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Despite recent advancements in cancer treatment, this disease still poses a serious threat to public health. Vaccines play an important role in preventing illness by preparing the body's adaptive and innate immune responses to combat diseases. As our understanding of malignancies and their connection to the immune system improves, there has been a growing interest in priming the immune system to fight malignancies more effectively and comprehensively. One promising approach involves utilizing nanoparticle systems for antigen delivery, which has been shown to potentiate immune responses as vaccines and/or adjuvants. In this review, we comprehensively summarized the immunological mechanisms of cancer vaccines while focusing specifically on the recent applications of various types of nanoparticles in the field of cancer immunotherapy. By exploring these recent breakthroughs, we hope to identify significant challenges and obstacles in making nanoparticle-based vaccines and adjuvants feasible for clinical application. This review serves to assess recent breakthroughs in nanoparticle-based cancer vaccinations and shed light on their prospects and potential barriers. By doing so, we aim to inspire future immunotherapies for cancer that harness the potential of nanotechnology to deliver more effective and targeted treatments.
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Vacinas Anticâncer , Nanopartículas , Neoplasias , Humanos , Nanovacinas , Imunoterapia , Vacinas Anticâncer/uso terapêutico , Neoplasias/tratamento farmacológico , Adjuvantes Imunológicos , Nanopartículas/uso terapêuticoRESUMO
PIN InGaAs short wavelength infrared (SWIR) focal plane array (FPA) detectors have attracted extensive attention due to their high detectivity, high quantum efficiency, room temperature operation, low dark current, and good radiation resistance. Furthermore, InGaAs FPA detectors have wide applications in many fields, such as aviation safety, biomedicine, camouflage recognition, and infrared night vision. Recently, extensive research has been conducted on the extension of the response spectrum from short wavelength infrared (SWIR) to visible light (VIS) through InP substrate removal and reserving the n-InP contact layer. However, there is little research on the absorption of InGaAs detectors in the ultraviolet (UV) band. In this paper, we present an ultra-broadband UV-VIS-SWIR 640 × 512 15 µm InGaAs FPA detector by removing the n-InP contact layer in the active area and reserving the InP contact layer around the pixels for n contact, creating incident light to be directly absorbed by the In0.53Ga0.47As absorption layer. In addition, the optical absorption characteristics of InGaAs infrared detectors with and without an n-InP contact layer are studied theoretically. The test results show that the spectral response is extended to the range of 200-1700 nm. The quantum efficiency is higher than 45% over a broad wavelength range of 300-1650 nm. The operability is up to 99.98%, and the responsivity non-uniformity is 3.28%. The imaging capability of InGaAs FPAs without the n-InP contact layer has also been demonstrated, which proves the feasibility of simultaneous detection for these three bands.
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Achieving single-band upconversion (UC) is a challenging but rewarding approach to attain optimal performance in diverse applications. In this paper, we successfully achieved single-band red UC luminescence in Yb2O3: Er transparent ceramics (TCs) through the utilization of a sensitizer-rich design. The Yb2O3 host, which has a maximum host lattice occupancy by Yb3+ sensitizers, facilitates the utilization of excitation light and enhances energy transfer to activators, resulting in improved UC luminescence. Specifically, by shortening the ionic spacing between sensitizer and activator, the energy back transfer and the cross-relaxation process are promoted, resulting in weakening of green energy level 4S3/2 and 2H11/2 emission and enhancement of red energy level 4F9/2 emission. The prepared Yb2O3: Er TCs exhibited superior optical properties with in-line transmittance over 80% at 600â nm. Notably, in the 980nm-excited UC spectrum, green emission does not appear, thus Yb2O3: Er TCs exhibit ultra-pure single band red emission, with CIE coordinates of (0.72, 0.28) and color purity exceeding 99.9%. To the best of our knowledge, this is the first demonstration of pure red UC luminescence in TCs. Furthermore, the luminescent intensity ratio (LIR) technique was utilized to apply this pure red-emitting TCs for temperature sensing. The absolute sensitivity of Yb2O3: Er TCs was calculated to be 0.319% K-1 at 304â K, which is the highest level of optical thermometry based on 4F9/2 levels splitting of Er3+ known so far. The integration between pure red UC luminescence and temperature sensing performance opens up new possibilities for the development of multi-functional smart windows.
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By conducting density functional theory (DFT) calculations, the detailed reaction mechanisms of aldimines with tributyltin cyanide under the catalytic influence of chiral oxazaborolidinium ion (COBI) have been uncovered. Three potential reaction pathways were examined, and two stereoselective routes were determined for the most energetically favorable mechanism. In the primary route, a proton is transferred from the COBI catalyst to the aldimine substrate, which is then followed by the C-C bond formation to produce the final product. Subsequently, NBO analyses of the stereoselectivity-determining transition states were conducted to identify the crucial role of hydrogen bond interactions in controlling stereoselectivity. These computed findings should prove invaluable in comprehending the detailed mechanisms and underlying origins of stereoselectivity for COBI-mediated reactions of this type.
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BACKGROUND: Aortic dissection (AD) is a serious and fatal vascular disease. The earlier the condition of AD patients can be assessed precisely, the more scientifically controlled the patient's condition will be. Therefore, timely and accurate diagnosis is significant for AD. Blood biomarker testing as a method of liquid biopsy can improve the diagnostic efficiency of AD. This study conducted a systematic review of the current blood diagnostic biomarkers of AD. METHODS: The PubMed, Cochrane Library, Web of Science, and Embase electronic databases were systematically searched from inception to January 1, 2023, using the terms "aortic dissection", "serum", "plasma" and "diagnosis". Stata 12.0 software was used to perform Random effects meta-analysis was performed using Stata 12.0 software to determine the effect sizes and corresponding 95% confidence intervals. Then, a summary receiver operator characteristic (SROC) curve was drawn, and the area under the ROC curve (AUC) was calculated. RESULTS: D-dimer had the best sensitivity and AUC for AD, with values of 0.96 (95% CI: 0.93-0.98) and 0.95 (95% CI: 0.93-0.97), respectively. The sensitivity and AUC values for D-dimer with a cut-off value of 500 ng/mL were 0.97 (95% CI: 0.95-0.99) and 0.94 (95% CI: 0.92-0.96), respectively. In contrast, microRNA had a better specificity value for AD, at 0.79 (95% CI: 0.73-0.83). CONCLUSIONS: D-dimer and microRNA have good accuracy in the diagnosis of AD, but the specificity of D-dimer is worse, and studies of microRNA are insufficient. The combination of different biomarkers can improve the diagnostic accuracy. Other blood biomarkers are related to the pathological progression of AD and can be selected according to pathological progress.
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Dissecção Aórtica , MicroRNAs , Humanos , Dissecção Aórtica/diagnóstico , Biomarcadores , Sensibilidade e EspecificidadeRESUMO
The large amount of schistosome eggs produced by mature female worms not only induce major pathological damage to the host but also lead to the transmission of schistosomiasis. Mature female schistosome worms need constant pairing contact with a male partner as male signaling is indispensable to female growth, development, and reproduction. The gynecophoral canal protein (GCP), a cell-surface glycoprotein, plays a potential role in the interaction between males and females and in stimulating female development and maturation. In this study, a yeast two-hybrid cDNA library of Schistosoma japonicum (Sj) parasites 18 days post-infection (dpi) was constructed; the Sjgcp gene was inserted into a pGBKT7-BD bait plasmid and used as a bait protein to screen for its molecular interactions using a yeast mating procedure. Twenty-four prey proteins that interacted with the SjGCP were selected after excluding false positives; the interactions between S.japonicum lethal giant larvae (SjLGL) and SjGCP, S.japonicum type V collagen (SjColV) and SjGCP, were verified by co-immunoprecipitation. The RNA interference against SjGCP, SjColV and SjGCP + SjColV led to severe underdevelopment of tegument in male worms and vitelline globules in female worms as well as reduced reproductive capacity of the females. Collectively, SjGCP and its interacting proteins may play pivotal roles in growth and development. The findings also suggested that SjGCP and its interacting protein partners might represent new candidate targets for drug development against schistosomiasis.
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Schistosoma japonicum , Esquistossomose Japônica , Animais , Feminino , Proteínas de Helminto/genética , Proteínas de Helminto/metabolismo , Masculino , Saccharomyces cerevisiae/genética , Schistosoma japonicum/genética , Técnicas do Sistema de Duplo-HíbridoRESUMO
Esophageal cancer is the ninth most common cancer and the sixth most common cause of cancer-related death worldwide, and the esophageal squamous cell carcinoma (ESCC) subtype accounts for about 90% of all cases of esophageal cancer globally. Currently, ESCC is usually diagnosed in late stages, and targeted therapy is lacking. Therefore, the development of ESCC-specific recognition molecules for an early detection and targeted treatment of ESCC is urgently needed. Aptamers are an excellent molecular recognition tool with unique advantages. In this manuscript, three aptamers (S2, S3, and S8) specific to ESCC cells were successfully screened via cell-SELEX. The experimental results displayed the high affinities of the three aptamers for target KYSE150 cells with dissociation constants in the nanomolar range. The specificity evaluation showed that S2 only bound target KYSE150 cells, but S3 and S8 were capable of targeting a series of ESCC cells. Moreover, several truncated aptamers were generated through sequence optimization. In particular, an ultrashort aptamer S3-2-3 with only 18 bases was successfully obtained; after labeling with Cy5 dyes, it was feasible for the specific imaging of ESCC tissues. Furthermore, the target types of the selected aptamers were preliminarily identified as membrane proteins, and target proteins could be captured by S3-2-3, which may be useful for biomarker discovery. Therefore, the selected aptamers hold great potential for clinical diagnosis, biomarker discovery, and the targeted therapy of ESCC.
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Aptâmeros de Nucleotídeos , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Linhagem Celular Tumoral , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Humanos , Técnica de Seleção de AptâmerosRESUMO
As efficient and stable nuclear waste forms, single-phase uranium (U6+)-incorporated La2Zr2O7 nanoparticles were designed and synthesized in an air atmosphere. To obtain a high U loading, divalent magnesium (Mg2+) was introduced to balance the extra charge from the substitution of tetravalent zirconium (Zr4+) by U6+ with a minimized impact to the lattice. There is a composition-driven phase transition from order pyrochlore to defect fluorite as the U concentration increases from 10 to 30 mol %, demonstrating both good solubility and stability of the La2Zr2O7 host for U and potentially for other actinides. La2(UxMgxZr1-2x)2O7 (x = 0-0.3) nanoparticles showed good dispersity and crystallinity with an average particle size of â¼48 nm. Furthermore, X-ray photoelectron spectroscopy, Raman spectroscopy, and emission spectroscopy revealed that U was stabilized in the hexavalent state in the form of a UO22+ ion. Spectroscopic methods also demonstrated that our samples caused a scintillating response with an orange emission (597 nm) by 230 nm excitation. In addition, density functional theory simulations were employed to investigate the atomic structures and electronic properties of the U-incorporated pyrochlores. The calculated bond lengths, atomic charges, and charge density confirm the existence of UO22+ ions. Supported by both experimental and computational results, a novel geometrical structure was proposed to explain the Mg2+-U6+ substitution. This work demonstrated the successful development of U-incorporated La2Zr2O7 nanoparticles and provided an efficient way to immobilize U in these ceramic waste matrixes.
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PURPOSE: The present study has proposed a novel orthodontic extraction method with a removable appliance to avoid inferior alveolar nerve (IAN) injury during impacted mandibular third molar removal. PATIENTS AND METHODS: In the present study, 16 patients were enrolled and divided into 2 groups per patient choice. In the orthodontic extraction group (n = 8), a removable appliance was first applied to move the root tips away from the IAN, and the tooth was subsequently removed. In the traditional extraction group (n = 8), each patient had the tooth removed immediately by the same surgeon. RESULTS: All teeth were extracted successfully. All 8 patients in the orthodontic extraction group had had their impacted mandibular third molar removed without IAN injury after surgery. In contrast, 4 patients in the traditional extraction group had experienced transient IAN injury, and the symptoms persisted for 2 to 8 weeks. None of the patients experienced permanent IAN damage. CONCLUSIONS: Orthodontic extraction with a removable appliance to separate the IAN and impacted mandibular third molar could be a good alternative treatment option to avoid IAN injury in high-risk cases.
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Dente Serotino , Extração Dentária , Dente Impactado , Traumatismos do Nervo Trigêmeo , Humanos , Mandíbula , Nervo Mandibular , Extração Dentária/efeitos adversos , Dente Impactado/cirurgia , Traumatismos do Nervo Trigêmeo/etiologiaRESUMO
Rapid and accurate bacterial detection is crucial to an early diagnosis for treating various infectious diseases. A recombinant tail fiber protein (P069) of the Pseudomonas aeruginosa ( P. aeruginosa) phage was expressed in Escherichia coli. After renaturation at a low temperature, the inclusion body of P069 was successfully transformed to an aqueous soluble protein that retained the capacity for recognizing P. aeruginosa. The recombinant P069 did not show lytic activity to P. aeruginosa, which facilitated the capture and manipulation of bacterial whole cells with a high flexibility for downstream identification and detection. Bioluminescent and fluorescent methods using this biorecognition element allowed P. aeruginosa detection with the detection limits of 6.7 × 102 CFU mL-1 and 1.7 × 102 CFU mL-1, respectively. Moreover, the specificity investigations showed that P069 was a species-specific protein. Therefore, it avoided the potential false negative results originating from the excessive high specificity of phage toward a given strain. It has been successfully applied to detect P. aeruginosa in spiked samples with acceptable recovery values ranging from 88% to 98%. The above results demonstrate that P069 is an ideal biorecognition element for the detection of P. aeruginosa in complicated sample matrixes.
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Bacteriófagos , Pseudomonas aeruginosa/metabolismo , Proteínas Recombinantes/metabolismo , Proteínas da Cauda Viral/metabolismo , Técnicas Biossensoriais , Humanos , Ligação Proteica , Pseudomonas aeruginosa/isolamento & purificação , Especificidade da EspécieRESUMO
This study aimed to investigate the protective effects of long non-coding RNA KCNQ1OT1 against myocardial ischemia/reperfusion (I/R) injury following acute myocardial infarction, as well as its regulatory mechanism. We used the cardiac muscle H9c2 cells under condition of oxygen glucose deprivation followed by reperfusion (OGD/R) to induce myocardial I/R injury. Then H9C2 cells were transfected with si-NC, si-KCNQ1OT1, pc-NC, pc-KCNQ1OT1, si-AdipoR1 and si-AdipoR2, respectively. The myocardial cell viability and apoptosis were respectively detected. In addition, the expression levels of inflammatory factors, apoptosis-related proteins and p38 MAPK/NF-κB pathway-related proteins were detected. Besides, an inhibitor of p38 MAPK/NF-κB pathway SB203580 was used to treat cells to verify the relationship between KCNQ1OT1 and p38 MAPK/NF-κB pathway. The expression of KCNQ1OT1 was significantly up-regulated in OGD/R-induced myocardial H9C2 cells. The OGD/R-induced decreased cell viability and AdipoR1 expression could be reversed after suppression of KCNQ1OT1. In addition, suppression of KCNQ1OT1 reduced OGD/R-induced increased expressions of TNF-α, IL-6 and IL-1ß and OGD/R-induced increased cell apoptosis, which were reversed after knockdown of AdipoR1. Besides, suppression of KCNQ1OT1 significantly down-regulated the OGD/R-induced increased expression of p-p38 and p-NF-κB, which were also reversed after knockdown of AdipoR1. Moreover, SB203580, an inhibitor of p38 MAPK/NF-κB signal pathway, could further enhance the inhibitory effects of KCNQ1OT1 suppression on the expression of p-p38, TNF-α, IL-6, IL-1ß and p-NF-κB in OGD/R-induced myocardial H9C2 cells. Suppression of KCNQ1OT1 may prevent myocardial I/R injury following acute myocardial infarction via regulating AdipoR1 and involving in p38 MAPK/NF-κB signal pathway.
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Regulação para Baixo , Infarto do Miocárdio/complicações , Traumatismo por Reperfusão Miocárdica/complicações , Traumatismo por Reperfusão Miocárdica/prevenção & controle , RNA Longo não Codificante/genética , Doença Aguda , Apoptose , Células Cultivadas , Humanos , Imidazóis/farmacologia , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Piridinas/farmacologiaRESUMO
OBJECTIVE: Resveratrol, a polyphenol of natural compounds, has beneficial cardiovascular effects, many of which are mediated by nitric oxide (NO). Resveratrol increases intracellular calcium and activates AMP-activated protein kinase (AMPK), all of which could increase NO production. We hypothesized that resveratrol via a calcium-dependent NO production lowers blood pressure (BP) in spontaneously hypertensive rats (SHR). METHODS: Acetylcholine (Ach)-induced endothelium-dependent relaxations in rat aortas were examined by organ chamber. Blood pressures were determined by radiotelemetry methods. RESULTS: Incubation of isolated aortas from SHR with resveratrol dramatically improved vasorelaxation induced by Ach. Preincubation of aortas with endothelial NO synthase (eNOS) inhibitor or calcium chelant blunted the effects of resveratrol on Ach-induced relaxation, as wells as NO production and eNOS phosphorylation. In animal studies, administration of resveratrol significantly lowered systemic BP in SHR. CONCLUSION: Resveratrol increases endothelial NO production to improve endothelial dysfunction and lowers BP in hypertensive rats, which depends on calcium-eNOS activation.
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Óxido Nítrico/metabolismo , Estilbenos , Vasodilatação/efeitos dos fármacos , Acetilcolina , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Aorta/efeitos dos fármacos , Aorta/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Cálcio/metabolismo , Modelos Animais de Doenças , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos , Ratos Endogâmicos SHR , Resveratrol , Estilbenos/metabolismo , Estilbenos/farmacologiaRESUMO
Lethal giant larvae (Lgl) are an evolutionarily conserved tumor suppressor present in fungi and animals. It plays an essential role in establishing apical-basal cell polarity, cell proliferation, differentiation, and tissue organization. Here, we report the presence of Lgl gene in the blood fluke Schistosoma japonicum (SjLgl) (GenBank: KF246684). SjLgl protein was mainly distributed in the unique surface tegument structure by immunofluorescence microscopic staining. Using a simple soaking method, a short interfering RNA (siRNA)-based RNA interference approach knocked down the expression of SjLgl in schistosomula in vitro by up to 89.0%. Moreover, tail vein injection of SjLgl-siRNA into the infected mice reduced SjLgl mRNA levels in vivo by 48.6-85.3%, depending on the duration of treatments. SjLgl-specific siRNA treatment during the infection in mice significantly altered the surface structure of adult worm, featured by the disappearance or significant reduction of sharp spines on the inner all of oral and ventral suckers. The siRNA also reduced the hatching rates in eggs produced by treated mice by up to 85.3%. These observations implied that Lgl plays an important role in the development of tegument in schistosomes, and may be explored as a novel target for developing immuno- and/or small molecule-based therapeutics to control and treat the infections caused by schistosome and other flatworms.
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Proteínas de Helminto/metabolismo , Schistosoma japonicum/ultraestrutura , Animais , Proteínas de Helminto/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óvulo/fisiologia , Interferência de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Coelhos , Ratos Wistar , Schistosoma japonicum/genética , Schistosoma japonicum/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismoRESUMO
The object scale of a small object scene changes greatly, and the object is easily disturbed by a complex background. Generic object detectors do not perform well on small object detection tasks. In this paper, we focus on small object detection based on FocusDet. FocusDet refers to the small object detector proposed in this paper. It consists of three parts: backbone, feature fusion structure, and detection head. STCF-EANet was used as the backbone for feature extraction, the Bottom Focus-PAN for feature fusion, and the detection head for object localization and recognition.To maintain sufficient global context information and extract multi-scale features, the STCF-EANet network backbone is used as the feature extraction network.PAN is a feature fusion module used in general object detectors. It is used to perform feature fusion on the extracted feature maps to supplement feature information.In the feature fusion network, FocusDet uses Bottom Focus-PAN to capture a wider range of locations and lower-level feature information of small objects.SIOU-SoftNMS is the proposed algorithm for removing redundant prediction boxes in the post-processing stage. SIOU multi-dimension accurately locates the prediction box, and SoftNMS uses the Gaussian algorithm to remove redundant prediction boxes. FocusDet uses SIOU-SoftNMS to address the missed detection problem common in dense tiny objects.The VisDrone2021-DET and CCTSDB2021 object detection datasets are used as benchmarks, and tests are carried out on VisDrone2021-det-test-dev and CCTSDB-val datasets. Experimental results show that FocusDet improves mAP@.5% from 33.6% to 46.7% on the VisDrone dataset. mAP@.5% on the CCTSDB2021 dataset is improved from 81.6% to 87.8%. It is shown that the model has good performance for small object detection, and the research is innovative.
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The spatial pattern of diseased forest trees is a product of the spatial pattern of host trees and the disease itself. Previous studies have focused on describing the spatial pattern of diseased host trees, and it remains largely unknown whether an antecedent spatial pattern of host/nonhost trees affects the infection pattern of a disease and how large the effect sizes of the spatial pattern of host/nonhost trees and host size are. The results from trivariate random labeling showed that the antecedent pattern of the host ash tree, Fraxinus mandshurica, but not of nonhost tree species, impacted the infection pattern of a stem fungal disease caused by Inonotus hispidus. To investigate the effect size of the spatial pattern of ash trees, we employed the SADIE (Spatial Analysis by Distance IndicEs) aggregation index and clustering index as predictors in the GLMs. Globally, the spatial pattern (vi index) of ash trees did not affect the infection likelihood of the focal tree; however, the spatial pattern of DBH (diameter at breast height) of ash trees significantly affected the infection likelihood of the focal tree. We sampled a series of circular plots with different radii to investigate the spatial pattern effect of host size on the infection likelihood of the focal tree locally. The results showed that the location (patch/gap) of the DBH of the focal tree, rather than that of the focal tree itself, significantly affected its infection likelihood in most plots of the investigated sizes. A meta-analysis was employed to settle the discrepancy between plots of different sizes, which led to results consistent with those of global studies. The results from meta-regression showed that plot size had no significant effects.
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Background: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory ailment influenced by a blend of genetic and environmental factors. Inflammatory response and an imbalance in oxidative-antioxidant mechanisms constitute the primary pathogenesis of COPD. Glutathione S-transferase P1(GSTP1) plays a pivotal role as an antioxidant enzyme in regulating oxidative-antioxidant responses in the pulmonary system. The activation of the NOD-like receptor thermal protein domain (NLRP3) inflammatory vesicle can trigger an inflammatory response. Several investigations have implicated GSTP1 and NLRP3 in the progression of COPD; nonetheless, there remains debate regarding this mechanism. Methods: Employing a case-control study design, 312 individuals diagnosed with COPD and 314 healthy controls were recruited from Gansu Province to evaluate the correlation between GSTP1 (rs4147581C>G and rs1695A>G) and NLRP3 (rs3806265T>C and rs10754558G>C) polymorphisms and the susceptibility to COPD. Results: The presence of the GSTP1 rs4147581G allele substantially elevated the susceptibility to COPD (CGvs.CC:OR=3.11,95% CI=1.961-4.935, P<0.001;GGvs.CC:OR=2.065,95% CI=1.273-3.350, P=0.003; CG+GGvs.CC:OR=2.594,95% CI=1.718-3.916, P<0.001). Similarly, the NLRP3rs3806265T allele significantly increased the susceptibility to COPD (TC:TT:OR=0.432,95% CI=0.296-0.630; TC+CCvs.TT:OR=2.132,95% CI=1.479-3.074, P<0.001). However, no statistically significant association was discerned between the rs1695A>G and rs10754558G>C polymorphisms and COPD susceptibility (P>0.05). Conclusion: In summary, this study ascertained that the GSTP1 rs4147581C>G polymorphism is associated with increased COPD susceptibility, with the G allele elevating the risk of COPD. Similarly, the NLRP3 rs3806265T>C polymorphism is linked to elevated COPD susceptibility, with the T allele heightening the risk of COPD.
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Doença Pulmonar Obstrutiva Crônica , Humanos , Antioxidantes , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Glutationa S-Transferase pi/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/genética , Fatores de RiscoRESUMO
BACKGROUND: Environmental and genetic factors are jointly involved in the development of chronic obstructive pulmonary disease (COPD). The EGLN1 gene is a major factor in upstream regulation of the hypoxia-inducible pathway. EGLN1 negatively regulates the hypoxia-inducible factors HIF-lα and HIF-2α by regulating the concentration of oxygen, mainly in a hypoxic environment. Hypoxia is a common physiologic condition during the progression of COPD, and several studies have identified genetic variants in EGLN1 as a key factor in the adaptation to hypoxic environments. However, it is still unclear whether there is an association between EGLN1 variants and the risk of developing COPD. METHODS: A case-control study was conducted in the Gannan Tibetan Autonomous Prefecture, Gansu Province. A total of 292 COPD patients and 297 healthy controls were enrolled to assess the association of EGLN1 single nucleotide polymorphisms (SNPs) (rs41303095 A>G, rs480902 C>T, rs12097901 C>G, rs2153364 G>A) with COPD susceptibility. RESULTS: The EGLN1 rs41303095 A>G, rs480902 C>T, rs12097901 C>G, and rs2153364 G>A polymorphisms were not associated with COPD susceptibility (p > 0.05). CONCLUSIONS: The EGLN1 rs41303095 A>G, rs480902 C>T, rs12097901 C>G and rs2153364 G>A polymorphisms were found in this study not to be associated with susceptibility to COPD in Gannan Tibetans.
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Altitude , População do Leste Asiático , Hipóxia , Humanos , Estudos de Casos e Controles , Hipóxia/genética , Polimorfismo de Nucleotídeo Único , Predisposição Genética para Doença , Prolina Dioxigenases do Fator Induzível por Hipóxia/genéticaRESUMO
Tumor cell-targeting molecules play a vital role in cancer diagnosis, targeted therapy, and biomarker discovery. Aptamers are emerging as novel targeting molecules with unique advantages in cancer research. In this work, we have developed several DNA aptamers through cell-based systematic evolution of ligands by exponential enrichment (Cell-SELEX). The selected SYL-6 aptamer can bind to a variety of cancer cells with high signal. Tumor tissue imaging demonstrated that SYL-6-Cy5 fluorescent probe was able to recognize multiple clinical tumor tissues but not the normal tissues, which indicates great potential of SYL-6 for clinical tumor diagnosis. Meanwhile, we identified prohibitin 2 (PHB2) as the molecular target of SYL-6 using mass spectrometry, pull-down and RNA interference assays. Moreover, SYL-6 can be used as a delivery vehicle to carry with doxorubicin (Dox) chemotherapeutic agents for antitumor targeted chemotherapy. The constructed SYL-6-Dox can not only selectively kill tumor cells in vitro, but also inhibit tumor growth with reduced side effects in vivo. This work may provide a general tumor cell-targeting molecule and a potential biomarker for cancer diagnosis and targeted therapy.
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Aptâmeros de Nucleotídeos , Neoplasias , Humanos , Aptâmeros de Nucleotídeos/metabolismo , Proibitinas , Doxorrubicina/farmacologia , Neoplasias/tratamento farmacológico , Biomarcadores , Técnica de Seleção de Aptâmeros/métodos , Linhagem Celular TumoralRESUMO
BACKGROUND: Hypertension has become prevalent among young and middle-age individuals. Many studies have identified a variety of risk factors for cardiovascular diseases, yet there have been few reports focusing on the young and middle-age hypertensive population. OBJECTIVE: To investigate the epidemiological characteristics of conventional risk factors of premature coronary artery disease (PCAD) in patients with hypertension. METHODS: The clinical and laboratory data of 267 hypertensive patients with PCAD and 96 hypertensive patients without any visible coronary disease according to angiography were compared. Potential coronary risk factors were analyzed using logistic regression. RESULTS: The PCAD group had lower levels of high-density lipoprotein cholesterol (HDL-C) (P<0.05). Multivariate logistic analysis showed positive family history, low HDL-C, hypertriglyceridemia, duration of diabetes mellitus and male sex were significantly associated with PCAD (P<0.05), with ORs of 12.317, 3.267, 2.894, 1.140 and 0.088, respectively. Plasma renin activities in PCAD patients were significantly higher than in control hypertensive patients (P=0.027), but there was no significant difference in angiotensin II and aldosterone levels between the two groups. CONCLUSION: Low HDL-C and hypertriglyceridemia are important coronary risk factors in Chinese individuals with hypertension.
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Objective: In this study, the advantages of the internal fixation configuration composed of uniplanar pedicle screws in the treatment of thoracolumbar fractures were verified by biomechanical experimental methods, which provided the basis for subsequent clinical experiments and clinical applications. Methods: A total of 24 fresh cadaveric spine specimens (T12-L2) were utilized to conduct biomechanical experiments. Two different internal fixation configurations, namely, the 6-screw configuration and the 4-screw/2-NIS (new intermediate screws) configuration, were tested using fixed-axis pedicle screws (FAPS), uniplanar pedicle screws (UPPS), and polyaxial pedicle screws (PAPS) respectively. The spine specimens were uniformly loaded with 8NM pure force couples in the directions of anteflexion, extension, left bending, right bending, left rotation, and right rotation, and the range of motion (ROM) of the T12-L1 and L1-L2 segments of the spine was measured and recorded to access biomechanical stability. Results: No structural damage such as ligament rupture or fracture occurred during all experimental tests. In the 6-screw configuration, the ROM of the specimens in the UPPS group was significantly better than that of the PAPS group but weaker than those of the FAPS group (p < 0.01). In the 4-screw/2-NIS configuration, the results were identical to the biomechanical test results for the 6-screw configuration (p < 0.01). Conclusion: Biomechanical test results show that the internal fixation configuration with UPPS can maintain the stability of the spine well, and the results are better than that of PAPS. UPPS has both the biomechanical advantages of FAPS and the superiority of easy operation of PAPS. We believe it is an optional internal fixation device for minimally invasive treatment of thoracolumbar fractures.