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In this study, tannic acid (TA) was applied as a stabilizing agent for synthesizing bimetallic copper-gold (CuAu) nanoparticles. Cu(NO3)2 and NaAuCl4 were used as the sources of copper and gold ions, respectively, and NaBH4 was employed as a reducing agent. The prepared TA-CuAu nanoparticles were extensively characterized via ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, transmission electron microscopy, X-ray diffraction, and zeta potential analyses. To evaluate their catalytic activity, the TA-CuAu nanoparticles and NaBH4 were applied in the degradation of 4-nitrophenol (4-NP) and rhodamine B (RB) individually and in a mixture. The individual degradation of 4-NP and RB was completed within 10 min, and the apparent rate constants were calculated as 0.3046 and 0.2628 min-1, respectively, emphasizing the efficient catalytic activity of the TA-CuAu nanoparticles. Additionally, controlled experiments were performed for the degradation of 4-NP and RB in the absence of catalysts or NaBH4 to investigate the kinetic feasibility of the catalytic reactions. A mixture of 4-NP and RB was successfully degraded within 10 min using the TA-CuAu nanoparticles as catalysts. Furthermore, the reuse of the catalysts after five successive cycles demonstrates an outstanding performance with no significant loss in the catalytic activity. Finally, the successful treatment of the tap and lake water samples spiked with 4-NP and RB using the TA-CuAu nanoparticles further confirmed their application potential as catalysts in environmental water remediation.
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Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Resultado del Tratamiento , Arteria Hepática/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Fluorouracilo/uso terapéutico , Infusiones IntraarterialesRESUMEN
Traditional control methods have drawbacks in controlling Verticillium wilt diseases caused by Verticillium dahliae Kleb.; therefore, an efficient and environmentally friendly strategy for disease control must be identified and the mechanisms determined. In this study, a soil-isolated strain SBB was identified as Bacillus velezensis based on 16S rRNA, gyrA, and gyrB gene sequences. In vitro, strain SBB had excellent inhibitory effects on V. dahliae, with the highest inhibition rate of 70.94%. Moreover, strain SBB inhibited production of the conidia of V. dahliae and suppressed the production of microsclerotia and melanin. Through gas chromatograph-mass spectrometer analysis, nine compounds were detected from the volatile organic compounds produced by SBB, among which 2-nonanol, 2-heptanone, 6-methyl-2-heptanone, and 2-nonanone could completely inhibit V. dahliae growth. Strain SBB produced cellulase, amylase, protease, and siderophore. During inhibitory action on V. dahliae, strain SBB showed upregulated expression of genes encoding non-volatile inhibitory metabolites, including difficidin, bacilysin, and bacillaene, at 1.923-, 1.848-, and 1.448-fold higher, respectively. Thus, our study proved that strain SBB had an efficient antagonistic effect on V. dahliae, suggesting strain SBB can be used as a potential biological control agent against Verticillium wilt.
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Volatile organic compounds (VOCs) produced by microorganisms are considered promising environmental-safety fumigants for controlling soil-borne diseases. Verticillium dahliae, a notorious fungal pathogen, causes economically important wilt diseases in agriculture and forestry industries. Here, we determined the antifungal activity of VOCs produced by Trichoderma koningiopsis T2. The VOCs from T. koningiopsis T2 were trapped by solid-phase microextraction (SPME) and tentatively identified through gas chromatography-mass spectrometry (GC/MS). The microsclerotia formation, cell wall-degrading enzymes and melanin synthesis of V. dahliae exposed to the VOC mixtures and selected single standards were examined. The results showed that the VOCs produced by strain T2 significantly inhibited the growth of V. dahliae mycelium and reduced the severity of Verticillium wilt in tobacco and cotton. Six individual compounds were identified in the volatilome of T. koningiopsis T2, and the dominant compounds were 3-octanone, 3-methyl-1-butanol, butanoic acid ethyl ester and 2-hexyl-furan. The VOCs of strain T2 exert a significant inhibitory effect on microsclerotia formation and decreased the activities of pectin lyase and endo-ß-1,4-glucanase in V. dahliae. VOCs also downregulated the VdT3HR, VdT4HR, and VdSCD genes related to melanin synthesis by 29. 41-, 10. 49-, and 3.11-fold, respectively. Therefore, T. koningiopsis T2 has potential as a promising biofumigant for the biocontrol of Verticillium wilt disease.
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Circular RNAs (circRNAs) are a novel class of regulatory RNA involved in many biological, physiological and pathological processes by functioning as a molecular sponge, transcriptional/epigenetic/splicing regulator, modulator of protein-protein interactions, and a template for encoding proteins. Cells are constantly dealing with stimuli from the microenvironment, and proper responses rely on both the precise control of gene expression networks and protein-protein interactions at the molecular level. The critical roles of circRNAs in the regulation of these processes have been heavily studied in the past decades. However, how the microenvironmental stimulation controls the circRNA biogenesis, cellular shuttling, translation efficiency and degradation globally and/or individually remains largely uncharacterized. In this review, how the impact of major microenvironmental stresses on the known transcription factors, splicing modulators and epitranscriptomic regulators, and thereby how they may contribute to the regulation of circRNAs, is discussed. These lines of evidence will provide new insight into how the biogenesis and functions of circRNA can be precisely controlled and targeted for treating human diseases.
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Genomic information for bacteria within the genus Rahnella remains limited. Rahnella sp. JZ-GX1 was previously isolated from the Pinus massoniana rhizosphere in China and shows potential as a plant growth-promoting (PGP) bacterium. In the present work, we combined the GridION Nanopore ONT and Illumina sequencing platforms to obtain the complete genome sequence of strain JZ-GX1, and the application effects of the strain in natural field environment was assessed. The whole genome of Rahnella sp. JZ-GX1 comprised a single circular chromosome (5,472,828 bp, G + C content of 53.53%) with 4,483 protein-coding sequences, 22 rRNAs, and 77 tRNAs. Based on whole genome phylogenetic and average nucleotide identity (ANI) analysis, the JZ-GX1 strain was reidentified as R. victoriana. Genes related to indole-3-acetic acid (IAA), phosphorus solubilization, nitrogen fixation, siderophores, acetoin, 1-aminocyclopropane-1-carboxylate (ACC) deaminase, gamma-aminobutyric acid (GABA) production, spermidine and volatile organic compounds (VOCs) biosynthesis were present in the genome of strain JZ-GX1. In addition, these functions were also confirmed by in vitro experiments. Importantly, compared to uninoculated control plants, Pyrus serotina, Malus spectabilis, Populus euramericana (Dode) Guinier cv. "San Martino" (I-72 poplar) and Pinus elliottii plants inoculated with strain JZ-GX1 showed increased heights and ground diameters. These findings improve our understanding of R. victoriana JZ-GX1 as a potential biofertilizer in agriculture.
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OBJECTIVE: We aim to evaluate the clinical effect of combined topical 20% autologous serum eye drops (ASEs) along with silicone-hydrogel soft contact lenses (SCLs) in the treatment of chemical burn-induced bilateral corneal persistent epithelial defects (PEDs) and to review the literature of related studies. METHODS: From January 1, 2017, to December 31, 2019, we conducted a retrospective chart review of 8 patients with chemical burn-induced bilateral corneal PEDs who were unsuccessfully treated with conventional medical therapy and were then treated with combined topical 20% (v/v) ASEs and silicone-hydrogel CLs. The clinical effects and effectiveness of the combined treatment were evaluated. RESULTS: The bilateral corneal PEDs healed in all sixteen eyes of the eight patients within 2 weeks. The patients did not report any discomfort associated with the combined treatment. Improved ocular comfort/visual acuity and decreased conjunctival injection correlated with healing. No recurrent corneal epithelial breakdown was noted during the 3-month posttreatment follow-up. CONCLUSIONS: The combined treatment of silicone-hydrogel CLs and ASEs can help to stabilize the ocular surface and successfully treat chemical burn-induced bilateral corneal PEDs. It may be considered as an alternative treatment method for patients with bilateral chemical burn-induced corneal PEDs with potential corneal melting.
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Quemaduras Químicas/complicaciones , Enfermedades de la Córnea/terapia , Soluciones Oftálmicas/uso terapéutico , Cicatrización de Heridas/efectos de los fármacos , Adulto , Quemaduras Químicas/tratamiento farmacológico , Enfermedades de la Córnea/etiología , Epitelio Corneal/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Trasplante Autólogo , Resultado del TratamientoRESUMEN
A series of dicyano-imidazole-based molecules with thermally activated delayed fluorescence (TADF) properties were synthesized to obtain pure blue-emitting organic light-emitting diodes (OLEDs). The targeted molecules used dicyano-imidazole with a short-conjugated system as the electron acceptor to strong intermolecular π-π interactions, and provide a relatively shallow energy level of the lowest unoccupied molecular orbital (LUMO). The cyano group was selected to improve imidazole as an electron acceptor due to its prominent electron-transporting characteristics. Four different electron donors, that is, 9,9-dimethyl-9,10-dihydroacridine (DMAC), 10H-spiro(acridine-9,9'-fluoren) (SPAC), and 9,9-diphenyl-9,10-dihydroacridine (DPAC), were used to alternate the highest occupied molecular orbital (HOMO) energy level to tune the emission color further. The crowded molecular structure in space makes the electron donor and acceptor almost orthogonal, reducing the energy gap (ΔEST ) between the first excited singlet (S1 ) and the triplet (T1 ) states and introducing significant TADF property. The efficiencies of the blue-emissive devices with imM-SPAC and imM-DMAC obtained in this work are the highest among the reported imidazole-based TADF-OLEDs, which are 13.8 % and 13.4 %, respectively. Both of Commission Internationale de l'Eclairage (CIE) coordinates are close to the saturated blue region at (0.17, 0.18) and (0.16, 0.19), respectively. Combining these tailor-made TADF compounds with specific device architectures, electroluminescent (EL) emission from sky-blue to deep-blue could be achieved, proving their great potential in EL applications.
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OBJECTIVE: To investigate the feasibility and effectiveness of ATAS acupuncture (Acupoints-Time-Space Acupuncture) as a non-pharmacological intervention to prevent or relieve chemotherapy-induced fatigue in breast cancer patients undergoing taxane chemotherapy. METHODS: A pilot study in Kunming center with the aim of evaluating 40 patients randomized to 3 groups: ATAS, sham and non-acupuncture with an unequal randomization of 2:1:1. Participants with stage I-III breast cancer were scheduled to receive adjuvant EC4P4 chemotherapy. Participants in the ATAS and sham acupuncture arms received 20 sessions of acupuncture over 20 weeks, non-acupuncture arm received usual care. Evaluation scales, including VAS-F, MFI-20, HDAS, ISI, and blood samples were collected at four timepoints (T1-T4). mRNA sequencing was performed to detect the mechanism of acupuncture. RESULTS: A total of 581 sessions of acupuncture were performed on patients in the acupuncture group. There was no difference between the three groups in terms of clinical characteristics. Patients randomized to ATAS acupuncture had improved symptoms including fatigue, anxiety and insomnia during the whole process of chemotherapy compared with the other two groups. The VAS-F score of ATAS acupuncture group was decreased compared with non-acupuncture group (P=0.004). The score of MFI-20 in ATAS acupuncture group was kept at low level, while the other two groups' scores kept climbing during chemotherapy (P=0.016; P=0.028, respectively). The mechanism of ATAS acupuncture which reduced fatigue and depression may be related to ADROA1, by regulating cGMP/PKG pathway. CONCLUSION: This pilot study has demonstrated that ATAS acupuncture can significantly reduce fatigue induced by chemotherapy. TRIAL REGISTRATION: Chinese Clinical Trials Registry, ChiCTR-IPR-17,013,652, registered Dec 3, 2017. http://www.chictr.org.cn/. PROTOCOL VERSION: Version 3.2 dated from 2018/04/20.
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Leukopenia or thrombocytopenia is sometimes observed in end-stage renal disease (ESRD) patients, but the association between chronic leukopenia or thrombocytopenia and hemodialysis (HD) is still unclear. We aimed to investigate the incidence of chronic leukopenia or thrombocytopenia in patients with ESRD who received HD and to determine the risk factors of this complication. We retrospectively analyzed ESRD patients treated with HD at Ditmanson Medical Foundation Chia-Yi Christian Hospital in 2018. The risk factors for the occurrence of chronic leukopenia and thrombocytopenia were analyzed by Cox regression models. Of the 473 patients in our study cohort, 46 (9.7%) patients had a hematologic abnormality, including 18 patients with chronic leukopenia, 18 with chronic thrombocytopenia, and 10 with pancytopenia. Multivariate analysis revealed that patient age ≥60 years at the initiation of dialysis was a significant predictor for both chronic leukopenia [adjusted hazard ratio (aHR), 2.71; 95% confidence interval (CI), 1.06-6.89] and chronic thrombocytopenia (aHR, 2.83; 95% CI, 1.08-7.35). Chronic liver disease (aHR, 3.31; 95% CI, 1.27-8.61) and serum ferritin levels >800 mg/dl (aHR, 3.29; 95% CI, 1.29-8.39) were risk factors for chronic thrombocytopenia. A trend showed that vitamin D from intravenous supplementation (aHR, 0.13; 95% CI, 0.01-1.16, P = 0.066) and serum phosphorous level (aHR, 0.73; 95% CI, 0.53-1.02, P = 0.068) may be associated with chronic thrombocytopenia. Our study demonstrated that hematological abnormality was a long-term complication of HD. These results reveal that older patients with HD and high serum ferritin levels are at an elevated risk for chronic cytopenia. Healthcare professionals should be aware of this risk when treating HD patients in order to improve their prognosis.
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OBJECTIVE: To evaluate the clinical effect of combined topical autologous serum eye drops (ASEs) and silicone hydrogel contact lens (CLs) for the treatment of corneal persistent epithelial defects (PEDs) after infectious corneal ulcers. METHODS: We conducted a retrospective chart review of 12 patients with postinfectious corneal PEDs who were unsuccessfully treated with conventional medical management and were then treated with combined topical 20% (v/v) ASEs and silicone hydrogel CLs from July 1, 2011, to June 30, 2014. The corneal ulcers were all initially managed with antibiotic eye drops until the infiltrates resolved but the lesions failed to epithelialize. The clinical effects of the combined treatment were evaluated. RESULTS: The PEDs healed in all 12 patients within 2 weeks. The combined treatment was associated with an improvement of best-corrected visual acuity (BCVA) at the final 3-month follow-up examination. All patients responded well to the combined treatment and no adverse events were noted in any patient. CONCLUSIONS: The combined use of silicone hydrogel CLs and ASEs can successfully treat postinfectious corneal PEDs and prevent continuous corneal melting during acute disease.
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Lentes de Contacto Hidrofílicos , Úlcera de la Córnea/terapia , Epitelio Corneal/patología , Infecciones Bacterianas del Ojo/terapia , Soluciones Oftálmicas/administración & dosificación , Suero , Adulto , Anciano , Antibacterianos/uso terapéutico , Terapia Combinada , Úlcera de la Córnea/microbiología , Úlcera de la Córnea/patología , Infecciones Bacterianas del Ojo/microbiología , Infecciones Bacterianas del Ojo/patología , Femenino , Humanos , Hidrogeles , Masculino , Persona de Mediana Edad , Repitelización , Estudios Retrospectivos , Elastómeros de SiliconaRESUMEN
INTRODUCTION: The diagnosis of concomitant pituitary adenoma (PA) and Rathke's cleft cyst (RCC) is difficult because PA and RCC cause similar symptoms. This study aimed to investigate magnetic resonance imaging (MRI) characteristics and surgical management of sellar lesions for concomitant PA and RCC. METHODS: A retrospective study was performed in 18 patients with concomitant PA and RCC who visited our hospital between June 2008 and May 2014. MRI features, surgical management, histopathological diagnosis and prognosis of concomitant PA and RCC were summarized. RESULTS: Of the 18 patients, 3 cases were diagnosed with concomitant PA and RCC and 2 with concomitant PA and intermedia cyst by preoperative MRI. The remaining 8 cases were misdiagnosed as cystic formation of PA, 3 cases were bleeding of PA, and 2 cases were RCC. Surgery via the trans-sphenoidal route was performed in 17 cases and trans-frontal approach was chosen for one patient. All PAs resected were diagnosed by histological examination and the diagnosis of concomitant PA and RCC was histologically confirmed. CONCLUSION: A non-enhancing cyst-like structure within the pars intermedia of PA usually located in the midline is a prominent MRI feature of coexisted PA and RCC. Total resection of coexisted RCC must be achieved and fat graft should be avoided during surgery because of high recurrence rate of RCC and complicated hypophysitis.
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Adenoma/diagnóstico , Quistes del Sistema Nervioso Central/diagnóstico , Imagen por Resonancia Magnética , Neoplasias Hipofisarias/diagnóstico , Adenoma/complicaciones , Adenoma/cirugía , Adulto , Quistes del Sistema Nervioso Central/complicaciones , Quistes del Sistema Nervioso Central/cirugía , Errores Diagnósticos , Femenino , Técnicas Histológicas , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/cirugía , Pronóstico , Estudios Retrospectivos , Cráneo/cirugía , Adulto JovenRESUMEN
We propose a novel method to generate triangular pulses based on the nonlinear polarization rotation (NPR) effect in a highly nonlinear fiber. A continuous wave probe beam is polarization-rotated by an intensity-modulated control beam via the NPR effect. A polarization-division-multiplexing emulator is exploited to split the probe beam into two orthogonally polarized states with imbalanced time delay. After detection by a photodetector, a 90° microwave phase shifter is used to compensate the phases of the fundamental and the third-order harmonic components in order to generate triangular pulses. Triangular pulses at 5 and 6 GHz with full duty cycles are experimentally generated. The root mean square errors between the generated and the simulated waveforms are 3.6e-4 and 1e-4 for triangular pulses at 5 and 6 GHz, respectively.
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We report a new radio-frequency (RF) phase stabilization approach for long-haul optical fiber distribution. The phase drift of an RF signal induced by fiber-length variations can be canceled out automatically via RF mixing without using active phase discrimination and dynamic phase tracking. A key significance of our approach is that no assistant local oscillator (LO) signal is needed. Consequently, frequency estimation of the received RF signal, as well as frequency locking between the LO and the received RF signal, is no longer required, which simplifies the system. A proof-of-concept experiment shows that the phase drift of the received RF signal at 9.6 GHz is significantly reduced using the proposed method. The root mean square (RMS) timing jitter is 0.76 ps when a tunable optical delay line (TODL) inserted between the remote antenna unit (RAU) and local station is changed from 0 to 300 ps.
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Although intracranial multiple aneurysms are not uncommon, multiple mirror aneurysms are relatively rare. A few isolated cases have been described. However, to the best of our knowledge, 3 pairs of pure symmetrical mirror aneurysms in one patient have not been reported yet. We present a case of multiple mirror aneurysms involving the bilateral middle cerebral artery (MCA) bifurcations and posterior communicating arteries (P-com A) confirmation by one-stage operation. The possibility of one-stage treatment must be considered before surgery. Missed diagnosis and misdiagnosis must be avoided before one-stage operation for multiple mirror aneurysms.
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Aneurisma Intracraneal/cirugía , Procedimientos Neuroquirúrgicos/métodos , Anciano , Craneotomía , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Aneurisma Intracraneal/complicaciones , Aneurisma Intracraneal/patología , Arteria Cerebral Media/patología , Arteria Cerebral Media/cirugía , Hemorragia Subaracnoidea/cirugía , Tomografía Computarizada por Rayos XRESUMEN
We report a novel approach to generating full-duty-cycle triangular waveforms based on a microwave photonic filter (MPF) with negative coefficient. It is known that the Fourier series expansion of a triangular waveform has only odd-order harmonics. In this work, the undesired even-order harmonics are suppressed by the MPF that has a periodic transmission response. A triangular waveform at fundamental frequency can be generated by setting the bias of a Mach-Zehnder modulator (MZM) at quadrature point. However, it is found that a broadband 90° microwave phase shifter has to be used after photodetection to adjust the phases of odd-order harmonics. Alternatively, a frequency doubling triangular waveform can be generated by setting the bias of the MZM at maximum or minimum transmission point. This approach is more promising because the broadband microwave phase shifter is no longer required in this case but it is more power consuming. The proposed approach is theoretically analyzed and experimentally verified.
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A widely tunable single bandpass microwave photonic filter (MPF) based on Brillouin-assisted optical carrier recovery in a highly nonlinear fiber (HNLF) with only one optical filter is proposed and experimentally demonstrated. The fundamental principle lies in the fact that the suppressed optical carrier of the phase modulated optical signal could be recovered by the stimulated Brillouin scattering (SBS) amplification effect. When phase modulated optical signals go through an optical filter with a bandpass response, the optical carrier and the upper sidebands suffer from the suppression of the optical filter because they fall in the stopband of that. In our system, the optical carrier could be recovered by the SBS operation around 38 dB. The MPF is achieved by one-to-one mapping from the optical domain to the electrical domain only when one of phase modulated sidebands lies in the bandpass of the optical filter. It shows an excellent selectivity with a 3-dB bandwidth of 170 MHz over a tuning frequency range of 9.5-32.5 GHz. The out-of-band suppression of the MPF is more than 20 dB. Moreover, the MPF shows an excellent shape factor with 10-dB bandwidth of only 520 MHz. The frequency response of the MPF could be widely tuned by changing the frequency difference between the frequency of the optical carrier and the center frequency of the bandpass of the optical filter. A proof-of-concept experiment is carried out to verify the proposed approach.
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Microondas , Óptica y Fotónica/instrumentación , Fotones , Procesamiento de Señales Asistido por ComputadorRESUMEN
BACKGROUND & AIMS: Many patients with pancreatic ductal adenocarcinoma (PDAC) develop recurrent or metastatic diseases after surgery, so it is important to identify those most likely to benefit from aggressive therapy. Disruption of tissue microarchitecture is an early step in pancreatic tumorigenesis and a parameter used in pathology grading of glandular tumors. We investigated whether changes in gene expression during pancreatic epithelial morphogenesis were associated with outcomes of patients with PDAC after surgery. METHODS: We generated architectures of human pancreatic duct epithelial cells in a 3-dimensional basement membrane matrix. We identified gene expression profiles of the cells during different stages of tubular morphogenesis (tubulogenesis) and of PANC-1 cells during spheroid formation. Differential expression of genes was confirmed by immunoblot analysis. We compared the gene expression profile associated with pancreatic epithelial tubulogenesis with that of PDAC samples from 27 patients, as well as with their outcomes after surgery. RESULTS: We identified a gene expression profile associated with tubulogenesis that resembled the profile of human pancreatic tissue with differentiated morphology and exocrine function. Patients with PDACs with this profile fared well after surgery. Based on this profile, we established a 6-28 gene tubulogenesis-specific signature that accurately determined the prognosis of independent cohorts of patients with PDAC (total n = 128; accuracy = 81.2%-95.0%). One gene, ASPM, was down-regulated during tubulogenesis but up-regulated in human PDAC cell lines and tumor samples; up-regulation correlated with patient outcomes (Cox regression P = .0028). Bioinformatic, genetic, biochemical, functional, and clinical correlative studies showed that ASPM promotes aggressiveness of PDAC by maintaining Wnt-ß-catenin signaling and stem cell features of PDAC cells. CONCLUSIONS: We identified a gene expression profile associated with pancreatic epithelial tubulogenesis and a tissue architecture-specific signature of PDAC cells that is associated with patient outcomes after surgery.
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Carcinoma Ductal Pancreático/patología , Diferenciación Celular/genética , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica/genética , Proteínas del Tejido Nervioso/fisiología , Conductos Pancreáticos/patología , Neoplasias Pancreáticas/patología , Transcriptoma/genética , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/fisiología , Carcinoma Ductal Pancreático/genética , Diferenciación Celular/fisiología , Movimiento Celular/genética , Movimiento Celular/fisiología , Modelos Animales de Enfermedad , Epitelio/patología , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica/fisiología , Xenoinjertos , Humanos , Ratones , Ratones Endogámicos NOD , Ratones SCID , Proteínas del Tejido Nervioso/genética , Neoplasias Pancreáticas/genética , Pronóstico , Estudios Retrospectivos , Transducción de Señal/genética , Transducción de Señal/fisiología , Transcriptoma/fisiología , Proteínas Wnt/fisiología , beta Catenina/fisiologíaRESUMEN
Histopathological classification of human prostate cancer (PCA) relies on the morphological assessment of tissue specimens but has limited prognostic value. To address this deficiency, we performed comparative transcriptome analysis of human prostatic acini generated in a three-dimensional basement membrane that recapitulates the differentiated morphological characteristics and gene expression profile of a human prostate glandular epithelial tissue. We then applied an acinar morphogenesis-specific gene profile to two independent cohorts of patients with PCA (total n = 79) and found that those with tumors expressing this profile, which we designated acini-like tumors, had a significantly lower risk of postoperative relapse compared with those tumors with a lower correlation (hazard ratio, 0.078; log-rank test P = 0.009). Multivariate analyses showed superior prognostic prediction performance using this classification system compared with clinical criteria and Gleason scores. We prioritized the genes in this profile and identified programmed cell death protein 4 (PDCD4) and Kruppel-like factor 6 (KLF6) as critical regulators and surrogate markers of prostatic tissue architectures, which form a gene signature that robustly predicts clinical prognosis with a remarkable accuracy in several large series of PCA tumors (total n = 161; concordance index, 0.913 to 0.951). Thus, by exploiting the genomic program associated with prostate glandular differentiation, we identified acini-like PCA and related molecular markers that significantly enhance prognostic prediction of human PCA.
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Células Acinares/patología , Proteínas Reguladoras de la Apoptosis/metabolismo , Perfilación de la Expresión Génica , Factores de Transcripción de Tipo Kruppel/metabolismo , Morfogénesis/genética , Próstata/patología , Neoplasias de la Próstata/patología , Proteínas Proto-Oncogénicas/metabolismo , Proteínas de Unión al ARN/metabolismo , Células Acinares/metabolismo , Anciano , Proteínas Reguladoras de la Apoptosis/genética , Biomarcadores de Tumor/metabolismo , Diferenciación Celular , Células Epiteliales/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Factor 6 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel/genética , Masculino , Persona de Mediana Edad , Especificidad de Órganos/genética , Pronóstico , Próstata/crecimiento & desarrollo , Próstata/metabolismo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/cirugía , Proteínas Proto-Oncogénicas/genética , Proteínas de Unión al ARN/genética , RecurrenciaRESUMEN
BACKGROUND: The McDonald MRI dissemination in space criteria have been found to be less sensitive when applied to Asians with classic multiple sclerosis. The Asian neurological community thus proposed modifications to the criteria with reduction of minimal number of T2 lesions from nine to four, and removal of restriction on spinal cord lesion length and morphology for use in Asians. OBJECTIVE: The study is to examine the accuracy of modified MRI dissemination in space criteria for prediction of conversion from clinically isolated syndrome to definite multiple sclerosis according to patients' baseline MRI. METHODS: From 2001 to 2007, we recruited 67 patients with clinically isolated syndrome. They had been followed-up until development of definite multiple sclerosis or remaining as clinically isolated syndrome for more than 2 years. The non-converters were taken as negative cases. The 67 patients' baseline MRIs were evaluated by two radiologists and determined as either fulfilling or not fulfilling McDonald and modified MRI criteria for dissemination in space. RESULTS: Thirty-two patients converted to definite multiple sclerosis and 35 did not. The modified criteria are slightly more sensitive (53.1% vs. 50.0%) and accurate (77.6% vs. 76.1%) as compared with McDonald criteria. However, further reduction of the cutoff of abnormal MRI criteria from three of four to two of four criteria yields best sensitivity (71.9%) and accuracy (83.6%). CONCLUSIONS: Modifications to the McDonald MRI dissemination in space criteria (by using fewer T2 lesions, removal of the restriction on the spinal cord lesion and reduction of the cutoff of MRI criteria) are more appropriate for use in the Taiwanese population for the diagnosis of classic multiple sclerosis.