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Dynamic covalent bonds endow liquid crystal elastomers (LCEs) with network rearrangeability, facilitating the fixation of mesogen alignment induced by external forces and enabling reversible actuation. In comparison, the bond exchange of supramolecular interactions is typically too significant to stably maintain the programmed alignment, particularly under intensified external stimuli. Nevertheless, the remaking and recycling of supramolecular interaction-based polymer networks are more accessible than those based on dynamic covalent bonds, as the latter are difficult to completely dissociate. Thus, preparing an LCE that possesses both supramolecular-like exchangeability and covalent bond-level stability remains a significant challenge. In this work, we addressed this issue by employing metal-ligand bonds as the crosslinking points of LCE networks. As such, mesogen alignment can be repeatedly encoded through metal-ligand bond exchange and stably maintained after programming, since the bond exchange rate is sufficiently slow when the programming and actuation temperatures are below the bond dissociation temperature. More importantly, the metal-ligand bonds can be completely dissociated at high temperatures, allowing the LCE network to be dissolved in a solvent and reshaped into desired geometries via solution casting. Building on these properties, our LCEs can be fabricated into versatile actuators, such as reversible folding origami, artificial muscles, and soft robotics.
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Fast and reliable semiconductor hydrogen sensors are crucially important for the large-scale utilization of hydrogen energy. One major challenge that hinders their practical application is the elevated temperature required, arising from undesirable surface passivation and grain-boundary-dominated electron transportation in the conventional nanocrystalline sensing layers. To address this long-standing issue, in the present work, we report a class of highly reactive and boundary-less ultrathin SnO2 films, which are fabricated by the topochemical transformation of 2D SnO transferred from liquid Sn-Bi droplets. The ultrathin SnO2 films are purposely made to consist of well-crystallized quasi-2D nanograins with in-plane grain sizes going beyond 30 nm, whereby the hydroxyl adsorption and grain boundary side-effects are effectively suppressed, giving rise to an activated (101)-dominating dangling-bond surface and a surface-controlled electrical transportation with an exceptional electron mobility of 209 cm2 V-1 s-1. Our work provides a new cost-effective strategy to disruptively improve the gas reception and transduction of SnO2. The proposed chemiresistive sensors exhibit fast, sensitive, and selective hydrogen sensing performance at a much-reduced working temperature of 60 °C. The remarkable sensing performance as well as the simple and scalable fabrication process of the ultrathin SnO2 films render the thus-developed sensors attractive for long awaited practical applications in hydrogen-related industries.
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Hidrogênio , Compostos de Estanho , Compostos de Estanho/química , Hidrogênio/química , Hidrogênio/análise , Propriedades de Superfície , Gases/análise , Gases/química , Nanoestruturas/química , SemicondutoresRESUMO
BACKGROUND: Deep vein thrombosis (DVT), a frequent complication following percutaneous nephrolithotomy (PCNL), may lead to severe conditions like pulmonary embolism. Current knowledge on postoperative DVT risk factors is, however, limited. The aim of our study was to investigate the risk of DVT after PCNL. METHODS: A retrospective study was conducted on patients who underwent PCNL from March 2020 to March 2023 at our institution. Patient demographics and clinical data, including, DVT-specific information, preoperative labs, and surgical details, was evaluated. RESULTS: One hundred patients were included. Thirty-two (20 males, 12 females, mean age 52.5 ± 7.4 years) developed lower limb DVT post-surgery, while the remaining 68 (48 males, 20 females, mean age 51.1 ± 5.5 years) had no DVT symptoms. Analysis revealed significant correlations between hyperlipidemia, operating time, postoperative bed rest duration, D-dimer level on the first day after surgery, Caprini risk assessment model (RAM) score, and DVT risk. D-dimer on the first day after percutaneous nephrolithotomy, postoperative bed rest time and Caprini RAM scores were independent risk factors for DVT after PCNL. Sex, age, hypertension status, diabetes status and smoking and drinking habits were not significantly associated with DVT risk. CONCLUSIONS: D-dimer on the first day after PCNL, postoperative bed rest time and Caprini RAM scores were independent risk factors for DVT after PCNL.
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Nefrolitotomia Percutânea , Complicações Pós-Operatórias , Trombose Venosa , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Trombose Venosa/etiologia , Trombose Venosa/epidemiologia , Estudos Retrospectivos , Nefrolitotomia Percutânea/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Duração da Cirurgia , Repouso em Cama , Medição de RiscoRESUMO
Incorporating photothermal agents into thermoresponsive liquid crystalline elastomers (LCEs) offers remote and spatio-temporal control in actuation. Typically, both the light responsiveness and actuation behaviors are fixed since the agent doping and mesogen alignment are conducted before network formation. Here, we report an approach that enables programming photoresponsive LCEs after synthesis via force-directed evaporation. Different photothermal agents can be doped or removed by swelling the fully cross-linked LCEs in a specific solution, achieving the introduction and erasing of the photoresponsiveness. Moreover, the network swelling deletes the registered alignment, which allows for redefining the molecular order via re-evaporating the solvent with force imposed. This "one stone, two birds" strategy paves the way to simultaneously program/reprogram the actuation mode and responsiveness of LCEs, even in a spatio-selective manner to achieve complex actuations. Our approach is expandable to three-dimensional (3D) printed LCEs to access geometrically sophisticated shape-changing.
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Bovine viral diarrhea virus (BVDV) has caused massive economic losses in the cattle business worldwide. Fatty acid synthase (FASN), a key enzyme of the fatty acid synthesis (FAS) pathway, has been shown to support virus replication. To investigate the role of fatty acids (FAs) in BVDV infection, we infected CD8+T lymphocytes obtained from healthy cattle with BVDV in vitro. During early cytopathic (CP) and noncytopathic (NCP) BVDV infection in CD8+ T cells, there is an increase in de novo lipid biosynthesis, resulting in elevated levels of free fatty acids (FFAs) and triglycerides (TG). BVDV infection promotes de novo lipid biosynthesis in a dose-dependent manner. Treatment with the FASN inhibitor C75 significantly reduces the phosphorylation of PI3K and AKT in BVDV-infected CD8+ T cells, while inhibition of PI3K with LY294002 decreases FASN expression. Both CP and NCP BVDV strains promote de novo fatty acid synthesis by activating the PI3K/AKT pathway. Further investigation shows that pharmacological inhibitors targeting FASN and PI3K concurrently reduce FFAs, TG levels, and ATP production, effectively inhibiting BVDV replication. Conversely, the in vitro supplementation of oleic acid (OA) to replace fatty acids successfully restored BVDV replication, underscoring the impact of abnormal de novo fatty acid metabolism on BVDV replication. Intriguingly, during BVDV infection of CD8+T cells, the use of FASN inhibitors prompted the production of IFN-α and IFN-ß, as well as the expression of interferon-stimulated genes (ISGs). Moreover, FASN inhibitors induce TBK-1 phosphorylation through the activation of RIG-1 and MDA-5, subsequently activating IRF-3 and ultimately enhancing the IFN-1 response. In conclusion, our study demonstrates that BVDV infection activates the PI3K/AKT pathway to boost de novo fatty acid synthesis, and inhibition of FASN suppresses BVDV replication by activating the RIG-1/MDA-5-dependent IFN response.
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Vírus da Diarreia Viral Bovina Tipo 1 , Vírus da Diarreia Viral Bovina , Bovinos , Animais , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Vírus da Diarreia Viral Bovina/fisiologia , Linfócitos T CD8-Positivos , Ácidos Graxos , LipídeosRESUMO
The aim of this study was to evaluate the effect of brown fishmeal in replacement of white fishmeal in the diet of Chinese soft-shelled turtles and to find the optimal amount of brown fishmeal to add. Five experimental groups were set up and fed to animals, and they were composed by different proportions of white and brown fishmeal: G1 (30% white and 25% brown fishmeal), G2 (25% white and 30% brown fishmeal), G3 (20% white and 35% brown fishmeal), G4 (15% white and 40% brown fishmeal), G5 (10% white and 45% brown fishmeal). G1 is regarded as the control group. Turtles were randomly divided into five experimental groups with four replicates each. The experiment lasted 72 days. The results showed that the WGR, SGR, FCR, and HSI of the G3 group were not significantly different from those of the control group (P > 0.05). In addition, brown fishmeal can increase the crude protein content in the muscles of them. Among the serum biochemical indices, there was no significant difference between the G3 group and the G1 group, except for the level of TG (P > 0.05). Meanwhile, the activities of AST, ALT, and CAT in the liver of the G3 group did not differ significantly from those of the G1 group (P > 0.05). However, the activities of ACP, AKP, and T-AOC were significantly decreased in the G3 group (P < 0.05). In addition, the alteration of fishmeal did not affect the digestive enzyme activities in the stomach, liver, and intestine, and there is no significant difference (P > 0.05). Importantly, with increasing brown fishmeal addition, the expression of Fas, Pparγ, Scd, and Stat3 showed a significant increase, while the expression of Bmp4 decreased significantly (P < 0.05). In this study, the addition of 20% white fishmeal and 35% brown fishmeal to the diet of Chinese soft-shelled turtles did not adversely affect growth performance. Therefore, 20% white fishmeal and 35% brown fishmeal are the most practical feed formulations for Chinese soft-shelled turtles in this study.
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Tartarugas , Animais , Tartarugas/metabolismo , Metabolismo dos Lipídeos , Músculos/metabolismo , Fígado/metabolismoRESUMO
Background: Infrarenal aortic occlusion (IAO) is a life-threatening condition that often causes lower limb ischemia. Although open surgery is the current recommendation for first-line treatment, recent technological innovations have made endovascular treatment (EVT) a promising alternative. This study aims to compare the clinical outcomes of bypass surgery and EVT in the treatment of IAO. Methods: This study is a single-center retrospective observative study at Peking Union Medical College Hospital. Consecutive 92 patients with chronic and atherosclerotic IAO were treated with either EVT (n=40) or bypass surgery (n=52) between 2011 and 2021. The baseline clinical factors (including demographic data and comorbidities), perioperative data (including Rutherford classification changes, technical success) and complication rates were evaluated. The mid-term patency and overall survival of EVT and bypass were assessed. Follow-up was defined as the time from surgery to the last outpatient visit. Continuous variables and category variables were statistically compared, respectively. Kaplan-Meier survival analyses were conducted for vascular patency. Results: The study found that the demographics and pre-operative Rutherford classification were evenly distributed between the two groups (P>0.05). As for technical success, clinical success, comorbidities, mortality, complication rate, and Rutherford classification after procedures, no significant differences were observed (P>0.05). The average post-procedure hospital stay was 5.15 days in the EVT group and was significantly shorter than that of the bypass group, which was 11.83 days (P<0.0001). As for short-term and long-term results, the 1-, 3-, and 5-year primary patency rates were 81.8%, 73.1%, and 73.1% in the EVT group and 97.8%, 80.6%, and 80.6% in the bypass group. The bypass group had significantly better primary patency (P=0.034). There was a significant difference in the secondary patency rate (Bypass 100% vs. EVT 81.6%; P=0.005). Moreover, survival rates were higher in the bypass surgery group than in the EVT group (P=0.035). Conclusions: Although EVT's primary patency rate was lower than that with the bypass surgery, its safety and efficacy were still comparable to anatomic bypass surgery for IAO with less severe perioperative complications and shorter hospital stay. Therefore, EVT could be a feasible option for IAO.
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Liquid crystalline elastomers (LCEs) exhibit muscle-like actuation upon an external stimulus. To control this, various alignment programming strategies have been developed over the past decades. Among them, force-directed solvent evaporation, namely, that the alignment depends on the applied external force during solvent evaporation, is appreciated for its universality in material design and versatility in attainable actuations. Here, we investigate the influence of network topology on the alignment programming of a liquid crystalline (LC) organo-gel via varying feeding ratios of the monomers. As a result, distinct self-supporting actuations can be repeatedly introduced into a topology-optimized LC organo-gel. Beyond this, the bond exchange reaction of the embedded ester groups can be activated upon heating, which enables alignment manipulation based on dynamic network reconfiguration after drying. The availability of inviting two distinct programming strategies into one LCE network allows us to regulate the LCE alignment at both the gel and dried states, offering ample room to diversify actuation manners. Our design principle shall be adopted by other dynamic LCE systems owing to its maneuverability.
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Objective: Uterine intravenous leiomyomatosis (IVL) is a rare and unique leiomyoma that is difficult to surgery due to its ability to extend into intra- and extra-uterine vasculature. And it is difficult to differentiate from uterine leiomyoma (LM) by conventional CT scanning, which results in a large number of missed diagnoses. This study aimed to evaluate the utility of a contrast-enhanced CT-based radiomic nomogram for preoperative differentiation of IVL and LM. Methods: 124 patients (37 IVL and 87 LM) were retrospectively enrolled in the study. Radiomic features were extracted from contrast-enhanced CT before surgery. Clinical, radiomic, and combined models were developed using LightGBM (Light Gradient Boosting Machine) algorithm to differentiate IVL and LM. The clinical and radiomic signatures were integrated into a nomogram. The diagnostic performance of the models was evaluated using the area under the curve (AUC) and decision curve analysis (DCA). Results: Clinical factors, such as symptoms, menopausal status, age, and selected imaging features, were found to have significant correlations with the differential diagnosis of IVL and LM. A total of 108 radiomic features were extracted from contrast-enhanced CT images and selected for analysis. 29 radiomics features were selected to establish the Rad-score. A clinical model was developed to discriminate IVL and LM (AUC=0.826). Radiomic models were used to effectively differentiate IVL and LM (AUC=0.980). This radiological nomogram combined the Rad-score with independent clinical factors showed better differentiation efficiency than the clinical model (AUC=0.985, p=0.046). Conclusion: This study provides evidence for the utility of a radiomic nomogram integrating clinical and radiomic signatures for differentiating IVL and LM with improved diagnostic accuracy. The nomogram may be useful in clinical decision-making and provide recommendations for clinical treatment.
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Periodontal disease, a prevalent oral disease, is an independent risk factor for atherosclerosis. Porphyromonas gingivalis (P.g), a keystone pathogen of periodontal disease, contributes to the pathogenesis of atherosclerosis. However, the exact mechanism remains unclear. An increasing number of studies have proposed the atherogenic influence of perivascular adipose tissue (PVAT) in pathological conditions including hyperlipidemia and diabetes. Nevertheless, the role of PVAT in atherosclerosis promoted by P.g infection has not been explored. In our study, we investigated the association between P.g colonization in PVAT and progression of atherosclerosis through experiments on clinical samples. We further investigated P.g invasion of PVAT, PVAT inflammation, aortic endothelial inflammation, aortic lipid deposition, and systemic inflammation in C57BL/6 J mice with or without P.g infection at 20, 24, and 28 weeks of age. PVAT inflammation, characterized by imbalance in Th1/Treg and dysregulated adipokine levels, was associated with P.g invasion, preceding endothelial inflammation that occurred independently of its direct invasion. The phenotype of systemic inflammation coincided with that of PVAT inflammation, but systemic inflammation occurred after endothelial inflammation. Therefore PVAT inflammation in early atherosclerosis could be a primary trigger of aortic endothelial inflammation and lipid deposition in chronic P.g infection, through the dysregulated paracrine secretion of T helper-1-related adipokines.
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Aterosclerose , Doenças Periodontais , Animais , Camundongos , Porphyromonas gingivalis , Adipocinas , Camundongos Endogâmicos C57BL , Tecido Adiposo/patologia , Aterosclerose/patologia , Inflamação/patologia , Doenças Periodontais/patologia , LipídeosRESUMO
BACKGROUND: Polycyclic triterpenoids (PTs) are common in plants, and have attracted considerable interest due to their remarkable biological activities. Currently, engineering the ergosterol synthesis pathway in Saccharomyces cerevisiae is a safe and cost-competitive way to produce triterpenoids. However, the strict regulation of ERG1 involved in the epoxidation of squalene limits the triterpenoid production. RESULTS: In this study, we found that the decrease in ERG7 protein level could dramatically boost the epoxidation of squalene by improving the protein stability of ERG1. We next explored the potential factors that affected the degradation process of ERG1 and confirmed that ERG7 was involved in the degradation process of ERG1. Subsequently, expression of four different triterpene cyclases utilizing either 2,3-oxidosqualene or 2,3:22,23-dioxidosqualene as the substrate in ERG7-degraded strains showed that the degradation of ERG7 to prompt the epoxidation of squalene could significantly increase triterpenoid production. To better display the potential of the strategy, we increased the supply of 2,3-oxidosqualene, optimized flux distribution between ergosterol synthesis pathway and ß-amyrin synthesis pathway, and modified the GAL-regulation system to separate the growth stage from the production stage. The best-performing strain ultimately produced 4216.6 ± 68.4 mg/L of ß-amyrin in a two-stage fed-fermentation (a 47-fold improvement over the initial strain). CONCLUSIONS: This study showed that deregulation of the native restriction in ergosterol pathway was an effective strategy to increase triterpenoid production in yeast, which provided a new insight into triterpenoids biosynthesis.
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BACKGROUND: During endovascular aneurysm repair (EVAR), commercial iliac branch devices (IBDs) have become an inescapable alternative for preserving antegrade internal iliac artery (IIA) blood flow. Due to the different morphological features of aneurysms, commercial IBDs may not be suitable for all patients. Reported experience with the implantation of the new surgeon-modified IBD (sm IBD) is limited. This investigation describes the indications, efficacy, and safety of the sm IBD. METHODS: Data from consecutive elective implantations of IBDs in patients between March 2011 and May 2021 in a single center were incorporated. The sm IBDs were indicated in patients with common iliac artery aneurysms (CIAAs) and with a challenging anatomy and in those patients with or without abdominal aortic aneurysm (AAA). RESULTS: Fifteen patients (15 male, mean age 67.6 ± 7.9 years) were included. Fifteen sm IBDs were implanted in 1 procedure (100%). Fourteen (93.3%) patients had simultaneous endovascular aneurysm repair (EVAR) and 1 (6.7%) patient previously had a bilateral CIAAs repair by EVAR. The mean common iliac artery (CIA) diameter was 36.6 ± 12.5 mm. Technical success was obtained in all patients (100%). The median operation time was 189.7 ± 78.6 min, with a median fluoroscopy time of 45.3 ± 15.9 min. Axillary artery access was used in 11 (73.3%) procedures. The mean total hospital stay was 5.6 ± 2.8 days, and the postoperative follow-up was 35.4 months (range 2-120). The estimated IIA bridge stent patency at 1 year after operation was 100% and 85.7% ± 13.2% 5 years postoperatively. One (6.7%) IIA branch was occluded, and this patient remained asymptomatic. One patient (6.7%) needed reintervention, and another (6.7%) patient had type II leakage, which is currently under close surveillance. CONCLUSIONS: Using an IBD to maintain the pelvic blood flow is an effective and feasible intravascular technique, especially for patients with an abnormal iliac artery anatomy. This novel technique has similar midterm procedural success rate compared to the use of commercial IBDs. Therefore, these devices are more suitable for patients with certain anatomic challenges and can be used as an alternative treatment.
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Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Aneurisma Ilíaco , Cirurgiões , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Artéria Ilíaca/diagnóstico por imagem , Artéria Ilíaca/cirurgia , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Prótese Vascular , Resultado do Tratamento , Aneurisma Ilíaco/diagnóstico por imagem , Aneurisma Ilíaco/cirurgia , Desenho de Prótese , StentsRESUMO
Heat stress (HS) causes imbalance of cellular homeostasis, growth impairment and extensively yield loss in crop production. In the present study, the tropic maize inbred CIMBL55 showed more thermotolerance than the maize temperate inbred B73, with less leaf damage rate and ROS accumulation. Transcriptome profiling of CIMBL55 and B73 upon (exposing at 45 â for 0, 1, and 6 h) and post (recovering at 28 â for 1 and 6 h) HS were further assessed and a total of 20204 DEGs were identified. Functional annotation revealed that HS activated unfolded protein response in endoplasmic reticulum in both two inbreds. Moreover, in CIMBL55, far more primary and secondary metabolism pathways were transcriptional altered. Afterwards, weighted gene co-expression analysis grouped all expressed genes into eighteen co-expressed modules. Four HS responsive and four CIMBL55 recovery-related modules were subsequently identified. Highly connected genes (hub genes) in these modules were characterized as transcription factors, heat shock proteins, Ca2+ signaling related genes and various enzymes. Moreover, one hub gene, ZmHsftf13 was verified to positively regulate thermotolerance by heterologous expressing in Arabidopsis and its Mu insertion mutant. The present research provides promising genes related to HS response in maize and is of great significance for breeding.
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Arabidopsis , Transcriptoma , Zea mays/metabolismo , Melhoramento Vegetal , Perfilação da Expressão Gênica , Resposta ao Choque Térmico/genética , Arabidopsis/genética , Regulação da Expressão Gênica de PlantasRESUMO
OBJECTIVE: To study the expression and significance of PD-1, PD-L1 and CTLA-4 tumor-associated antigens in multiple myeloma. METHODS: Bone marrow specimens from 122 patients with multiple myeloma were collected and divided into new-onset group (NDMM), complete remission group (CRMM) and relapsed and refractory group (RRMM) according to the disease progression stage. The proportion of CD4+ T lymphocytes, CD8+ T lymphocytes, Treg cells and plasma cells in the specimens and the expressions of PD-1, PD-L1 and CTLA-4 were detected by multi-parameter flow cytometry. RESULTS: There was no significant difference in the proportion of CD8+T and Treg cells among the three groups (P>0.05), while the proportions of CD4+T cells and PC in NDMM group were significantly higher than those in the CRMM group (P<0.05), the ratios of CD4+ to CD8+T in the NDMM and RRMM groups were significantly higher than those in the CRMM group (P<0.05). The expressions of PD-1, PD-L1 and CTLA-4 in CD8+ T cells was no significant difference among NDMM, CRMM and RRMM groups (P>0.05). While the expressions of PD-1, PD-L1 and CTLA-4 in CD4+ T cells and PC in the NDMM group were significantly lower than that in the CRMM group (P<0.05). There was significantly difference among the three groups in the expression of PD-1 in Treg cells, of which the NDMM group was significantly lower than that of the CRMM group (all P<0.05). The expressions of PD-1 and CTLA-4 in PC were significantly higher than those in CD8+ T, CD4+ T and Treg cells (P<0.05), the expression of PD-L1 in CD8+ T cells was significantly higher than that in CD4+ T and Treg cells (P<0.05). CONCLUSION: There is a correlation between the immune status of multiple myeloma and the expressions of PD-1, PD-L1 and CTLA-4 in plasma cells and lymphocyte subsets in vivo.
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Medula Óssea , Mieloma Múltiplo , Humanos , Antígeno B7-H1 , Linfócitos T CD8-Positivos , Receptor de Morte Celular Programada 1RESUMO
The adverse consequences resulting from diabetes are often presented as severe complications. Diabetic wounds are one of the most commonly occurring complications in diabetes, and the control and treatment of this is costly. Due to a series of pathophysiological mechanisms, diabetic wounds remain in the inflammatory phase for a prolonged period of time, and face difficulty in entering the proliferative phase, thus leading to chronic non-healing wounds. The current consensus on the treatment of diabetic wounds is through multidisciplinary comprehensive management, however, standard wound treatment methods are still limited and therefore, more effective methods are required. In recent years, defensins have been found to play diverse roles in a variety of diseases; however, the molecular mechanisms underlying these activities are still largely unknown. Defensins can be constitutively or inductively produced in the skin, therefore, their local distribution is affected by the microenvironment of these diabetic wounds. Current evidence suggests that defensins are involved in the diabetic wound pathogenesis, and can potentially promote the early completion of each stage, thus making research on defensins a promising area for developing novel treatments for diabetic wounds. In this review, we describe the complex function of human defensins in the development of diabetic wounds, and suggest potential thera-peutic benefits.
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OBJECTIVE: To compare the effects of direct fluorescence in situ hybridization (D-FISH) detection without sorting and CD138 immunomagnetic bead sorting technology combined with FISH (MACS-FISH) on cytogenetic analysis of patients with multiple myeloma (MM). METHODS: FISH test results of 229 patients with initial MM were retrospectively analyzed. The patients were divided into two groups, 140 patients were tested with D-FISH and 89 patients with MACS-FISH. The combination probe was designed as P53, D13S319, RB1, 1q21, and IgH. Cytogenetic detection results were compared between the two groups. RESULTS: The total detection rate of cytogenetic abnormalities in D-FISH group was 52.9%, and that in MACS-FISH group was 79.8%. There was a significant difference in the cytogenetic abnormality rate between the two groups (P=0.020). The abnormal genes with the highest detection rate in the two groups were 1q21 and IgH, respectively, while the lowest was P53. There was no significant difference in the percentage of P53 positive cells (positive rate) between the two groups, while D13S319, RB1, 1q21, and IgH showed significant difference in positive cell rate (P=0.0002, P<0.0001, P=0.0033, P=0.0032). There was no significant correlation between the proportion of plasma cells (PC) detected by bone marrow morphology and cytogenetic abnormality rate in the D-FISH group, while there was a correlation between the proportion of PC detected by flow cytometry and cytogenetic abnormality rate (r=0.364). The PC proportion detected by bone marrow morphology and flow cytometry in the MACS-FISH group had no correlation with the cytogenetic abnormality rate and positive cell rate of the 5 genes mentioned above. Additionally, the PC proportion detected by bone marrow morphology and flow cytometry showed significant difference (P<0.0001). CONCLUSION: CD138 immunomagnetic bead sorting combined with FISH technology can significantly improve the abnormality detection rate of MM cytogenetics.
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Mieloma Múltiplo , Sindecana-1/imunologia , Aberrações Cromossômicas , Humanos , Hibridização in Situ Fluorescente/métodos , Mieloma Múltiplo/genética , Estudos Retrospectivos , Proteína Supressora de Tumor p53/genéticaRESUMO
The precise manipulation of the quantum states of individual atoms/molecules adsorbed on metal surfaces is one of the most exciting frontiers in nanophysics, enabling us to realize novel single molecular logic devices and quantum information processing. Herein, by modeling an iron phthalocyanine molecule adsorbed on the Au(111) surface with a two-impurity Anderson model, we demonstrate that the quantum states of such a system could be adjusted by the uniaxial magnetic anisotropy Dz. For negative Dz, the ground state is dominated by a parallel configuration of the z component of local spins, whereas it turns to be an antiparallel one when Dz becomes positive. Interestingly, we found that these two phases are separated by a Kosterlitz-Thouless-type quantum phase transition, which is confirmed by the critical behaviors of the transmission coefficient and the local magnetic moment. Both phases are associated with spin correlation anisotropy, thus move against the Kondo effect. When the external magnetic field is applied, it first plays a role in compensating for the effect of Dz, and then it contributes significantly to the Zeeman effect for positive Dz, accompanied by the reappearance and the splitting of the Kondo peak, respectively. For fixed negative Dz, only the Zeeman behavior is revealed. Our results provide deep insights into the manipulation of the quantum phase within a single molecular junction.
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Atherosclerotic disease has become the major cause of death worldwide. Smoking, as a widespread independent risk factor, further strengthens the health burden of atherosclerosis. Irisin is a cytokine that increases after physical activity and shows an atheroprotective effect, while its specific mechanism in the process of atherosclerosis is little known. The reversal effect of irisin on intimal thickening induced by smoking-mediated atherosclerosis was identified in Apoe -/- mice through the integrin αVß5 receptor. Endothelial cells treated with nicotine and irisin were further subjected to RNA-seq for further illustrating the potential mechanism of irisin in atherosclerosis, as well as the wound healing assays, CCK-8 assays, ß-gal staining and cell cycle determination to confirm phenotypic alterations. Endothelial differential expressed gene enrichment showed focal adhesion for migration and proliferation, as well as the P53 signaling pathway for cell senescence and cell cycle control. Irisin exerts antagonistic effects on nicotine-mediated migration and proliferation via the integrin αVß5/PI3K pathway. In addition, irisin inhibits nicotine-mediated endothelial senescence and cell cycle arrest in G0/G1 phase via P53/P21 pathway. This study further illustrates the molecular mechanism of irisin in atherosclerosis and stresses its potential as an anti-atherosclerotic therapy.
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The study aims to enhance ß-amyrin production in Saccharomyces cerevisiae by peroxisome compartmentalization. First, overaccumulated squalene was determined as a key limiting factor for the production of ß-amyrin since it could inhibit the activity of ß-amyrin synthase GgbAs1. Second, to mitigate the inhibition effect, the enhanced squalene synthesis pathway was compartmentalized into peroxisomes to insulate overaccumulated squalene from GgbAs1, and thus the specific titer of ß-amyrin reached 57.8 mg/g dry cell weight (DCW), which was 2.6-fold higher than that of the cytosol engineering strain. Third, by combining peroxisome compartmentalization with the "push-pull-restrain" strategy (ERG1 and GgbAs1 overexpression and ERG7 weakening), the production of ß-amyrin was further increased to 81.0 mg/g DCW (347.0 mg/L). Finally, through fed-batch fermentation in a 5 L fermenter, the titer of ß-amyrin reached 2.6 g/L, which is the highest reported to date. The study provides a new perspective to engineering yeasts as a platform for triterpene production.
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Engenharia Metabólica , Ácido Oleanólico/biossíntese , Saccharomyces cerevisiae , Esqualeno , Microbiologia Industrial , Transferases Intramoleculares , Ácido Oleanólico/análogos & derivados , Saccharomyces cerevisiae/genéticaRESUMO
In our studies, cyclin B1 (CCNB1) mRNA and protein were overexpressed in hepatocellular carcinoma (HCC) tissues compared with non-HCC tissues. Moreover, CCNB1 was overexpressed in the serum of HCC patients. The expression of CCNB1 was associated with several crucial clinicopathologic characteristics, and the HCC patients with overexpressed CCNB1 had worse overall survival outcomes. In the screening of interactional genes, a total of 266 upregulated co-expression genes, which were positively associated with CCNB1, were selected from the datasets, and 67 downregulated co-expression genes, which were negatively associated with CCNB1, were identified. The key genes might be functionally enriched in DNA replication and the cell cycle pathways. CDC20, CCNA2, PLK1, and FTCD were selected for further research because they were highly connected in the protein-protein interaction networks. Upregulated CDC20, CCNA2, and PLK1 and downregulated FTCD might result in undesirable overall survival outcomes for HCC patients. The univariate Cox analysis results showed that CDC20 and PLK1 might be two independent risk factors, while FTCD might be protective in HCC. Therefore, CCNB1 may participate in the cell cycle of HCC by regulating DNA replication, and CCNB1 may provide a direction for the diagnosis of early-stage HCC and targeted HCC therapy.