RESUMEN
Many lung immune cells are known to respond to inhaled particulate matter. However, current known responses cannot explain how particles induce thrombosis in the lung and how they translocate to distant organs. Here, we demonstrate that lung megakaryocytes (MKs) in the alveolar and interstitial regions display location-determined characteristics and act as crucial responders to inhaled particles. They move rapidly to engulf particles and become activated with upregulation in inflammatory responses and thrombopoiesis. Comprehensive in vivo, in vitro and ex vivo results unraveled that MKs were involved in particle-induced lung damages and shed particle-containing platelets into blood circulation. Moreover, MK-derived platelets exhibited faster clotting, stronger adhesion than normal resting platelets, and inherited the engulfed particles from parent MKs to assist in extrapulmonary particle transportation. Our findings collectively highlight that the specific responses of MKs towards inhaled particles and their roles in facilitating the translocation of particles from the lungs to extrapulmonary organs for clearance.
Asunto(s)
Plaquetas , Pulmón , Megacariocitos , Ratones Endogámicos C57BL , Material Particulado , Animales , Pulmón/patología , Pulmón/inmunología , Plaquetas/metabolismo , Ratones , Masculino , Neumonía/patología , Neumonía/inmunología , Neumonía/metabolismo , Trombopoyesis , HumanosRESUMEN
Senescent cells are typically characterized by a stable proliferation arrested in dividing cells accompanied with a senescence-associated secretory phenotype (SASP). Skin cellular senescence is the primary cause of skin aging, whereas the lack of identified skin senescence markers limits our understanding of the mechanisms involved in skin aging. Recent studies have revealed that intracellular calcium signaling has emerged as a key player in regulating cellular senescence and aging. However, the implication and roles of calcium signaling in skin keratinocyte senescence remain only partially understood. In this study, we developed a model for skin keratinocyte senescence using ionizing radiation (I/R) stimulation and found that the calcium-associated gene transglutaminase 2 (TGM2) was significantly induced compared with normal control. Interestingly, inhibition of TGM2 was found to delay skin keratinocyte senescence by suppressing I/R-promoted intracellular calcium signaling, accumulation of reactive oxygen species (ROS), DNA damage, as well as NF-κB-mediated SASP secretion. Taken together, our findings demonstrate that inhibition of TGM2 contributes to bypassing I/R-induced skin keratinocyte senescence and sheds light on novel strategies against skin stresses caused by I/R.
RESUMEN
Background: Bacterial image analysis plays a vital role in various fields, providing valuable information and insights for studying bacterial structural biology, diagnosing and treating infectious diseases caused by pathogenic bacteria, discovering and developing drugs that can combat bacterial infections, etc. As a result, it has prompted efforts to automate bacterial image analysis tasks. By automating analysis tasks and leveraging more advanced computational techniques, such as deep learning (DL) algorithms, bacterial image analysis can contribute to rapid, more accurate, efficient, reliable, and standardised analysis, leading to enhanced understanding, diagnosis, and control of bacterial-related phenomena. Methods: Three object detection networks of DL algorithms, namely SSD-MobileNetV2, EfficientDet, and YOLOv4, were developed to automatically detect Escherichia coli (E. coli) bacteria from microscopic images. The multi-task DL framework is developed to classify the bacteria according to their respective growth stages, which include rod-shaped cells, dividing cells, and microcolonies. Data preprocessing steps were carried out before training the object detection models, including image augmentation, image annotation, and data splitting. The performance of the DL techniques is evaluated using the quantitative assessment method based on mean average precision (mAP), precision, recall, and F1-score. The performance metrics of the models were compared and analysed. The best DL model was then selected to perform multi-task object detections in identifying rod-shaped cells, dividing cells, and microcolonies. Results: The output of the test images generated from the three proposed DL models displayed high detection accuracy, with YOLOv4 achieving the highest confidence score range of detection and being able to create different coloured bounding boxes for different growth stages of E. coli bacteria. In terms of statistical analysis, among the three proposed models, YOLOv4 demonstrates superior performance, achieving the highest mAP of 98% with the highest precision, recall, and F1-score of 86%, 97%, and 91%, respectively. Conclusions: This study has demonstrated the effectiveness, potential, and applicability of DL approaches in multi-task bacterial image analysis, focusing on automating the detection and classification of bacteria from microscopic images. The proposed models can output images with bounding boxes surrounding each detected E. coli bacteria, labelled with their growth stage and confidence level of detection. All proposed object detection models have achieved promising results, with YOLOv4 outperforming the other models.
RESUMEN
Objective: To study the effectiveness of liver transplantation (LT) in treating mitochondrial DNA depletion syndrome (MDS) caused by the MPV17 gene variant. Case presentation: A boy aged 2.8 years presented with edema of the lower limbs and abdomen, which persisted for over 10 days and was of unknown origin; this was accompanied by abnormal liver function, intractable hypoglycemia, and hyperlactatemia. During the second week of onset, he developed acute-on-chronic liver failure and was diagnosed with MDS due to homozygous variant c.293C>T in the MPV17 gene. Subsequently, he underwent LT from a cadaveric donor. At follow-up after 15 months, his liver function was found to be normal, without any symptoms. Additionally, a literature review was performed that included MDS patients with the MPV17 variant who underwent LT. The results demonstrated that the survival rates for MDS patients who underwent LT were 69.5%, 38.6%, 38.6%, and 38.6% at 1-year, 5-year, 10-year, and 20-year intervals, respectively. Sub-group analyses revealed the survival rate of MDS patients with isolated liver disease (83.33%, 5/6) was higher than that of hepatocerebral MDS patients (44.44%, 8/18). Fifteen variants were identified in the MPV17 gene, and patients with the c.293C>T (p.P98l) variant exhibited the highest survival rate. Conclusion: Hepatocerebral MDS patients without neurological symptoms may benefit from LT.
RESUMEN
The recycling and utilization of precious metals have emerged as a critical research focus in advancing the development of the circular economy. Among numerous methods for recovering precious metals such as gold, adsorbents with both high adsorption selectivity and capacity have become key technologies. This article incorporated the N-phenylpyrrolidine into a flexible porous polynorbornene backbone to create a class of distinctive porous organic polymers, named BIT-POP-14-BIT-POP-17. Through a reductive capture mechanism, the reductive adsorption sites of N-phenylpyrrolidine coordinate selectively with precious metals, the reduced metal is captured by the hierarchically porous polymers with flexible backbone. This approach leads to remarkable gold recovery efficiency, achieving a record of 2321 mg g-1 at ambient conditions, and 3020 mg g-1 under UV light, surpassing the theoretical limit. The porous polymers are filled in a column for a continuous uptake of gold from waste printed circuit boards (PCBs), showing recovery efficiency toward gold as high as 95% after 84 h. Overall, this work offers a new perspective on designing novel adsorbents for precious metal recovery, providing inspiration for researchers to explore novel adsorption modes and contribute to the advancement of the circular economy.
RESUMEN
BACKGROUND: Galactosemia is an autosomal recessive disorder resulting from an enzyme defect in the galactose metabolic pathway. The most severe manifestation of classic galactosemia is caused by galactose-1-phosphate uridylyltransferase (GALT) deficiency, and this condition can be fatal during infancy if left untreated. It also may result in long-term complications in affected individuals. CASE PRESENTATION: This report describes a patient whose initial clinical symptoms were jaundice and liver dysfunction. The patient's liver and coagulation functions did not improve after multiple admissions and treatment with antibiotics, hepatoprotective and choleretic agents and blood transfusion. Genetic analysis revealed the presence of two variants in the GALT gene in the compound heterozygous state: c.377 + 2dup and c.368G > C (p.Arg123Pro). Currently, the variant locus (c.377 + 2dup) in the GALT gene has not been reported in the Human Gene Mutation Database (HGMD), while c.368G > C (p.Arg123Pro) has not been reported in the Genome Aggregation Database (GnomAD) nor the HGMD in East Asian population. We postulated that the two variants may contribute to the development of classical galactosemia. CONCLUSIONS: Applications of whole-exome sequencing to detect the two variants can improve the detection and early diagnosis of classical galactosemia and, more specifically, may identify individuals who are compound heterozygous with variants in the GALT gene. Variants in the GALT gene have a potential therapeutic significance for classical galactosemia.
Asunto(s)
Galactosemias , UTP-Hexosa-1-Fosfato Uridililtransferasa , Humanos , Galactosemias/genética , Galactosemias/diagnóstico , UTP-Hexosa-1-Fosfato Uridililtransferasa/genética , Masculino , Femenino , Mutación , LactanteRESUMEN
The segmented ringed gamma scanning (SRGS) technique represents an advancement in segmented gamma scanning (SGS) technology used for detecting the density of radioactive waste drums, offering enhanced measurement accuracy. However, significant occur errors in the reconstruction of matrix densities due to the non-uniform distribution of density in radioactive waste and the conical beam emitted from the transmission source collimator. This paper proposes a density correction method based on dichotomy to address this issue. The efficacy of this method was verified through both simulations and experiments on a sample containing five different materials, utilizing 137Cs and 60Co for transmission and emission measurements, respectively. The experimental results demonstrate that the errors in the corrected matrix densities are reduced, falling within a margin of 16.8%. Additionally, the corrected reconstruction error of the activity is approximately 25% of the uncorrected results.
RESUMEN
PURPOSE: Major Depressive Disorder (MDD) and Insomnia Disorder (ID) are prevalent psychiatric conditions often occurring concurrently, leading to substantial impairment in daily functioning. Understanding the neurobiological underpinnings of these disorders and their comorbidity is crucial for developing effective interventions. This study aims to analyze changes in functional connectivity within attention networks and default mode networks in patients with depression and insomnia. METHODS: The functional connectivity alterations in individuals with MDD, ID, comorbid MDD and insomnia (iMDD), and healthy controls (HC) were assessed from a cohort of 174 participants. They underwent rs-fMRI scans, demographic assessments, and scale evaluations for depression and sleep quality. Functional connectivity analysis was conducted using region-of-interest (ROI) and whole-brain methods. RESULTS: The MDD and iMDD groups exhibited higher Hamilton Depression Scale (HAMD) scores compared to HC and ID groups (P < 0.001). Both ID and MDD groups displayed enhanced connectivity between the left and right orbital frontal cortex compared to HC (P < 0.05), while the iMDD group showed reduced connectivity compared to HC and ID groups (P < 0.05). In the left insula, reduced connectivity with the right medial superior frontal gyrus was observed across patient groups compared to HC (P < 0.05), with the iMDD group showing increased connectivity compared to MDD (P < 0.05). Moreover, alterations in functional connectivity between the left thalamus and left temporal pole were found in iMDD compared to HC and MDD (P < 0.05). Correlation analyses revealed associations between abnormal connectivity and symptom severity in MDD and ID groups. CONCLUSIONS: Our findings demonstrate distinct patterns of altered functional connectivity in individuals with MDD, ID, and iMDD compared to healthy controls. These findings contribute to a better understanding of the pathophysiology of depression and insomnia, which could be used as a reference for the diagnosis and treatments of these patients.
Asunto(s)
Red en Modo Predeterminado , Trastorno Depresivo Mayor , Imagen por Resonancia Magnética , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Trastornos del Inicio y del Mantenimiento del Sueño/fisiopatología , Trastornos del Inicio y del Mantenimiento del Sueño/diagnóstico por imagen , Masculino , Femenino , Adulto , Trastorno Depresivo Mayor/fisiopatología , Persona de Mediana Edad , Red en Modo Predeterminado/fisiopatología , Red Nerviosa/fisiopatología , Red Nerviosa/diagnóstico por imagen , Atención/fisiología , Comorbilidad , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , ConectomaRESUMEN
PURPOSE: To summarize the clinical and biochemical characteristics of patients with ceftriaxone-induced liver injury and guide the selection of safe medication. METHODS: Retrieved domestic and foreign databases from inception to October 2023, collected case data conforming to ceftriaxone-induced liver injury, and statistically analyzed the data. RESULTS: A total of 617 articles were retrieved, and 16 articles with 33 cases (10 children, 23 adults) were included. Males represented 60% (18/30), with a male-to-female ratio of 1.5:1. The age of onset ranged from 2 days to 96 years, with 15 of 23 adults (65%) over 55 years old. The time from ceftriaxone use to liver injury fluctuated between 0.5 and 47 days. Only 9 patients (27.3%, 9/33) had clinical symptoms, and the clinical classification was dominated by cholestatic injury (46.2%, 12/26). There was a significant difference in the clinical classification of ceftriaxone-induced liver injury between children and adults (P = 0.0126), with hepatocellular injury predominating in children and cholestatic injury predominating in adults. The severity of liver injury was mainly mild (66.7%, 12/18). Peak values of alanine aminotransferase ranging from 228.5 to 8098 U/L, aspartate aminotransferase ranging from 86.7 to 21575 U/L, alkaline phosphatase ranging from 143 to 2434 U/L, and total bilirubin ranging from 3.35 to 66.1 mg/dL. There was a significant difference in peak values of alkaline phosphatase between children and adults (P = 0.027), with a higher peak value of alkaline phosphatase in adults (1039 ± 716.4 U/L vs. 257 ± 134.9 U/L). Patients with normal imaging examinations accounted for the majority (61.5%, 7/13). The prognosis of 32 patients (97%, 32/33) was good, and one child with sickle cell anemia who developed immune hemolysis, progressive renal failure, and acute liver injury after using ceftriaxone died in the end. CONCLUSION: Ceftriaxone-induced liver injury can occur at any age, with a higher risk in the elderly, and age may be related to the clinical classification. Although the clinical manifestations are not specific, close monitoring of liver biochemical indicators during the use can detect liver injury early. Most cases have a good prognosis, but for people with concomitant sickle cell anemia, it is necessary to be vigilant about the occurrence of severe hemolytic anemia.
Asunto(s)
Antibacterianos , Ceftriaxona , Enfermedad Hepática Inducida por Sustancias y Drogas , Humanos , Ceftriaxona/efectos adversos , Masculino , Femenino , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Niño , Adulto , Persona de Mediana Edad , Preescolar , Antibacterianos/efectos adversos , Adolescente , Anciano , Lactante , Adulto Joven , Anciano de 80 o más Años , Recién Nacido , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Fosfatasa Alcalina/sangreRESUMEN
The separation of acetylene from carbon dioxide is challenging due to their almost identical molecular sizes and volatilities. Metal-organic frameworks (MOFs) in general are strong candidates for the separation of gas mixtures owing to the presence of functional pore surfaces that can selectively capture specific target molecules. Herein, we report a stable and easily synthesized bismuth-based MOF, Bi-BTC, which can achieve the separation of acetylene and carbon dioxide. We performed a detailed analysis of the sorption properties of the Bi-MOF. Bi-BTC shows good adsorption capacities for C2H2 with a capacity of 53.8 cm3 g-1 at 298 K and 1.0 bar, and C2H2/CO2 selectivity of 5.14/7.69 at 298 K and 1.0/0.1 bar. IAST selectivity calculations indicate that Bi-BTC possesses good separation capacity, and dynamic breakthrough experiments were performed to prove the separation of C2H2 and CO2. Bi-MOFs as a group of relatively less studied types of MOFs have interesting adsorption characteristics, and this study on Bi-based MOF will enrich three-dimensional Bi-MOF adsorbents for gas adsorption and separation applications.
RESUMEN
OBJECTIVES: To investigate the clinical characteristics and prognosis of pneumococcal meningitis (PM), and drug sensitivity of Streptococcus pneumoniae (SP) isolates in Chinese children. METHODS: A retrospective analysis was conducted on clinical information, laboratory data, and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country. RESULTS: Among the 160 children with PM, there were 103 males and 57 females. The age ranged from 15 days to 15 years, with 109 cases (68.1%) aged 3 months to under 3 years. SP strains were isolated from 95 cases (59.4%) in cerebrospinal fluid cultures and from 57 cases (35.6%) in blood cultures. The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87) and 27% (21/78), respectively. Fifty-five cases (34.4%) had one or more risk factors for purulent meningitis, 113 cases (70.6%) had one or more extra-cranial infectious foci, and 18 cases (11.3%) had underlying diseases. The most common clinical symptoms were fever (147 cases, 91.9%), followed by lethargy (98 cases, 61.3%) and vomiting (61 cases, 38.1%). Sixty-nine cases (43.1%) experienced intracranial complications during hospitalization, with subdural effusion and/or empyema being the most common complication [43 cases (26.9%)], followed by hydrocephalus in 24 cases (15.0%), brain abscess in 23 cases (14.4%), and cerebral hemorrhage in 8 cases (5.0%). Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old, with rates of 91% (39/43) and 83% (20/24), respectively. SP strains exhibited complete sensitivity to vancomycin (100%, 75/75), linezolid (100%, 56/56), and meropenem (100%, 6/6). High sensitivity rates were also observed for levofloxacin (81%, 22/27), moxifloxacin (82%, 14/17), rifampicin (96%, 25/26), and chloramphenicol (91%, 21/23). However, low sensitivity rates were found for penicillin (16%, 11/68) and clindamycin (6%, 1/17), and SP strains were completely resistant to erythromycin (100%, 31/31). The rates of discharge with cure and improvement were 22.5% (36/160) and 66.2% (106/160), respectively, while 18 cases (11.3%) had adverse outcomes. CONCLUSIONS: Pediatric PM is more common in children aged 3 months to under 3 years. Intracranial complications are more frequently observed in children under 1 year old. Fever is the most common clinical manifestation of PM, and subdural effusion/emphysema and hydrocephalus are the most frequent complications. Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates. Adverse outcomes can be noted in more than 10% of PM cases. SP strains are high sensitivity to vancomycin, linezolid, meropenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.
Asunto(s)
Empiema , Hidrocefalia , Meningitis Neumocócica , Efusión Subdural , Lactante , Femenino , Masculino , Humanos , Niño , Recién Nacido , Adolescente , Meningitis Neumocócica/tratamiento farmacológico , Meningitis Neumocócica/epidemiología , Meropenem , Vancomicina , Levofloxacino , Linezolid , Moxifloxacino , Estudios Retrospectivos , Rifampin , Streptococcus pneumoniae , CloranfenicolRESUMEN
Ionizing irradiation, as a new pretreatment method for the anaerobic fermentation of organic pollutants, is featured with fast reaction speed, good treatment effect, no need to add any chemical reagents, and no secondary pollution. This study explores the mechanism of improving anaerobic fermentation performance of rice samples pretreated by cobalt-60 gamma irradiation through the influence on fermentation substrate, acidogenic phase and methanogenic phase. The results reveal that the soluble chemical oxygen demand of the irradiated rice sample at an absorbed dose of 9.6 kGy increases by 12.4 times due to the dissolution of small molecules of fat-soluble organic matter. The yield of biogas in the acidogenic phase increases by 22.2% with a slight increase in hydrogen gas content. The yield of biogas and methane gas content in the methanogenic phase increases by 27.3% and 15%, respectively. Microbial genome analysis, performed with MiSeq high-throughput sequencing and metagenomic methods, suggests the microbial abundance and metabolic functions in the anaerobic fermentation process change significantly as a result of the pretreatment by gamma irradiation.
Asunto(s)
Oryza , Fermentación , Anaerobiosis , Oryza/metabolismo , Biocombustibles/análisis , Ácidos , Metano/análisis , Reactores Biológicos , Aguas del AlcantarilladoRESUMEN
Drought and soil salinization substantially impact agriculture. While proline's role in enhancing stress tolerance is known, the exact molecular mechanism by which plants process stress signals and control proline synthesis under stress is still not fully understood. In tomato (Solanum lycopersicum L.), drought and salt stress stimulate nitric oxide (NO) production, which boosts proline synthesis by activating Δ1-pyrroline-5-carboxylate synthetase (SlP5CS) and Δ1-pyrroline-5-carboxylate reductase (SlP5CR) genes and the P5CR enzyme. The crucial factor is stress-triggered NO production, which regulates the S-nitrosylation of SlP5CR at Cys-5, thereby increasing its NAD(P)H affinity and enzymatic activity. S-nitrosylation of SlP5CR enables tomato plants to better adapt to changing NAD(P)H levels, boosting both SlP5CR activity and proline synthesis during stress. By comparing tomato lines genetically modified to express different forms of SlP5CR, including a variant mimicking S-nitrosylation (SlP5CRC5W), we found that SlP5CRC5W plants show superior growth and stress tolerance. This is attributed to better P5CR activity, proline production, water use efficiency, reactive oxygen species scavenging, and sodium excretion. Overall, this study demonstrates that tomato engineered to mimic S-nitrosylated SlP5CR exhibits enhanced growth and yield under drought and salt stress conditions, highlighting a promising approach for stress-tolerant tomato cultivation.
Asunto(s)
Sequías , Ingeniería Genética , Plantas Modificadas Genéticamente , Pirrolina Carboxilato Reductasas , Solanum lycopersicum , Solanum lycopersicum/genética , Pirrolina Carboxilato Reductasas/genética , Pirrolina Carboxilato Reductasas/metabolismo , delta-1-Pirrolina-5-Carboxilato Reductasa , Tolerancia a la Sal/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Prolina/metabolismo , Estrés Fisiológico/genética , Regulación de la Expresión Génica de las Plantas , Plantas Tolerantes a la Sal/genética , Plantas Tolerantes a la Sal/metabolismoRESUMEN
Numerous scientific satellites require micronewton thrusters for compensating environmental disturbances. The mass flow control proportional valve plays a crucial role in precisely regulating the thrust. To meet the high resolution and wide range requirements of the thrusters, this paper introduces a novel proportional valve with two sets of independently controllable piezoelectric stack. One set of the piezo-stack is used to compensate the stroke loss of the valve core, mainly caused by the deformation of the valve seat. The valve sealing mechanism is carefully analyzed to reduce the stroke loss. Another set of the stack works as the primary actuator, enabling the high mass flow control resolution. Two sets of independently controlled piezoelectric stacks not only expand the range and improve the range ratio but also provide redundancy and enhance reliability. This means that the actuator can still operate at lower ranges even if one piezo-stack is damaged. The piezo-actuators are assembled using U-shaped connectors, creating a compact and space-efficient overall design. Experimental tests have been conducted to verify the performance of the valve, which demonstrated a mass flow range of 0-675 µg/s with a resolution better than 0.1 µg/s and a flow noise below 0.1 µg/s/Hz1/2 at 0.1 mHz-1 Hz.
RESUMEN
Purpose: To investigate the intestinal inflammatory response and the abundance of intestinal bacteria in rats with high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) and assess the intervention effects of taurine (TAU). Methods: Forty male Sprague-Dawley rats were randomly divided into five groups: group I, normal diet and normal saline gavage; group II, normal diet and TAU gavage; group III, HFD and normal saline gavage; group IV, HFD and TAU gavage (from the 1st week); group V, HFD and TAU gavage (from the 10th week). At the end of the 16th week, all the animals were sacrificed. Body weight, liver weight, liver function, and serum lipid levels were measured. The histopathologies of the liver and ileum were observed. The mRNA and protein expression levels of interleukin 17 (IL-17) and IL-10 in the ileum were detected by reverse transcription quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Three types of bacteria were detected in intestinal feces using the 16S rDNA qPCR method. Results: The ileal IL-17 level in group III was significantly higher than those in the other four groups (P < 0.01). The ileal IL-10 mRNA levels in group IV was significantly higher than those in groups III and V (P < 0.05), and IL-10 protein MOD levels in group III was significantly lower than those in the other four groups (P < 0.01). The numbers of Lactobacillus in group III were significantly lower than those in the other four groups (P < 0.01 or P < 0.05). The numbers of Bifidobacteria in groups IV and V were significantly increased compared with that in group III (P < 0.05). Conclusion: TAU may down-regulate the expression of IL-17, up-regulate the expression of IL-10 and regulate the intestinal flora, and alleviate the liver and intestinal damage in rats with HFD-induced NAFLD.
RESUMEN
BACKGROUND: Zinc Gluconate (ZG) is a safe and effective supplement for zinc. However, there is limited research on the optimal dosage for intravenous injection and the safety evaluation of animal models for ZG. This study aims to determine the safe dose range of ZG for intravenous injection in C57BL/6J mice. METHODS: A Dose titration experiment was conducted to determine the LD50 and 95% confidence interval (95%CI) of ZG in mice. Based on the LD50, four sub-lethal doses (SLD) of ZG were evaluated. Following three injections of each SLD and monitoring for seven days, serum zinc levels were measured, and pathological changes in the liver, kidney, and spleen tissues of mice were determined by histological staining. RESULTS: The dose titration experiment determined the LD50 of ZG in mice to be 39.6 mg/kg, with a 95%CI of 31.8-49.3 mg/kg. There was a statistically significant difference in the overall serum zinc levels (H = 36.912, P < 0.001) following SLD administration. Pairwise comparisons showed that the serum zinc levels of the 1/2 LD50 and 3/4 LD50 groups were significantly higher than those of the control group (P < 0.001); the serum zinc level of the 3/4 LD50 group was significantly higher than those of the 1/8 LD50 and 1/4 LD50 groups (P < 0.05). There was a positive correlation between the different SLDs of ZG and the serum zinc levels in mice (rs = 0.973, P < 0.001). H&E staining showed no significant histological abnormalities or lesions in the liver, kidney, and spleen tissues of mice in all experimental groups. CONCLUSION: The appropriate dose range of ZG for intravenous injection in C57BL/6J mice was clarified, providing a reference for future experimental research.
Asunto(s)
Gluconatos , Riñón , Zinc , Ratones , Animales , Ratones Endogámicos C57BL , Dosificación Letal Mediana , Zinc/toxicidadRESUMEN
During nuclear accidents, large amounts of short-lived radionuclides are released into the environment, causing acute health hazards to local populations. Therefore, it is particularly important to obtain source-term information to assist nuclear emergency decision makers in determining emergency protective measures. However, it is extremely difficult to obtain reliable contaminant monitoring instrument readings to estimate the source term based on core conditions, release routes, and release conditions. Currently, a wide variety of source-term inversion methods are attracting increasing attention. In this study, the release rates of four typical short-lived nuclides (Kr-88, Sr-91, Te-132, I-131) in two complex nuclear accident scenarios were estimated using a machine-learning method. The results show that the best estimation performance is obtained with the long short-term memory network, and the mean absolute percentage errors for the release rates of the four nuclides at 10 h under the two nuclear accidents are 9.87% and 11.08%, 17.49% and 16.51%, 7.16% and 8.35%, and 38.83% and 41.87%, respectively. Meanwhile, the mean absolute percentage errors for Te-132 (7.16% and 8.35%) were the lowest among all the estimated nuclides. In addition, stability analysis showed that the gamma dose rate was the key parameter affecting the estimation accuracy.
RESUMEN
Arctigenin belongs to a major bioactive component of Fructus arctii and has been found with cardioprotective effects on rats with ischemiaâreperfusion (I/R) injury. The application of arctigenin is limited due to poor water solubility and low bioavailability. Hydrogel drug delivery systems can improve the efficacy and safety of drugs, increase drug utilization, and reduce side effects. We hypothesized that hydrogels containing arctigenin would facilitate the effect of arctigenin and alleviate I/R injury in the rat heart. Presently, adult Sprague-Dawley (SD) rats were subjected to 1 h of I/R injury, then hydrogels comprising arctigenin were implanted into the myocardium of rats. Triphenyl tetrazolium chloride staining, hematoxylin-eosin staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining and Western blot were performed for evaluating the infarct size, histopathological, and vital protein alterations of hearts. It was discovered that the hydrogel combined with arctigenin abated apoptosis and reduced infarct size. In addition, the results of echocardiography and Masson staining suggested that the hydrogel with arctigenin improved cardiac function, restrained myocardial fibrosis, and activated AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1). Collectively, the injectable hydrogel delivery system enhances the effect of arctigenin, which may play a protective role in I/R injury by activating AMPK and SIRT1.
Asunto(s)
Furanos , Hidrogeles , Lignanos , Daño por Reperfusión Miocárdica , Ratas Sprague-Dawley , Animales , Lignanos/farmacología , Lignanos/química , Lignanos/administración & dosificación , Furanos/química , Furanos/farmacología , Furanos/administración & dosificación , Ratas , Hidrogeles/química , Hidrogeles/farmacología , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/metabolismo , Masculino , Sistemas de Liberación de Medicamentos , Miocardio/patología , Miocardio/metabolismo , Apoptosis/efectos de los fármacos , InyeccionesRESUMEN
Torsion pendulums are widely used for the measurement of small forces. In this study, we investigated the impact of temperature fluctuations on a torsion pendulum using heating devices to modulate the environmental temperature at different specific frequencies. The response coefficient between the temperature variation and the torque of the torsion pendulum was found to vary at different frequencies, with values from 4 × 10-15 N mK-1 at 0.1 mHz to 3 × 10-13 N mK-1 at 10 mHz. A passive thermal-insulation system was used to reduce the torque response within this frequency band, which is dominated by temperature noise. The results demonstrate that this modulation method provides a useful way to independently investigate the noise in a torsion pendulum resulting from environmental temperature fluctuations over a wide frequency band.
RESUMEN
OBJECTIVE: This meta-analysis of randomized controlled trials (RCTs) evaluated the overall efficacy and safety of bilateral theta-burst stimulation (TBS) as an intervention for patients with mood disorders. METHODS: A systematic search (up to December 7, 2022) of RCTs was conducted to address the study aims. A random-effects meta-analysis was performed by including study-defined responses and remission as primary outcomes. RESULTS: Analyses included six RCTs comprising 285 participants with major depressive disorder (MDD) (n = 233) or a depressive episode in the course of bipolar disorder (BD) (n = 52) who had undergone active bilateral TBS (n = 142) versus sham stimulation (n = 143). Active bilateral TBS outperformed sham stimulation with respect to study-defined improvements (55.1 % versus 20.3 %, 4 RCTs, n = 152, 95%CI: 1.63 to 4.39, P < 0.0001; I2 = 0 %) and remission rates (37.2 % versus 14.3 %, 2 RCTs, n = 85, 95%CI: 1.13 to 5.95, P = 0.02; I2 = 0 %) in MDD patients but not those with bipolar or unipolar mixed depression. Superiority of active bilateral TBS over sham stimulation was confirmed for improvements in depressive symptoms at post-bilateral TBS assessments and 8-week follow-ups in patients with either MDD or mixed depression (all P < 0.05). Discontinuation rates due to any reason and adverse events (i.e., headache, dizziness) were similar between TBS and sham stimulation groups with MDD or mixed depression (all P > 0.05). CONCLUSION: Bilateral TBS targeting the dorsolateral prefrontal cortex (DLPFC) appears to be a well-tolerated form of repetitive transcranial magnetic stimulation (rTMS) that has substantial antidepressant effects, particularly in patients with MDD. Effects of bilateral TBS on bipolar and unipolar mixed depression should be further investigated.