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1.
J Pharm Biomed Anal ; 177: 112848, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31479998

RESUMO

Metabolic syndrome (MetS) is an important risk factor for type 2 diabetes, cardiovascular diseases and all-cause morbidity and mortality. Biomarkers can provide insight into the mechanism, facilitate early detection, and monitor progression of MetS and its response to therapeutic interventions. To identify potential biomarkers, we applied a non-targeted and targeted lipidomics method to characterize plasma metabolic profile in MetS patients. Metabolic profiling was performed on a non-target set (40 cases and 40 controls) on UHPLC-Q-TOF/MS and target set (80 MetS patients and 80 healthy controls) on UHPLC-Q-orbitrap MS. Using comprehensive screening and validation workflow, we identified a panel of three metabolites including PC(18:1/P-16:0), PC(o-22:3/22:3), PC(P-18:1/16:1). Our results indicated that the identified biomarkers may improve the risk prediction and provide a novel tool for monitoring of the progression of disease and response to treatment in MetS patients.

2.
Int J Rheum Dis ; 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31631507

RESUMO

AIM: The characteristics and the pathogenesis of the concomitant antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) and immunoglobulin G4-related disease (IgG4-RD) have not been elucidated. METHOD: We included 92 AAV patients with renal biopsy results. Among them, 10 patients met both AAV and IgG4-RD criteria (concomitant group). The IgG subclasses of myeloperoxidase (MPO)-ANCA in both serum and renal tissue were measured and complement activation components were detected in serum. RESULTS: Patients in the concomitant group had both elevated serum IgG4 levels and positive MPO-ANCA. They had higher levels of eosinophil counts, serum globulin, IgG, IgE and C-reactive protein than patients in the AAV alone group. All 10 patients had glomerulonephritis with crescents and seven patients also had segmental necrosis of the glomerular capillary wall. Most of them also presented with storiform fibrosis and lymphoplasmacytic infiltration in renal interstitium with IgG4 positive plasma cells more than 10/high-power field. Eight patients achieved remission with improved renal function, the other two patients were on maintenance dialysis. The IgG4 subclass of MPO-ANCA was higher in the concomitant group than that in AAV alone group. A merge of IgG4 and MPO immunofluorescence was observed in parts of the mesangium of concomitant AAV and IgG4-RD patients. For complement components, Bb and mannose-binding lectin were elevated in serum of concomitant AAV and IgG4-RD patients. CONCLUSION: We showed a new overlap syndrome of AAV and IgG4-RD, in which the IgG4 subclass of ANCA may be a pathogenic factor.

3.
BMJ Open ; 9(9): e026328, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519667

RESUMO

OBJECTIVES: The aim of this study was to explore perspectives and reasoning of medical staff from Class A tertiary hospitals about the factors hindering and facilitating the uptake and use of clinical practice guidelines (CPGs) during medical procedures. DESIGN: Mixed-method research study to collect and analyse both quantitative and qualitative data. SETTING: Class A tertiary hospitals in China. PARTICIPANTS: The inclusion criteria for the questionnaire survey and qualitative research were (1) medical practitioners and (2) years of practice: above 5 years in a tertiary hospital. METHODS: Questionnaires were distributed to medical staff in 11 cities to collect quantitative data. Frequency and ranking of barriers and enablers were analysed. Spearman correlations were computed to explore the correlation between years of practice, professional title ranking and educational background with self-reported guideline adherence. Using a constructivist grounded theory method, qualitative data were generated via in-depth face-to-face interviews with Chinese medical practitioners. RESULTS: A total of 359 medical practitioners were surveyed and 32 medical practitioners interviewed in 11 cities. Higher frequency and higher ranking of barriers all converged on 'lack of access', 'less convenient', 'lack of applicability' and 'lack of evidence from Chinese sample'. Higher frequency and higher ranking of enablers converged on 'Short formats presentation', 'Utilisation of various media', 'Information visualisation' and 'Linking to patient electronic medical records'. There were no relationships between characteristics of respondents with self-reported adherence. This research produced a theoretical understanding of the experience of medical practitioners when using guidelines. Themes identified were as follows: existing intrinsic flaws in guidelines, deficient or incomplete system mechanism and being ambiguous. CONCLUSION: Our findings provide a comprehensive and culturally sensitive perspective in understanding guideline implementation in China. Strategies addressing those barriers should be further discussed and researched in the future.

4.
J Agric Food Chem ; 67(36): 10222-10234, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31385700

RESUMO

The emergence and rapid spread of methicillin-resistant Staphylococcus aureus (MRSA) critically requires alternative therapeutic options. New antibacterial drugs and strategies are urgently needed to combat MRSA-associated infections. Here, we investigated the antibacterial activity of flavones from Morus alba and the potential mode of action against MRSA. Kuwanon G, kuwanon H, mulberrin, and morusin displayed high efficiency in killing diverse MRSA isolates. On the basis of structure-activity analysis, the cyclohexene-phenyl ketones and isopentenyl groups were critical to increase the membrane permeability and to dissipate the proton motive force. Meanwhile, mechanistic studies further showed that kuwanon G displayed rapid bactericidal activity in vitrowith difficulty in developing drug resistance. Kuwanon G targeted phosphatidylglycerol and cardiolipin in the cytoplasmic membrane through the formation of hydrogen bonds and electrostatic interactions. Additionally, kuwanon G promoted wound healing in a mouse model of MRSA skin infection. In summary, these results indicate that flavones are promising lead compounds to treat MRSA-associated infections through disrupting the proton motive force and membrane permeability.


Assuntos
Antibacterianos/farmacologia , Flavonas/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/metabolismo , Morus/química , Extratos Vegetais/farmacologia , Infecções Estafilocócicas/microbiologia , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Permeabilidade da Membrana Celular/efeitos dos fármacos , Feminino , Flavonas/química , Flavonas/isolamento & purificação , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Humanos , Masculino , Meticilina/farmacologia , Staphylococcus aureus Resistente à Meticilina/genética , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Raízes de Plantas/química , Força Próton-Motriz/efeitos dos fármacos
5.
Biomater Sci ; 7(10): 4388-4398, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31441908

RESUMO

Degenerative changes to rotator cuff tendons are often diagnosed in elderly patients. Spontaneous healing of degenerative tendons is rather inefficient as a result of the lack of a suitable microenvironment for tendon stem cell differentiation and vascularization. Herein, multilayer hyaluronic acid/chitosan (HA/CS) nanofilms were assembled by a layer-by-layer assembly method onto aligned poly(ε-caprolactone) (PCL) nanofibers for use in healing degenerative tendons. Materials testing showed that the number of layers of HA/CS nanofilms could adjust the hydrophilicity and wettability of the nanofibrous membranes. In vitro, the optimal 8-layer (termed as 8LP) membrane afforded aligned morphology of tendon stem/progenitor cells (TSPCs) and up-regulated mRNA expression of tenogenic markers (SCX, BGN). In a rabbit model with disorganized rotator cuff tendons, the 8LP group up-regulated mRNA levels of collagen I/III and tenascin (TNC) at 6 weeks, but not 12 weeks, post-surgery as compared to the native PCL group. Next, vascular endothelial growth factor-loaded 8LP (termed as 8LP-V) was prepared. Compared to 8LP, 8LP-V produced higher levels of angiogenesis in the tendons at 6 or 12 weeks post-surgery, thus supplying endogenous pre-tendon growth factors (TGF-ß, IGF-1) to further enhance tenogenic transcriptional factors. As a result, 8LP-V yielded thicker collagen fibers and/or higher tendon stiffness as compared to the 8LP and clinical pericardial patch groups. This study highlights the rational design of LbL-assembled multilayer HA/CS films to upregulate tenogenesis for robust healing of degenerative rotator cuff tendons.

6.
Cancer Imaging ; 19(1): 55, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375145

RESUMO

The Editors have retracted this article [1] because figure 2 has been substantially duplicated from a previously published article by Chen B et al., 2018 [2]. There is also significant and uncited overlap in the patient population between the two articles resulting in concerns relating to the scientific validity and novelty of the data.

7.
Oncogene ; 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31444411

RESUMO

Genomic amplification of the oncogene MYCN is a major driver in the development of high-risk neuroblastoma, a pediatric cancer with poor prognosis. Given the challenge in targeting MYCN directly for therapy, we sought to identify MYCN-dependent metabolic vulnerabilities that can be targeted therapeutically. Here, we report that the gene encoding glycine decarboxylase (GLDC), which catalyzes the first and rate-limiting step in glycine breakdown with the production of the one-carbon unit 5,10-methylene-tetrahydrofolate, is a direct transcriptional target of MYCN. As a result, GLDC expression is markedly elevated in MYCN-amplified neuroblastoma tumors and cell lines. This transcriptional upregulation of GLDC expression is of functional significance, as GLDC depletion by RNA interference inhibits the proliferation and tumorigenicity of MYCN-amplified neuroblastoma cell lines by inducing G1 arrest. Metabolomic profiling reveals that GLDC knockdown disrupts purine and central carbon metabolism and reduces citrate production, leading to a decrease in the steady-state levels of cholesterol and fatty acids. Moreover, blocking purine or cholesterol synthesis recapitulates the growth-inhibitory effect of GLDC knockdown. These findings reveal a critical role of GLDC in sustaining the proliferation of neuroblastoma cells with high-level GLDC expression and suggest that MYCN amplification is a biomarker for GLDC-based therapeutic strategies against high-risk neuroblastoma.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31429146

RESUMO

RATIONALE: In the process of identification of unknown metabolites, the most important thing is to determine their real chemical formulae according to the accurate mass which were detected by high-resolution mass spectrometry (HRMS). However, high mass accuracy alone is not enough to exclude false candidates. Use of isotopic fine structures (IFSs) derived from FT-ICR MS as a single further constraint could decisively determine the molecular formula for unknown metabolites. METHODS: Gastrodin, an active constituent from Gastrodia elata Bl., which could penetrate through the blood-brain barrier and rapidly decompose to p-hydroxybenzyl alcohol in the brain, was selected as the model drug. The accurate mass, possible chemical formulae and IFSs of its metabolites in rat plasma were acquired by FT-ICR MS. RESULTS: Besides gastrodin, a total of eight metabolites including two phase I and six phase II metabolites were detected. Their chemical formulae were decisively determined by IFSs. Furthermore, their chemical structures were identified by comparing their fragment ions with those of gastrodin. Results indicated that metabolic pathways of gastrodin in rats including deglycosylation, oxidation, glucuronidation, sulfate conjugation and glycine conjugation. CONCLUSIONS: It demonstrated that IFSs were effective in unambiguous determination of chemical formulae of metabolite. It could be used as a feasible strategy to enhance the reliability of metabolite identification in drug metabolism studies.

9.
Nephron ; : 1-6, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31454804

RESUMO

BACKGROUND/AIM: The aim of this study was to investigate the prevalence and significance of antiphospholipid antibodies in patients with membranous nephropathy (MN). METHODS: Patients hospitalized with MN during June 2015 to June 2017 were selected and patients with minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS) in the same period were selected as controls. RESULTS: Overall, 267 patients with MN and 131 patients with MCD/FSGS (n = 101 MCD and n = 30 FSGS) were analyzed. There was a significant difference in the detection rate of anti-ß2-glycoprotein I (anti-ß2-GPI) antibodies (11.9% in MN vs. 4.5% in MCD/FSGS, p = 0.018) and IgG-anti-ß2-GPI antibodies (3.7% in MN vs. 0% in MCD/FSGS, p = 0.034) between the 2 groups. Anti-ß2-GPI antibody-positive MN patients (n = 32) had a lower serum C4 level than anti-ß2-GPI antibody-negative MN patients (n = 235; 21.6 ± 7.6 vs. 24.6 ± 7.1 mg/dL, p = 0.030). Anti-ß2-GPI antibody-positive MN patients had significant improvement of serum creatinine compared to anti-ß2-GPI antibody-negative patients after 24 weeks of treatment (p = 0.006). CONCLUSIONS: Anti-ß2-GPI antibody may play a role in the progression of MN, and this process might involve classic complement activation.

10.
J Exp Clin Cancer Res ; 38(1): 319, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31466523

RESUMO

BACKGROUND: High rates of recurrence and metastasis are the major cause of the poor outcomes for patients with lung cancer. In previous research, we have demonstrated that Tac2-N promotes tumor growth by suppressing p53 signaling in lung cancer. Beyond that, other biological functions and clinical significance of Tac2-N in lung cancer progression are still unknown. METHODS: Tissue microarrays of 272 lung cancer patients were constructed to assess the association of Tac2-N expression and prognosis of lung cancer patients with different clinical stages. The protein expression of Tac2-N in metastatic and non-metastatic specimens were detected by IHC. In vitro migration and invasion and in vivo nude mice metastasis model were used to evaluate the effect of Tac2-N ectopic expression on metastasis capability of lung cancer cells. The downstream signaling pathway of Tac2-N was explored using luciferase reporter assays and WB. RESULTS: The expression of Tac2-N was associated with advanced stages, but not with early stages (P = 0.513). Tac2-N expression is sharply overexpressed in metastatic tumors compared with non-metastatic tumors. In vitro and in vivo assays suggested that Tac2-N facilitated migration and invasion of lung cancer cells in vitro and promoted tumor metastasis in vivo. Mechanistically, Tac2-N increased the degradation of IκB by promoting its phosphorylation, and subsequently activated NF-κB activity by facilitating the nuclear translocation of NF-κB and stimulating the transcription of targets, MMP7 and MMP9. Notably, the C2B domain of Tac2-N was crucial for Tac2-N to activate NF-κB signal. Blockage of NF-κB by shRNA or inhibitor attenuates the function of Tac2-N in the promotion of metastasis. CONCLUSIONS: Our study provided proof of principle to show that Tac2-N serves as a novel oncogene gene and plays an important role in the progression and metastasis of lung cancer.

11.
Cancer Med ; 8(10): 4633-4643, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31268626

RESUMO

PURPOSE: To define the clinical characteristics and prognostic value of pre-retreatment plasma Epstein-Barr virus (EBV) DNA, we investigated EBV status in locoregional recurrent nasopharyngeal carcinoma (lrNPC) patients. METHODS: Between April 2008 and August 2016, the data of patients with nonmetastatic lrNPC were retrospectively reviewed. The survival indexes of patients between different pre-retreatment EBV status groups were compared. RESULTS: A total of 401 patients with nonmetastatic lrNPC were enrolled, and 197 (49.1%) patients had detectable pre-retreatment plasma EBV DNA. Treatment included radiotherapy alone (n = 37 patients), surgery alone (n = 105), radiotherapy (n = 208), surgery combined with radiotherapy (n = 20), chemotherapy and targeted therapy (n = 31). Median follow-up was 32 months. The 3-year locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates for the entire cohort were 64.8%, 89.4%, and 58.8%, respectively. The estimated 3-year LRRFS, DMFS, and OS rates for the pre EBV-positive group vs the pre EBV-negative group were 54.2% vs 75.0% (P < 0.001), 86.6% vs 91.9% (P = 0.05), 51.6% vs 65.9% (P = 0.01), respectively. Among patients in the clinical stage rI/II, there were 17 patients in the radiotherapy alone group and 49 patients in the surgery alone group. And there was no significant difference in overall survival between radiotherapy and surgery, even among the different pre-EBV statuses (P > 0.05). In terms of long-term toxic and side effects, the incidence of radioactive temporal lobe injury in the radiotherapy group was higher than that in the surgery group (35.3% vs 8.2%, P < 0.001), and no statistically significant difference was found in other long-term toxic and side effects. CONCLUSIONS: The positive rate of pre-retreatment plasma EBV DNA in lrNPC is lower than primary NPC. The prognosis of EBV DNA negative group is better than positive group. For locally early-stage lrNPC, regardless of EBV DNA status, radiotherapy and surgery are available options and both can achieve better long-term survival.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31263979

RESUMO

PURPOSE: To compare microstructural features of sleep in young and middle-aged adults with differing severities of obstructive sleep apnea syndrome (OSAS), and to investigate the relationship between sleep microstructural fragmentation and cognitive impairment, as well as daytime sleepiness, in these patients. METHODS: A total of 134 adults with snoring (mean age, 37.54 ± 7.66 years) were classified into four groups based on apnea-hypopnea index: primary snoring, mild OSAS, moderate OSAS, and severe OSAS. Overnight polysomnography was performed to assess respiratory, sleep macrostructure (N1, N2, N3, and R), and sleep microstructure (arousal, cyclic alternating pattern [CAP]) parameters. Cognitive function and daytime sleepiness were assessed using Montreal Cognitive Assessment (MoCA) and Epworth Sleepiness Scale (ESS). RESULTS: As OSAS severity increased, MoCA gradually decreased and ESS gradually increased. N1%, N2%, and N3% sleep were significantly different between the severe OSAS group and the primary snoring, mild OSAS, and moderate OSAS groups (all P < 0.05). Overall arousal index, respiratory-related arousal index, CAP time, CAP rate, phase A index, number of CAP cycles, and phase A average time differed significantly in the moderate and severe OSAS groups compared with the mild OSAS and primary snoring groups (all P < 0.05). The strongest correlations identified by stepwise multiple regression analysis were between phase A3 index and the MoCA and ESS scores. CONCLUSIONS: Sleep microstructure exhibited significant fragmentation in patients with moderate and severe OSAS, which was associated with decreased MoCA and increased ESS scores. This suggests that phase A3 index is a sensitive indicator of sleep fragmentation in OSAS.

13.
Cell Death Differ ; 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31273299

RESUMO

The amino acid antiporter system Xc- is important for the synthesis of glutathione (GSH) that functions to prevent lipid peroxidation and protect cells from nonapoptotic, iron-dependent death (i.e., ferroptosis). While the activity of system Xc- often positively correlates with the expression level of its light chain encoded by SLC7A11, inhibition of system Xc- activity by small molecules (e.g., erastin) causes a decrease in the intracellular GSH level, leading to ferroptotic cell death. How system Xc- is regulated during ferroptosis remains largely unknown. Here we report that activating transcription factor 3 (ATF3), a common stress sensor, can promote ferroptosis induced by erastin. ATF3 suppressed system Xc-, depleted intracellular GSH, and thereby promoted lipid peroxidation induced by erastin. ATF3 achieved this activity through binding to the SLC7A11 promoter and repressing SLC7A11 expression in a p53-independent manner. These findings thus add ATF3 to a short list of proteins that can regulate system Xc- and promote ferroptosis repressed by this antiporter.

15.
J Exp Clin Cancer Res ; 38(1): 321, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31324197

RESUMO

BACKGROUND: Recurrence and metastasis are the leading causes of tumour-related death in patients with oesophageal squamous cell carcinoma (ESCC). Tumour-infiltrating natural killer cells (NK cells) display powerful cytotoxicity to tumour cells and play a pivotal role in tumour therapy. However, the phenotype and functional regulation of NK cells in oesophageal squamous cell carcinoma (ESCC) remains largely unknown. METHODS: Single cell suspensions from blood and tissue samples were isolated by physical dissociation and filtering through a 70 µm cell strainer. Flow cytometry was applied to profile the activity and function of NK cells, and an antibody chip experiment was used to identify and quantitate cytokine levels. We studied IL-6 and IL-8 function in primary oesophageal squamous carcinoma and NK cell co-cultures in vitro and by a xenograft tumour model in vivo. Western blotting was used to quantitate STAT3 (signal transducer and activator of transcription 3) and p-STAT3 levels. Finally, we performed an IHC array to analyse IL-6/IL-8 (interleukin 6/interleukin 8) expression in 103 pairs of tumours and matched adjacent tissues of patients with ESCC to elucidate the correlation between IL-6 or IL-8 and clinical characteristics. RESULTS: The percentages of NK cells in both peripheral blood and tumour tissues from patients with ESCC were significantly increased in comparison with those in the controls and correlated with the clinical characteristics. Furthermore, the decrease in activating receptors and increase in inhibitory receptors on the surface of tumour-infiltrating NK cells was confirmed by flow cytometry. The level of granzyme B, the effector molecule of tumour-infiltrating NK cells, was also decreased. Mechanistically, primary ESCC cells activated the STAT3 signalling pathway on NK cells through IL-6 and IL-8 secretion, leading to the downregulation of activating receptors (NKp30 and NKG2D) on the surface of NK cells. An ex vivo study showed that blockade of STAT3 attenuated the IL-6/IL-8-mediated impairment of NK cell function. Moreover, the expression of IL-6 or IL-8 in tumour tissues was validated by immunohistochemistry to be positively correlated with tumour progression and poor survival, respectively. CONCLUSIONS: Tumour cell-secreted IL-6 and IL-8 impair the activity and function of NK cells via STAT3 signalling and contribute to oesophageal squamous cell carcinoma malignancy.

16.
N Engl J Med ; 381(12): 1124-1135, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31150573

RESUMO

BACKGROUND: Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma. Additional gemcitabine and cisplatin induction chemotherapy has shown promising efficacy in phase 2 trials. METHODS: In a parallel-group, multicenter, randomized, controlled, phase 3 trial, we compared gemcitabine and cisplatin as induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone. Patients with locoregionally advanced nasopharyngeal carcinoma were randomly assigned in a 1:1 ratio to receive gemcitabine (at a dose of 1 g per square meter of body-surface area on days 1 and 8) plus cisplatin (80 mg per square meter on day 1), administered every 3 weeks for three cycles, plus chemoradiotherapy (concurrent cisplatin at a dose of 100 mg per square meter every 3 weeks for three cycles plus intensity-modulated radiotherapy) or chemoradiotherapy alone. The primary end point was recurrence-free survival (i.e., freedom from disease recurrence [distant metastasis or locoregional recurrence] or death from any cause) in the intention-to-treat population. Secondary end points included overall survival, treatment adherence, and safety. RESULTS: A total of 480 patients were included in the trial (242 patients in the induction chemotherapy group and 238 in the standard-therapy group). At a median follow-up of 42.7 months, the 3-year recurrence-free survival was 85.3% in the induction chemotherapy group and 76.5% in the standard-therapy group (stratified hazard ratio for recurrence or death, 0.51; 95% confidence interval [CI], 0.34 to 0.77; P = 0.001). Overall survival at 3 years was 94.6% and 90.3%, respectively (stratified hazard ratio for death, 0.43; 95% CI, 0.24 to 0.77). A total of 96.7% of the patients completed three cycles of induction chemotherapy. The incidence of acute adverse events of grade 3 or 4 was 75.7% in the induction chemotherapy group and 55.7% in the standard-therapy group, with a higher incidence of neutropenia, thrombocytopenia, anemia, nausea, and vomiting in the induction chemotherapy group. The incidence of grade 3 or 4 late toxic effects was 9.2% in the induction chemotherapy group and 11.4% in the standard-therapy group. CONCLUSIONS: Induction chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival and overall survival, as compared with chemoradiotherapy alone, among patients with locoregionally advanced nasopharyngeal carcinoma. (Funded by the Innovation Team Development Plan of the Ministry of Education and others; ClinicalTrials.gov number, NCT01872962.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Cisplatino/administração & dosagem , Desoxicitidina/análogos & derivados , Quimioterapia de Indução , Carcinoma Nasofaríngeo/tratamento farmacológico , Adolescente , Adulto , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Feminino , Humanos , Quimioterapia de Indução/efeitos adversos , Leucopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/terapia , Análise de Sobrevida , Adulto Jovem
17.
Cell Death Dis ; 10(7): 498, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31235687

RESUMO

After publication of this article, it came to the attention of the authors that their names had been reordered. Professor. Jia Cao and Prof. Jin-yi Liu are the co-corresponding authors, and Prof. Jin-yi Liu should be the last author.

18.
Nat Commun ; 10(1): 2409, 2019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31160579

RESUMO

An ideal anti-counterfeiting technique has to be inexpensive, mass-producible, nondestructive, unclonable and convenient for authentication. Although many anti-counterfeiting technologies have been developed, very few of them fulfill all the above requirements. Here we report a non-destructive, inkjet-printable, artificial intelligence (AI)-decodable and unclonable security label. The stochastic pinning points at the three-phase contact line of the ink droplets is crucial for the successful inkjet printing of the unclonable security labels. Upon the solvent evaporation, the three-phase contact lines are pinned around the pinning points, where the quantum dots in the ink droplets deposited on, forming physically unclonable flower-like patterns. By utilizing the RGB emission quantum dots, full-color fluorescence security labels can be produced. A convenient and reliable AI-based authentication strategy is developed, allowing for the fast authentication of the covert, unclonable flower-like dot patterns with different sharpness, brightness, rotations, amplifications and the mixture of these parameters.

19.
Cell ; 178(1): 176-189.e15, 2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31155231

RESUMO

RLR-mediated type I IFN production plays a pivotal role in elevating host immunity for viral clearance and cancer immune surveillance. Here, we report that glycolysis, which is inactivated during RLR activation, serves as a barrier to impede type I IFN production upon RLR activation. RLR-triggered MAVS-RIG-I recognition hijacks hexokinase binding to MAVS, leading to the impairment of hexokinase mitochondria localization and activation. Lactate serves as a key metabolite responsible for glycolysis-mediated RLR signaling inhibition by directly binding to MAVS transmembrane (TM) domain and preventing MAVS aggregation. Notably, lactate restoration reverses increased IFN production caused by lactate deficiency. Using pharmacological and genetic approaches, we show that lactate reduction by lactate dehydrogenase A (LDHA) inactivation heightens type I IFN production to protect mice from viral infection. Our study establishes a critical role of glycolysis-derived lactate in limiting RLR signaling and identifies MAVS as a direct sensor of lactate, which functions to connect energy metabolism and innate immunity.

20.
Nat Commun ; 10(1): 2875, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253766

RESUMO

The charge and spin of the electrons in solids have been extensively exploited in electronic devices and in the development of spintronics. Another attribute of electrons-their orbital nature-is attracting growing interest for understanding exotic phenomena and in creating the next-generation of quantum devices such as orbital qubits. Here, we report on orbital-flop induced magnetoresistance anisotropy in CeSb. In the low temperature high magnetic-field driven ferromagnetic state, a series of additional minima appear in the angle-dependent magnetoresistance. These minima arise from the anisotropic magnetization originating from orbital-flops and from the enhanced electron scattering from magnetic multidomains formed around the first-order orbital-flop transition. The measured magnetization anisotropy can be accounted for with a phenomenological model involving orbital-flops and a spin-valve-like structure is used to demonstrate the viable utilization of orbital-flop phenomenon. Our results showcase a contribution of orbital behavior in the emergence of intriguing phenomena.

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