Chlormequat chloride (CCC), as a widely used plant growth regulator, can cause impaired sperm quality and decreased testosterone synthesis in pubertal rats, but the underlying mechanism remains unclear. The purpose of this study was to elucidate the toxicokinetics and tissue distribution of CCC, as well as the possible mechanism of CCC-induced impairment in sperm quality. The concentration of CCC reached its peak 1 h after a single dose (200 mg/kg·bw) administration in mice plasma, and a bimodal phenomenon appeared in the testes, liver, and epididymis. In vivo, 200 mg/kg CCC caused testicular damage and impaired sperm quality in pubertal mice, and the expression of p-tyrosine and GSK3α decreased in cauda epididymidis, sperm and testes. CCC also caused the down-regulation of AKAP4 and the up-regulation of calmodulin (CaM), and activated the PI3K/AKT signaling pathway in the testes. In vitro, CCC reduced the levels of p-tyrosine, AKAP4 and GSK3α, increased the level of CaM and activated the PI3K/AKT signaling pathway in GC-1 cells. CaM antagonist (W-7 hydrochloride) and PI3K inhibitor (LY294002) can effectively improve the expression of GSK3α and AKAP4 by suppressing the PI3K/AKT signaling pathway in GC-1 cells treated with CCC. It was indicated that CCC induced impairment in sperm quality might be partially related to the activation of PI3K/AKT signaling pathway mediated by CaM.
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Acetatos , Clormequat , Fenoles , Proteínas Proto-Oncogénicas c-akt , Ratones , Ratas , Masculino , Animales , Clormequat/metabolismo , Clormequat/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Calmodulina/metabolismo , Calmodulina/farmacología , Semen/metabolismo , Transducción de Señal , Espermatozoides , Tirosina/metabolismoRESUMEN
Lanthanum (La) is widely used in modern industry and agriculture because of its unique physicochemical properties and is broadly exposed in the population. Some studies have shown that La may have some effects on adipogenesis, but there is a lack of related in vivo evidence. In this study, the effects of La(NO3 )3 on adipogenesis and its associated mechanism were studied using C57BL/6J mouse model. The results showed that La(NO3 )3 exposure caused a decrease in body weight and the percentage of fat content in mice. In addition, the adipose marker molecules and specific adipogenic transcription factors decreased in both white adipose tissue (WAT) and brown adipose tissue (BAT). Detection of signaling pathway-related molecules revealed that canonical wnt/ß-catenin pathway-related molecules were upregulated in both adipose tissues. In summary, in vivo exposure to La(NO3 )3 might inhibited adipogenesis in mice, possibly through upregulation of the canonical Wnt/ß-catenin signaling pathway.
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Adipogénesis , Lantano , Ratones , Animales , Lantano/toxicidad , Ratones Endogámicos C57BL , Vía de Señalización Wnt , beta Catenina/metabolismo , Diferenciación CelularRESUMEN
Bis (2-ethylhexyl) tetrabromophthalate (TBPH) is a new type of brominated flame retardant. Some studies suggest that TBPH exposure may be associated with thyroid damage. However, there is a paucity of research on the authentic exposure-related effects and molecular mechanisms in animals or cells. In this study, we used male Sprague-Dawley (SD) rats and the Nthy ori3-1 cell line (the human thyroid follicular epithelial cell) to explore the potential effects of TBPH (5, 50, 500 mg/kg and 1, 10, 100 nM) on the thyroid. The genes and their proteins of cytokines and thyroid-specific proteins, thyroglobulin (TG), thyroid peroxidase (TPO), and sodium iodide cotransporter (NIS) were examined to investigate the possible mechanisms. At the end of the experiment, it was found that 50 and 500 mg/kg TBPH could increase the levels of total thyroxine (TT4) and free thyroxine (FT4) significantly. The messenger RNAs (mRNAs) of Tg, Tpo, Interleukin-6 (Il6), and Interleukin-10 (Il10) in the thyroid tissues from the rats treated with 500 mg/kg were enhanced clearly. Meanwhile, the mRNAs of TG, TPO, IL6, and IL10 were elevated in Nthy ori3-1 cells treated with 100 nM TBPH as well. The mRNAs of TG and TPO were elevated after the knockdown of IL6. To our surprise, after the knockdown of IL10 or the treatment of anti-IL-10-receptor (anti-IL-10-R) antibody, the mRNAs of TG and TPO were significantly reduced, and the effects of TBPH were diminished. In conclusion, our results suggested that the IL-10-IL-10R-TG/TPO-T4 axis is one important target of TBPH in the thyroid.
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Tiroglobulina , Glándula Tiroides , Masculino , Humanos , Ratas , Animales , Tiroglobulina/genética , Tiroglobulina/metabolismo , Tiroglobulina/farmacología , Interleucina-10/genética , Tiroxina , Interleucina-6/metabolismo , Ratas Sprague-Dawley , Yoduro Peroxidasa/genética , Yoduro Peroxidasa/metabolismo , ARN Mensajero/metabolismoRESUMEN
Difficulties of in vitro culture and genetic manipulation of Eimeria tenella have hindered the screening of virulence factors in this parasite. In this study, the E. tenella rhoptry protein 30 (EtROP30) was expressed in Toxoplasma gondii (RH∆Ku80-EtROP30), and its effect on the proliferation and virulence of parasites was investigated. The results revealed that the expression of EtROP30 had no impact on the invasion and egress processes. However, the RH∆Ku80-EtROP30 strain formed larger plaques compared to the RH∆Ku80, indicating that the EtROP30 expression promotes T. gondii proliferation. Furthermore, the RH∆Ku80-EtROP30 strain exhibited greater pathogenicity, resulting in earlier mortality and shorter overall survival time compared to RH∆Ku80. These results imply that EtROP30 expression facilitates parasite intracellular proliferation and virulence in mice, suggesting that EtROP30 might be a candidate virulence factor of E. tenella.
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Eimeria tenella , Toxoplasma , Animales , Ratones , Eimeria tenella/genética , Eimeria tenella/metabolismo , Virulencia , Factores de Virulencia/genética , Factores de Virulencia/metabolismo , Animales Modificados Genéticamente , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismoRESUMEN
Background: Hyperammonemia is critical to the development of hepatic encephalopathy (HE) and is associated with mortality in end-stage liver disease. This study investigated the clinical value of ammonia variation in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients. Methods: A total of 276 patients with HBV-ACLF were retrospectively recruited. Patients' ammonia levels were serially documented. Baseline ammonia, Peak ammonia (highest level), and Trough ammonia (lowest level) were particularly corrected to the upper limit of normal (AMM-ULN). The primary endpoint was 28-day mortality. Results: The 28-day, 3-month, and 12-month mortality rates were 19.2, 25.7, and 28.2%, respectively. A total of 51 (18.4%) patients had overt HE (grade 2/3/4). Peak AMM-ULN was significantly higher in patients with overt HE and non-survivors compared with their counterparts (P < 0.001). Following adjustment for significant confounders, high Peak AMM-ULN was an independent predictor of overt HE (hazard ratio, 1.031, P < 0.001) and 28-day mortality (hazard ratio, 1.026, P < 0.001). The cut-off of Peak AMM-ULN was 1.8, determined by using the X-tile. Patients with Peak AMM-ULN appearing on days 1-3 after admission had a higher proportion of overt HE and mortality compared to other groups. Patients with decreased ammonia levels within 7 days had better clinical outcomes than those with increased ammonia. Conclusion: Serum Peak ammonia was independently associated with overt HE and mortality in HBV-ACLF patients. Serial serum ammonia may have prognostic value.
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Accurate assessment of blood content in biological tissues is critical for the diagnosis and monitoring of various diseases, including cardiovascular disease, tumors, trauma, and the success rate of organ transplants. In this study, a multispectral endoscopic imaging system was built for capturing tissue reflection optical images in 18 bands across the wavelength range from 400 nm to 760 nm, non-invasively. The system was characterized by six tri-channel narrowband filters installed in front of the light source to achieve spectral separation and was equipped with a specially designed color CCD for achieving a speed of 24 multispectral imaging cubes per second. A method based on linear matrix inversion was proposed to calibrate the CCD spectral response overlaps, while a spectral analysis algorithm was developed for evaluating blood content and detecting tissue composition. The developed system was implemented in an in vivo mouse model for illustrating the blood volume, blood oxygen saturation index, and scattering particle size of the intestinal wall mucosa. The observations not only helped us to understand the blood supply situation in the intestinal mucosa, but also further testified the feasibility of our presented system. Meanwhile, the developed system could provide critical non-invasive optical information for intracavitary cancer diagnosis, surgery guidance, and treatment assessment.
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Diagnóstico por Imagen , Oximetría , Animales , Ratones , AlgoritmosRESUMEN
This study aims to investigate the association between sleep duration and osteoporosis. In addition, sleep-related gene methylation was also detected in this study and we explored its relationship with osteoporosis. The epidemiological investigation section of this study was designed as a retrospective cross-sectional study. We gathered 148 postmenopausal women from two communities and used questionnaires to collect data of sleep duration and other sleep patterns. Biochemical variables were tested, and bone mineral density was measured by dual-energy X-ray absorptiometry. In addition, sleep-related gene (PER2 and PER3) methylation was tested, and the association with osteoporosis was further studied. Twenty-nine of the 148 participants (aged from 65 to 86 years) who suffered from osteoporosis were tested for osteopenia. A significant difference was observed in the association between sleep duration and osteoporosis; the p-value was 0.013. In addition, in our study, we found that short sleep duration (<7 hours) may increase the risk of osteoporosis compared with longer sleep duration. Moreover, sleep-related genes such as PER2 and PER3 and their CpG island methylation were tested, and there was no significant difference between PER2 and PER3 CpG island methylation and osteoporosis. Short sleep duration may increase the risk of osteoporosis. However, the association between sleep-related gene methylation and osteoporosis was not found.
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Osteoporosis , Posmenopausia , Humanos , Femenino , Posmenopausia/genética , Duración del Sueño , Estudios Retrospectivos , Estudios Transversales , Osteoporosis/genética , Densidad Ósea/genética , Sueño/genética , Absorciometría de Fotón , Metilación , ChinaRESUMEN
As an alternative to octabromodiphenyl ether (octa-BDE), 1, 2-bis (2,4, 6-tribromophenoxy) ethane (BTBPE) has been widely used in a variety of combustible materials, such as plastics, textiles and furniture. Previous studies have demonstrated the thyroid toxicity of traditional brominated flame retardants for example octa-BDE clearly. Nevertheless, little is known about the thyroid toxicity of alternative novel brominated flame retardants BTBPE. In this study, it was demonstrated that BTBPE in vivo exposure induced FT4 reduction in 2.5, 25 and 250 mg/kg bw treated group and TT4 reduction in 25 mg/kg bw treated group. TG, TPO and NIS are key proteins of thyroid hormone synthesis. The results of Western blot and RT-PCR from thyroid tissue showed decreased protein levels and gene expression levels of TG, TPO and NIS as well as regulatory proteins PAX8 and TTF2. To investigate whether the effect also occurred in humans, anthropogenic Nthy-ori 3-1 cells were selected. Similar results were seen in vitro condition. 2.5 mg/L BTBPE reduced the protein levels of PAX8, TTF1 and TTF2, which in turn inhibited the protein levels of TG and NIS. The results in vitro experiment were consistent with that in vivo, suggesting possible thyrotoxic effects of BTBPE on humans. It was indicated that BTBPE had the potential interference of T4 generation and the study provided more evidence of the effects on endocrine disorders.
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2-Acetyl-4-tetrahydroxybutylimidazole (THI), a by-product of Class â ¢ caramel color, is generally recognized to cause lymphopenia in mammals. However, it remains unknown whether THI exposure during gestation and lactation causes damage to the immune system of offspring. In this study, pregnant Balb/c mice were gavaged with 0, 0.5, 2.5 and 12.5 mg/kg THI from gestation day (GD) 6 to postanal day (PND) 21, after which we treated another batch of dams from GD6 to PND21 and the offspring for 3 weeks after weaning with 0, 2, 10, 50 mg/L THI in drinking water respectively, and investigated the immunological anomalies of dams and offspring. The results showed that lymphopenia was observed in dams but not in weaning pups on PND21, which were exposed to THI during gestation and lactation. 2 mg/L THI and 2.5 mg/kg THI began to cause a remarkable reduction of the numbers of white blood cells and lymphocytes in dams. Besides both the cellular and the humoral immune response was not affected in weaning pups, which were measured by plaque-forming cell (PFC) assay and delayed-type hypersensitivity (DTH) assay respectively. Furthermore, THI could be detected in the plasma of dams with a dose-dependent manner, but not in that of both female and male weaning pups. In both male and female offspring being treated with 10 and 50 mg/L THI for another 3 weeks after weaning, lymphocytopenia was observed and T lymphocytes including CD4+ and CD8+ cells were significantly reduced in their spleens except lymph nodes. 10 and 50 mg/L THI treatment increased CD4+ and CD8+ single positive cells in thymus of female and male weaning mice. Mitogen-induced proliferation ability of T cells in the spleen and lymph nodes was impaired in female weaning mice exposed 50 mg/L THI, while male weaning mice treated with 10 and 50 mg/L THI showed impairment in the spleen but not lymph nodes. Based on the results in this study, no observed adverse effect level (NOAEL) for 3-week THI treatment in weaning mice was considered to be 2 mg/L (0.30 mg/kg bw for female mice and 0.34 mg/kg bw for male mice). And NOAEL for THI treatment in dams might be set to 0.5 mg/kg bw/day. Collectively from the perspective of NOAEL, offspring are not more sensitive than dams or adult mice.
Asunto(s)
Linfopenia , Efectos Tardíos de la Exposición Prenatal , Humanos , Ratones , Femenino , Animales , Masculino , Embarazo , Ratones Endogámicos BALB C , Lactancia , Inmunidad , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , MamíferosRESUMEN
MORN proteins play a key role in the cytoskeletal structure of eukaryotes and are essential for the close arrangement of the endoplasmic reticulum and plasma membrane. A gene with nine MORN motifs (TGGT1_292120, named TgMORN2) was identified in the Toxoplasma gondii genome; it was presumed to belong to the MORN protein family and to have the function of forming the cytoskeleton, which affects the survival of T. gondii. However, the genetic deletion of MORN2 did not noticeably affect parasite growth and virulence. Using adjacent protein labeling techniques, we identified a network of TgMORN2 interactions, which mainly included endoplasmic reticulum stress (ER stress)-related proteins. In exploring these data, we found that the pathogenicity of the KO-TgMORN2 strain was significantly reduced in the case of tunicamycin-induced ER stress. Reticulon TgRTN (TGGT1_226430) and tubulin ß-Tubulin were identified as interaction proteins of TgMORN2. Collectively, TgMORN2 plays a role in ER stress, which lays a foundation for further research on the function of the MORN protein in T. gondii.