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Thrombosis and inflammation are primary contributors to the onset and progression of ischemic stroke. The contact-kinin pathway, initiated by plasma kallikrein (PK) and activated factor XII (FXIIa), functions bidirectionally with the coagulation and inflammation cascades, providing a novel target for therapeutic drug development in ischemic stroke. In this study, we identified a bat-derived oligopeptide from Myotis myotis (Borkhausen, 1797), designated LE6 (Leu-Ser-Glu-Glu-Pro-Glu, 702 Da), with considerable potential in stroke therapy due to its effects on the contact kinin pathway. Notably, LE6 demonstrated significant inhibitory effects on PK and FXIIa, with inhibition constants of 43.97 µmol/L and 6.37 µmol/L, respectively. In vitro analyses revealed that LE6 prolonged plasma recalcification time and activated partial thromboplastin time. In murine models, LE6 effectively inhibited carrageenan-induced mouse tail thrombosis, FeCl 3-induced carotid artery thrombosis, and photochemically induced intracerebral thrombosis. Furthermore, LE6 significantly decreased inflammation and stroke injury in transient middle cerebral artery occlusion models. Notably, the low toxicity, hemolytic activity, and bleeding risk of LE6, along with its synthetic simplicity, underscore its clinical applicability. In conclusion, as an inhibitor of FXIIa and PK, LE6 offers potential therapeutic benefits in stroke treatment by mitigating inflammation and preventing thrombus formation.
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Oligopéptidos , Accidente Cerebrovascular , Animales , Ratones , Oligopéptidos/farmacología , Accidente Cerebrovascular/tratamiento farmacológico , Quirópteros , Trombosis , Inflamación , Masculino , Antiinflamatorios/farmacologíaRESUMEN
Four different structural compositions of organophosphate, 3d transition metal, 4f lanthanide and polyoxoniobate (PONb) are unified in a system for the first time to form a new type of organophosphate 3d-4f heterometallic inorganic-organic hybrid PONb nanowire. Interesting magnetic anisotropy and slow magnetic relaxation are found in the PONb nanowire.
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In the present study, the complete mitochondrial genome (mitogenome) of the Papilio macilentus (Lepidoptera: Papilionoidea: Papilionidae) was sequenced by next-generation sequencing method. The mitochondrial genome is a circular DNA molecule of 15,264 bp in size with 80.7% AT content, including 37 genes (13 protein-coding genes, 2 rRNA genes, and 22 tRNA genes), and a long non-coding region (Control region). All protein-coding genes are initiated by ATN codons, and terminated with TAA, TAG, or single T. All tRNAs can be folded into common clover leaf secondary structure, except trn-S1. Phylogenetic analyses based on 13 protein-coding genes and 2 rRNA genes using maximum likelihood and Bayesian inference confirmed that P. macilentus and Papilio memnon are clustered into a clade, and revealed the relationships between Papilionini, Troidini, Teinopaippini and Leptocircini.
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Introduction: Ovarian yolk sac tumor (OYST) during pregnancy is rare and usually missed. There are few PET/CT studies on OYST in the literature. We reported a case of OYST detected by 18F-FDG PET/CT in a woman after induction of labor. Case Presentation: A 19-year-old woman after induction of labor because of severe malformation presented with abdominopelvic mass, laboratory tests revealed significantly elevated serum alpha-fetoprotein (AFP) level and elevated carbohydrate antigen 125 level. Abdomino-pelvic CT showed a cysticsolid mass of 82×152×167mm arising from the right ovary with abundant intratumoral vessels and intense enhancement in the solid part. Further evaluation of 18F-FDG PET/CT imaging showed significantly increased 18FDG uptake (SUVmax7.7) by the solid component of the ovarian mass and slight 18FDG-avid perihepatic effusion. The mass was resected and was confirmed to be the right OYST, After four courses of chemotherapy, the patient was followed up by PET/CT and had a complete metabolic response. Discussion: 18F-FDG PET/CT is a useful imaging modality for diagnosis and evaluation of OYST.
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In order to better support the construction of the capital water conservation functional area and ecological environment support areaï¼ research on the chemical characteristics of groundwater and its formation mechanism in the dry period in the Zhangjiakou area can provide a great reference for the rational development and utilization of groundwater resources. A total of 41 groups of groundwater samples were collectedï¼ and the hydrochemical typesï¼ composition characteristicsï¼ and control factors of groundwater in the study area were analyzed by using the combined method of descriptive statistical analysisï¼ Piper triplotï¼ correlation analysisï¼ Gibbs plotï¼ and ion ratio. The results showed that the groundwater in the study area was weakly alkalineï¼ with the total hardness and ρï¼TDSï¼ ranging from 105.00 mg·L-1 to 1 433.00 mg·L-1 and 137.00 mg·L-1 to 2 286.00 mg·L-1ï¼ respectively. The total hardness and TDS mass concentrations of groundwater in the Bashang area were higher than those in the Baxia area. HCO3- and Na+ were the main dominant anions and cations in the groundwater in the study area. The highest overstandard rate of the main components in groundwater was that of total hardness ï¼36.59%ï¼. The overstandard rate and maximum excess multiple of each component in groundwater in the Bashang area were greater than those in the Baxia area. HCO3-Ca·Mg·Na was the main type of groundwater hydrochemistry in the study areaï¼ and there was little difference between the Bashang area and the Baxia area. SO42-ï¼ Cl-ï¼ HCO3-ï¼ Na+ï¼ and Mg2+ contributed the most to TDS. The chemical characteristics of groundwater were affected by weathering and filtration of rock minerals such as salt rockï¼ albiteï¼ and dolomiteï¼ cation exchangeï¼ and human activities. Evaporative crystallization and atmospheric precipitation contributed to a small part of the main ion source of groundwater in the area. The effect of human activities on groundwater in the Bashang area was greater than that in the Baxia areaï¼ and NO3- mainly originated from agricultural activities.
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A series of proof-of-concept models of polyoxomolybdates with different protonated disubstituted aniline counterions and the same ß-Mo8O26 polyanion were synthesized to study the mechanism governing the formation of the intermolecular charge transfer (inter-CT) band.
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PURPOSE: To compare computed tomography (CT)-guided transthoracic lung biopsies (CTLB) with and without pre-procedure 18F-fluorodeoxgyglucose positron emission tomography (18F-FDG PET)/CT images in the diagnosis of pulmonary nodules/masses. METHODS: This is a case-control study in a single center. The data of patients with a transthoracic lung biopsy guided by CT and pre-procedure 18F-FDG PET/CT (group 2, here called the "PETCTLB" group), including demographics, clinical characteristics, and biopsy-related parameters, were collected. The PET/CT scan was performed within 15 days before the biopsy. The data from patients with CTLB were used as controls (group 1). Biopsies for all patients were performed by the same physician between January 2019 and December 2021. The final diagnosis was based on surgical outcomes, or imaging findings, and the results of at least one 6-month follow-up. The demographics and clinical characteristics of patients, lesions and biopsy-related variables, diagnostic yields, and incidence of complications were compared between the two groups. Two-tailed t-tests were used to compare the mean values in the two independent groups, while categorical variables were compared using the Pearson chi-squared test, and P values < 0.05 were considered to be significant. RESULTS: A total of 84 patients were included, and 84 biopsies of 84 lung nodules/masses were analyzed. The demographics and clinical characteristics of group 2 (n = 39; 21 men; mean age, 63.2 ± 9.29 years) and group 1 (n = 45; 30 men; mean age, 61.2 ± 12.3 years) had no significant difference (P = 0.230 and 0.397, respectively). The procedure duration (11.1 ± 3.0 vs. 12.9 ± 3.3 minutes, P = 0.008), the number of samples (2.6 ± 0.5 vs. 3.1 ± 0.4, P < 0.001), diagnostic accuracy (97.4% vs. 82.2%, P = 0.033), and bleeding complication (25.6% vs. 42.2%, P = 0.034) of group 2 and group 1 were statistically different. CONCLUSION: A biopsy guided by CT plus pre-procedure 18F-FDG PET/CT (PETCTLB) is a safe procedure that can provide a precise diagnosis in the majority of lung nodules/masses. It has better diagnostic performance than CTLB.
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Neuropilin-1 (NRP1), a transmembrane glycoprotein, plays an important role in the malignant progression of gliomas; however, its role in chemoresistance is not fully understood. In this study, we observed the effects of NRP1 on the stemness and chemoresistance of glioma cells and the mediating role of Yes-associated protein (YAP). We constructed NRP1 overexpressing LN-229 glioma cells. Cells were treated with recombinant NRP1 protein (rNRP1) and the YAP inhibitor Super-TDU when necessary. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect the sensitivity of cells to temozolomide (TMZ). Sphere and clone formation assays were performed to detect the sphere- and clone-forming abilities of cells. Western blotting was performed to detect cellular CD133, CD44, p-LATS1, and p-YAP protein expression. Immunofluorescence and flow cytometry were used to detect the subcellular localization of YAP and apoptosis, respectively. We found that both NRP1 overexpression and rNRP1 treatment enhanced self-renewal, TMZ resistance, and CD133 and CD44 protein expression in LN-229 cells. NRP1 overexpression and rNRP1 treatment also induced LATS1 and YAP dephosphorylation and YAP nuclear translocation. Super-TDU inhibits NRP1 overexpression-induced enhanced self-renewal and TMZ resistance in LN-229 cells. Our study suggests that NRP1 induces increased stemness in glioma cells, resulting in chemoresistance, and that this effect is associated with YAP activation.
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Glioma , Neuropilina-1 , Humanos , Línea Celular Tumoral , Proliferación Celular , Resistencia a Antineoplásicos , Glioma/metabolismo , Neuropilina-1/genética , Proteínas Serina-Treonina Quinasas , Temozolomida/farmacología , Proteínas Señalizadoras YAPRESUMEN
BACKGROUND/AIM: The quantity and the phenotypes of desired T cell receptor engineered T (TCR-T) cells in the final cell product determine their in vivo anti-tumor efficacy. Optimization of key steps in the TCR-T cell production process, such as T cell activation, has been shown to improve cell quality. MATERIALS AND METHODS: Using a modified TCR (mTCR) derived from mice transducing PBMCs, we assessed the proportions of low-density lipoprotein receptor (LDL-R) and mTCR expressing cells under the various activation conditions of CD3/CD28-Dynabeads or OKT3 via flow cytometry. RESULTS: We demonstrate that the proportion of T cells expressing LDL-R post activation is positively correlated with the percentage of mTCR+CD8+ T cells with their less differentiated subtypes in the final product. In addition, we show that shifting the CD3/CD28-Dynabeads activation duration from a typical 48 h to 24 h can significantly increase the production of the desired mTCR+CD8+ T cells. Importantly, the percentages of TCR-T cells with less-differentiated phenotypes, namely mTCR central memory T cells (TCM), were found to be preserved with markedly higher efficiency when T cell activation was optimized. CONCLUSION: Our findings suggest that the proportion of LDL-R+ T cells may serve as an early assessment parameter for evaluating TCR-T cell quality, possibly facilitating the functional and economical improvement of current adoptive therapy.
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Linfocitos T CD8-positivos , Neoplasias , Ratones , Animales , Complejo CD3 , Antígenos CD28/metabolismo , Receptores de Antígenos de Linfocitos T/genética , Neoplasias/terapia , Activación de LinfocitosRESUMEN
Background: Magnetic resonance imaging (MRI) plays an important role in the diagnosis of leptomeningeal metastases (LM); however, some sub-centimeter lesions may be missed. Positron emission tomography/computed tomography (PET/CT) has a high sensitivity and may play a synergistic role with MRI in diagnosing spinal LM (SLM). We aimed to retrospectively evaluate the detection of SLM with 18F-fluorodeoxyglucose PET/CT (18F-FDG PET/CT) compared to that of whole spinal cord MRI in a single center. Methods: Patients with SLM who had undergone 18F-FDG PET/CT and MRI were enrolled. 18F-FDG PET/CT imaging findings were independently reviewed by 2 nuclear medicine physicians. 18F-FDG PET/CT findings of SLMs were described. A consistency test was conducted to assess the patient-based diagnostic results obtained by the 2 physicians. Patient-based sensitivity, accuracy, and specificity in diagnosing SLM between 18F-FDG PET/CT and MRI of the whole spinal cord were compared using the chi-square or Fisher's exact test. A P value of <0.05 was considered statistically significant. The receiver operating characteristic (ROC) curve was obtained to assess the diagnostic performance of maximum standardized uptake value (SUVmax) to diagnose SLM. Results: A total of 16 patients with SLM were included in this study from October 2010 to April 2022. The primary tumor involved the lungs, liver, ovaries, prostate, esophagus, and unknown primary site. The mean age of patients, including 13 males and 3 females, was 57.8±11.2 (range, 34-73) years. Of 16 patients with SLM, 10 had nodular diseases, 2 had linear diseases, and 4 had mixed diseases. The kappa value of the consistency test of the 2 radiologists' diagnostic results was 0.765. The patient-based sensitivity, specificity, and accuracy of 18F-FDG PET/CT in diagnosing SLM were 87.5%, 89.2%, and 88.7%, respectively and those of whole spinal cord MRI were 75.0%, 100.0%, and 92.5%, respectively. There were no significant differences in sensitivity, specificity, and accuracy between the 2 methods, with P values of 0.654, 0.115, and 0.506, respectively. However, more nodular diseases were observed on PET/CT. The area under the ROC curve (AUC) for the prediction of SLM by SUVmax was 0.907 [95% confidence interval (CI): 0.831-0.983]. When SUVmax ≥2.45, the Youden index was the largest, and the sensitivity and specificity were 89.3% and 75.7%, respectively. Conclusions: 18F-FDG PET/CT is a good choice of imaging modality for assessing SLM. In the diagnosis of SLMs, PET/CT and enhanced MRI can play a better synergistic role.
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The methylation of m6A (N6-position of adenosine) has been found to be associated with inflammatory response. We hypothesize that m6A modification plays a role in the inflammation of airway epithelial cells during lung inflammation. However, the precise changes and functions of m6A modification in airway epithelial cells in acute lung injury (ALI) are not well understood. Here we report that METTL3 (methyltransferase-like 3)-mediated m6A of GATA6 (GATA-binding factor 6) mRNA inhibits ALI and the secretion of proinflammatory cytokines in airway epithelial cells. The expression of METTL3 and m6A levels decrease in lung tissues of mice with ALI. In cocultures, peripheral blood monocytes secreted TNF-α, which reduces METTL3 and m6A levels in the human bronchial epithelial cell line BEAS-2B. Knockdown of METTL3 promotes IL-6 and TNF-α release in BEAS-2B cells. Conversely, overexpression of METTL3 increases total RNA m6A level and reduces the levels of proinflammatory cytokines TNF-α, transforming growth factor-ß, and thymic stromal lymphopoietin. Increasing METTL3 in mouse lungs prevented LPS-induced ALI and reduced the synthesis of proinflammatory cytokines. Mechanistically, sequencing and functional analysis show that METTL3 catalyzes m6A in the 3' untranslated region of GATA6 read by YTH N6-Methyladenosine RNA Binding Protein 2 and triggers mRNA degradation. GATA6 knockdown rescues TNF-α-induced inflammatory cytokine secretion of epithelial cells, indicating that GATA6 is a main substrate of METTL3 in airway epithelial cells. Overall, this study provides evidence of a novel role for METTL3 in the inflammatory cytokine release of epithelial cells and provides an innovative therapeutic target for ALI.
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Lesión Pulmonar Aguda , Citocinas , Animales , Humanos , Ratones , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/genética , Factor de Transcripción GATA6/genética , Metilación , Metiltransferasas/genética , Factor de Necrosis Tumoral alfaRESUMEN
Taking the soil of a vegetable planting area in Wanquan District of Zhangjiakou City as the research object, 132 surface and 80 deep soil samples were collected to test and analyze the contents of eight heavy metals such as As, Cd, Cr, Hg, Cu, Ni, Pb, and Zn and the occurrence forms of Cr and Ni. By applying geostatistical analysis and the PMF receptor model and combining three heavy metal pollution evaluation methods, the spatial distribution characteristics of soil heavy metals in the study area, the degree of heavy metal pollution, and the distribution of Cr and Ni fugitive forms in the vertical layer were clarified, and the sources and contribution rates of soil heavy metal pollution were analyzed. The results showed that the average contents of Cd and Pb in surface soils were higher than the background values of soils in Hebei Province, and the spatial distribution characteristics of Cr, Ni, Cu, Cd, Pb, and Zn in surface soils were similar. The ground accumulation index method showed that the study area was mainly free of pollution, with a small number of lightly polluted sites, and most of them were polluted with Cd. The enrichment factor method showed that the study area was mainly free-weakly polluted, with medium pollution of all elements; the significantly polluted elements in the background area were As, Pb, and Hg, and the significantly polluted element in the key area was Cd. The potential ecological risk index method showed that the study area was mainly lightly polluted, with local distribution. The potential ecological risk index method showed that the study area was mainly lightly polluted, with a local distribution of "medium" and "strong" risk points, with "very strong" risk points for Hg in the background area and "very strong" risk points for Cd in the focus area. These three evaluation results indicated that the background area was dominated by Cd and Hg pollution, whereas the focus area was dominated by Cd pollution. The study on the fugitive morphology of vertical soil showed that Cr was dominated by the residue state (F4) and supplemented by the oxidizable state (F3), and the vertical direction was dominated by the surface aggregation type and supplemented by the weak migration type. Ni was dominated by the residue state (F4) and supplemented by the reducible state (F2), and the vertical direction was dominated by the strong migration type and supplemented by the weak migration type. The sources of heavy metals in the surface soil were divided into three categories; Cr, Cu, and Ni were mainly from natural geological background sources. The contributions of Cr, Cu, and Ni were 66.9%, 66.9%, and 76.1%, respectively. As, Cd, Pb, and Zn were mainly from anthropogenic sources, with contributions of 77.38%, 59.2%, 83.5%, and 59.5%, respectively. Hg was mainly from dry and wet atmospheric deposition, with a contribution of 87.8%.
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BACKGROUND: Unplanned extubation is a common adverse event and an important indicator of quality and safety of care. It is well recognized that the incidence of unplanned extubation of nasogastric/nasoenteric tubes is higher than that of other devices. Theory and previous research have suggested that cognitive bias in conscious patients with nasogastric/nasoenteric tubes may lead to unplanned extubation, and that social support, anxiety, and hope are influencing factors of cognitive bias. Therefore, the objective of this study was to investigate the effects of social support, anxiety, and hope levels on cognitive bias in patients with nasogastric/nasoenteric tubes. METHODS: In this cross-sectional study, 438 patients with nasogastric/nasoenteric tubes were selected from 16 hospitals in Suzhou from December 2019 to March 2022 by convenience sampling method. The participants were assessed using the General Information Questionnaire, Perceived Social Support Scale, Generalized Anxiety Disorder-7, Herth Hope Index, and Cognitive Bias Questionnaire for patients with nasogastric/nasoenteric tubes. The structural equation model was established with AMOS 22.0 software. RESULTS: The cognitive bias score of patients with nasogastric/nasoenteric tubes was 2.82±0.61. Patients' perceived levels of social support and hope were negatively correlated with their cognitive bias (r=-0.395 and -0.427, respectively, P<0.05), and anxiety was positively correlated with cognitive bias (r=0.446, P<0.05). Structural equation model analysis showed that anxiety had a direct positive effect on cognitive bias, with an effect value of 0.35 (P<0.001), and hope level had a direct negative effect on cognitive bias with an effect value of -0.33 (P<0.001). Social support had a direct negative effect on cognitive bias and was also shown to indirectly affect cognitive bias through anxiety and hope levels. The effect values were -0.22, -0.12, and -0.19 (P<0.001), for social support, anxiety, and hope, respectively. Social support, anxiety, and hope explained 46.2% of the total variation in cognitive bias. CONCLUSIONS: Moderate cognitive bias is noted in patients with nasogastric/nasoenteric tubes, and social support significantly affects cognitive bias. Anxiety and hope level play a mediating role in social support and cognitive bias. Positive psychological intervention and the obtention of positive support could improve the cognitive bias of patients with nasogastric/nasoenteric tubes.
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Trastornos de Ansiedad , Ansiedad , Humanos , Estudios Transversales , Ansiedad/etiología , Apoyo Social , CogniciónRESUMEN
Taking straws of corn, wheat, and millet as raw materials, we pretreated them with alkaline hydrogen peroxide, and then hydrolyzed by cellulase and xylanase. We selected the total sugar content in the hydrolysate as the indicator to evaluate the hydrolysis of the straws from three crop species, and further optimized the conditions. Then, the hydrolysates of three types of crop straws were used as carbon source for Chlorella sorokiniana culture to assess their effects on microalgal cultivation. The results showed that the optimal hydrolysis conditions for the three crop straws were identified as solid-liquid ratio of 1:15, temperature of 30 â, and treatment time of 12 h. Under such optimal condition, the total sugar contents increased up to 1.677, 1.412, and 1.211 g·L-1 in the corn, millet and wheat straw hydrolysate, respectively. The hydrolysates from the three crop straw could significantly increase both algal biomass and lipid content of C. sorokiniana. Corn straw hydrolysate had the best effect, with high levels of algal biomass (1.801 g·L-1) and lipid content (30.1%). Therefore, we concluded that crop straw hydrolysates as carbon source could significantly promote microalgal biomass and lipid enrichment. The results could lay the foundation for the efficient conversion and utilization of straw lignocellulose raw materials, provide new knowledge for the resource utilization of agricultural wastes, as well as the theoretical basis for the efficient cultivation of microalgae using crop straw hydrolysates.
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Chlorella , Hidrólisis , Lípidos , Carbono , Azúcares , BiomasaRESUMEN
The vegetable planting base in the Beixintun area of Zhangjiakou City was selected as the study area, divided into the focus area and regional range as well as the upstream area. A total of 132 surface soil samples, 16 vertical soil profiles, 3 groups of surface profiles, and 4 samples each of colored pepper fruit, purple kale fruit, and corn fruit were collected. From the soil, rock, and crop sample Sc, Cr, Mo, Cd, V, Zn, Sr, Pb, Co Ni, Cu, Ge, and REE on the basis of the referenced germanium (Ge) enrichment standards and enrichment factor levels, it was found that the regional Ge enrichment rate was not high (19.7%), whereas the key area had a high Ge enrichment rate (52%). The spatial distribution of Ge and rare earth elements in the soils of the regional scope and the focal area showed a more obvious consistency, and further comparison of the correlation characteristics of Ge and rare earth elements in soil and crops showed that the ranking of rare earth content was purple kale>colored pepper>maize, whereas the ranking of the Ge element uptake intensity was maize (weak uptake)>purple kale (very weak uptake)>colored pepper (very weak uptake), and there was no obvious synergy between the uptake of Ge and rare earth elements by crops. The PMF and RDA analysis of 28 elements and indicators of soil in the study area showed that the source of regional Ge was dominated by natural geological background factors (66.3%), supplemented by anthropogenic activity-influenced factors (27%) and river deposition factors (6.7%). The source of Ge in the focal area was dominated by natural geological background factors (33.8%) and anthropogenic activity-influenced factors (27.2%), with river sedimentation factors (18.5%) and atmospheric dry and wet deposition factors Ge (20.5%) being supplemented. Soil Ge was positively correlated with rare earth elements and trace elements such as Cd, Zn, Mn, Ni, V, Co, and Cr and negatively correlated with the main elements CNa2[KG-*2/5]Oî, SiO2, and K2[KG-*2/5]O and pH. Finally, by combining the analysis of soil lateral profiles with vertical profiles, it was found that the Ge migrating from the source area to the area was primarily in the main river pathway, supplemented by the secondary river and flood flow pathways.
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Aeromonas dhakensis possesses dual flagellar systems for motility under different environments. Flagella-mediated motility is necessary for biofilm formation through an initial attachment of bacteria to the surface, but this has not been elucidated in A. dhakensis. This study investigates the role of polar (flaH, maf1) and lateral (lafB, lafK and lafS) flagellar genes in the biofilm formation of a clinical A. dhakensis strain WT187 isolated from burn wound infection. Five deletion mutants and corresponding complemented strains were constructed using pDM4 and pBAD33 vectors, respectively, and analyzed for motility and biofilm formation using crystal violet staining and real-time impedance-based assays. All mutants were significantly reduced in swimming (p < 0.0001), swarming (p < 0.0001) and biofilm formation using crystal violet assay (p < 0.05). Real-time impedance-based analysis revealed WT187 biofilm was formed between 6 to 21 h, consisting of early (6-10 h), middle (11-18 h), and late (19-21 h) stages. The highest cell index of 0.0746 was recorded at 22-23 h and biofilms began to disperse starting from 24 h. Mutants Δmaf1, ΔlafB, ΔlafK and ΔlafS exhibited reduced cell index values at 6-48 h when compared to WT187 which indicates less biofilm formation. Two complemented strains cmaf1 and clafB exhibited full restoration to wild-type level in swimming, swarming, and biofilm formation using crystal violet assay, hence suggesting that both maf1 and lafB genes are involved in biofilm formation through flagella-mediated motility and surface attachment. Our study shows the role of flagella in A. dhakensis biofilm formation warrants further investigations.
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Aeromonas , Violeta de Genciana , Aeromonas/genética , Biopelículas , Movimiento Celular , Flagelos/genética , Flagelos/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismoRESUMEN
Background and Aims: Hepatocellular carcinoma (HCC) is one of the most common types of cancer, often resulting in death. Augmenter of liver regeneration (ALR), a widely expressed multifunctional protein, has roles in liver disease. In our previous study, we reported that ALR knockdown inhibited cell proliferation and promoted cell death. However, there is no study on the roles of ALR in HCC. Methods: We used in vitro and in vivo models to investigate the effects of ALR in HCC as well as its mechanism of action. We produced and characterized a human ALR-specific monoclonal antibody (mAb) and investigated the effects of the mAb in HCC cells. Results: The purified ALR-specific mAb matched the predicted molecular weight of IgG heavy and light chains. Thereafter, we used the ALR-specific mAb as a therapeutic strategy to suppress tumor growth in nude mice. Additionally, we assessed the proliferation and viability of three HCC cell lines, Hep G2, Huh-7, and MHC97-H, treated with the ALR-specific mAb. Compared with controls, tumor growth was inhibited in mice treated with the ALR-specific mAb at 5 mg/kg, as shown by hematoxylin and eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling. Simultaneous treatment with the ALR-specific mAb and adriamycin promoted apoptosis, whereas treatment with the ALR-specific mAb alone inhibited cell proliferation. Conclusions: The ALR-specific mAb might be a novel therapy for HCC by blocking extracellular ALR.
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Objective: To study the influence of steroid withdrawal protection strategy on height growth in pediatric patients after kidney transplantation. Methods: The prospective cohort study enrolled 40 stage 5 chronic kidney disease children receiving kidney transplantation from July 2017 to September 2022 at Guangzhou Women and Children's Medical Center. Based on the primary preoperative disease, patients with immune abnormality-associated glomerular diseases or unknown causes were assigned to the steroid maintenance group, in which patients received steroid tapering within 3 months after surgery to a maintenance dose of 2.5 to 5.0 mg/d. While patients with hereditary kidney disease or congenital urinary malformations were assigned to the steroid withdrawal group, in which patients had steroids tapered off within 3 months. The characteristics of height catch-up growth and clinical data were compared between the 2 groups at baseline, 6, 12, 18 and 24 months after kidney transplantation. T-test, repeated measurement of variance analysis, Mann-Whitney U test, and Fisher exact test were used for the comparison between the 2 groups. Results: Among the 40 children, 17 were males, 23 were females, 25 were in the steroid withdraw group ((7.8±2.8) years old when receiving kidney transplantation) and 15 cases were in the steroid maintenance group ((7.6±3.5) years old when receiving kidney transplantation). The study population was followed up for (26±12) months. The total dose per unit body weight of steroids in the steroid withdrawal group was lower than that in the steroid maintenance group ((0.13±0.06) vs. (0.36±0.19) mg/(kg·d), t=5.83, P<0.001). The height catch-up rate (ΔHtSDS) in the first year after kidney transplantation in the steroid withdraw and steroid maintenance groups was 1.0 (0.7, 1.4) and 0.4 (0.1, 1.0), respectively; in the second year, the ΔHtSDS in the steroid withdraw group was significantly higher than that in the steroid maintenance group (1.1 (0.2, 1.7) vs. 0.3 (0, 0.8), U=28.00, P=0.039). The HtSDS in the steroid withdrawal group at the five follow-up time points was -2.5±0.8, -2.0±0.8, -1.5±0.8, -1.3±0.9 and -0.5±0.3, respectively, while in the steroid maintenance was -2.4±1.3, -2.2±1.1, -2.0±1.0, -1.8±1.0 and -1.6±1.0, respectively. There were statistically significant differences in HtSDS at different follow-up time points in both 2 groups (F=19.81, P<0.01), but no statistical differences in overall impact between the 2 groups (F=1.13, P=0.204). The steroid treatment was interaction with the increase of follow-up time (F=3.62, P=0.009). At the 24th month after transplantation, the HtSDS in the steroid withdrawal group was significantly higher than that in the steroid maintenance group (P=0.047). Six patients in the steroid withdrawal group experienced antibody-mediated immune rejection (AMR), while 3 did in the steroid maintenance group. Moreover, there was no significant difference in AMR between the two groups (χ2=0.06, P=0.814). Conclusion: The steroid withdrawal protection strategy favors the height catch-up growth in pediatric patients after kidney transplantation and does not increase the risk of postoperative antibody-mediated immune rejection.
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Masculino , Humanos , Niño , Femenino , Preescolar , Trasplante de Riñón , Estudios Prospectivos , Esteroides/uso terapéutico , Anticuerpos , Peso CorporalRESUMEN
Background: Synchronous multiple primary malignant neoplasms occurring at the same time (SMPMNS) are not currently uncommon in clinical oncological practice; however, the diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for SMPMNS needs further elucidation. Purpose: This study aimed to evaluate the application of 18F-FDG PET/CT in patients with SMPMNS. Materials and methods: The clinical and imaging data of 37 patients with SMPMNS who had undergone 18F-FDG PET/CT from October 2010 to December 2020 were retrospectively analyzed. The kappa consistency test was applied to evaluate the consistency of the diagnostic performance between PET/CT and conventional imaging (CI). The sensitivity, specificity, and accuracy of PET/CT and CI in the detection of metastatic lesions were compared. Results: This retrospective diagnostic study included 74 lesions identified in 37 patients with SMPMNS, with 94.6% of patients having double primary tumors. Of the incidences of SMPMNS, 18.9% occurred in the same organ system, with respiratory tumors being the most common type of neoplasm (43.2%) and the lung being the most common primary site (40.5%). The overall survival of SMPMNS patients without metastases was longer than that of those with metastases (χ 2 = 12.627, p = 0.000). The maximum standardized uptake value (SUVmax), the SUVmax ratio (larger SUVmax/smaller SUVmax), and the difference index of SUVmax (DISUVmax) [(larger SUVmax - smaller SUVmax)/larger SUVmax] of the primary lesions ranged from 0.9 to 41.7 (average = 12.3 ± 7.9), from 0.3 to 26.7 (average = 4.4 ± 6.9), and from 0.0% to 96.3% (average = 50.3% ± 29.3%), respectively. With regard to diagnostic accuracy, PET/CT and CI showed poor consistency (κ = 0.096, p = 0.173). For the diagnosis of primary lesions (diagnosed and misdiagnosed), PET/CT and CI also showed poor consistency (κ = 0.277, p = 0.000), but the diagnostic performance of PET/CT was better than that of CI. In the diagnosis of metastases, the patient-based sensitivity, specificity, and accuracy of PET/CT were 100.0%, 81.8%, and 89.2%, respectively, while those of CI were 73.3%, 100.0%, 89.2%, respectively. The sensitivity and specificity values were significantly different, with PET/CT having higher sensitivity (p = 0.02) and CI showing higher specificity (p = 0.02). Conclusions: 18F-FDG PET/CT improves the diagnostic performance for SMPMNS and is a good imaging modality for patients with SMPMNS.
RESUMEN
The repetitive applications of vaccine boosters have been brought up in face of continuous emergence of SARS-CoV-2 variants with neutralization escape mutations, but their protective efficacy and potential adverse effects remain largely unknown. Here, we compared the humoral and cellular immune responses of an extended course of recombinant receptor binding domain (RBD) vaccine boosters with those from conventional immunization strategy in a Balb/c mice model. Multiple vaccine boosters after the conventional vaccination course significantly decreased RBD-specific antibody titers and serum neutralizing efficacy against the Delta and Omicron variants, and profoundly impaired CD4+ and CD8+T cell activation and increased PD-1 and LAG-3 expressions in these T cells. Mechanistically, we confirmed that extended vaccination with RBD boosters overturned the protective immune memories by promoting adaptive immune tolerance. Our findings demonstrate potential risks with the continuous use of SARS-CoV-2 vaccine boosters, providing immediate implications for the global COVID-19 vaccination enhancement strategies.