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Interactions between bacteria and cyanobacteria influence the occurrence and development of harmful cyanobacterial blooms (HCBs). Bloom-forming cyanobacteria and cyanotoxin-degrading bacteria are essential in HCBs, nonetheless, their interactions and the underlying mechanisms remain unclear. To address this gap, a typical microcystin-LR (MC-LR)-degrading bacterium and a toxic Microcystis aeruginosa strain were co-cultivated to investigate their interactions. The cyanobacterial growth was enhanced by 24.8 %-44.3 % in the presence of the bacterium in the first 7 days, and the cyanobacterium enhanced the bacterial growth by 59.2 %-117.5 % throughout the growth phases, suggesting a mutualistic relationship between them. The presence of the bacterium increased cyanobacterial intracellular MC-LR content on days 4, 8, and 10 while reducing the extracellular MC-LR concentration, revealing the dual roles of the bacterium in enhancing cyanotoxin production and degrading cyanotoxins. The bacterium alleviated the oxidative stress, which may be crucial in promoting cyanobacterial growth. Critical functional genes related to cyanobacterial photosynthesis and MC-LR synthesis, and bacterial MC-LR degradation were up-regulated in the presence of the bacterium and cyanobacterium, respectively. Moreover, extracellular polymeric substances (EPS) were produced at the cell interface, implying EPS play a role in cyanobacterial-bacterial interactions. This study is the first to unveil the interaction mechanisms between cyanotoxin-degrading bacteria and bloom-forming cyanobacteria, shedding light on the dynamics of HCBs.
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Uranium (U) contamination of rice is an urgent ecological and agricultural problem whose effective alleviation is in great demand. Sphingopyxis genus has been shown to remediate heavy metal-contaminated soils. Rare research delves into the mitigation of uranium (U) toxicity to rice by Sphingopyxis genus. In this study, we exposed rice seedlings for 7 days at U concentrations of 0, 10, 20, 40, and 80 mg L-1 with or without the Sphingopyxis sp. YF1 in the rice nutrient solution. Here, we firstly found YF1 colonized on the root of rice seedlings, significantly mitigated the growth inhibition, and counteracted the chlorophyll content reduction in leaves induced by U. When treated with 1.1 × 107 CFU mL-1 YF1 with the amendment of 10 mg L-1 U, the decrease of U accumulation in rice seedling roots and shoots was the largest among all treatments; reduced by 39.3% and 32.1%, respectively. This was associated with the redistribution of the U proportions in different organelle parts, leading to the alleviation of the U damage to the morphology and structure of rice root. Interestingly, we found YF1 significantly weakens the expression of antioxidant enzymes genes (CuZnSOD,CATA,POD), promotes the up-regulation of metal-transporters genes (OsHMA3 and OsHMA2), and reduces the lipid peroxidation damage induced by U in rice seedlings. In summary, YF1 is a plant-probiotic with potential applications for U-contaminated rice, benefiting producers and consumers.
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Oryza , Raíces de Plantas , Uranio , Oryza/efectos de los fármacos , Oryza/metabolismo , Oryza/crecimiento & desarrollo , Oryza/genética , Uranio/toxicidad , Raíces de Plantas/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Sphingomonadaceae/metabolismo , Sphingomonadaceae/genética , Sphingomonadaceae/efectos de los fármacos , Plantones/efectos de los fármacos , Plantones/metabolismo , Plantones/crecimiento & desarrollo , Hojas de la Planta/metabolismo , Hojas de la Planta/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Clorofila/metabolismoRESUMEN
Vehicle pose detection plays a vital role in modern automotive technology, which can improve driving safety, enhance vehicle stability and provide important support for the development of autonomous driving technology. The current pose estimation methods have the problems of accumulation errors, large algorithm computing power, and expensive cost, so they cannot be widely used in intelligent connected vehicles. This paper proposes a vehicle pose detection method based on an RSU (Roadside Unit). First, the on-board GPS performs the positioning of the target vehicle and transmits the positioning information to the RSU through the UDP (User Data Protocol). Next, the RSU transmits a forward command to the OBU (On-board Unit) through the UDP. The OBU sends the command to the ECU (Electronic Control Unit) to control the vehicle forward. Then, the RSU detects and tracks the vehicle. The RSU takes pictures of two images before and after the movement and obtains the coordinates of the four angle points and the center point by image processing. The vehicle heading direction is determined by the moving direction of the center point of the front and rear two images. Finally, the RSU captures the vehicle images in real time, performs the process of tracking, rectangular fitting and pose calculation to obtain the pose information and transmits the information to the OBU to complete the whole process of vehicle pose detection and information transmission. Experiments show that the method can realize accurate and efficient detection of vehicle pose, meet the real-time requirements of vehicle pose detection, and can be widely used in intelligent vehicles.
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The types of obstacles encountered in the road environment are complex and diverse, and accurate and reliable detection of obstacles is the key to improving traffic safety. Traditional obstacle detection methods are limited by the type of samples and therefore cannot detect others comprehensively. Therefore, this paper proposes an obstacle detection method based on longitudinal active vision. The obstacles are recognized according to the height difference characteristics between the obstacle imaging points and the ground points in the image, and the obstacle detection in the target area is realized without accurately distinguishing the obstacle categories, which reduces the spatial and temporal complexity of the road environment perception. The method of this paper is compared and analyzed with the obstacle detection methods based on VIDAR (vision-IMU based detection and range method), VIDAR + MSER, and YOLOv8s. The experimental results show that the method in this paper has high detection accuracy and verifies the feasibility of obstacle detection in road environments where unknown obstacles exist.
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Acute kidney injury (AKI) has considerably high morbidity and mortality but we do not have proper treatment for it. There is an urgent need to develop new prevention or treatment methods. Gut microbiota has a close connection with renal diseases and has become the new therapy target for AKI. In this study, we found the oral administration of the probiotic Limosilactobacillus reuteri had a prevention effect on the AKI induced by lipopolysaccharide (LPS). It reduced serum concentration of creatinine and urea nitrogen and protected the renal cells from necrosis and apoptosis. Meanwhile, L. reuteri improved the gut barrier function, which is destroyed in AKI, and modulated the gut microbiota and relevant metabolites. Compared with the LPS group, L. reuteri increased the proportion of Proteobacteria and reduced the proportion of Firmicutes, changing the overall structure of the gut microbiota. It also influenced the fecal metabolites and changed the metabolite pathways, such as tyrosine metabolism, pentose and glucuronate interconversions, galactose metabolism, purine metabolism, and insulin resistance. These results showed that L. reuteri is a potential therapy for AKI as it helps in sustaining the gut barrier integrity and modulating gut microbiota and related metabolites.
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Lesión Renal Aguda , Microbioma Gastrointestinal , Limosilactobacillus reuteri , Probióticos , Microbioma Gastrointestinal/efectos de los fármacos , Limosilactobacillus reuteri/fisiología , Limosilactobacillus reuteri/metabolismo , Animales , Lesión Renal Aguda/prevención & control , Lesión Renal Aguda/metabolismo , Ratones , Lipopolisacáridos/metabolismo , Masculino , Riñón/microbiología , Riñón/metabolismo , Heces/microbiología , Modelos Animales de Enfermedad , Creatinina/sangre , Ratones Endogámicos C57BL , Apoptosis/efectos de los fármacosRESUMEN
Radiation enteritis is a common complication of abdominal and pelvic radiotherapy. Several previous studies showed that fecal microbiota transplantation (FMT) could alleviate radiation enteritis. In this study, we investigated the efficacy of FMT in alleviating radiation enteritis and explored the mechanisms by multi-omics approaches. Briefly, C57BL/6J mice were subjected to 9 Gy irradiation to the localized abdominal field, and randomized received FMT from healthy donor mice or saline. H&E staining of harvested small intestine showed FMT decreased epithelial injury. Radiation-induced microbiota dysbiosis, characterized by a decrease in beneficial bacteria Lactobacillaceae and Lachnospiraceae, while these bacteria were restored by FMT. Fecal metabolomics analysis revealed that FMT modulated metabolic dysregulation. Two tryptophan pathway metabolites, indole-3-acetaldehyde and N-Acetyl-5-hydroxytryptamine were decreased after irradiation, whereas these metabolites showed a pronounced recovery in mice receiving FMT. Proteomics analysis of small intestine indicated that radiation enteritis triggered immune-inflammatory responses, which were potentially mitigated by FMT. In 21 patients receiving pelvic radiotherapy for cervical cancer, those who developed enteritis (n = 15) had higher abundance in Lachnospiraceae. Moreover, Indole-3-acetaldehyde was reduced after irradiation. These findings provide insights into the therapeutic effects of FMT in radiation enteritis and highlight Lachnospiraceae and the tryptophan metabolite, Indole-3-acetaldehyde may protect against radiation enteritis.
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Enteritis , Trasplante de Microbiota Fecal , Microbioma Gastrointestinal , Ratones Endogámicos C57BL , Triptófano , Animales , Triptófano/metabolismo , Enteritis/terapia , Enteritis/metabolismo , Enteritis/microbiología , Enteritis/etiología , Microbioma Gastrointestinal/efectos de la radiación , Ratones , Femenino , Humanos , Traumatismos por Radiación/terapia , Traumatismos por Radiación/metabolismo , Traumatismos por Radiación/microbiología , MasculinoRESUMEN
INTRODUCTION: Postpartum depression (PPD) is a growing mental health concern worldwide and has detrimental effects on the social and cognitive health of both mothers and infants. This review was performed to assess the risk of PPD in women with postpartum hemorrhage (PPH) and to identify potential moderators. MATERIAL AND METHODS: The review protocol was registered in the PROSPERO database on June 17, 2023 (registration number: CRD42023432955). Two researchers independently performed a literature search of the PubMed, Embase, and Web of Science databases for articles published before May 25, 2023, with no filters and no language or location restrictions. Study quality was evaluated using the Newcastle-Ottawa Scale. The primary outcome was the odds ratio (OR) and 95% confidence interval (CI) of PPD in women with vs. without PPH. We performed sensitivity analyses and meta-regression analyses to resolve heterogeneity. Meta-regression analyses included the effects of age, maternal smoking, marital status, preterm labor, maternal education level, preeclampsia, anemia during pregnancy, and cesarean section. RESULTS: In total, seven studies involving 540 558 participants met the eligibility criteria and were included in the meta-analysis. Women with PPH were at increased risk of PPD compared with women without PPH (OR 1.10; 95% CI 1.03-1.16), and heterogeneity was low (I2 = 23%; τ2 = 0.0007; p = 0.25). Moreover, the results of the sensitivity analyses showed that the I2 value decreased from 23% to 0% after excluding one particular study, which may have been a source of heterogeneity. In the meta-regression analyses, the OR of PPD was greatly affected by maternal smoking (OR -0.26; 95% CI -0.30 to -0.22; p < 0.001). However, we did not observe any effects for maternal age, marital status, preterm labor, maternal education level, preeclampsia, anemia during pregnancy, or cesarean section. CONCLUSIONS: Women with PPH must be closely monitored because they have a higher risk of PPD than women without PPH. Early recognition and management of these patients will improve treatment outcomes, maternal health, and newborn development.
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Depresión Posparto , Hemorragia Posparto , Humanos , Femenino , Depresión Posparto/epidemiología , Hemorragia Posparto/epidemiología , Embarazo , Factores de RiesgoRESUMEN
BACKGROUND: Workplace violence is one of the most serious public health issues worldwide in healthcare occupations, nurse is a profession which faces the greatest risk of exposure to workplace violence among healthcare occupations. OBJECTIVE: The present study aimed to explore the relationship between workplace psychological violence and empathy among Chinese nurses, and further examine the mediation role of resilience in this relationship. METHOD: A cross-sectional survey was conducted among a convenience sample of clinical registered nurses in Xinjiang China from 29 September 2023 to 19 October 2023.The online questionnaire, contained the general information form, the Workplace Psychologically Violent Behaviors Instrument, the Jefferson Scale of Empathy-Healthcare Professionals Version, and the Connor-Davidson Resilience Scale, was used to collect data. The IBM SPSS statistics software version 22.0 was used to perform data analyses in forms of descriptive statistics, correlation analysis, and mediation analysis. RESULT: This survey recruited a convenience sample of 1613 clinical registered nurses aged 22 to 55 years who come from diverse ethnicities and worked in different departments. A total of 534 nurse experienced psychological violent, which yielded a positive rate of 33.1% for psychological violent among nurses. Pearson analysis reported a negative correlation between psychological violences and empathy (r=-0.724, P < 0.01) as well as a negative correlation between psychological violences and resilience (r=-0.681, P < 0.01). Mediation analysis reported that resilience mediated the negative relationship between psychological violence and empathy, the mediation effect accounted for ab/(ab + c') = 23.40% of the total effect. CONCLUSION: This study supported an inverse ralationship between psychological violence and empathy among Chinese nurses where resilience acted as a protective factor to mediated the negative impacts of psychological violences on empathy These results directed health policies and clinical interventions to equip nurses with resilience to copy with and recover from workplace psychological violence.
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Importance: Despite the expansion of published electronic alerts for acute kidney injury (AKI), there are still concerns regarding their effect on the clinical outcomes of patients. Objective: To evaluate the effect of the AKI alert combined with a care bundle on the care and clinical outcomes of patients with hospital-acquired AKI. Design, Setting, and Participants: This single-center, double-blind, parallel-group randomized clinical trial was conducted in a tertiary teaching hospital in Nanjing, China, from August 1, 2019, to December 31, 2021. The inclusion criteria were inpatient adults aged 18 years or older with AKI, which was defined using the Kidney Disease: Improving Global Outcomes creatinine criteria. Participants were randomized 1:1 to either the alert group or the usual care group, which were stratified by medical vs surgical ward and by intensive care unit (ICU) vs non-ICU setting. Analyses were conducted on the modified intention-to-treat population. Interventions: A programmatic AKI alert system generated randomization automatically and sent messages to the mobile telephones of clinicians (alert group) or did not send messages (usual care group). A care bundle accompanied the AKI alert and consisted of general, nonindividualized, and nonmandatory AKI management measures. Main Outcomes and Measures: The primary outcome was maximum change in estimated glomerular filtration rate (eGFR) within 7 days after randomization. Secondary patient-centered outcomes included death, dialysis, AKI progression, and AKI recovery. Care-centered outcomes included diagnostic and therapeutic interventions for AKI. Results: A total of 2208 patients (median [IQR] age, 65 [54-72] years; 1560 males [70.7%]) were randomized to the alert group (n = 1123) or the usual care group (n = 1085) and analyzed. Within 7 days of randomization, median (IQR) maximum absolute changes in eGFR were 3.7 (-6.4 to 19.3) mL/min/1.73 m2 in the alert group and 2.9 (-9.2 to 16.9) mL/min/1.73 m2 in the usual care group (P = .24). This result was robust in all subgroups in an exploratory analysis. For care-centered outcomes, patients in the alert group had more intravenous fluids (927 [82.6%] vs 670 [61.8%]; P < .001), less exposure to nonsteroidal anti-inflammatory drugs (56 [5.0%] vs 119 [11.0%]; P < .001), and more AKI documentation at discharge (560 [49.9%] vs 296 [27.3%]; P < .001) than patients in the usual care group. No differences were observed in patient-centered secondary outcomes between the 2 groups. Conclusions and Relevance: Results of this randomized clinical trial showed that the electronic AKI alert did not improve kidney function or other patient-centered outcomes but changed patient care behaviors. The findings warrant the use of a combination of high-quality interventions and AKI alert in future clinical practice. Trial Registration: ClinicalTrials.gov Identifier: NCT03736304.
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Lesión Renal Aguda , Alarmas Clínicas , Diálisis Renal , Anciano , Humanos , Masculino , Lesión Renal Aguda/terapia , Lesión Renal Aguda/diagnóstico , Creatinina , Hospitales de Enseñanza , Unidades de Cuidados Intensivos , Femenino , Persona de Mediana EdadRESUMEN
This paper presents a VIDAR (a Vision-IMU based detection and ranging method)-based approach to road-surface pothole detection. Most potholes on the road surface are caused by the further erosion of cracks in the road surface, and tires, wheels and bearings of vehicles are damaged to some extent as they pass through the potholes. To ensure the safety and stability of vehicle driving, we propose a VIDAR-based pothole-detection method. The method combines vision with IMU to filter, mark and frame potholes on flat pavements using MSER to calculate the width, length and depth of potholes. By comparing it with the classical method and using the confusion matrix to judge the correctness, recall and accuracy of the method proposed in this paper, it is verified that the method proposed in this paper can improve the accuracy of monocular vision in detecting potholes in road surfaces.
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Microcystins (MCs) are a class of biologically active cyclic heptapeptide pollutants produced by the freshwater alga Microcystis aeruginosa. With increased environmental pollution, MCs have become a popular research topic. In recent years, the hepatotoxicity of MCs and associated effects and mechanisms have been studied extensively. Current epidemiological data indicate that long-term human exposure to MCs can lead to severe liver toxicity, acute toxicity, and death. In addition, current toxicological studies on the liver, a vital target organ of MCs, indicate that MC contamination is associated with the development of liver cancer, nonalcoholic fatty liver, and liver fibrosis. MCs produce hepatotoxicity that affects the metabolic homeostasis of the liver, induces apoptosis, and acts as a pro-cancer factor, leading to liver lesions. MCs mainly mediate the activation of signaling pathways, such as the ERK/JNK/p38 MAPK and IL-6-STAT3 pathways, which leads to oxidative damage and even carcinogenesis. Moreover, MCs can act synergistically with other pollutants to produce combined toxicity. However, few systematic reviews have been performed on these new findings. This review systematically summarizes the toxic effects and mechanisms of MCs on the liver and discusses the combined liver toxicity effects of MCs and other pollutants to provide reference for subsequent research. The toxicity of different MC isomers deserves further study. The detection methods and limit standards of MCs in agricultural and aquatic products will represent important research directions in the future. Standard protocols for fish sampling during harmful algal blooms or to evaluate the degree of MC toxicity in nature are lacking. In future, bioinformatics can be applied to offer insights into MC toxicology research and potential drug development for MC poisoning. Further research is essential to understand the molecular mechanisms of liver function damage in combined-exposure toxicology studies to establish treatment for MC-induced liver damage.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Contaminantes Ambientales , Microcystis , Animales , Humanos , Microcistinas/análisis , Hígado/metabolismo , Microcystis/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Contaminantes Ambientales/metabolismoRESUMEN
BACKGROUND: Sepsis is a leading cause of death worldwide. However, little has been known concerning the status of discharge against medical advice (DAMA) in sepsis patients. OBJECTIVE: To identify factors associated with DAMA, evaluate the association of DAMA with 30-day unplanned readmission and readmitted outcomes after sepsis hospitalization. METHODS: Using the National Readmission Database, we identified sepsis patients who discharged routinely or DAMA in 2017. Multivariable models were used to identify factors related to DAMA, evaluate the association between DAMA and readmission, and elucidate the relationship between DAMA and outcomes in patients readmitted within 30 days. RESULTS: Among 1,012,650 sepsis cases, patients with DAMA accounted for 3.88% (n = 39,308). The unplanned 30-day readmission rates in patients who discharged home and DAMA were 13.08% and 27.21%, respectively. Predictors of DAMA in sepsis included Medicaid, diabetes, smoking, drug abuse, alcohol abuse, and psychoses. DAMA was statistically significantly associated with 30-day (odds ratio [OR] 2.18, 95% confidence interval [CI] 2.09-2.28), 60-day (OR 1.98, 95% CI 1.90-2.06), and 90-day (OR 1.88, 95% CI 1.81-1.96) readmission. DAMA is also associated with higher mortality in patients readmitted within 30 days (OR 1.38, 95% CI 1.17-1.63), whereas there were no statistically significant differences in length of stay and costs between patients who discharged home or DAMA. CONCLUSIONS: DAMA occurs in nearly 3.88% of sepsis patients and is linked to higher readmission and mortality. Those at high risk of DAMA should be early identified to motivate intervention to avoid premature discharges and associated adverse outcomes.
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Cadmium (Cd) contamination of rice is an urgent ecological and agricultural problem. Strontium (Sr) has been shown to promote plant growth. However, the effect of Sr on rice seedlings under Cd stress is currently unclear. In this work hydroponic experiments were used to assess the impact of Sr on rice seedling growth under Cd stress. The findings demonstrated that foliar application of 0.5 mg L-1 Sr had no discernible impact on the development of rice seedlings. However, Sr significantly alleviated growth inhibition and toxicity in rice seedlings when threatened by Cd. Compared with the Cd treatment (Cd, 2.5 mg L-1), the root length, shoot height, and whole plant length of rice seedlings in the Cd + Sr treatment (Cd, 2.5 mg L-1; Sr, 0.5 mg L-1) increased by 4.96 %, 12.47 % and 9.60 %, respectively. The content of Cd in rice decreased by 23.34 % (roots) and 5.79 % (shoots). Sr lessened the degree of membrane lipid peroxidation damage (lower MDA concentration) among the seedlings of rice under Cd stress by controlling the activities of antioxidant enzymes and GSH content. By changing the expression of antioxidant enzyme-encoding genes and downregulating the heavy metal transporter gene (OsNramp5), Sr reduced accumulation and the detrimental effects of Cd on rice seedlings. Our study provides a new solution to the problem of Cd contamination in rice, which may promote the safe production of rice and benefit human health.
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Cadmio , Oryza , Humanos , Cadmio/metabolismo , Antioxidantes/metabolismo , Plantones , Estrés Oxidativo , Estroncio/toxicidad , Estroncio/metabolismo , Raíces de Plantas/metabolismoRESUMEN
Road obstacle detection is an important component of intelligent assisted driving technology. Existing obstacle detection methods ignore the important direction of generalized obstacle detection. This paper proposes an obstacle detection method based on the fusion of roadside units and vehicle mounted cameras and illustrates the feasibility of a combined monocular camera inertial measurement unit (IMU) and roadside unit (RSU) detection method. A generalized obstacle detection method based on vision IMU is combined with a roadside unit obstacle detection method based on a background difference method to achieve generalized obstacle classification while reducing the spatial complexity of the detection area. In the generalized obstacle recognition stage, a VIDAR (Vision-IMU based identification and ranging) -based generalized obstacle recognition method is proposed. The problem of the low accuracy of obstacle information acquisition in the driving environment where generalized obstacles exist is solved. For generalized obstacles that cannot be detected by the roadside unit, VIDAR obstacle detection is performed on the target generalized obstacles through the vehicle terminal camera, and the detection result information is transmitted to the roadside device terminal through the UDP (User Data Protocol) protocol to achieve obstacle recognition and pseudo-obstacle removal, thereby reducing the error recognition rate of generalized obstacles. In this paper, pseudo-obstacles, obstacles with a certain height less than the maximum passing height of the vehicle, and obstacles with a height greater than the maximum passing height of the vehicle are defined as generalized obstacles. Pseudo-obstacles refer to non-height objects that appear to be "patches" on the imaging interface obtained by visual sensors and obstacles with a height less than the maximum passing height of the vehicle. VIDAR is a vision-IMU-based detection and ranging method. IMU is used to obtain the distance and pose of the camera movement, and through the inverse perspective transformation, it can calculate the height of the object in the image. The VIDAR-based obstacle detection method, the roadside unit-based obstacle detection method, YOLOv5 (You Only Look Once version 5), and the method proposed in this paper were applied to outdoor comparison experiments. The results show that the accuracy of the method is improved by 2.3%, 17.4%, and 1.8%, respectively, compared with the other four methods. Compared with the roadside unit obstacle detection method, the speed of obstacle detection is improved by 1.1%. The experimental results show that the method can expand the detection range of road vehicles based on the vehicle obstacle detection method and can quickly and effectively eliminate false obstacle information on the road.
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Kinase inhibitors against Cyclin Dependent Kinase 4 and 6 (CDK4/6i) are promising cancer therapeutic drugs. However, their effects are limited by primary or acquired resistance in virtually all tumor types. Here, we demonstrate that Leucine Rich Pentatricopeptide Repeat Containing (LRPPRC) controls CDK4/6i response in lung cancer by forming a feedback loop with CDK6. LRPPRC binds to CDK6-mRNA, increasing the stability and expression of CDK6. CDK6 and its downstream E2F Transcription Factor 1 (E2F1), bind to the LRPPRC promoter and elevate LRPPRC transcription. The activation of the LRPPRC-CDK6 loop facilitates cell cycle G1/S transition, oxidative phosphorylation, and cancer stem cell generation. Gossypol acetate (GAA), a gynecological medicine that has been repurposed as a degrader of LRPPRC, enhances the CDK4/6i sensitivity in vitro and in vivo. Our study reveals a mechanism responsible for CDK4/6i resistance and provides an enlightening approach to investigating the combinations of CDK4/6 and LRPPRC inhibitors in cancer therapy.
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Antineoplásicos , Neoplasias Pulmonares , Humanos , Línea Celular Tumoral , Quinasa 4 Dependiente de la Ciclina/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Quinasa 6 Dependiente de la Ciclina/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas de Neoplasias/genéticaRESUMEN
BACKGROUND: Prophylactic vasopressor infusion can effectively assist with fluid loading to prevent spinal anesthesia-induced hypotension. However, the ideal dose varies widely among individuals. We hypothesized that hypotension-susceptible patients requiring cesarean section (C-section) could be identified using combined ultrasound parameters to enable differentiated prophylactic medical interventions. METHODS: This prospective observational trial was carried out within a regional center hospital for women and children in Sichuan Province, China. Singleton pregnant women undergoing combined spinal-epidural anesthesia for elective C-sections were eligible. Women with contraindications to spinal anesthesia or medical comorbidities were excluded. Velocity time integral (VTI) and left ventricular end-diastolic area (LVEDA) in the supine and left lateral positions were measured on ultrasound before anesthesia. Stroke volume, cardiac output, and the percentage change (%) in each parameter between two positions were calculated. Vital signs and demographic data were recorded. Spinal anesthesia-induced hypotension was defined as a mean arterial pressure decrease of > 20% from baseline. The area under the receiver operating characteristic curve (AUROC) was used to analyze the associations of ultrasound measurements, vital signs, and demographic characteristics with spinal anesthesia-induced hypotension. This exploratory study did not have a predefined outcome; however, various parameter combinations were compared using the AUROC to determine which combined parameters had better predictive values. RESULTS: Patients were divided into the normotension (n = 31) and hypotension groups (n = 57). A combination of heart rate (HR), LVEDAs, and VTI% was significantly better at predicting hypotension than was HR (AUROC 0.827 vs. 0.707, P = 0.020) or LVEDAs (AUROC 0.827 vs. 0.711, P = 0.039) alone, but not significantly better than VTI% alone (AUROC 0.827 vs. 0.766, P = 0.098). CONCLUSION: The combined parameters of HR and LVEDAs with VTI% may predict spinal anesthesia-induced hypotension more precisely than the single parameters. Future research is necessary to determine whether this knowledge improves maternal and neonatal outcomes. TRIAL REGISTRATION: ChiCTR1900025191.
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Anestesia Obstétrica , Anestesia Raquidea , Hipotensión Controlada , Hipotensión , Recién Nacido , Niño , Femenino , Embarazo , Humanos , Cesárea/efectos adversos , Anestesia Raquidea/efectos adversos , Anestesia Obstétrica/efectos adversos , Hipotensión/inducido químicamente , Hipotensión/diagnóstico por imagenRESUMEN
Background: The alanine-serine-cysteine transporter 2, ASCT2 (solute carrier family 1 member 5, SLC1A5), is a major transporter of the amino acid, glutamine. Although SLC1A5 has been reported to be associated with some types of cancer, less pan-cancer analysis, which would give a comprehensive understanding of SLC1A5 across human cancers, has been carried out. Methods: We used the TCGA and GEO databases to investigate the oncogenic role of SLC1A5. We examined gene and protein expression, survival, genetic mutations, protein phosphorylation, immunocyte infiltration and the related genes correlated pathways. In HCT116 cells, SLC1A5 was silenced by siRNAs and the mRNA and protein was checked by Q-PCR and WB, respectively and the cellular function was assessed by CCK8, cell cycle and apoptosis. Results: We found that SLC1A5 was over-expressed in multiple types of cancer and that elevated expression of SLC1A5 was associated with poor survival in many cancers. The missense mutation of R330 H/C was associated with poor survival, especially in uterine carcinosarcoma. Furthermore, we found enhanced phosphorylation of S503 in uterine corpus endometrial carcinoma and lung adenocarcinoma. In addition, elevated SLC1A5 expression was associated with immune cell infiltration in many cancers. KEGG and GO analysis showed that SLC1A5 and its related genes were involved in central carbon metabolism in cancer, due to their amino acid transport activity. The cellular function indicated that SLC1A5 may influence the cell proliferation by affecting DNA synthesis. Conclusions: Our findings highlighted the important role of SLC1A5 in tumorigenesis and provided insights into potential cancer treatment strategies.
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Telomere length (TL), which is maintained by human telomerase reverse transcriptase (hTERT; component of telomerase) and/or TRF1/TRF2 (core components of shelterin) via different mechanisms, is essential for chromosomal stability and cell survival. Folates comprise a group of essential B9 vitamin that involve in DNA synthesis and methylation. This study aimed to evaluate the effects of folic acid (FA) and 5-methyltetrahydrofolate (5-MeTHF) on TL, chromosome stability, and cell survival of telomerase-negative BJ and telomerase-positive A375 cells in vitro. BJ and A375 cells were cultured in modified medium with FA or 5-MeTHF (22.6 or 2260 nM) for 28 days. TL and mRNA expression were determined by RT-qPCR. Chromosome instability (CIN) and cell death were measured by CBMN-Cyt assay. Results showed that abnormal TL elongation was observed in FA- and 5-MeTHF-deficient BJ cells. The TL of A375 cells showed no obvious alterations under the FA-deficient condition but was significantly elongated under the 5-MeTHF-deficient condition. In both BJ and A375 cells, FA and 5-MeTHF deficiency caused decreased TRF1, TRF2, and hTERT expression, increased CIN and cell death; while a high concentration of 5-MeTHF induced elongated TL, elevated CIN, increased TRF1 and TRF2 expression, and decreased hTERT expression, when compared with the FA counterpart. These findings concluded that folate deficiency induced TL instability in both telomerase-negative and -positive cells, and FA was more efficient in maintaining TL and chromosome stability compared with 5-MeTHF.
Asunto(s)
Melanoma , Telomerasa , Humanos , Ácido Fólico/farmacología , Telomerasa/genética , Telomerasa/metabolismo , Telómero/metabolismo , Inestabilidad Cromosómica , Fibroblastos/metabolismoRESUMEN
Telomere length (TL), which is maintained by human telomerase reverse transcriptase (hTERT; component of telomerase) and/or TRF1/TRF2 (core components of shelterin) via different mechanisms, is essential for chromosomal stability and cell survival. Folates comprise a group of essential B9 vitamin that involve in DNA synthesis and methylation. This study aimed to evaluate the effects of folic acid (FA) and 5-methyltetrahydrofolate (5-MeTHF) on TL, chromosome stability, and cell survival of telomerase-negative BJ and telomerase-positive A375 cells in vitro. BJ and A375 cells were cultured in modified medium with FA or 5-MeTHF (22.6 or 2260 nM) for 28 days. TL and mRNA expression were determined by RT-qPCR. Chromosome instability (CIN) and cell death were measured by CBMN-Cyt assay. Results showed that abnormal TL elongation was observed in FA and 5-MeTHF deficient BJ cells. The TL of A375 cells showed no obvious alterations under the FA-deficient condition but was significantly elongated under the 5-MeTHF-deficient condition. In both BJ and A375 cells, FA and 5-MeTHF deficiency caused decreased TRF1, TRF2, and hTERT expression, increased CIN and cell death; while a high concentration of 5-MeTHF induced elongated TL, elevated CIN, increased TRF1 and TRF2 expression and decreased hTERT expression, when compared with the FA counterpart. These findings concluded that folate deficiency induced TL instability in both telomerase-negative and -positive cells, and FA was more efficient in maintaining TL and chromosome stability compared with 5-MeTHF.