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BACKGROUND: Chemotherapy and chemoradiation have become essential adjuncts to improve the survival of patients with resectable esophageal squamous cell carcinoma (ESCC) in the perioperative period. Although preoperative treatment plus surgery is commonly used, controversy remains regarding the optimal treatment strategy for patients with locally advanced ESCC. METHODS: A retrospective review of clinical stage II and III ESCC patients who underwent esophagectomy at Henan Cancer Hospital between October 2014 and October 2017 was performed. The patients were divided into a neoadjuvant chemotherapy (NAC) group and an adjuvant chemotherapy (AC) group. Propensity score matching (PSM) was used to exclude confounders. Survival was estimated using KaplanâMeier analysis and compared by the log-rank test. The Cox proportional hazards regression model was used for both the univariate and multivariate analyses. RESULTS: A total of 684 patients were enrolled, including 365 (53.4%) patients in the NAC group. After PSM, 294 pairs of patients were left. NAC prolonged the OS (not reached versus 57.3 months, P = 0.002) and DFS (57.2 vs. 36.4 months, P = 0.010) and decreased the total rate of recurrence (50.1% vs. 59.2%, P = 0.025) and local recurrence (27.9% vs. 36.7%, P = 0.022) compared with AC. The multivariable analyses showed that NAC plus surgery modality was an independent predictor for improved OS (HR: 0.582, 95% CI: 0.467-0.786, P = 0.001). CONCLUSION: NAC plus surgery prolonged OS and DFS, and significantly decreased the total rate of recurrence compared with surgery plus AC in patients with clinical stage II and III ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Terapia Neoadjuvante , Quimioterapia Adjuvante , Quimiorradioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Esofagectomia , Estudos Retrospectivos , Estadiamento de NeoplasiasRESUMO
BACKGROUND: The effect of neoadjuvant chemotherapy (NACT) in gallbladder cancer (GBC) patients remains controversial. The aim of this study was to assess the impact of NACT on overall survival (OS) and cancer specific survival (CSS) in patients with localized or locoregionally advanced GBC, and to explore possible protective predictors for prognosis. METHODS: Data for patients with localized or locoregionally advanced GBC (i.e., categories cTx-cT4, cN0-2, and cM0) from 2004 to 2020 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients in the NACT and non-NACT groups were propensity score matched (PSM) 1:3, and the Kaplan-Meier method and log-rank test were performed to analyze the impact of NACT on OS and CSS. Univariable and multivariable Cox regression models were applied to identify the possible prognostic factors. Subgroup analysis was conducted to identify patients who would benefit from NACT. RESULTS: Of the 2676 cases included, 78 NACT and 234 non-NACT patients remained after PSM. In localized or locoregionally advanced GBC patients, the median OS of the NACT and non-NACT was 31 and 16 months (log-rank P < 0.01), and the median CSS of NACT and non-NACT was 32 and 17 months (log-rank P < 0.01), respectively. Longer median OS (31 vs 17 months, log-rank P < 0.01) and CSS (32 vs 20 months, log-rank P < 0.01) was associated with NACT compared with surgery alone. Multivariable Cox regression analysis showed that NACT, stage, and surgery type were prognostic factors for OS and CSS in GBC patients. Subgroup analysis revealed that the survival hazard ratios (HRs) of NACT vs non-NACT for localized or locoregionally advanced GBC patients were significant in most subgroups. CONCLUSIONS: NACT may provide therapeutic benefits for localized or locoregionally advanced GBC patients, especially for those with advanced stage, node-positive, poorly differentiated or undifferentiated disease. NACT combined with radical surgery was associated with a survival advantage. Therefore, NACT combined with surgery may provide a better treatment option for resectable GBC patients.
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Neoplasias da Vesícula Biliar , Terapia Neoadjuvante , Pontuação de Propensão , Programa de SEER , Humanos , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias da Vesícula Biliar/terapia , Feminino , Masculino , Terapia Neoadjuvante/métodos , Terapia Neoadjuvante/estatística & dados numéricos , Pessoa de Meia-Idade , Prognóstico , Idoso , Quimioterapia Adjuvante/estatística & dados numéricos , Quimioterapia Adjuvante/métodos , Estadiamento de Neoplasias , Estimativa de Kaplan-MeierRESUMO
Shellfish poisoning is a common food poisoning. To comprehensively characterize proteome changes in the whole brain due to shellfish poisoning, Tandem mass tag (TMT)-based differential proteomic analysis was performed with a low-dose chronic shellfish poisoning model in mice. A total of 6798 proteins were confidently identified, among which 123 proteins showed significant changes (fold changes of >1.2 or <0.83, p < 0.05). In positive regulation of synaptic transmission, proteins assigned to a presynaptic membrane (e.g., Grik2) and synaptic transmission (e.g., Fmr1) changed. In addition, altered proteins in nervous system development were observed, suggesting that mice suffered nerve damage due to the nervous system being activated. Ion transport in model mice was demonstrated by a decrease in key enzymes (e.g., Kcnj11) in voltage-gated ion channel activity and solute carrier family (e.g., Slc38a3). Meanwhile, alterations in transferase activity proteins were observed. In conclusion, these modifications observed in brain proteins between the model and control mice provide valuable insights into understanding the functional mechanisms underlying shellfish poisoning.
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Doenças Transmitidas por Alimentos , Intoxicação por Frutos do Mar , Animais , Camundongos , Proteômica , Alimentos Marinhos , Encéfalo , Proteína do X Frágil da Deficiência IntelectualRESUMO
The terahertz (THz) band has a great potential for the development of communication technology, but it has not been fully utilized due to the lack of practical devices, especially actively controllable multifunctional devices. Here, we propose and demonstrate a Ge2Sb2Te5 (GST)-based metamaterial device, where an actively controllable function is experimentally verified by inducing the crystallization process with thermal activation. Cross-polarization conversion in the reflection mode and circular-to-linear polarization conversion in the transmission mode are obtained under crystalline and amorphous GST conditions, respectively. The combination of GST and THz waves has a wide range of applications and will further advance the THz field.
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Sulfur mustard [HD; bis-(2-chloroethyl) sulfide] and other analogues are a kind of highly toxic vesicant and have been prohibited by the Organization for the Prohibition of Chemical Weapons (OPCW) since 1997. Exposures to HD could generate several adducts in the plasma and hydrolysis products in the urine, which are widely applied as biomarkers to identify HD exposure in forensic analysis. Several methods have been developed for the detection of related biomarkers. However, most methods are based on complex derivatization, and not enough attention is paid to HD analogues. A modified and convenient analytical method reported herein includes simultaneous incubation and organic solvent extraction. The biomarkers such as thiodiglycol and 1,2-bis (2-hydroxyethylthio) are transferred to HD and 1,2-bis(2-chloroethylthio) ethane via hydrochloric acid at the appropriate temperature. The analytes are analyzed by gas chromatography tandem mass spectrometry (GC-MS/MS) with 2-chloroethyl ethyl sulfide (2-CEES) applied as the internal standard. The interday and intraday study according to FDA rules has been achieved to evaluate the accuracy and precision of the method. The two targets are detected with a good linearity (R2 > 0.99) in the concentration ranges from 5 to 1000 ng/mL and 10 to 1000 ng/mL, with small relative standard deviations (RSD ≤6.62% and RSD ≤6.93%) and favorable recoveries between 90.3 and 107.3% and between 89.4 and 108.7%, respectively. The established method can be used for retrospective detection of sulfur mustards in biological samples and successfully applied in the biomedical proficiency testing organized by the OPCW.
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Sulfetos , Espectrometria de Massas em Tandem , Humanos , Estudos Retrospectivos , Cromatografia Gasosa-Espectrometria de Massas , Biomarcadores , EtanoRESUMO
Carbamate nerve agents (CMNAs) are a type of lethal cholinesterase inhibitor with one or more quaternary amine centres and aromatic rings. CMNAs have been recently added to the Annex on Chemicals of the Chemical Weapons Convention (CWC) and Schedules of Controlled Chemicals of China. In this study, a rapid, sensitive and selective method was developed for the fluorescence detection of ambenonium chloride (AC) through host-guest and electrostatic dual interactions between AC and cyclodextrin/11-mercaptoundecanoic acid (CD/MUA) dually functionalized gold nanoclusters (AuNCs). Through this method, AC was detected with a limit of detection of 10.0 ng/mL. Method evaluation showed high selectivity towards AC over other related compounds. The practical applicability was verified, as satisfactory recoveries were obtained for AC spiked in river water and urine, as well as Proficiency Test samples from Organisation for the Prohibition of Chemical Weapons (OPCW). In addition, a fluorescence sensing array comprising four AuNCs was designed to distinguish six carbamates and structurally similar compounds. This method provides a potential approach for the rapid, sensitive and selective recognition and detection of CMNAs.
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Nanopartículas Metálicas , Agentes Neurotóxicos , Ouro/química , Carbamatos , Espectrometria de Fluorescência/métodos , China , Nanopartículas Metálicas/química , Limite de DetecçãoRESUMO
No adjuvant treatment has been established for patients who remain at high risk of recurrence and incidental pathologic lymph node metastasis for esophageal squamous cell carcinoma (ESCC). In this open-label, multicenter, phase III, randomized controlled trial, ESCC patients who did not achieve pathologic complete response after neoadjuvant chemotherapy plus surgery and clinical T1-2 N0 patients with incidental pathologic lymph node metastasis following initial surgery were randomized at a 2:1 ratio to receive either a sintilimab regimen or observational management (NCT05495152). The primary end point was disease-free survival for all randomized patients. The results of this randomized controlled trial addressed controversy regarding the survival benefits of adjuvant sintilimab treatment for patients with resected locally advanced ESCC. Clinical Trial Registration: NCT05495152 (ClinicalTrials.gov).
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Adjuvantes Imunológicos , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Metástase LinfáticaRESUMO
X-ray ptychography is a popular variant of coherent diffraction imaging that offers ultrahigh resolution for extended samples. In x-ray ptychography instruments, the Fresnel zone-plate (FZP) is the most commonly used optical probe system for both soft x-ray and hard x-ray. In FZP-based ptychography with a highly curved defocus probe wavefront, the reconstructed image quality can be significantly impacted by the initial probe function form, necessitating the construction of a suitable initial probe for successful reconstruction. To investigate the effects of initial probe forms on FZP-based ptychography reconstruction, we constructed four single-mode initial probe models (IPMs) and three multi-mode IPMs in this study, and systematically compared their corresponding simulated and experimental reconstructions. The results show that the Fresnel IPM, spherical IPM, and Fresnel-based multi-mode IPMs can result in successful reconstructions for both near-focus and defocus cases, while random IPMs and constant IPMs work only for near-focus cases. Consequently, for FZP-based ptychography, the elaborately constructed IPMs that closely resemble real probes in wavefront phase form are more advantageous than natural IPMs such as the random or constant model. Furthermore, these IPMs with high phase similarity to the high-curvature large-sized probe adopted in experiments can help greatly improve ptychography experiment efficiency and decrease radiation damage to samples.
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Flavonoids are a kind of secondary metabolite which widely exist in plants. They contain a lot of active hydroxyls, which can react with toxic chemicals to produce potential exposure biomarkers. In this article, the model plant Arabidopsis thaliana (L.) was exposed to the nerve agent O-Ethyl N,N-dimethyl phosphoramidocyanidate (Tabun). By comparing with the plant not exposed to Tabun, some characteristic ions were identified by quadrupole-time of flight mass spectrometry in the acetonitrile extract of the exposed leaves. These characteristic ions were selected as parent ions to produce product ion mass spectra (PIMS). Some interesting fragmentation pathways were revealed, including neutral loss of glucoside, rhamnose and ethylene. O-Ethyl N,N-dimethyl phosphoryl modified flavonoids were deduced from assignment of the PIMS. The element components and the accurate mass of the product ions from each parent ion matched well with those of the proposed fragmentation pathways. Through comparison with the PIMS of structurally closely related chemical of Isobutyl methylphosphonyl modified flavonoids, the structures and the fragmentation pathways of the O-Ethyl N,N-dimethyl phosphoryl modified flavonoids were finally confirmed. Successfully finding and identifying these three specific exposure biomarkers in plants provided a new strategy for the retrospective analysis of organophosphorus exposure and forensic analysis.
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Arabidopsis , Agentes Neurotóxicos , Flavonoides/química , Espectrometria de Massas em Tandem/métodos , Estudos Retrospectivos , Cromatografia Líquida de Alta Pressão/métodos , PlantasRESUMO
BACKGROUND: Gallbladder cancer (GBC) is a highly aggressive malignant cancer in the biliary system with poor prognosis. XPO1 (chromosome region maintenance 1 or CRM1) mediates the nuclear export of several proteins, mainly tumor suppressors. Thus, XPO1 functions as a pro-oncogenic factor. KPT-330 (Selinexor) is a United States Food and Drug Administration approved selective inhibitor of XPO1 that demonstrates good therapeutic effects in hematologic cancers. However, the function of XPO1 and the effect of KPT-330 have not been reported in GBC. METHODS: We analyzed the correlation between XPO1 expression levels by q-PCR and clinical features of GBC patients. Cell proliferation assays were used to analyze the in vitro antitumor effects of XPO1 inhibitor KPT-330. mRNA sequencing was used to explore the underlying mechanisms. Western blot was performed to explore the relationship between apoptosis and autophagy. The in vivo antitumor effect of KPT-330 was investigated in a nude mouse model of gallbladder cancer. RESULTS: We found that high expression of XPO1 was related to poor prognosis of GBC patients. We observed that XPO1 inhibitor KPT-330 inhibited the proliferation of GBC cells in vitro. Furthermore, XPO1 inhibitor KPT-330 induced apoptosis by reducing the mitochondrial membrane potential and triggering autophagy in NOZ and GBC-SD cells. Indeed, XPO1 inhibitor KPT-330 led to nuclear accumulation of p53 and activated the p53/mTOR pathway to regulate autophagy-dependent apoptosis. Importantly, KPT-330 suppressed tumor growth with no obvious toxic effects in vivo. CONCLUSION: XPO1 may be a promising prognostic indicator for GBC, and KPT-330 appears to be a potential drug for treating GBC effectively and safely.
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Neoplasias da Vesícula Biliar , Carioferinas/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Animais , Apoptose , Autofagia , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias da Vesícula Biliar/tratamento farmacológico , Hidrazinas , Carioferinas/genética , Camundongos , RNA Mensageiro , Serina-Treonina Quinases TOR/metabolismo , Triazóis , Proteína Supressora de Tumor p53/metabolismo , Proteína Exportina 1RESUMO
Various kinds of metasurfaces have been proposed because they can be tailored to achieve the desired modulations on electromagnetic wave that do not occur in nature. Compared to conventional metamaterials, coding metasurfaces integrated with information science theory possess numerous distinctive advantages - simple design, time-saving and compatibility with digital devices. Here we propose terahertz multifunctional anisotropic reflective metasurfaces with a metal-insulator-metal cavity structure whose top constructional layer consists of a pair of gold arc-rings and a gold cut-wire located between them. Two different functions of narrow-band absorption and broadband polarization conversion are realized based on different coding matrices using the binary codes '0' and '1'. Furthermore, we integrate a specific coding metasurface with vanadium dioxide (VO2) to realize a temperature-controlled active metasurface. Through the temperature change, dynamic functionalities switching between a narrow-band polarization converter with a polarization conversion ratio over 94% and an efficient low-pass filter are achieved under the phase transition of VO2, and the active metasurface is polarization independent. The proposed coding metasurfaces are verified numerically and experimentally, and have promising applications in terahertz modulation and functional devices.
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Previous studies have reported that exosomes bearing certain microRNAs (miRNAs) are related to the physiological functions of different types of cancer cells. Our study aimed to elucidate the role of miR-200a in esophageal squamous cell carcinoma (ESCC). We observed that miR-200a expression is higher in esophageal carcinoma cells, tissues, and exosomes than in normal cells and healthy tissues. We showed that exosome-shuttled miR-200a promotes the proliferation, migration, and invasion of esophageal cells and inhibits apoptosis, thereby leading to the progression of ESCC. We showed that miR-200a exerts its effects through its interaction with Keap1, thus altering the Keap1/Nrf2 signaling pathway. Our results suggest that exosome-shuttled miR-200a might be useful as a biomarker for prognosis in patients with ESCC.
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Movimento Celular , Proliferação de Células , Neoplasias Esofágicas/metabolismo , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteína 1 Associada a ECH Semelhante a Kelch/biossíntese , MicroRNAs/metabolismo , Proteínas de Neoplasias/biossíntese , RNA Neoplásico/metabolismo , Idoso , Linhagem Celular Tumoral , Neoplasias Esofágicas/genética , Exossomos/genética , Feminino , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , RNA Neoplásico/genéticaRESUMO
A major challenge for the unequivocal verification of alleged exposure to sulfur mustard (HD) lies in identifying its multiple modifications on endogenous proteins and utilizing these modified proteins to achieve accurate, sensitive, and rapid detection for retrospective analysis of HD exposure. As the most abundant protein in human plasma, human serum albumin (HSA) can react with many xenobiotics, such as HD, to protect the body from damage. The HSA adducts induced by HD have been used as biomarkers for the verification of HD exposure. In this study, the modification sites on HSA by HD were identified through application of the bottom-up strategy used in proteomics, and 41 modified sites were discovered with seven types of amino acids, of which 3 types were not previously reported. Then, different enzymes, including pepsin, endoproteinase Glu-C, and pronase, were applied to digest HD-HSA to produce adducts with hydroxyethylthioethyl (HETE) groups, which may be used as potential biomarkers for HD exposure. As candidates for retrospective analysis, sixteen adducts were obtained and characterized with ultra-high-pressure liquid chromatography coupled with quadrupole-Orbitrap mass spectrometry (UHPLC-QE Focus MS). These potential biomarkers were evaluated in human plasma that was exposed in vitro to HD and five of its analogues. This study integrated the identification of modification sites through application of the bottom-up strategy of proteomics and screening biomarkers, providing a novel strategy for retrospective detection of the exposure of xenobiotic chemicals.
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Substâncias para a Guerra Química , Gás de Mostarda , Biomarcadores/análise , Substâncias para a Guerra Química/análise , Humanos , Gás de Mostarda/análise , Proteômica , Estudos Retrospectivos , Albumina Sérica Humana/química , Espectrometria de Massas em Tandem/métodosRESUMO
Pancreatic cancer (PC) is one of the most fatal and chemoresistant malignancies with a poor prognosis. The current therapeutic options for PC have not achieved satisfactory results due to drug resistance. Therefore, it is urgent to develop novel treatment strategies with enhanced efficacy. This study sought to investigate the anticancer effect of gemcitabine and XCT790, an estrogen-related receptor alpha (ERRα) inverse agonist, as monotherapies or in combination for the treatment of PC. Here we demonstrated that the drug combination synergistically suppressed PC cell viability, its proliferative, migratory, invasive, apoptotic activities, and epithelial-to-mesenchymal transition (EMT), and it triggered G0/G1 cell cycle arrest and programmed cell death in vitro. In addition, in vivo assays using xenograft and mini-PDX (patient-derived xenograft) models further confirmed the synergistic antitumor effect between gemcitabine and XCT790 on PC. Mechanistically, gemcitabine and XCT790 suppressed PC by inhibiting ERRα and MEK/ERK signaling pathway. In conclusion, our current study demonstrated for the first time that gemcitabine combined with XCT790 displayed synergistic anticancer activities against PC, suggesting that their combination might be a promising treatment strategy for the therapy of PC.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Desoxicitidina/análogos & derivados , Nitrilas/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Receptores de Estrogênio/efeitos dos fármacos , Tiazóis/farmacologia , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Desoxicitidina/farmacologia , Sinergismo Farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Gencitabina , Receptor ERRalfa Relacionado ao EstrogênioRESUMO
BACKGROUND: Inflammation is often related to cancer, and several inflammatory scores have been established to predict the prognosis of various types of cancer. Our study aimed to determine the prognostic value of the preoperative lymphocyte to C-reactive protein ratio (LCR) for predicting postoperative outcomes in patients with resectable gallbladder cancer (GBC). METHODS: A retrospective analysis of 104 GBC patients who received curative surgery at Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine from January 2000 to December 2016 was performed. A time-dependent receiver operating characteristic curve was constructed to evaluate the accuracy of different markers. Univariate and multivariate Cox proportional hazard models were used to define factors associated with overall survival. RESULTS: Among the assessed variables, the preoperative LCR showed the highest accuracy in predicting the overall survival of GBC patients (AUC: 0.736). Decreased preoperative LCR was significantly associated with advanced tumor stage, including tumor invasion (P = 0.018), lymph node metastasis (P = 0.011) and TNM stage (P = 0.022). A low preoperative LCR (cutoff threshold = 145.5) was an independent risk factor for overall survival in patients with resectable GBC (P < 0.001). CONCLUSIONS: The preoperative LCR is a novel and valuable prognostic indicator of postoperative survival in patients with resectable GBC.
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Carcinoma in Situ , Neoplasias da Vesícula Biliar , Proteína C-Reativa/análise , Carcinoma in Situ/patologia , China , Neoplasias da Vesícula Biliar/patologia , Humanos , Linfócitos , Estadiamento de Neoplasias , Neutrófilos/química , Neutrófilos/metabolismo , Neutrófilos/patologia , Prognóstico , Estudos RetrospectivosRESUMO
Ricin is a type II ribosome-inactivating protein toxin consisting of A and B chains linked by one interchain disulfide bond. Because of its high toxicity depending on both chains together, confirming the presence of both A and B chains of intact ricin is required during the investigation of the illegal production and application. Here, we report a novel and sensitive acetonitrile (ACN)-assisted trypsin digestion method for unambiguous identification of intact ricin by simultaneous detection of its marker peptides from A and B chains. Marker peptides were generated with a simple procedure by direct cleaving the native ricin at 45 °C for 4 h using Promega modified sequencing grade trypsin under the assistance of 10% ACN, and then directly analyzed by ultrahigh performance liquid chromatography tandem mass spectrometry. The type of trypsin was found to be one critical factor for cleavage of intact ricin based on a significant difference in the yields of specific peptides generated while using various types of trypsin. A low content of ACN in enzymatic buffer significantly reduced the digestion time from overnight to 4 h. There was commonly a better MS response of marker peptides when using the developed ACN-assisted trypsin digestion method than methanol-assisted trypsin digestion within the same 4 h. Totally, seven specific peptides with high sensitivity and specificity including three in the A-chain (TA7, TA11, and TA10) and four in the B-chain (TB6, TB14-ss-TB16, TB20, and TB18) were obtained as good marker peptides for unambiguous identification of intact ricin. The lowest concentration of native ricin for unambiguous identification was 20 ng/mL, in which three marker peptides from both the A-chain and B-chain could be measured with a minimum of three ion transitions. Combined with affinity enrichment, the developed approach was successfully applied for the measurement of intact ricin from the complicated matrix samples of the second, third, and fourth biotoxin exercises organized by the Organisation for the Prohibition of Chemical Weapons (OPCW). This study has provided a recommended detection method combined with one novel ACN-assisted trypsin digestion with MS for forensic unambiguous confirmation of trace ricin intact with high confidence.
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Ricina , Acetonitrilas , Cromatografia Líquida , Digestão , Peptídeos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas em Tandem , TripsinaRESUMO
Extracellular plaque deposits of ß-amyloid peptide (Aß) are one of the main pathological features of Alzheimer's disease (AD). The aggregation of Aß42 species, especially Aß42 oligomers, is still an active research field in AD pathogenesis. Secretory clusterin protein (sCLU), an extracellular chaperone, plays an important role in AD pathogenesis. Although sCLU interacts directly with Aß42 in vitro and in vivo, the mechanism is not clear. In this paper, His-tagged sCLU (sCLU-His) was cloned, expressed and purified, and we applied florescence resonance energy transfer-fluorescence correlation spectroscopy (FRET-FCS) to investigate the direct interaction of sCLU-His and Aß42 at the single-molecule fluorescence level in vitro. Here, we chose four different fluorescently labeled Aß42 oligomers to form two different groups of aggregation models, easy or difficult to aggregate. The results showed that sCLU-His could form complexes with both aggregation models, and sCLU-His inhibited the aggregation of Aß42/RB ~ Aß42/Atto647 (easy to aggregate model). The complexes were produced as the Aß42/Label adhered to the sCLU-His, which is similar to a "strawberry model," as strawberry seeds are dotted on the outer surface of strawberries. This work provided additional insight into the interaction mechanism of sCLU and Aß42 .
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Peptídeos beta-Amiloides/antagonistas & inibidores , Clusterina/farmacologia , Fragmentos de Peptídeos/antagonistas & inibidores , Algoritmos , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Clonagem Molecular , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes , Humanos , Modelos Químicos , Fragmentos de Peptídeos/metabolismo , Espectrometria de FluorescênciaRESUMO
BACKGROUND: Rice is a crop that is very sensitive to low temperature, and its morphological development and production are greatly affected by low temperature. Therefore, understanding the genetic basis of cold tolerance in rice is of great significance for mining favorable genes and cultivating excellent rice varieties. However, there have been limited studies focusing on cold tolerance at the bud burst stage; therefore, considerable attention should be given to the genetic basis of cold tolerance at this stage. RESULTS: In this study, a natural population consisting of 211 rice landraces collected from 15 provinces in China and other countries was used for the first time to evaluate cold tolerance at the bud burst stage. Population structure analysis showed that this population was divided into two groups and was rich in genetic diversity. Our evaluation results confirmed that japonica rice was more tolerant to cold at the bud burst stage than indica rice. A genome-wide association study (GWAS) was performed with the phenotypic data of 211 rice landraces and a 36,727 SNP dataset under a mixed linear model. Twelve QTLs (P < 0.0001) were identified for the seedling survival rate (SR) after treatment at 4 °C, in which there were five QTLs (qSR2-2, qSR3-1, qSR3-2, qSR3-3 and qSR9) that were colocalized with those from previous studies and seven QTLs (qSR2-1, qSR3-4, qSR3-5, qSR3-6, qSR3-7, qSR4 and qSR7) that were reported for the first time. Among these QTLs, qSR9, harboring the most significant SNP, explained the most phenotypic variation. Through bioinformatics analysis, five genes (LOC_Os09g12440, LOC_Os09g12470, LOC_Os09g12520, LOC_Os09g12580 and LOC_Os09g12720) were identified as candidates for qSR9. CONCLUSION: This natural population consisting of 211 rice landraces combined with high-density SNPs will serve as a better choice for identifying rice QTLs/genes in the future, and the detected QTLs associated with cold tolerance at the bud burst stage in rice will be conducive to further mining favorable genes and breeding rice varieties under cold stress.
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Temperatura Baixa , Resposta ao Choque Frio/genética , Flores/crescimento & desenvolvimento , Flores/genética , Oryza/crescimento & desenvolvimento , Oryza/genética , Locos de Características Quantitativas/genética , Produtos Agrícolas/genética , Produtos Agrícolas/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Variação Genética , Estudo de Associação Genômica Ampla , GenótipoRESUMO
INTRODUCTION: McKeown minimally invasive esophagectomy (McKeown-MIE) offers advantages in short-term outcomes compared with McKeown open esophagectomy (McKeown-OE); however, debate as to whether MIE is equivalent or better than OE regarding survival outcomes is ongoing. OBJECTIVE: The aim of this study was to compare long-term survival between McKeown-MIE and McKeown-OE in a large cohort of esophageal cancer (EC) patients. METHODS: We used a prospective database (independently managed by LinkDoc company) of the Thoracic Surgery Department at Henan Cancer Hospital and included patients who underwent McKeown-MIE and McKeown-OE for EC from 1 January 2015 to 6 January 2018. The perioperative data and overall survival (OS) rate in the two groups were retrospectively compared. RESULTS: We included 502 patients who underwent McKeown-MIE (n = 306) or McKeown-OE (n = 196) for EC. The median age in the total patient population was 63 years. All baseline characteristics were well-balanced between the two groups. There was a significantly shorter mean operative time (269.76 min vs. 321.14 min, p < 0.001) in the OE group. The 30-day and in-hospital mortality rates were 0, and there was no difference in 90-day mortality (p = 0.053) between the groups. The postoperative stay was shorter in the MIE group and was 14 days and 18 days in the MIE and OE groups, respectively (p < 0.001). The OS at 60 months was 58.8% and 41.6% in the MIE and OE groups, respectively (p < 0.001) [hazard ratio 1.783, 95% confidence interval 1.347-2.359]. CONCLUSIONS: These results showed that McKeown-MIE was associated with better long-term survival than McKeown-OE for patients with resectable EC.
Assuntos
Neoplasias Esofágicas , Procedimentos Cirúrgicos Minimamente Invasivos , Neoplasias Esofágicas/cirurgia , Esofagectomia , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Resultado do TratamentoRESUMO
A metal-free intramolecular [3+2] cycloaddtion has been achieved by treating benzene-linked propynol-ynes with AcOH/H2O in a one-pot manner. The reaction provides greener, 100% atom-economic, highly regioselective, and more practical access to functionalized naphtho[1,2-c]furan-5-ones with valuable and versatile applications. The regioselective α-deuteration of naphtho[1,2-c]furan-5-ones has been also presented with excellent deuterium incorporation and chemical yields. Moreover, the fluorescent properties of naphtho[1,2-c]furan-5-one products have been investigated in solution.