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RATIONALE: Traumatic brain injury frequently leads to prolonged coma, posing significant medical management challenges. Complementary therapies, including traditional Chinese herbal medicine, have been investigated as potential interventions in comatose patients. Chinese aromatic herbs, such as Borneolum (Bingpian), Moschus (Shexiang), and Acori tatarinowii rhizoma (Shichangpu), have long been believed to be "resuscitation with aromatics" based on traditional Chinese medicines theory. PATIENT CONCERNS: A 16-year-old male was admitted to the intensive rehabilitation unit for further treatment due to prolonged coma and frequent seizures following traumatic brain injury. DIAGNOSES: Western medicine diagnosed the patient as coma, diffuse axonal injury, and epilepsy. According to traditional Chinese medicine theory, the syndrome differentiation indicates a Yin-closed disease. INTERVENTIONS: According to the patient's condition, we use the Chinese aromatic herbs as a complementary therapy. OUTCOMES: Following a month-long administration, the patient's consciousness and electroencephalogram (EEG) background progressively improved. A 6-month follow-up demonstrated full arousal, though with ambulatory EEG revealing mild to moderate abnormality in the background. LESSONS: The addition of Chinese aromatic herbs appears to have a beneficial effect on the patient's consciousness and EEG background. This could be attributed to the herbs' inherent pharmacological properties, as well as their potential to enhance the permeability of the blood-brain barrier to other drugs. This makes them a promising option for complementary therapy.
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Coma , Drugs, Chinese Herbal , Humans , Male , Coma/etiology , Coma/drug therapy , Coma/therapy , Drugs, Chinese Herbal/therapeutic use , Adolescent , Electroencephalography , Complementary Therapies/methods , Brain Injuries, Traumatic/complications , Medicine, Chinese Traditional/methodsABSTRACT
BACKGROUND: Pancreatic cancer (PC) is characterized by a poor prognosis and limited treatment options. Ferroptosis plays an important role in cancer, SET and MYND domain-containing protein 2 (SMYD2) is widely expressed in various cancers. However, the role of SMYD2 in regulating ferroptosis in PC remains unexplored. This study aimed to investigate the role of SMYD2 in mediating ferroptosis and its mechanistic implications in PC progression. METHODS: The levels of SMYD2, c-Myc, and NCOA4 were assessed in PC tissues, and peritumoral tissues. SMYD2 expression was further analyzed in human PC cell lines. In BxPC3 cells, the expression of c-Myc, NCOA4, autophagy-related proteins, and mitochondrial morphology, was evaluated following transfection with si-SMYD2 and treatment with autophagy inhibitors and ferroptosis inhibitors. Ferroptosis levels were quantified using flow cytometry and ELISA assays. RNA immunoprecipitation was conducted to elucidate the interaction between c-Myc and NCOA4 mRNA. A xenograft mouse model was constructed to validate the impact of SMYD2 knockdown on PC growth. RESULTS: SMYD2 and c-Myc were found to be highly expressed in PC tissues, while NCOA4 showed reduced expression. Among the PC cell lines studied, BxPC3 cells exhibited the highest SMYD2 expression. SMYD2 knockdown led to decreased c-Myc levels, increased NCOA4 expression, reduced autophagy-related protein expression, mitochondrial shrinkage, and heightened ferroptosis levels. Additionally, an interaction between c-Myc and NCOA4 was identified. In vivo, SMYD2 knockdown inhibited tumor growth. CONCLUSIONS: Targeting SMYD2 inhibits PC progression by promoting ferritinophagy-dependent ferroptosis through the c-Myc/NCOA4 axis. These findings provide insights into potential diagnostic and therapeutic strategies for PC.
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Vertebral tumors in patients with tumor-induced osteomalacia (TIO) have a low diagnostic rate and poor postoperative outcomes. The application of 68 Ga-DOTATATE-PET/CT significantly increased the detection rate. Compared with tumor curettage, segmental resection was recommended as the preferred surgical type due to its high recovery rate. PURPOSE: Tumor-induced osteomalacia (TIO) is an acquired hypophosphatemic osteomalacia, and surgery is the first-line therapy. Most TIO tumors are found in the bones of the appendicular skeleton, cranium, and paranasal sinuses but rarely in the vertebrae. Tumor curettage and segmental resection are the two main surgical options for vertebral TIO patients. However, research on the clinical characteristics and surgical prognosis of vertebral TIO patients is rare. In the present study, for the first time, we investigated the clinical characteristics of 16 vertebral TIO patients and compared the surgical outcomes of patients who underwent surgery via two different surgical methods. METHODS: This was a retrospective cohort study. In this study, we included 16 adult TIO patients with lesions in vertebrae from Peking Union Medical College Hospital (PUMCH), all of whom underwent surgery. Baseline laboratory data were collected through medical records review. Technetium-99 m octreotide scintigraphy (99Tcm-OCT) and 68gallium-DOTA-TATE-positron emission tomography/computed tomography (68 Ga-DOTATATE-PET/CT) were conducted at the Department of Nuclear Medicine of PUMCH. The tumor histopathology was confirmed by a senior pathologist at our center. RESULTS: Vertebral TIO patients had lower serum phosphorus and TmP/GFR and higher serum alkaline phosphatase (ALP), serum parathyroid hormone (PTH), and serum C-terminal cross-linked telopeptide of type I collagen (ß-CTX) levels than the normal range. The sensitivity of 68 GaâDOTATATE PET/CT was 100%, significantly greater than that of 99Tcm-OCT (40%). After comparing the outcomes between the two surgical methods, we found that the recovery rate after segmental resection (62.5%) was greater than that after tumor curettage (12.5%). In the thoracic and sacral vertebrae, segmental resection surgery had a good prognosis. CONCLUSION: 68 Ga-DOTATATE PET/CT could serve as the first diagnostic tool in patients with vertebral TIO, and segmental resection could be used as the preferred surgery. This study would raise awareness of the clinical features and management of these rare vertebral TIO patients.
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Avian influenza virus (AIV) subtype H9N2 has significantly threatened the poultry business in recent years by having become the predominant subtype in flocks of chickens, ducks, and pigeons. In addition, the public health aspects of H9N2 AIV pose a significant threat to humans. Early and rapid diagnosis of H9N2 AIV is therefore of great importance. In this study, a new method for the detection of H9N2 AIV based on fluorescence intensity was successfully established using CRISPR/Cas13a technology. The Cas13a protein was first expressed in a prokaryotic system and purified using nickel ion affinity chromatography, resulting in a high-purity Cas13a protein. The best RPA (recombinase polymerase amplification) primer pairs and crRNA were designed and screened, successfully constructing the detection of H9N2 AIV based on CRISPR/Cas13a technology. Optimal concentration of Cas13a and crRNA was determined to optimize the constructed assay. The sensitivity of the optimized detection system is excellent, with a minimum detection limit of 10° copies/µL and didn't react with other avian susceptible viruses, with excellent specificity. The detection method provides the basis for the field detection of the H9N2 AIV.
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INTRODUCTION: Asthma is associated with upper airway diseases and allergic diseases; however, the causal effects need to be investigated further. Thus, we performed this two-sample Mendelian randomization (MR) analysis to explore and measure the causal effects of asthma on allergic rhinitis (AR), vasomotor rhinitis (VMR), allergic conjunctivitis (AC), atopic dermatitis (AD), and allergic urticaria (AU). METHODS: The data for asthma, AR, VMR, AC, AD, and AU were obtained from large-scale genome-wide association studies summarized recently. We defined single-nucleotide polymorphisms satisfying the MR assumptions as instrumental variables. Inverse-variance weighted (IVW) approach under random-effects was applied as the dominant method for causal estimation. The weighted median approach, MR-Egger regression analysis, MR pleiotropy residual sum and outlier test, and leave-one-out sensitivity analysis were performed as sensitivity analysis. Horizontal pleiotropy was measured using MR-Egger regression analysis. Significant causal effects were attempted for replication and meta-analysis. RESULTS: We revealed that asthma had causal effects on AR (IVW, odds ratio [OR] = 1.93; 95% confidence interval [CI], 1.74-2.14; p < 0.001), VMR (IVW, OR = 1.40; 95% CI, 1.15-1.71; p < 0.001), AC (IVW, OR = 1.65; 95% CI, 1.49-1.82; p < 0.001), and AD (IVW, OR = 2.13; 95% CI, 1.82-2.49; p < 0.001). No causal effect of asthma on AU was observed. Sensitivity analysis further assured the robustness of these results. The evaluation of the replication stage and meta-analysis further confirmed the causal effect of asthma on AR (IVW OR = 1.81, 95% CI 1.62-2.02, p < 0.001), AC (IVW OR = 1.44, 95% CI 1.11-1.87, p < 0.001), and AD (IVW OR = 1.85, 95% CI 1.42-2.41, p < 0.001). CONCLUSIONS: We revealed and quantified the causal effects of asthma on AR, VMR, AC, and AD. These findings can provide powerful causal evidence of asthma on upper airway diseases and allergic diseases, suggesting that the treatment of asthma should be a preventive and therapeutic strategy for AR, VMR, AC, and AD.
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Innovation, which is a pivotal force behind the sustained growth of enterprises, has garnered significant attention across various industries. As the epicenter of corporate decision-making, the board of directors plays a pivotal role in allocating resources and overseeing the execution of strategy. Consequently, it inevitably impacts the innovation capabilities of a business. Previous research has focused primarily on single board member characteristics, such as age, gender, tenure, and educational qualifications, overlooking the cumulative influence of multiple attributes. Therefore, this study aims to investigate the impact of faultlines arising from the intersection of these characteristics within a board on innovation performance. Using panel data from China's A-share listed companies from 2010 to 2021, this research constructs a framework to analyze board faultlines based on gender, age, education, director tenure, independence status, and occupational background. A comprehensive examination reveals a positive association between board faultlines and innovation performance, indicating that diversity within a board can foster enhanced innovative outputs. These findings persist even after rigorous robustness tests, including two-stage instrumental variable regression using lagged innovation performance as well as when substituting explanatory variables and sample intervals. Further analysis reveals that the influence of board faultlines on innovation performance is significant only under certain contextual conditions: when equity concentration is low, industry competition is intense, and risk aversion is greater. This study offers valuable insights for optimizing board membership configurations and thus, ultimately, enhancing the innovation capabilities of enterprises.
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Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant health challenge, characterized by its widespread prevalence, intricate natural progression and multifaceted pathogenesis. Although NAFLD initially presents as benign fat accumulation, it may progress to steatosis, non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. Mesenchymal stem cells (MSCs) are recognized for their intrinsic self-renewal, superior biocompatibility, and minimal immunogenicity, positioning them as a therapeutic innovation for liver diseases. Therefore, this review aims to elucidate the potential roles of MSCs in alleviating the progression of NAFLD by alteration of underlying molecular pathways, including glycolipid metabolism, inflammation, oxidative stress, endoplasmic reticulum stress, and fibrosis. The insights are expected to provide further understanding of the potential of MSCs in NAFLD therapeutics, and support the development of MSC-based therapy in the treatment of NAFLD.
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The purpose of this study was to investigate the relationship between Inflammatory Prognostic Index (IPI) levels and Contrast-Induced Nephropathy (CIN) risk and postoperative clinical outcomes in patients undergoing coronary angiography (CAG) and/or percutaneous coronary intervention (PCI). A total of 3,340 consecutive patients who underwent CAG and/or PCI between May 2017 and December 2022 were enrolled in this study. Based on their baseline IPI levels, patients were categorized into four groups. Clinical characteristics and postoperative outcomes were compared among these groups. In-hospital outcomes focused on CIN risk, repeated revascularization, major bleeding, and major adverse cardiovascular events (MACEs), while the long-term outcome examined the all-cause readmission rate. Quartile analysis found a significant link between IPI levels and CIN risk, notably in the highest quartile (P < 0.001). Even after adjusting for baseline factors, this association remained significant, with an adjusted Odds Ratio (aOR) of 2.33 (95%CI 1.50-3.64; P = 0.001). Notably, baseline IPI level emerged as an independent predictor of severe arrhythmia, with aOR of 0.50 (95%CI 0.35-0.69; P < 0.001), particularly driven by the highest quartile. Furthermore, a significant correlation between IPI and acute myocardial infarction was observed (P < 0.001), which remained significant post-adjustment. For patients undergoing CAG and/or PCI, baseline IPI levels can independently predict clinical prognosis. As a comprehensive inflammation indicator, IPI effectively identifies high-risk patients post-procedure. This study underscores IPI's potential to assist medical professionals in making more precise clinical decisions, ultimately reducing mortality and readmission rates linked to cardiovascular disease (CVD).
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Contrast Media , Coronary Angiography , Percutaneous Coronary Intervention , Humans , Percutaneous Coronary Intervention/adverse effects , Male , Female , Coronary Angiography/adverse effects , Contrast Media/adverse effects , Aged , Prognosis , Middle Aged , Inflammation , Kidney Diseases/chemically induced , Risk Factors , Predictive Value of Tests , Retrospective StudiesABSTRACT
Hypervirulent Klebsiella pneumoniae (hvKP) typically causes severe invasive infections affecting multiple sites in healthy individuals. In the past, hvKP was characterized by a hypermucoviscosity phenotype, susceptibility to antimicrobial agents, and its tendency to cause invasive infections in healthy individuals within the community. However, there has been an alarming increase in reports of multidrug-resistant hvKP, particularly carbapenem-resistant strains, causing nosocomial infections in critically ill or immunocompromised patients. This presents a significant challenge for clinical treatment. Early identification of hvKP is crucial for timely infection control. Notably, identifying hvKP has become confusing due to its prevalence in nosocomial settings and the limited predictive specificity of the hypermucoviscosity phenotype. Novel virulence predictors for hvKP have been discovered through animal models or machine learning algorithms, while standardization of identification criteria is still necessary. Timely source control and antibiotic therapy have been widely employed for the treatment of hvKP infections. Additionally, phage therapy is a promising alternative approach due to escalating antibiotic resistance. In summary, this narrative review highlights the latest research progress in the development, virulence factors, identification, epidemiology of hvKP, and treatment options available for hvKP infection.
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BACKGROUND: Transposable elements play a critical role in maintaining genome architecture during neurodevelopment. Short Interspersed Nuclear Elements (SINEs), a major subtype of transposable elements, are known to harbor binding sites for the CCCTC-binding factor (CTCF) and pivotal in orchestrating chromatin organization. However, the regulatory mechanisms controlling the activity of SINEs in the developing brain remains elusive. RESULTS: In our study, we conduct a comprehensive genome-wide epigenetic analysis in mouse neural precursor cells using ATAC-seq, ChIP-seq, whole genome bisulfite sequencing, in situ Hi-C, and RNA-seq. Our findings reveal that the SET domain bifurcated histone lysine methyltransferase 1 (SETDB1)-mediated H3K9me3, in conjunction with DNA methylation, restricts chromatin accessibility on a selective subset of SINEs in neural precursor cells. Mechanistically, loss of Setdb1 increases CTCF access to these SINE elements and contributes to chromatin loop reorganization. Moreover, de novo loop formation contributes to differential gene expression, including the dysregulation of genes enriched in mitotic pathways. This leads to the disruptions of cell proliferation in the embryonic brain after genetic ablation of Setdb1 both in vitro and in vivo. CONCLUSIONS: In summary, our study sheds light on the epigenetic regulation of SINEs in mouse neural precursor cells, suggesting their role in maintaining chromatin organization and cell proliferation during neurodevelopment.
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Chromatin , Histone-Lysine N-Methyltransferase , Neural Stem Cells , Short Interspersed Nucleotide Elements , Animals , Histone-Lysine N-Methyltransferase/genetics , Histone-Lysine N-Methyltransferase/metabolism , Neural Stem Cells/metabolism , Neural Stem Cells/cytology , Mice , Chromatin/metabolism , DNA Methylation , CCCTC-Binding Factor/metabolism , CCCTC-Binding Factor/genetics , Epigenesis, Genetic , Histones/metabolism , Brain/metabolism , Brain/cytologyABSTRACT
Background: Vasopressors remain an important strategy for managing spinal anesthesia-induced hypotension in women with preeclampsia. The aim of this study was to investigate the ED90s and efficacy ratio of phenylephrine and norepinephrine in managing spinal anesthesia-induced hypotension in women with preeclampsia during cesarean delivery. Methods: 60 women with preeclampsia, who underwent cesarean delivery, were randomly assigned to receive either a continuous intravenous infusion of phenylephrine or norepinephrine following spinal anesthesia. The initial dosage of phenylephrine or norepinephrine for the first women was 0.5 or 0.05 µg/kg/min, respectively, and subsequent infusion dosages were adjusted based on their efficacy in preventing spinal anesthesia-induced hypotension (defined as a systolic blood pressure less than 80% of the baseline level). The incremental or decremental doses of phenylephrine or norepinephrine were set at 0.1 or 0.01 µg/kg/min. The primary outcomes were the ED90s and efficacy ratio of phenylephrine and norepinephrine infusions for preventing spinal anesthesia-induced hypotension prior to delivery. Results: The results obtained from isotonic regression analysis revealed that the ED90 values of the phenylephrine and norepinephrine group for preventing spinal anesthesia-induced hypotension were 0.597 (95% CI: 0.582-0.628) and 0.054 (95% CI: 0.053-0.056) µg/kg/min, respectively, with an efficacy ratio of 11.1:1. The results of Probit regression analysis revealed that the ED90 values were determined to be 0.665 (95% CI: 0.576-1.226) and 0.055 (95% CI: 0.047-0.109) µg/kg/min, respectively, with an efficacy ratio of 12.1:1. Conclusion: The administration of 0.6 µg/kg/min phenylephrine and 0.05 µg/kg/min norepinephrine has been found to effectively manage a 90% incidence of spinal anesthesia-induced hypotension in women with preeclampsia.
Subject(s)
Anesthesia, Spinal , Cesarean Section , Hypotension , Norepinephrine , Phenylephrine , Pre-Eclampsia , Humans , Female , Pregnancy , Phenylephrine/administration & dosage , Pre-Eclampsia/drug therapy , Anesthesia, Spinal/adverse effects , Hypotension/prevention & control , Hypotension/chemically induced , Norepinephrine/administration & dosage , Adult , Infusions, Intravenous , Dose-Response Relationship, Drug , Vasoconstrictor Agents/administration & dosage , Blood Pressure/drug effects , Young AdultABSTRACT
OBJECTIVES: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major nosocomial infectious pathogen with rapidly increasing prevalence. The genomic epidemiological characteristics of CRKP nationwide, especially the evolving trends within the predominant clones, should be evaluated clearly. METHODS: We collected 3415 K. pneumoniae strains from 28 hospitals across China. Antimicrobial susceptibility testing and WGS were performed. Subsequent genomic analyses, including sequence typing, K-locus (KL) identification, antimicrobial resistance gene screening, and virulence score assessment were performed. The phylogenetic relationship of clonal group 11 was determined based on core-genome analysis, and the presence of the pLVPK-like virulence plasmid in ST11 isolates was confirmed using plasmid core-gene analysis. Additionally, the trends of the ST11 lineage with different KL types on a global scale were investigated using Beast2. RESULTS: Of the K. pneumoniae strains, 708 were identified as CRKP isolates (20.7%), of which 97.7% were MDR. ST11 was the predominant clone, and KPC-2 was the prevalent carbapenemase in China, although the prevalence of specific clones and carbapenemases varied by geographic region. Among ST11 isolates, KL47 and KL64 were the predominant KL types, and KL64 gradually replaced KL47, with a higher percentage of KL64 isolates harbouring the pLVPK-like plasmid. Global genome data showed a significant increase in the effective population size of KL64 over the last 5 years. CONCLUSIONS: The prevalence of CRKP was very high in certain regions in China. The increasing convergence of virulence and resistance, particularly in ST11-KL64 isolates, should be given more attention and further investigation.
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BACKGROUND: Capitellar injury (CI) includes capitellar cartilage injury (CCI) and capitellar fracture (CF). A comprehensive classification of CI concurrent with radial head fracture (RHF) that can guide surgical strategy is lacking in the literature. Therefore, this study aimed to introduce a comprehensive classification of CI concurrent with RHF and investigate its value. METHODS: A total of 35 patients with CI concurrent with RHF confirmed by surgical exploration were retrospectively analyzed, includingmales in 19 cases and females in 16 cases. RHF was classified according to the Mason classification, and CI was classified into six types, including 3 types of CCI and CF, each based on the site and degrees of injuries (comprehensive classification method proposed in this study). The classification results were analyzed. Two radiologists were selected to independently classify the CI, and the inter- and intra-observer agreements were analyzed with kappa statistics. RESULTS: Mason Type I, II, III, and IV RHF accounted for 14.3%, 48.6%, 37.1%, and 0% of cases, respectively. Type I, II, III, IV, V, and VI CIs accounted for 22.9%, 34.3%, 25.7%, 11.4%, 2.9%, and 2.9% of cases, respectively. Therewas no obvious relationship between the CI and RHF types (p > 0.05). All Type I CIs underwent removal, 9 Type II CIs underwent microfracture repair, and 3 Type II CIs underwent removal. All Type III CIs underwent fixation, one Type IV CI underwent removal, and 3 Type IV CIs underwent fixation, one Type V CI underwent fixation, and one Type VI CI underwent arthroplasty. The inter- and intra-observer kappa coefficients were 0.830 ~ 0.905 and 0.805 ~ 0.892, respectively. At 12 months postoperatively, the elbow function evaluated by MEPS was 91, with an excellent and good rate of 97%. CONCLUSION: Different types of CI differ not only in pathology but also in treatment methods. The CI comprehensive classification put forth in this paper for the first time reflects different types of pathology well, with high consistency and repeatability, and can guide the selection of surgical methods, leading to satisfactory postoperative results.
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Background: The objective of this study was to investigate the association between pre-operative body mass index (BMI) and surgical infection in perihilar cholangiocarcinoma (pCCA) patients treated with curative resection. Methods: Consecutive pCCA patients were enrolled from four tertiary hospitals between 2008 and 2022. According to pre-operative BMI, the patients were divided into three groups: low BMI (≤18.4 kg/m2), normal BMI (18.5-24.9 kg/m2), and high BMI (≥25.0 kg/m2). The incidence of surgical infection among the three groups was compared. Multivariable logistic regression models were used to determine the independent risk factors associated with surgical infection. Results: A total of 371 patients were enrolled, including 283 patients (76.3%) in the normal BMI group, 30 patients (8.1%) in the low BMI group, and 58 patients (15.6%) in the high BMI group. The incidence of surgical infection was significantly higher in the patients in the low BMI and high BMI groups than in the normal BMI group. The multivariable logistic regression model showed that low BMI and high BMI were independently associated with the occurrence of surgical infection. Conclusions: The pCCA patients with a normal BMI treated with curative resection could have a lower risk of surgical infection than pCCA patients with an abnormal BMI.
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OBJECTIVES: Leukemia cell-derived exosomes (LEXs), carrying leukemia cell-specific antigens, can serve as a source of antigen for dendritic cell (DC) vaccine loading. However, LEX-targeted DC-based vaccines have demonstrated limited antitumor immune effects in clinical trials, attributed to the low immunogenicity of LEXs and the scant levels of costimulatory molecules on DCs. The costimulatory molecules CD80 and CD86, which are crucial to DC function, play a significant role in enhancing immune efficacy. In this study, we explored the anti-leukemia immune response of costimulatory molecule gene-modified LEX-targeted DCs (LEX-8086) in vitro and in animal models. METHODS: DCs were incubated with LEX-8086 to produce LEX-8086-targeted DCs (DCsLEX-8086). ELISA, cytotoxicity assays and flow cytometry utilized to assess the antitumor efficacy of DCsLEX8086 in vitro. Flow cytometry was used to evaluate the immunomodulatory function of DCsLEX8086 in animal models. RESULTS: Our findings indicated that LEX-8086 enhanced the maturation and antigen-presenting ability of DCs. Immunization with DCsLEX8086 significantly activated CD8+ T cells and boosted the CTL response in vitro. More importantly, DCsLEX-8086 effectively suppressed tumor growth and exerted anti-leukemia effects in both prophylactic and therapeutic animal models. Furthermore, DCsLEX-8086 promoted the proportion of CD4+ T cells, CD8+ T cells and M1 macrophages in the tumor environments both prophylactically and therapeutically. Treatment with DCsLEX-8086 showed no significant difference in the levels of M2 macrophages but decreased the proportion of Tregs within the tumor bed during therapeutic experiments. CONCLUSION: The results suggested that DCsLEX-8086 induces a more effective anti-leukemia immunity compared to DCsLEX-null in vivo and in vitro. DCsLEX-8086 might achieve antitumor effects by elevating the numbers of CD4+ T cells, CD8+ T cells, and M1 macrophages in tumors. Our findings indicate that DCsLEX-8086 could be leveraged to develop a new, highly effective vaccine for anti-leukemia immunity.
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Heterocyclic amines (HAs) are a group of mutagenic and carcinogenic compounds produced from the processing of high-protein foods, which include 2-amino-3-methylimidazo[4, 5-f]quinoline (IQ) showing the strongest carcinogenic effect. Camels are able to digest HAs in foods, which provide rich microbial resources for the study. Thus, camel rumen and intestinal microbiota were used to degrade IQ, and the dominant microorganisms and their degradation characteristics were investigated. After three generations of culture with IQ as the sole carbon source, the highest abundance in rumen and intestinal microbes was found in the Proteobacteria phylum. The strains of third generation of the rumen contents were mainly attributed to the genera Brevundimonas and Pseudomonas, and the dominant genera in intestine were Ochrobactrum, Bacillus, and Pseudomonas. Microorganisms were further isolated and purified from the third generation cultures. These 27 strains from the rumen (L1-L27) and 23 strains from the intestine (C1-C23) were obtained. Among them, four strains with the most effective degrading abilities were as follows: L6 (28.55% of IQ degrading rate) and C1 (25.19%) belonged to the genus Ochrobactrum, L15 (23.41%) belonged to the genus Pseudomonas, and C16 (20.89%) were of the genus Bacillus. This study suggested the application of abundant microbial resources from camels' digestive tract to biodegrade foodborne toxins.
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Previous research has established a correlation between PM2.5 exposure and aging-related cardiovascular diseases, primarily in blood vessels. However, the impact of PM2.5 on cardiomyocyte aging remains unclear. In this study, we observed that extractable organic matter (EOM) from PM2.5 exposure led to cellular senescence in H9c2 cardiomyoblast cells, as characterized by an increase in the percentage of ß-galactosidase-positive cells, elevated expression levels of p16 and p21, and enhanced H3K9me3 foci. EOM also induced cell cycle arrest at the G1/S stage, accompanied by downregulation of CDK4 and Cyclin D1. Furthermore, EOM exposure led to a significant elevation in intracellular reactive oxygen species (ROS), mitochondrial ROS, and DNA damage. Supplementation with the antioxidant NAC effectively attenuated EOM-induced cardiac senescence. Our findings also revealed that exposure to EOM activated the aryl hydrocarbon receptor (AhR) signaling pathway, as evidenced by AhR translocation to the nucleus and upregulation of Cyp1a1 and Cyp1b1. Importantly, the AhR antagonist CH223191 effectively mitigated EOM-induced oxidative stress and cellular senescence. In conclusion, our results indicate that PM2.5-induced AhR activation leads to oxidative stress, DNA damage, and cell cycle arrest, leading to cardiac senescence. Targeting the AhR/ROS axis might be a promising therapeutic strategy for combating PM2.5-induced cardiac aging.
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This report describes a copper-catalyzed, photoinduced N-to-alkyl radical relay Sonogashira-type reactions at benzylic sites in o-alkylbenzamides with alkynes. The process employs an N-to-alkyl radical mechanism, initiated through the copper-catalyzed reductive generation of nitrogen radicals. Radical translocation is facilitated by a 1,5-hydrogen atom transfer (1,5-HAT), leading to the formation of translocated carbon radicals. These radicals are then subjected to copper-catalyzed alkynylation. The methodology exhibits broad sub-strate scope and applicability to the synthesis of complex natural products.
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BACKGROUND: Workplace violence can threaten the physical and mental health of emergency nurses, increasing their mobility and burnout rates. However, little research has focused on how to mitigate the negative effects of workplace violence. OBJECTIVES: To investigate the relationships among resilience scores, perceived organizational support, and workplace violence and to explore the mediating role of perceived organizational support in the relationship between resilience scores and workplace violence among emergency nurses. RESEARCH DESIGN: A quantitative, cross-sectional study. METHODS: From June to July 2023, 466 valid questionnaires were collected via the WeChat app Credamo Seeing Numbers. Participants were assessed using the Connor-Davidson Resilience Scale, the Perceived Organizational Support Scale, and the Fear of Future Violence at Work Scale. ETHICAL CONSIDERATION: The study was approved by the Ethics Committee of Hunan Normal University (No. 2023-389). FINDINGS: The Connor-Davidson resilience scores of emergency nurses were negatively associated with workplace violence and positively associated with emergency nurses' perceived organizational support. Emergency nurses' perceived organizational support was negatively associated with workplace violence. Perceived organizational support moderated the relationship between Connor-Davidson resilience scores and workplace violence among emergency nurses to some extent. DISCUSSION: High levels of Connor-Davidson resilience scores can mitigate the negative effects of workplace violence. Perceived organizational support can increase with increasing levels of Connor-Davidson resilience scores. When nurses face workplace violence, support from the organization can, on the one hand, reduce the negative impacts of stress and, on the other hand, elicit positive emotions. CONCLUSION: To mitigate the effects of workplace violence on emergency nurses, interventions aimed at both internal and external organizational conditions must be developed to establish a supportive environment that can increase emergency nurses' Connor-Davidson resilience scores and sense of perceived organizational support, and decrease workplace violence.