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Despite incorporation of organic groups into silica-based aerogels to enhance their mechanical flexibility, the wide temperature reliability of the modified silicone aerogel is inevitably degraded. Therefore, facile synthesis of soft silicone aerogels with wide-temperature stability remains challenging. Herein, novel silicone aerogels containing a high content of Si are reported by using polydimethylvinylsiloxane (PDMVS), a hydrosilylation adduct with water-repellent groups, as a "flexible chain segment" embedded within the aerogel network. The poly(2-dimethoxymethylsilyl)ethylmethylvinylsiloxane (PDEMSEMVS) aerogel is fabricated through a cost-effective ambient temperature/pressure drying process. The optimized aerogel exhibits exceptional performance, such as ultra-low density (50 mg cm-3), wide-temperature mechanical flexibility, and super-hydrophobicity, in comparison to the previous polysiloxane aerogels. A significant reduction in the density of these aerogels is achieved while maintaining a high crosslinking density by synthesizing gel networks with well-defined macromolecules through hydrolytic polycondensation crosslinking of PDEMSEMVS. Notably, the pore/nanoparticle size of aerogels can be fine-tuned by optimizing the gel solvent type. The as-prepared silicone aerogels demonstrate selective absorption, efficient oil-water separation, and excellent thermal insulation properties, showing promising applications in oil/water separation and thermal protection.
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The tumor suppressor p53 has been implicated in the pathogenesis of liver fibrosis. HERC5-mediated posttranslational ISG modification of the p53 protein is critical for controlling its activity. Here, we demonstrated that the expression of HERC5 and ISG15 is highly elevated, whereas p53 is downregulated, in fibrotic liver tissues of mice and transforming growth factor-ß1 (TGF-ß1)-induced LX2 cells. HERC5 siRNA clearly increased the protein expression of p53, but the mRNA expression of p53 was not obviously changed. The inhibition of lincRNA-ROR (ROR) downregulated HERC5 expression and elevated p53 expression in TGF-ß1-stimulated LX-2 cells. Furthermore, the expression of p53 was almost unchanged after TGF-ß1-stimulated LX-2 cells were co-transfected with a ROR-expressing plasmid and HERC5 siRNA. We further confirmed that miR-145 is a target gene of ROR. In addition, we also showed that ROR regulates the HERC5-mediated ISGylation of p53 through mir-145/ZEB2. Together, we propose that ROR/miR-145/ZEB2 might be involved in the course of liver fibrosis by regulating ISGylation of the p53 protein.
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MicroRNAs , RNA Longo não Codificante , Humanos , Fator de Crescimento Transformador beta1/metabolismo , RNA Longo não Codificante/genética , Cirrose Hepática/metabolismo , Fibrose , RNA Interferente Pequeno , MicroRNAs/genética , Peptídeos e Proteínas de Sinalização Intracelular , Homeobox 2 de Ligação a E-box com Dedos de ZincoRESUMO
Cancer, a chronic disease characterized by uncontrolled cell development, kills millions of people globally. The WHO reported over 10 million cancer deaths in 2020. Anticancer medications destroy healthy and malignant cells. Cancer treatment induces neuropathy. Anticancer drugs cause harm to spinal cord, brain, and peripheral nerve somatosensory neurons, causing chemotherapy-induced neuropathic pain. The chemotherapy-induced mechanisms underlying neuropathic pain are not fully understood. However, neuroinflammation has been identified as one of the various pathways associated with the onset of chemotherapy-induced neuropathic pain. The neuroinflammatory processes may exhibit varying characteristics based on the specific type of anticancer treatment delivered. Neuroinflammatory characteristics have been observed in the spinal cord, where microglia and astrocytes have a significant impact on the development of chemotherapy-induced peripheral neuropathy. The patient's quality of life might be affected by sensory deprivation, loss of consciousness, paralysis, and severe disability. High cancer rates and ineffective treatments are associated with this disease. Recently, histone deacetylases have become a novel treatment target for chemotherapy-induced neuropathic pain. Chemotherapy-induced neuropathic pain may be treated with histone deacetylase inhibitors. Histone deacetylase inhibitors may be a promising therapeutic treatment for chemotherapy-induced neuropathic pain. Common chemotherapeutic drugs, mechanisms, therapeutic treatments for neuropathic pain, and histone deacetylase and its inhibitors in chemotherapy-induced neuropathic pain are covered in this paper. We propose that histone deacetylase inhibitors may treat several aspects of chemotherapy-induced neuropathic pain, and identifying these inhibitors as potentially unique treatments is crucial to the development of various chemotherapeutic combination treatments.
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Antineoplásicos , Inibidores de Histona Desacetilases , Neuralgia , Neuralgia/tratamento farmacológico , Neuralgia/induzido quimicamente , Humanos , Inibidores de Histona Desacetilases/farmacologia , Animais , Antineoplásicos/efeitos adversos , Neoplasias/tratamento farmacológico , Qualidade de VidaRESUMO
Cyclic peptides with cyclophane linkers are an attractive compound type owing to the fine-tuned rigid three-dimensional structures and unusual biophysical features. Cytochrome P450 enzymes are capable of catalyzing not only the C-C and C-O oxidative coupling reactions found in vancomycin and other nonribosomal peptides (NRPs), but they also exhibit novel catalytic activities to generate cyclic ribosomally synthesized and post-translationally modified peptides (RiPPs) through cyclophane linkage. To discover more P450-modified multicyclic RiPPs, we set out to find cryptic and unknown P450-modified RiPP biosynthetic gene clusters (BGCs) through genome mining. Synergized bioinformatic analysis reveals that P450-modified RiPP BGCs are broadly distributed in bacteria and can be classified into 11â classes. Focusing on two classes of P450-modified RiPP BGCs where precursor peptides contain multiple conserved aromatic amino acid residues, we characterized 11 novel P450-modified multicyclic RiPPs with different cyclophane linkers through heterologous expression. Further mutation of the key ring-forming residues and combinatorial biosynthesis study revealed the order of bond formation and the specificity of P450s. This study reveals the functional diversity of P450 enzymes involved in the cyclophane-containing RiPPs and indicates that P450 enzymes are promising tools for rapidly obtaining structurally diverse cyclic peptide derivatives.
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Produtos Biológicos , Ciclofanos , Peptídeos/química , Peptídeos Cíclicos/química , Biologia Computacional/métodos , Sistema Enzimático do Citocromo P-450/metabolismo , Processamento de Proteína Pós-Traducional , Produtos Biológicos/químicaRESUMO
BACKGROUND. Consensus is lacking regarding optimal embolic agents for transcatheter arterial embolization (TAE) of renal angiomyolipomas (AMLs). OBJECTIVE. The purpose of our study was to compare the safety and efficacy of TAE with polyvinyl alcohol (PVA) and TAE with a combination of ethiodized oil (Lipiodol)-bleomycin emulsion and N-butyl cyanoacrylate (NBCA)-Lipiodol emulsion for the treatment of patients with large or symptomatic AMLs. METHODS. This prospective study enrolled patients referred for TAE of a large (> 4 cm) or symptomatic renal AML from July 2007 to December 2018. Patients were randomized to undergo TAE using PVA particles or a combination of Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion. Patients underwent serial clinical follow-up visits and follow-up CT or MRI examinations after TAE. Outcomes were compared between groups. RESULTS. Seventy-eight patients were enrolled. After exclusions, the analysis included 72 patients (15 men, 57 women; mean age, 35.0 years; 51 patients with hematuria, 66 patients with flank pain): 35 patients were randomized to treatment by PVA and 37 were randomized to treatment by a combination of Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion. Complete occlusion of all angiographically visible arterial supply was achieved in all patients. No major adverse event occurred in any patient. The mean follow-up after TAE was 77 ± 45 (SD) months (range, 37-180 months). The frequency of resolution of hematuria after initial TAE without recurrence was greater after treatment by Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion than by PVA (100.0% vs 80.0%, respectively; p = .03). At 12-month follow-up, the frequency of complete resolution of flank pain was higher after treatment by Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion than by PVA (100.0% vs 75.0%, p = .03). Mean reduction in AML volume at 36 months or longer after TAE versus at baseline was greater in patients treated by Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion than in those treated by PVA (98.0% vs 85.7%, respectively; p = .04). The frequency of complete response by modified RECIST (mRECIST) criteria at 36 months or longer after TAE was greater in patients treated by Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion than by PVA (94.6% vs 74.3%, p = .04). The rate of repeat TAE was higher among patients treated by PVA than among those treated by Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion (25.7% vs 8.1%, p = .04). CONCLUSION. Superior outcomes after TAE of AML were achieved using Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion than using PVA. CLINICAL IMPACT. TAE using a combination of Lipiodol-bleomycin emulsion and NBCA-Lipiodol emulsion is a safe and effective treatment option for large or symptomatic AMLs. TRIAL REGISTRATION. Chinese Clinical Trial Registry ChiCTR2100053296.
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Angiomiolipoma , Embolização Terapêutica , Embucrilato , Neoplasias Renais , Leucemia Mieloide Aguda , Masculino , Humanos , Feminino , Adulto , Óleo Etiodado/uso terapêutico , Bleomicina , Estudos Prospectivos , Álcool de Polivinil/uso terapêutico , Angiomiolipoma/diagnóstico por imagem , Angiomiolipoma/terapia , Emulsões , Embucrilato/uso terapêutico , Dor no Flanco , Hematúria , Neoplasias Renais/terapia , Neoplasias Renais/tratamento farmacológico , Embolização Terapêutica/métodos , Resultado do Tratamento , Leucemia Mieloide Aguda/tratamento farmacológicoRESUMO
The feature of low-density and thermal insulation properties of polydimethylsiloxane (PDMS) foam is one of the important challenges of the silicone industry seeking to make these products more competitive compared to traditional polymer foams. Herein, we report a green, simple, and low-cost strategy for synthesizing ultra-low-density porous silicone composite materials via Si-H cross-linking and foaming chemistry, and the sialylation-modified hollow glass microspheres (m-HM) were used to promote the HM/PDMS compatibility. Typically, the presence of 7.5 wt% m-HM decreases the density of pure foam from 135 mg/cm-3 to 104 mg/cm-3 without affecting the foaming reaction between Si-H and Si-OH and produces a stable porous structure. The optimized m-HM-modified PDMS foam composites showed excellent mechanical flexibility (unchanged maximum stress values at a strain of 70% after 100 compressive cycles) and good thermal insulation (from 150.0 °C to 52.1 °C for the sample with ~20 mm thickness). Our results suggest that the use of hollow microparticles is an effective strategy for fabricating lightweight, mechanically flexible, and thermal insulation PDMS foam composite materials for many potential applications.
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Termites are serious pests in agriculture and forestry, causing significant economic losses to property and the construction industry. However, only a few entomopathogenic fungi attack termites that are dominant members of most terrestrial biomes. This study contributes to the taxonomic knowledge of entomopathogenic fungi with the description of a new pathogen on termites collected from the Pu Luong Nature Reserve in Vietnam. The new termite pathogen, Ophiocordyceps puluongensis, is introduced on the basis of morphological and multigene phylogenetic evidence. Based on the combined dataset of five genes including the nuclear ribosomal small and large subunits (nrSSU and nrLSU), the elongation factor 1α (tef-1α), and the largest and the second largest subunits of RNA polymerase II (rpb1 and rpb2), phylogenetic analyses were performed by Maximum Likelihood and Bayesian inference methods to determine the phylogenetic position of O. puluongensis. Three samples of O. puluongensis are clustered in the Hirsutella thompsonii subclade of Hirsutella lineages in Ophiocordyceps, and clustered together with O. asiatica to form a separate clade from other Ophiocordyceps species. Morphologically, O. puluongensis differs from O. asiatica by its smaller and shorter perithecia, asci and ascospores, pink to reddish-orange stipes of stromata, as well as smaller fusiform or citriform conidia. The distinctiveness of this termite pathogen is strongly supported by both molecular phylogeny and morphology. The entomopathogenic fungus O. puluongensis could have the potential to be used as bioinsecticides to control termites.
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Hypocreales , Isópteros , Animais , Teorema de Bayes , Hypocreales/genética , Filogenia , Esporos Fúngicos/genética , VietnãRESUMO
PURPOSE: To evaluate the safety and efficacy of prostatic artery embolization (PAE) using the combination of 50-µm and 100-µm polyvinyl alcohol (PVA) particles versus 100-µm PVA particles alone in the treatment of patients with symptomatic benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Over a 5-year period, 120 patients treated with PAE for lower urinary tract symptoms (LUTS) secondary to BPH were randomized to undergo embolization with 50-µm plus 100-µm PVA particles (group A) or 100-µm PVA particles alone (group B). Mean follow-up time was 34 months (range, 12-57 mo). There were no differences between groups regarding baseline data. Primary outcome measurements included change in International Prostate Symptom Score (IPSS) and incidence of adverse events. Secondary outcome measurements included procedure-associated pain, prostate ischemia measured on magnetic resonance (MR) imaging 1 week after PAE, and changes over time in quality of life (QOL) questionnaire, peak urinary flow rate (Qmax), postvoid residual (PVR) volume, prostate volume (PV), prostate-specific antigen (PSA) level, and International Index of Erectile Function (IIEF) were evaluated. Recurrence of LUTS following PAE was defined as relief of LUTS temporally but increased IPSS ≥ 8 or QOL score ≥ 3 or decrease in Qmax to < 7 mL/s. RESULTS: Mean follow-up periods were 35 months ± 22 in group A and 33 months ± 25 in group B (P = .629). No differences between groups regarding procedural details, pain scores, or adverse events were noted (P > .05). At 24 month of follow-up, patients in group A had a greater decrease in mean IPSS (18.7 ± 12.5 vs 14.8 ± 13.5), QOL score (3.7 ± 1.5 vs 2.4 ± 1.8), Qmax (10.5 mL ± 9.5 vs 6.8 mL ± 5.0), PVR (92.0 mL ± 75.0 vs 60.0 mL ± 55.0), and PV (37.0 mL ± 19.5 vs 25.5 mL ± 15.0) compared with patients in group B (P < .05 for all). Mean ratios of prostate ischemic volume at 1 week after PAE were 70% ± 20 in group A and 41% ± 25 in group B (P = .021); mean PSA levels at 24 hour after PAE were 92.5 ng/mL ± 55.0 in group A and 77.5 ng/mL ± 45.0 in group B (P = .031); LUTS recurrence rates were 3.6% in group A and 14.6% in group B (P = .024). The mean IIEF-5 was not significantly different from baseline in either group. CONCLUSIONS: PAE with 50-µm plus 100-µm PVA particles resulted in greater improvement in clinical and imaging outcomes and no significant differences in adverse events compared with 100-µm PVA particles alone.
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Embolização Terapêutica/métodos , Sintomas do Trato Urinário Inferior/terapia , Álcool de Polivinil/administração & dosagem , Próstata/irrigação sanguínea , Hiperplasia Prostática/terapia , Idoso , Idoso de 80 Anos ou mais , Pequim , Método Duplo-Cego , Embolização Terapêutica/efeitos adversos , Humanos , Sintomas do Trato Urinário Inferior/diagnóstico , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Microesferas , Pessoa de Meia-Idade , Álcool de Polivinil/efeitos adversos , Estudos Prospectivos , Hiperplasia Prostática/complicações , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/fisiopatologia , Qualidade de Vida , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Prostatic artery embolization (PAE) has been proved effective in the treatment of lower urinary tracts (LUTS) secondary to benign prostatic hyperplasia (BPH) with low complications, and most of the them are due to non-target embolization of adjacent organs, such as bladder, rectum, seminal vesicles and penis. Aim of this study was to present seminal vesicle (SV) abnormalities following prostatic artery embolization (PAE) for the treatment of symptomatic benign prostatic hyperplasia. METHODS: We reviewed 139 BPH patients who received PAE during the period of February 2009 and January 2015 at a single institution, highlighting seminal vesicle abnormalities and their clinical relevance after PAE. PAE was performed using 90~ 180-µm (mean 100-µm) polyvinyl alcohol foam particles. RESULTS: Nine of 139 patients with SV abnormalities (6.5%) were identified by magnetic resonance imaging (MRI), including subacute haemorrhage in 3 patients and ischaemia in 6 patients. Using cone-beam computed tomography (CB-CT), the seminal vesicle arteries were identified 8 of the 9 patients. All 9 patients complained of a few episodes of mild haematospermia during the 1-4 weeks after PAE; the haematospermia disappeared spontaneously without any treatment. CONCLUSION: SV haemorrhage and ischaemia may occur after PAE, and these patients may present with transient and self-limited haematospermia.
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Embolização Terapêutica/efeitos adversos , Hemospermia/etiologia , Sintomas do Trato Urinário Inferior/terapia , Próstata/irrigação sanguínea , Hiperplasia Prostática/complicações , Glândulas Seminais/irrigação sanguínea , Idoso , Artérias , Tomografia Computadorizada de Feixe Cônico , Humanos , Isquemia/diagnóstico por imagem , Isquemia/etiologia , Sintomas do Trato Urinário Inferior/etiologia , Angiografia por Ressonância Magnética , Masculino , Glândulas Seminais/diagnóstico por imagemRESUMO
Purpose To describe findings in prostatic arteries (PAs) at digital subtraction angiography (DSA) and cone-beam computed tomography (CT) that allow identification of benign prostatic hyperplasia and to determine the value added with the use of cone-beam CT. Materials and Methods This retrospective single-institution study was approved by the institutional review board, and the requirement for written informed consent was waived. From February 2009 to December 2014, a total of 148 patients (mean age ± standard deviation, 70.5 years ± 14.5) underwent DSA of the internal iliac arteries and cone-beam CT with a flat-detector angiographic system before they underwent prostate artery embolization. Both the DSA and cone-beam CT images were evaluated by two interventional radiologists to determine the number of independent PAs and their origins and anastomoses with adjacent arteries. The exact McNemar test was used to compare the detection rate of the PAs and the anastomoses with DSA and with cone-beam CT. Results The PA anatomy was evaluated successfully by means of cone-beam CT in conjunction with DSA in all patients. Of the 296 pelvic sides, 274 (92.6%) had only one PA. The most frequent PA origin was the common gluteal-pudendal trunk with the superior vesicular artery in 118 (37.1%), followed by the anterior division of the internal iliac artery in 99 (31.1%), and the internal pudendal artery in 77 (24.2%) pelvic sides. In 67 (22.6%) pelvic sides, anastomoses to adjacent arteries were documented. The numbers of PA origins and anastomoses, respectively, that could be identified were significantly higher with cone-beam CT (301 of 318 [94.7%] and 65 of 67 [97.0%]) than with DSA (237 [74.5%] and 39 [58.2%], P < .05). Cone-beam CT provided essential information that was not available with DSA in 90 of 148 (60.8%) patients. Conclusion Cone-beam CT is a useful adjunctive technique to DSA for identification of the PA anatomy and provides information to help treatment planning during prostatic arterial embolization. © RSNA, 2016.
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Angiografia Digital , Artérias/anatomia & histologia , Tomografia Computadorizada de Feixe Cônico , Embolização Terapêutica , Próstata/irrigação sanguínea , Hiperplasia Prostática/diagnóstico por imagem , Hiperplasia Prostática/terapia , Idoso , Artérias/diagnóstico por imagem , Meios de Contraste , Humanos , Masculino , Pessoa de Meia-Idade , Interpretação de Imagem Radiográfica Assistida por Computador , Estudos RetrospectivosRESUMO
PURPOSE: To compare the safety and efficacy of PAE for the treatment of benign prostatic hyperplasia (BPH) in men ≥75 years, who we defined as elderly, to those <75 years. METHODS: A total of 157 patients diagnosed with lower urinary tract symptoms (LUTS) due to BPH underwent PAE. Group A (n = 52) included patients ≥75 years, and group B (n = 105) included patients <75 years. Follow-up was performed using the International Prostate Symptoms Score (IPSS), quality of life (QoL), peak urinary flow rate (Q max), post-void residual volume (PVR), the International Index of Erectile Function short form (IIEF-5), prostatic-specific antigen (PSA), and prostate volume (PV), at 1, 3, 6, and every 6 months thereafter. RESULTS: More coexistent systemic diseases were identified in group A than in group B (P < 0.05). Technical success rate of PAE was 90.4 % in group A and 95.2 % in group B (P = 0.06). A total of 147 patients had completed the follow-up with a mean of 20 months. Compared with the baseline, there were significant improvements in IPSS, QoL, Q max, PV, PVR, and PSA in both groups after PAE. There were no significant differences in the changes of IPSS, Q max, PVR, PSA, and IIEF-5 between groups after PAE. No major complications were noted. CONCLUSION: PAE could be used as an effective, safe, and well tolerable method in the treatment of elderly symptomatic BPH patients, similarly to younger patients, and it may play an important role in patients in whom medical therapy has failed, who are at high surgical and anesthetic risk or who refuse the standard surgical therapy.
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Artérias , Embolização Terapêutica , Próstata/irrigação sanguínea , Hiperplasia Prostática/terapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Hiperplasia Prostática/diagnósticoRESUMO
BACKGROUND: Currently, large prostate size (>80 mL) of benign prostatic hyperplasia (BPH) still pose technical challenges for surgical treatment. This prospective study was designed to explore the safety and efficacy of prostatic arterial embolization (PAE) as an alternative treatment for patients with lower urinary tract symptoms (LUTS) due to largeBPH. METHODS: A total of 117 patients with prostates >80 mL were included in the study; all were failure of medical treatment and unsuited for surgery. PAE was performed using combination of 50-µm and 100-µm particles in size, under local anaesthesia by a unilateral femoral approach. Clinical follow-up was performed using the international prostate symptoms score (IPSS), quality of life (QoL), peak urinary flow (Qmax), post-void residual volume (PVR), international index of erectile function short form (IIEF-5), prostatic specific antigen (PSA) and prostatic volume (PV) measured by magnetic resonance (MR) imaging, at 1, 3, 6 and every 6 months thereafter. RESULTS: The prostatic artery origins in this study population were different from previously published results. PAE was technically successful in 109 of 117 patients (93.2%). Follow-up data were available for the 105 patients with a mean follow-up of 24 months. The clinical improvements in IPSS, QoL, Qmax, PVR, and PV at 1, 3, 6, 12, and 24 months was 94.3%, 94.3%, 93.3%, 92.6%, and 91.7%, respectively. The mean IPSS (pre-PAE vs post-PAE 26.0 vs 9.0; P < .0.01), the mean QoL (5.0 vs 3.0; P < 0.01), the mean Qmax (8.5 vs 14.5; P < 0.01), the mean PVR (125.0 vs 40.0; P < 0.01), and PV (118.0 vs 69.0, with a mean reduction of 41.5%; P < 0.01 ) at 24-month after PAE were significantly different with respect to baseline. The mean IIEF-5 was not statistically different from baseline. No major complications were noted. CONCLUSIONS: PAE is a safe and effective treatment method for patients with LUTS due to large volume BPH. PAE may play an important role in patients in whom medical therapy has failed, who are not candidates for open surgery or TURP or refuse any surgical treatment.
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Embolização Terapêutica/métodos , Disfunção Erétil/etiologia , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/prevenção & controle , Hiperplasia Prostática/complicações , Hiperplasia Prostática/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , China , Embolização Terapêutica/efeitos adversos , Disfunção Erétil/diagnóstico , Disfunção Erétil/prevenção & controle , Humanos , Sintomas do Trato Urinário Inferior/diagnóstico , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Hiperplasia Prostática/diagnóstico , Qualidade de Vida , Medição de Risco , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the change of CD4+ CD25+ FoxP3+ regulatory T cells (Treg)in peripheral blood (PB)and synovial fluid (SF) in patients with rheumatoid arthritis (RA) and its role in RA immune tolerance imbalance. METHODS: The frequency of CD4+ CD25+ FoxP3+ Treg in PB and SF cells in active RA patients and healthy volunteers were determined using flow cytometry. The expression of FoxP3 gene in mononuclear cells was analyzed by real-time PCR. The correlation between the frequency of CD4+ CD25+ FoxP3+ Treg in PB cells and disease activity indices was evaluated. RESULTS: (1) Active RA patients had a higher level of CD4+ CD25+ FoxP3+ Treg in SF cells (7.56% +/- 2.89%) than in PB cells (1.84% +/- 0.97%). Their level of CD4+ CD25+ FoxP3+ Treg in SF cells was also higher than that of healthy volunteers (2.19% +/- 0.54%). Anti-CCP antibody (ACPA) positive RA patients had a lower level of CD4+ CD25+ FoxP3+ Treg (1.40% +/- 0.63%) in PB cells compared with the ACPA negative RA patients (2.85 +/- 0.87%). (2) Active RA patients had a higher mRNA level of FoxP3 in SF mononuclear cells than those inactive RA patients and healthy volunteers (P < 0.01). (3) The frequency of CD4+ CD25+ FoxP3+ Treg in PB cells in active RA patients had no correlation with disease activity indices (P > 0.05). CONCLUSION: Altered frequency of CD4+ CD25+ FoxP3+ Treg in SF cells of RA patients might contribute to RA immune tolerance imbalance in inflammatory joints.
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Artrite Reumatoide/imunologia , Tolerância Imunológica , Linfócitos T Reguladores/citologia , Estudos de Casos e Controles , Citometria de Fluxo , Fatores de Transcrição Forkhead/metabolismo , Humanos , Líquido Sinovial/citologiaRESUMO
This study conducted an analysis of the variations in nitrogen metabolism pathways within constructed wetlands (CWs) using zeolite (CW-Z), ceramsite (CW-C), and lava (CW-L) under high concentration sulfamethoxazole (SMX) stress. The introduction of SMX hindered the formation of hydrogen bonds on the substrate surfaces; however, these surfaces still maintained a dense and thick biofilm. CW-Z exhibited superior removal efficiencies for ammonium nitrogen (NH4+-N) and nitrate nitrogen (NO3--N) compared to CW-C and CW-L, with removal rates of 92.54 ± 2.88 % and 89.39 ± 6.74 %, respectively. Interestingly, the proportion of genes involved in nitrification, denitrification and nitrate reduction genes in CW-C (36.05 %) were higher than that in CW-C (29.81 %) and CW-L (29.70 %) but the interactions among nitrogen functional bacteria in CW-Z were much more complex. Further analysis of the nitrogen metabolism pathway indicated that under CW-Z enhanced dissimilatory nitrate reduction SMX stress, while CW-L enhanced assimilatory nitrate reduction process compared to CW-C.
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Eliminação de Resíduos Líquidos , Águas Residuárias , Desnitrificação , Nitratos/análise , Sulfametoxazol , Áreas Alagadas , Compostos Orgânicos , Nitrogênio/análiseRESUMO
Four new diterpenoids, including three secolathyrane diterpenoids (1-3) and one lathyrane diterpenoid (4), together with seven known diterpenoids, were obtained in the shelled seeds of Euphorbia lathyris. In particular, 1-3 possess a rare split ring structure, and currently only one compound with the same skeleton has been identified in E. lathyris. Compound 4 furnishes an unprecedented oxygen bridge structure. The structures were identified using various spectral techniques, including NMR, HR-ESI-MS, single-crystal X-ray diffraction and calculated electronic circular dichroism (ECD). The biosynthetic pathway of 1-4 was inferred. Furthermore, the cytotoxic activities of all compounds (1-11) were measured on three human tumor cells. New compounds 2 and 3 showed moderate cytotoxic activities against U937 cells with IC50 values of 22.18 and 25.41 µM, respectively.
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Antineoplásicos Fitogênicos , Diterpenos , Euphorbia , Compostos Fitoquímicos , Sementes , Euphorbia/química , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Diterpenos/química , Humanos , Estrutura Molecular , Sementes/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Linhagem Celular Tumoral , China , Células U937RESUMO
BACKGROUND: Circulating tumor cells (CTCs) play a crucial role in the early diagnosis and prognosis of lung cancer. Identification of a more suitable sample source could be a breakthrough towards enhancing CTC detectability in early-stage lung cancer. We investigated the differences in detectable CTCs between peripheral arterial and venous blood in early- and mid-stage lung cancer patients undergoing surgery and analyzed the association between clinicopathological factors and detectable CTCs in peripheral arterial and venous blood. METHODS: Peripheral arterial and venous blood was collected in 5-mL samples from 56 patients with surgically resected and pathologically clear at early- or mid-stage lung cancer. Blood specimens were enriched for CTCs based on isolation by size of epithelial tumor cells. The CTCs were identified using Swiss Giemsa staining and immunohistochemistry for CD45/CD31. RESULTS: In stage I lung cancer, CTC-positive rate was significantly higher in peripheral arterial than in venous blood (45.45% vs. 17.39%). There was no significant difference in the number of detectable CTCs between peripheral arterial and venous blood. A low degree of differentiation was associated with a high positive rate of CTCs in peripheral venous blood. The number of circulating tumor microemboli was significantly higher in patients with tumor size >3 cm compared with ≤3 cm. CONCLUSION: CTC levels in peripheral arterial and venous blood differed little in lung cancer patients.Compared to peripheral venous blood, peripheral arterial blood had a higher CTC positivity rate in early-stage lung cancer.This study was favorable for early detection and monitoring of lung cancer.
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Neoplasias Pulmonares , Células Neoplásicas Circulantes , Humanos , Neoplasias Pulmonares/patologia , Células Neoplásicas Circulantes/patologia , Prognóstico , Biomarcadores TumoraisRESUMO
Recent years have witnessed the explosive development of highly sensitive smart sensors based on conductive polymer foam materials. However, the design and development of multifunctional polymeric foam composites as smart sensors applied in complex solvent and oil environments remain a critical challenge. Herein, we design and synthesize vinyl-terminated polytrifluoropropylmethylsiloxane through anionic ring-opening polymerization to fabricate fluorosilicone rubber foam (FSiRF) materials with nanoscale wrinkled surfaces and reactive Si-H groups via a green and rapid chemical foaming strategy. Based on the strong adhesion between FSiRF materials and consecutive oxidized ketjen black (OKB) nano-network, multifunctional FSiRF nanocomposites were prepared by a dip-coating strategy followed by fluoroalkylsilane modification. The optimized F-OKB@FSiRF nanocomposites exhibit outstanding mechanical flexibility in wide-temperature range (100 cycle compressions from -20 to 200 °C), structure stability (no detached particles after being immersed into various aqueous solutions for up to 15 days), surface superhydrophobicity (water contact angle of 154° and sliding angle of â¼7°), and tunable electrical conductivity (from 10-5 to 10-2 S m-1). Additionally, benefiting from the combined actions of multiple lines of defense (low surface energy groups, physical barriers, and "shielding effect"), the F-OKB@FSiRF sensor presents excellent anti-swelling property and high sensitivity in monitoring both large-deformation and tiny vibrations generated by knocking the beaker, ultrasonic action, agitating, and sinking objects in weak-polar or nonpolar solvents. This work conceivably provides a chemical strategy for the fabrication of multifunctional polymeric foam nanocomposite materials as smart sensors for broad applications.
RESUMO
Glutathione (GSH) depletion, mitochondrial damage, and oxidative stress have been implicated in the pathogenesis of acetaminophen (APAP) hepatotoxicity. Here, we demonstrated that the expression of histone deacetylase 6 (HDAC6) is highly elevated, whereas malate dehydrogenase 1 (MDH1) is downregulated in liver tissues and AML-12 cells induced by APAP. The therapeutic benefits of LT-630, a novel HDAC6 inhibitor on APAP-induced liver injury, were also substantiated. On this basis, we demonstrated that LT-630 improved the protein expression and acetylation level of MDH1. Furthermore, after overexpression of MDH1, an upregulated NADPH/NADP+ ratio and GSH level and decreased cell apoptosis were observed in APAP-stimulated AML-12 cells. Importantly, MDH1 siRNA clearly reversed the protection of LT-630 on APAP-stimulated AML-12 cells. In conclusion, LT-630 could ameliorate liver injury by modulating MDH1-mediated oxidative stress induced by APAP.
Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Doença Hepática Induzida por Substâncias e Drogas , Desacetilase 6 de Histona , Leucemia Mieloide Aguda , Animais , Humanos , Camundongos , Acetaminofen , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Glutationa/metabolismo , Desacetilase 6 de Histona/antagonistas & inibidores , Leucemia Mieloide Aguda/metabolismo , Fígado/patologia , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacosRESUMO
MXene-based thermal camouflage materials have gained increasing attention due to their low emissivity, however, the poor anti-oxidation restricts their potential applications under complex environments. Various modification methods and strategies, e.g., the addition of antioxidant molecules and fillers have been developed to overcome this, but the realization of long-term, reliable thermal camouflage using MXene network (coating) with excellent comprehensive performance remains a great challenge. Here, a MXene-based hybrid network comodified with hyaluronic acid (HA) and hyperbranched polysiloxane (HSi) molecules is designed and fabricated. Notably, the presence of appreciated HA molecules restricts the oxidation of MXene sheets without altering infrared stealth performance, superior to other water-soluble polymers; while the HSi molecules can act as efficient cross-linking agents to generate strong interactions between MXene sheets and HA molecules. The optimized MXene/HA/HSi composites exhibit excellent mechanical flexibility (folded into crane structure), good water/solvent resistance, and long-term stable thermal camouflage capability (with low infrared emissivity of ≈0.29). The long-term thermal camouflage reliability (≈8 months) under various outdoor weathers and the scalable coating capability of the MXene-coated textile enable them to disguise the IR signal of various targets in complex environments, indicating the great promise of achieved material for thermal camouflage, IR stealth, and counter surveillance.
RESUMO
OBJECTIVE: To study the clinical effect of arthroscopic anterior cruciate ligament (ACL) construction with different transplants. METHODS: From March 2006 to April 2009, 86 patients including 60 male and 26 female undergoing arthroscopic ACL reconstruction were prospectively randomized consecutively into autograft group (44 patients, using autogeneic hamstring tendons) and allograft group (42 patients, using allogenic lower extremity tendons). The age of those patients were 22 - 56 years, averaging (32 ± 7) years. The operations were made by the same doctor with the standard technology. The postoperative effects were assessed by the range of motion and tibia forward distance, Lachman test, pivot shift test, Daniel test, IKDC scores systems, Lysholm-Tegner scores. RESULTS: Seventy-nine patients were followed up, 41 patients in autograft groups averaged 39.6 months and 38 patients in allograft group averaged 37.4 months. The operation time of autograft group was (87 ± 11) minutes, that of allograft group was (55 ± 10) minutes (t = 15.732, P < 0.05). The time of postoperative fever of autograft group was (3.2 ± 1.4) days, that of allograft groups was (7.6 ± 5.3) days (t = 5.740, P < 0.05). The Lysholm scores of autograft group was 42 ± 7 before operation, and 89 ± 8 at final follow-up. The Lysholm scores of allograft group was 44 ± 6 before operation, and 87 ± 9 at final follow-up. There was statistic difference in both groups between before operation and final follow-up (t = 13.534 and 17.768, P < 0.05).But no statistic difference existed between the two groups (P > 0.05). The Tegner scores of autograft group was 2.9 ± 2.1 before operation, and 7.7 ± 1.2 at final follow-up. The Tegner scores of allograft group was 2.7 ± 1.4 before operation, and 7.1 ± 1.6 at final follow-up. There was statistic difference in both groups between before operation and final follow-up (t = 16.004 and 12.338, P < 0.05).No statistic difference existed between the two groups (P > 0.05). The KT2000 results showed that the anterior displacement of autograft groups was (10.7 ± 3.5) mm before operation and (5.0 ± 2.7) mm at final follow-up, the anterior displacement of allograft groups was (10.9 ± 2.9) mm before operation and (6.5 ± 2.4) mm at final follow-up, there was statistic difference between before and after operation in anterior displacement in two groups (t = 16.354 and 13.296 P < 0.05). There was no difference between two groups before operation and at final follow-up. Compared to before operation, the IKDC scores were improved greatly after operation (P < 0.05). CONCLUSION: The clinical effect of arthroscopic ACL construction with allograft transplants is near to autograft.