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Acute myeloid leukemia (AML) is a common hematological malignancy with overall poor prognosis. Exploring novel targets is urgent and necessary to improve the clinical outcome of relapsed and refractory (RR) AML patients. Through clinical specimens, animal models and cell-level studies, we explored the specific mechanism of 3-hydroxy-3-methylglutaryl coenzyme A synthase 1 (HMGCS1) in AML and the mechanism of targeting HMGCS1 to attenuate cell proliferation, increase chemotherapy sensitivity and improve the occurrence and development of AML. Here, we reveal that HMGCS1 is overexpressed in RR patients and negatively related to overall survival (OS). Knocking out HMGCS1 in AML cells attenuated cell proliferation and increased chemotherapy sensitivity, while stable overexpression of HMGCS1 had the opposite effects. Mechanistically, we identified that knockout of HMGCS1 suppressed mitogen-activated protein kinase (MAPK) pathway activity, while overexpression of HMGCS1 could remarkably enhance the pathway. U0126, a MEK1 inhibitor, offset the effects of HMGCS1 overexpression, indicating that HMGCS1 promotes RR AML through the MAPK pathway. Further, we verified that hymeglusin, a specific inhibitor of HMGCS1, decreases cell growth both in AML cell lines and primary bone marrow cells of AML patients. Furthermore, combination of hymeglusin and the common chemotherapeutic drug cytarabine and adriamycin (ADR) had synergistic toxic effects on AML cells. Our study demonstrates the important role of HMGCS1 in AML, and targeting this protein is promising for the treatment of RR AML.
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BACKGROUND AND OBJECTIVE: The prevalence of 12-hour shift work is increasing in various occupations. Shift work has been linked to circadian rhythm disruption, which may lead to hormonal changes and metabolic disorders, including alterations in glucose, lipid, and purine metabolism. Despite this, there is limited research on the potential connection between work shifts and abnormal serum uric acid (SUA) levels. Furthermore, the factors that contribute to abnormal SUA levels in shift workers are not well-understood. Therefore, this study aimed to analyze the SUA levels of shift workers employed in an aircraft maintenance company, investigate the potential association between shift work and SUA levels, and explore the factors that may influence abnormal SUA levels in shift workers. METHODS: A total of 2263 male workers from an aircraft maintenance company were included in this study using the cluster sampling method. The workers were divided into two groups based on their working shifts: night shift (N = 1047, 46.27%) and day working (N = 1216, 53.73%). A survey was conducted between April 1st and June 30th, 2022 to gather information on work, lifestyle, physical examination results, and other relevant factors. The survey included a self-designed demographic information questionnaire to collect data on workers' characteristics, medical history, years of employment, smoking and drinking habits, and main lifestyle behaviors. The workers' SUA levels were measured using uricase colorimetry. One-way ANOVA was used to compare the difference in the abnormal detection rate of SUA between the two groups, and multi-factor logistic regression analysis was used to identify the factors that influence abnormal SUA levels. RESULTS: The study indicated that 48.9% of night shift workers and 43.8% in the regular day workers had abnormal SUA levels, with a significant difference between the two groups (χ2 = 6.125, P = 0.013). Factors such as circadian rhythm type, shift work, age, the taste of diet, type of diet, smoking, overweight or obesity based on body mass index (BMI), concentration of urine creatinine (CREA), total cholesterol, triglyceride, and low-density lipoprotein cholesterol were found to be correlated with SUA abnormalities (P < 0.05). The risk of developing SUA abnormalities was found to be higher in individuals with an intermittent (OR = 1.34, 95% CI: 0.83-2.12, P < 0.05) or evening circadian rhythm type (OR = 1.45, 95% CI: 0.86-2.43, P > 0.05) compared to those with a morning type. Additionally, factors such as night shift work, a high-sodium diet, smoking, a diet high in meat and low in vegetables, being overweight or obese, and higher levels of CREA were also found to increase the risk of developing SUA abnormalities. The study also revealed a significant dose-response relationship between BMI and abnormal uric acid levels. After controlling for other factors, the risk of developing SUA abnormalities was found to be 1.18 times higher in the night shift work group than in the day work group (OR = 1.18, 95% CI:1.02-1.34, P = 0.01). CONCLUSION: Shift work has been linked to a higher risk of developing SUA abnormalities, and there are several factors that may contribute to this risk. To prevent diseases, it is recommended that enterprises implement better health monitoring and management practices for shift workers.
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Aeronaves , Jornada de Trabalho em Turnos , Ácido Úrico , Humanos , Masculino , Ácido Úrico/sangue , Adulto , Pessoa de Meia-Idade , Fatores de Risco , Tolerância ao Trabalho Programado/fisiologia , Ritmo Circadiano/fisiologia , Inquéritos e Questionários , China/epidemiologiaRESUMO
Visual simultaneous localization and mapping (VSLAM) enhances the navigation of autonomous agents in unfamiliar environments by progressively constructing maps and estimating poses. However, conventional VSLAM pipelines often exhibited degraded performance in dynamic environments featuring mobile objects. Recent research in deep learning led to notable progress in semantic segmentation, which involves assigning semantic labels to image pixels. The integration of semantic segmentation into VSLAM can effectively differentiate between static and dynamic elements in intricate scenes. This paper provided a comprehensive comparative review on leveraging semantic segmentation to improve major components of VSLAM, including visual odometry, loop closure detection, and environmental mapping. Key principles and methods for both traditional VSLAM and deep semantic segmentation were introduced. This paper presented an overview and comparative analysis of the technical implementations of semantic integration across various modules of the VSLAM pipeline. Furthermore, it examined the features and potential use cases associated with the fusion of VSLAM and semantics. It was found that the existing VSLAM model continued to face challenges related to computational complexity. Promising future research directions were identified, including efficient model design, multimodal fusion, online adaptation, dynamic scene reconstruction, and end-to-end joint optimization. This review shed light on the emerging paradigm of semantic VSLAM and how deep learning-enabled semantic reasoning could unlock new capabilities for autonomous intelligent systems to operate reliably in the real world.
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Intelligent compaction (IC) has emerged as a breakthrough technology that utilizes advanced sensing, data transmission, and control systems to optimize asphalt pavement compaction quality and efficiency. However, accurate assessment of compaction status remains challenging under real construction conditions. This paper reviewed recent progress and applications of smart sensors and machine learning (ML) to address existing limitations in IC. The principles and components of various advanced sensors deployed in IC systems were introduced, including SmartRock, fiber Bragg grating, and integrated circuit piezoelectric acceleration sensors. Case studies on utilizing these sensors for particle behavior monitoring, strain measurement, and impact data collection were reviewed. Meanwhile, common ML algorithms including regression, classification, clustering, and artificial neural networks were discussed. Practical examples of applying ML to estimate mechanical properties, evaluate overall compaction quality, and predict soil firmness through supervised and unsupervised models were examined. Results indicated smart sensors have enhanced compaction monitoring capabilities but require robustness improvements. ML provides a data-driven approach to complement traditional empirical methods but necessitates extensive field validation. Potential integration with digital construction technologies such as building information modeling and augmented reality was also explored. In conclusion, leveraging emerging sensing and artificial intelligence presents opportunities to optimize the IC process and address key challenges. However, cooperation across disciplines will be vital to test and refine technologies under real-world conditions. This study serves to advance understanding and highlight priority areas for future research toward the realization of IC's full potential.
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With the continuous development of large-scale maintenance of infrastructure, accurate, reasonable, and efficient mechanical behavior evaluation and performance prediction of civil materials and structures have become the keys to improving service durability and intelligent maintenance management for infrastructure [...].
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Hydrogen sulfide (H2S) is a typical odour compound mainly causing respiratory and central nervous system symptoms. However, the immunotoxicity of inhaled H2S and the underlying mechanisms remain largely unknown. In this study, a low-dose inhalation exposure to H2S was arranged to observe inflammatory response and immunotoxicity in lung tissue of rats. Low concentrations of H2S exposure affected the immune level of pulmonary tissue and peripheral blood. Significant pathological changes in lung tissue in the exposure group were observed. At low concentration, H2S not only induced the upregulation of AQP-4 and MMP-9 expression but also stimulated immune responses, initiating various anti-inflammatory and inflammatory factors, altering tissue homeostatic environments. The TNF and chemokine signaling pathway played an important role which can promote the deterioration of pulmonary inflammatory processes and lead to lung injury and fibrosis. Excessive immune response causes an inflammatory effect and blood-gas barrier damage. These data will be of value in evaluating future occupational health risks and providing technical support for the further development of reliable, sensitive, and easy-to-use screening indicators of exposure injury.
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Sulfeto de Hidrogênio , Exposição por Inalação , Pulmão , Animais , Sulfeto de Hidrogênio/toxicidade , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/imunologia , Ratos , Exposição por Inalação/efeitos adversos , Masculino , Inflamação/induzido quimicamente , Inflamação/patologia , Ratos Sprague-Dawley , Metaloproteinase 9 da Matriz/metabolismo , Poluentes Atmosféricos/toxicidadeRESUMO
Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) clinical isolations have rapidly increased in pediatric patients. To investigate a possible health care-associated infections of CRKP in a tertiary pediatric hospital, the circulating clones and carbapenem-resistant pattern between CRKP and carbapenem-resistant Acinetobacter baumannii (CRAB) isolates were compared to classify their epidemiological characteristics. The results will help to identify the epidemic pattern of the CRKP transmission in the hospital. Methods: Ninety-six CRKP and forty-eight CRAB isolates were collected in Kunming Children's Hospital from 2019 through 2022. These isolates were genotyped using repetitive extragenic palindromic-PCR (REP-PCR). Carbapenemase phenotypic and genetic characterization were investigated using a disk diffusion test and singleplex PCR, respectively. In addition, these characteristics of the two pathogens were compared. Results: The rates of CRKP and CRAB ranged from 15.8% to 37.0% at the hospital. Forty-nine and sixteen REP genotypes were identified among the 96 and 48 CRKP and CRAB isolates tested, respectively. The CRKP isolates showed more genetic diversity than the CRAB isolates. Of the 96 CRKP isolates, 69 (72%) produced Class B carbapenemases. However, all 48 CRAB isolates produced Class D carbapenemase or extended-spectrum ß-lactamases (ESBL) combined with the downregulation of membrane pore proteins. Furthermore, the carbapenemase genes bla KPC, bla IMP, and bla NDM were detected in CRKP isolates. However, CRAB isolates were all positive for the bla VIM, bla OXA-23, and bla OXA-51 genes. Conclusions: These CRKP isolates exhibited different biological and genetic characteristics with dynamic changes, suggesting widespread communities. Continuous epidemiological surveillance and multicenter research should be carried out to strengthen the prevention and control of infections.
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Acinetobacter baumannii , Enterobacteriáceas Resistentes a Carbapenêmicos , Humanos , Criança , Antibacterianos/farmacologia , Klebsiella pneumoniae , Genótipo , Hospitais Pediátricos , Farmacorresistência Bacteriana , beta-Lactamases/genética , beta-Lactamases/metabolismo , Carbapenêmicos/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Objective: To evaluate whether using a cocktail of intercostal nerve blocks (TINB) during thoracoscopic surgery results in better clinical outcomes than patient-controlled analgesia (PCIA). Methods: Patients in two medical groups undergoing video-assisted thoracoscopic surgery (VATS) for pulmonary nodules in West China Hospital of Sichuan University were collected consecutively between March 2022 and December 2022. The groups were divided into two subgroups based on their analgesic program, which were TINB group and PCIA group. The primary outcome was the visual analogue scale (VAS) of the two groups at different stage after surgery and after discharge. Any analgesic related adverse events (ARAEs) were also recorded. Results: A total of 230 patients who underwent VATS were enrolled, in which 113 patients (49.1%) received a cocktail TINB after surgery, and 117 patients (50.9%) received a PCIA. After PSM, 62 patients in each group were selected. The difference of resting VAS (RVAS) and active VAS (AVAS) at different stage during hospitalization was only related to the change of period (p < 0.05, p < 0.05), and the two groups showed no significant differences in RVAS or AVAS during hospitalization (p = 0.271, p = 0.915). However, the rates of dizziness (4.84% vs 25.81%, p = 0.002), nausea and vomiting (0 vs 22.58%, p < 0.05), fatigue (14.52% vs 34.87%, p = 0.012), and insomnia (0 vs 58.06%, p < 0.05) in TINB group were lower than that in PCIA group. Besides, AVAS and RVAS at 7, 14, and 30 days after discharge in TINB group were both significantly lower than that in PCIA group (p < 0.05, p < 0.05). Conclusion: Cocktail TINB provided better analgesia after discharge and reduced the incidence of ARAEs in patients undergoing VATS.
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Tyrosine kinase inhibitors (TKIs) have been recognized as crucial agents for treating various tumors, and one of their key targets is the intracellular site of the vascular endothelial growth factor receptor (VEGFR). While TKIs have demonstrated their effectiveness in solid tumor patients and increased life expectancy, they can also lead to adverse cardiovascular effects including hypertension, thromboembolism, cardiac ischemia, and left ventricular dysfunction. Among the TKIs, sorafenib was the first approved agent and it exerts anti-tumor effects on hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC) by inhibiting angiogenesis and tumor cell proliferation through targeting VEGFR and RAF. Unfortunately, the adverse cardiovascular effects caused by sorafenib not only affect solid tumor patients but also limit its application in curing other diseases. This review explores the mechanisms underlying sorafenib-induced cardiovascular adverse effects, including endothelial dysfunction, mitochondrial dysfunction, endoplasmic reticulum stress, dysregulated autophagy, and ferroptosis. It also discusses potential treatment strategies, such as antioxidants and renin-angiotensin system inhibitors, and highlights the association between sorafenib-induced hypertension and treatment efficacy in cancer patients. Furthermore, emerging research suggests a link between sorafenib-induced glycolysis, drug resistance, and cardiovascular toxicity, necessitating further investigation. Overall, understanding these mechanisms is crucial for optimizing sorafenib therapy and minimizing cardiovascular risks in cancer patients.
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Antineoplásicos , Carcinoma Hepatocelular , Hipertensão , Neoplasias Renais , Neoplasias Hepáticas , Humanos , Sorafenibe/efeitos adversos , Carcinoma Hepatocelular/patologia , Antineoplásicos/efeitos adversos , Fator A de Crescimento do Endotélio Vascular , Niacinamida , Compostos de Fenilureia/efeitos adversos , Neoplasias Hepáticas/tratamento farmacológico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Hipertensão/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversosRESUMO
Short-chain Perfluorinated compounds (PFCs), used as substitutes for highly toxic long-chain PFCs, are increasingly entering the aquatic environment. However, the toxicity of short-chain PFCs in the environment is still controversial. This study investigated the effects of short-chain perfluorobutanesulfonic acid (PFBS) at different concentrations (2.5, 6, 14.4, 36, and 90 mg/L) on M. aeruginosa growth under 12-day exposure and explored the molecular mechanism of toxicity using transcriptomics. The results showed that M. aeruginosa exhibited hormetic effects after exposure to PFBS. Low PFBS concentrations stimulated algal growth, whereas high PFBS concentrations inhibited it, and this inhibitory effect became progressively more pronounced with increasing PFBS exposure concentrations. Transcriptomics showed that PFBS promoted the pathways of photosynthesis, glycolysis, energy metabolism and peptidoglycan synthesis, providing the energy required for cell growth and maintaining cellular morphology. PFBS, on the other hand, caused growth inhibition in algae mainly through oxidative stress, streptomycin synthesis, and genetic damage. Our findings provide new insights into the toxicity and underlying mechanism of short-chain PFCs on algae and inform the understanding of the hormetic effect of short-chain PFCs, which are crucial for assessing their ecological risks in aquatic environments.
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Fluorocarbonos , Microcystis , Ácidos Sulfônicos , Microcystis/genética , Ciclo Celular , Proliferação de Células , Metabolismo EnergéticoRESUMO
OBJECTIVE: We conducted a community-based cohort study to predict the 3-year occurrence of chronic kidney disease (CKD) among population aged ≥60 years. METHOD: Participants were selected from two communities through randomized cluster sampling in Jiading District of Shanghai, China. The two communities were randomly divided into a development cohort (n = 12012) and a validation cohort (n = 6248) with a 3-year follow-up. Logistic regression analysis was used to determine the independent predictors. A nomogram was established to predict the occurrence of CKD within 3 years. The area under the curve (AUC), the calibration curve and decision curve analysis (DCA) curve were used to evaluate the model. RESULT: At baseline, participants in development cohort and validation cohort were with the mean age of 68.24 ± 5.87 and 67.68 ± 5.26 years old, respectively. During 3 years, 1516 (12.6%) and 544 (8.9%) new cases developed CKD in the development and validation cohorts, respectively. Nine variables (age, systolic blood pressure, body mass index, exercise, previous hypertension, triglycerides, fasting plasma glucose, glycated hemoglobin and serum creatinine) were included in the prediction model. The AUC value was 0.742 [95% confidence interval (CI), 0.728-0.756] in the development cohort and 0.881(95%CI, 0.867-0.895) in the validation cohort, respectively. The calibration curves and DCA curves demonstrate an effective predictive model. CONCLUSION: Our nomogram model is a simple, reasonable and reliable tool for predicting the risk of 3-year CKD in community-dwelling elderly people, which is helpful for timely intervention and reducing the incidence of CKD.
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Insuficiência Renal Crônica , Idoso , Humanos , Pessoa de Meia-Idade , Área Sob a Curva , Índice de Massa Corporal , China/epidemiologia , Estudos de Coortes , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologiaRESUMO
BMP and activin membrane-bound inhibitor (BAMBI) is a transmembrane glycoprotein, known as a pseudo-receptor for TGFß, as, while its extracellular domain is similar to that of type I TGFß receptors, its intracellular structure is shorter and lacks a serine/threonine phosphokinase signaling motif. BAMBI can regulate numerous biological phenomena, including glucose and lipid metabolism, inflammatory responses, and cell proliferation and differentiation. Furthermore, abnormal expression of BAMBI at the mRNA and protein levels contributes to various human pathologies, including obesity and cancer. In the present review, the structure of BAMBI is briefly introduced and its associated signaling pathways and physiological functions are described. Understanding of BAMBI structure and function may contribute to knowledge regarding the occurrence of diseases, including obesity and diabetes, among others. The present review provides a theoretical foundation for the development of BAMBI as a potential biomarker or therapeutic target.
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Background: The molecular mechanisms underlying window of implantation (WOI) displacement in patients with recurrent implantation failure (RIF) remain unclear. This study aims to explore the transcriptomic signatures of endometrium with normal and displaced WOIs and to identify the causes of endometrial receptivity (ER) abnormalities and WOI displacement in RIF patients. Methods: In this study, 40 RIF patients were recruited and underwent personalized embryo transfer (pET) guided by the predicted results of endometrial receptivity diagnosis (ERD) model. Transcriptome analysis of endometrium from patients with clinical pregnancies after pET was performed to identify differentially expressed genes (DEGs) associated with WOI displacement. Gene expression data from HRT and natural cycle endometrium were compared to identify specific gene expression patterns of ER-related genes during WOI. Results: The ERD results indicated that 67.5% of RIF patients (27/40) were non-receptive in the conventional WOI (P+5) of the HRT cycle. The clinical pregnancy rate in RIF patients improved to 65% (26/40) after ERD-guided pET, indicating the effectiveness of transcriptome-based WOI prediction. Among the 26 patients with clinical pregnancy, the gene expression profiles of P+5 endometrium from advanced (n=6), normal (n=10) and delayed (n=10) WOI groups were significantly different from each other. Furthermore, 10 DEGs identified among P+5 endometrium of 3 groups were involved in immunomodulation, transmembrane transport and tissue regeneration, which could accurately classify the endometrium with different WOIs. Additionally, a large number of ER-related genes showed significant correlation and similar gene expression patterns in P+3, P+5, and P+7 endometrium from HRT cycles and LH+5, LH+7, and LH+9 endometrium from natural cycles. Conclusion: Our study shows that ER-related genes share similar gene expression patterns during WOI in both natural and HRT cycles, and their aberrant expression is associated with WOI displacements. The improvement of pregnancy outcomes in RIF patients by adjusting ET timing according to ERD results demonstrates the importance of transcriptome-based endometrial receptivity assessment and the clinical efficiency of ERD model.