Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 522
Filtrar
1.
Thyroid ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35019770

RESUMO

BACKGROUND: It is important to understand patient preferences on managing low risk papillary thyroid cancer (PTC). METHODS: We prospectively followed patients with low risk PTC < 2 cm in maximal diameter, who were offered the choice of thyroidectomy or active surveillance (AS) (NCT03271892) at the University Health Network (UHN), in Toronto, Canada. The primary outcome was the frequency of AS choice (percentage with 95% confidence interval). Univariate and multivariable analyses were performed to identify predictors of the choice of AS. RESULTS: We enrolled 200 patients of median age 51 years (interquartile range 42, 62). The primary tumor measured > 1cm in 55.5% of (111/200) of participants. AS was chosen by 77.5% (71.2%, 82.7%, 155/200) of participants. In a backwards conditional regression model, clinical and demographic factors independently associated with choosing AS included: older age (compared to referent group < 40 years) - age 40 to 64 years - Odds Ratio (OR) 2.78 [95% confidence interval, 1.23, 6.30, p = 0.014], age ≥ 65 years - OR 8.43 (2.13, 33.37, p = 0.002), and education level of high school or lower - OR 4.41 (1.25, 15.53, p = 0.021); AS was inversely associated with the patient's surgeon of record being affiliated with the study hospital- OR 0.29 (0.11, 0.76, p = 0.012). In a separate backwards conditional logistic regression model examining associations with psychological characteristics, AS choice was independently associated with a fear of needing to take thyroid hormone after thyroidectomy - OR 1.24 (1.11, 1.39, p < 0.001), but inversely associated with fear of PTC progression - OR 0.94 (0.90, 0.98, p = 0.006) and an active coping mechanism ('doing something') - OR 0.43 (0.28, 0.66, p < 0.001). CONCLUSIONS: Approximately three-quarters of our participants chose AS over surgery. Factors associated with choosing AS included older age, lower education level, and having a surgeon outside the study institution. Patients' fears about either their PTC progressing or taking thyroid hormone replacement as well as level of active coping style were associated with the decision. Our results inform the understanding of patients' decisions on managing low risk PTC.

2.
Chem Commun (Camb) ; 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34981089

RESUMO

Porous NiCo2S4@SiO2 is employed as the sulfur host. The negatively charged SiO2 can increase the charge density and conductivity of NiCo2S4 and accelerate the conversion of sulfur. The charge transfer effect would in turn reduce the electrostatic repulsion between SiO2 and negatively charged polysulfide, thereby enhancing the adsorption of polysulfides.

3.
Oral Oncol ; 125: 105716, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35038657

RESUMO

BACKGROUND AND PURPOSE: This study aims to evaluate the reliability of radiologic nodal feature assessment in clinical node-positive human papillomavirus-positive oropharyngeal carcinoma. MATERIALS AND METHODS: Baseline CTs or MRIs of clinical node-positive human papillomavirus-positive oropharyngeal carcinoma diagnosed between 2012 and 2015 were reviewed independently by two neuroradiologists for seven nodal features: radiologic nodal involvement, cystic change, presence of necrosis, clustering, conglomeration, coalescence, and extranodal extension. Consensus operating definitions were derived after discussion. The features were re-reviewed in a randomly selected cohort. Levels of certainty (probability of presence: <25%, ∼50%, ∼75%, and >90%) were recorded. Interrater concordance was calculated using Cohen's kappa coefficient. RESULTS: A total of 413 patients (826 necks) were eligible. At initial review, the inter-rater kappa values for: radiologic nodal involvement, cystic change, necrosis, clustering, conglomeration, coalescence, and extranodal extension were 0.92, 0.64, 0.48, 0.32, 0.32, 0.62, and 0.56, respectively. A re-review of 94 randomly selected cases (188 necks) after consolidation of operating definitions for nodal features showed that the inter-rater kappa values of these features were 0.83, 0.62, 0.58, 0.32, 0.18, 0.68, and 0.74 when considering ≥50% certainty as positive, and improved to 0.94, 0.66, 0.59, 0.33, 0.19, 0.76, and 0.86 when considering ≥75% certainty as positive. CONCLUSION: Clearly defined nomenclature results in improved interrater reliability when assessing radiologic nodal features, especially for coalescent adenopathy and extranodal extension. Higher levels of certainty are associated with higher inter-rater agreement. Radiology reporting should include clear definitions of clinically relevant nodal features as well as levels of certainty to serve various needs in clinical care and research.

4.
Brain Behav Immun ; 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35026421

RESUMO

Inflammatory and neuropathic-like components underlie rheumatoid arthritis (RA)-associated pain and lysophosphatidic acid (LPA) is linked to both joint inflammation in RA patients and to neuropathic pain. Thus, we investigated a role for LPA signalling using the collagen antibody-induced arthritis (CAIA) model. Pain-like behavior during the inflammatory phase and the late, neuropathic-like phase of CAIA was reversed by a neutralizing antibody generated against LPA and by an LPA1/3 receptor inhibitor, but joint inflammation was not affected. Autotaxin, an LPA synthesizing enzyme was upregulated in dorsal root ganglia (DRG) neurons during both CAIA phases, but not in joints or spinal cord. Late-phase pronociceptive neurochemical changes in the DRG were blocked in Lpar1 receptor deficient mice and reversed by LPA neutralization. In vitro and in vivo studies indicated that LPA regulates pain-like behavior via the LPA1 receptor on satellite glia cells (SGCs), which is expressed by both human and mouse SGCs in the DRG. Furthermore, CAIA-induced SGC activity is reversed by phospholipid neutralization and blocked in Lpar1 deficient mice. Our findings suggest that the regulation of CAIA-induced pain-like behavior by LPA signalling is a peripheral event, associated with the DRGs and involving increased pronociceptive activity of SGCs, which in turn act on sensory neurons.

5.
Front Pharmacol ; 12: 754185, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34880754

RESUMO

Background and Aims: The diagnosis of Wilson's disease (WD) is challenging by clinical or genetic criteria. A typical early pathological change of WD is the increased liver lipid deposition and lowered serum triglyceride (TG). Therefore, the contents of serum lipids may provide evidence for screening of biomarkers for WD. Methods: 34 WD patients, 31 WD relatives, and 65 normal controls were enrolled in this study. Serum lipidomics data was acquired by an ultra-high-performance liquid chromatography high-resolution mass spectrometry system, and the data were analyzed by multivariate statistical methods. Results: Of all 510 identified lipids, there are 297 differential lipids between the WD and controls, 378 differential lipids between the relatives and controls, and 119 differential lipids between the patients and relatives. In WD, the abundances of most saturated TG were increased, whereas other unsaturated lipids decreased, including phosphatidylcholine (PC), sphingomyelin (SM), lysophosphatidylcholine (LPC), ceramide (Cer), and phosphatidylserine (PS). We also found many serum lipid species may be used as biomarkers for WD. The areas under the receiver operating characteristic curve (AUC) of PS (35:0), PS (38:5), and PS (34:0) were 0.919, 0.843, and 0.907. The AUCs of TG (38:0) and CerG1 (d42:2) were 0.948 and 0.915 and the AUCs of LPC (17:0) and LPC (15:0) were 0.980 and 0.960, respectively. The lipid biomarker panel exhibits good diagnostic performance for WD. The correlation networks were built among the different groups and the potential mechanisms of differential lipids were discussed. Interestingly, similar lipid profile of WD is also found in their relatives, which indicated the changes may also related to the mutation of the ATP7B gene. Conclusions: Lipid deregulation is another important hallmark of WD besides the deposition of copper. Our lipidomic results provide new insights into the diagnostic and therapeutic targets of WD.

6.
J Phys Chem Lett ; : 11834-11842, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34870988

RESUMO

Using density functional theory combined with ab initio molecular dynamics, we comprehensively investigated the performance enhancement mechanism of the device after surface reconstruction by passivating different halogen groups (i.e., F or Cl) at the ETL/perovskite interface. We demonstrated that the halogen group at the ETL layer could stabilize the geometric structure of the perovskite surface by balancing the interfacial interaction, ionic migration, and lead iodide framework. Even though halogen passivation decreased and increased the interface charge transfer at the O- and SnO-terminated MAPbI3/SnO2 interfaces, respectively, halogen passivation optimized surface reconstruction and could theoretically relieve the interface carrier recombination according to the changes in conduction band offsets generated by halogen passivation. Furthermore, the interfacial carrier recombination of the MAPbI3/SnO2 interface was also connected to the interfacial gap states, which were smaller for O-terminated MAPbI3/SnO2 interfaces with halogen passivation-induced surface reconstruction but larger for the SnO-terminated cases. Hence, our findings have implications for the design of buried interface optimization in perovskite optoelectronic devices.

7.
Zookeys ; 1071: 109-126, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34887696

RESUMO

Diglyphus species are ecologically and economically important on agromyzid leafminers. In 2018, a thelytokous species, Diglyphuswani Liu, Zhu & Yefremova, was firstly reported and described. Subsequently, the arrhenotokous D.wani were discovered in Yunnan and Guizhou Provinces of China. We compared the morphological characteristics of thelytokous and arrhenotokous strains. However, the females of two strains had a strongly similar morphology and showed subtle differences in fore- and hind-wings. The difference was that forewing of arrhenotokous female was with denser setae overall, showing that costal cell with 2 ~ 4 rows of setae on dorsal surface and the setae of basal cell with 15 ~ 21 hairs and forewing of thelytokous female was with two rows of setae on dorsal surface and basal cell with 10 ~ 15 hairs generally. The setation beneath the marginal vein of the hind-wing of arrhenotokous female is denser than the same area of thelytokous female. To explore the genetic divergence between thelytokous and arrhenotokous strains of D.wani, the mitochondrial and nuclear gene were applied and sequenced. The polygenic analyses revealed that two strains can be distinguished by COI, ITS1 and ITS2. The mean sequence divergence between the two strains was 0.052, 0.010 and 0.007, respectively. Nevertheless, the 28S gene was unfeasible due to its containing a sharing haplotype between different strains. The two strains of D.wani are dominant parasitoids against agromyzid leafminers and such effective discernible foundation provides future in-depth studies on biological characteristics, along with insight into field application of two strains of D.wani.

8.
J Neurosci ; 2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34907025

RESUMO

The dorsal anterior cingulate cortex (dACC) plays a critical role in cognitive control over different domains of tasks. The dACC activities uniformly represent task-generic intensities of control signals across different tasks. However, it remains unclear whether the dACC activities could also encode task identities of control signals across different tasks. If so, how the two types of control information are coherently organized in the dACC? Decision uncertainty is an internally-generated control signal by retrospective monitoring, namely, metacognition, even with no external feedback. We here investigated neural representations of decision uncertainty accompanying three decision-making tasks in the domains of perception, rule-based inference, and memory using trial-by-trial univariate and multivariate analyses on functional magnetic imaging data acquired on human male and female healthy subjects. Our results demonstrated that the dACC represented decision uncertainty commonly across the three decision-making tasks. Further, the multivariate fMRI analyses revealed a mosaic form of neural representations of decision uncertainty across tasks in the dACC. The identity and intensity information was separately represented in two dissociable components--the high-dimensional pattern and the scalar magnitude--of the dACC multi-voxel fMRI activities. Lastly, a follow-up behavioral experiment confirmed that this mosaic form of neural representations of parallelly existing decision uncertainty across different tasks should lead to mutual interferences more on the intensity, but less on the identity of control signals. Thus, our findings suggest that the dACC with the mosaic form of neural representations could provide task-generic and task-specific metacognitive control signals to guide appropriate control on different decision-making tasks.SIGNIFICANCE STATEMENTMetacognition is a form of cognitive control using internally generated decision uncertainty to guide behavior adjustment with no needs of external feedback. Decision uncertainty as a generalizable control signal is commonly encoded in the human dACC accompanying different decision-making tasks. It remains unknown whether or not the task-specific control information is represented in the dACC. We here revealed that multi-voxel fMRI activities associated with decision uncertainty in the dACC concurrently represented the identity and intensity information. The mixtures of neural representations of decision uncertainty across different tasks should cause specific interferences on each other. Hence, the neural representations of control signals in the human dACC should be task-generic and task-specific.

9.
Exp Eye Res ; 215: 108851, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34896307

RESUMO

We aimed to investigate the change patterns in corneal sub-basal nerve morphology and corneal intrinsic aberrations in dry eye disease (DED). Our study included 229 eyes of 155 patients with DED and 40 eyes of 20 healthy control. We used the Oculus keratograph and the ocular surface disease index questionnaire to assess their signs and symptoms. In vivo confocal microscopy was used to observe the corneal sub-basal nerves, corneal endothelial cells, and Langerhans cells (LCs). An artificial intelligence (AI) technique run by the deep learning model generated the sub-basal nerve fibre parameters. Furthermore, we used the Pentacam HR system to measure the corneal intrinsic aberrations and corneal surface regularity indices. DED patients more frequently had increased anterior and total corneal aberrations than controls (P < 0.05). In addition, DED had decreased average density and maximum length of corneal nerve. (Both P < 0.01) The LC number was significantly correlated with maximum length (CC = -0.19, P = 0.01) of the sub-basal nerve fibre. Furthermore, the corneal nerve average density was negatively correlated with IHD, and anterior, posterior, and total corneal aberrations (All P < 0.05) especially the higher-order aberrations. Significant correlations were seen between corneal nerve morphology changes, analysed by AI and corneal intrinsic aberrations, particularly higher-order aberrations.

10.
Percept Mot Skills ; : 315125211059407, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34911404

RESUMO

Our objective in this paper was to systematically review evaluations of the effects of exercises on pain symptoms and activities of daily living (ADL) in middle-aged and elderly patients with low back pain (LBP). We searched Web of Science, PubMed, EBSCO, and China National Knowledge Internet (CNKI) databases for randomized controlled trials (RCTs) on this topic. We evaluated the methodological quality of included articles using the Physiotherapy Evidence Database (PEDro) scale, and we statistically analyzed these studies using RevMan software. We reviewed 18 RCTs (23 comparison groups) with a total of 910 participants, and our meta-analysis confirmed that exercises significantly improved both pain and ADLs measured on visual analog scales (VAS) (SMD = -0.91, 95% CI: [-1.3, -0.52], p < 0.00001) and on the Oswestry Disability Index (ODI) (SMD = -2.07, 95% CI: [-3.19, -0.96], p < 0.00001). We conclude that exercises can reduce pain severity and improve ADL capacity in middle-aged and elderly persons with LBP, confirming that exercise can serve as a medical intervention for these indivdiuals. However, given the high heterogeneity of responses among individual participants, there remains a need for further study.

11.
Mar Drugs ; 19(12)2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34940650

RESUMO

Alcalase, neutral protease, and pepsin were used to hydrolyze the skin of Takifugu flavidus. The T. flavidus hydrolysates (TFHs) with the maximum degree of hydrolysis (DH) and angiotensin-I-converting enzyme (ACE)-inhibitory activity were selected and then ultra-filtered to obtain fractions with components of different molecular weights (MWs) (<1, 1-3, 3-10, 10-50, and >50 kDa). The components with MWs < 1 kDa showed the strongest ACE-inhibitory activity with a half-maximal inhibitory concentration (IC50) of 0.58 mg/mL. Purification and identification using semi-preparative liquid chromatography, Sephadex G-15 gel chromatography, RP-HPLC, and LC-MS/MS yielded one new potential ACE-inhibitory peptide, PPLLFAAL (non-competitive suppression mode; IC50 of 28 µmmol·L-1). Molecular docking and molecular dynamics simulations indicated that the peptides should bind well to ACE and interact with amino acid residues and the zinc ion at the ACE active site. Furthermore, a short-term assay of antihypertensive activity in spontaneously hypertensive rats (SHRs) revealed that PPLLFAAL could significantly decrease the systolic blood pressure (SBP) and diastolic blood pressure (DBP) of SHRs after intravenous administration. These results suggested that PPLLFAAL may have potential applications in functional foods or pharmaceuticals as an antihypertensive agent.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34962680

RESUMO

A series of luminescent frameworks were synthesized from the selective combination of AIE-linker tetra-(4-carboxylphenyl)ethylene (H 4 TCPE) and Zn 2+ . Complex 1 was formed by the close packing of Zn-TCPE hinge, and isostructural complexes 2 - 5 were constructed by the linkage of Zn-TCPE layer and pillar ligand. These complexes exhibit highly efficient multiphoton excited photoluminescence (MEPL) concomitant third-harmonic generation (THG). Interestingly, multiphoton apparent parameters of 1 are far superior to some excellent multiphoton emission materials, even the perovskite nanocrystal. The incorporation of pillar linkers slows down the charge transfer between layers of Zn-TCPE, and the aromatic core of pillar linkers has a great influence on the MEA performance of corresponding frameworks. The unprecedented structural and optical tuning of high performance MPA crystalline materials provides efficient suggestion for the design of next generation multiphoton absorption materials.

13.
Nat Commun ; 12(1): 6364, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34737305

RESUMO

Lysocin E is a lipopeptide with antibiotic activity against methicillin-resistant Staphylococcus aureus. For unclear reasons, the antibacterial activity of lysocin E in a mouse systemic infection model is higher than expected from in vitro results, and the in vitro activity is enhanced by addition of bovine serum. Here, we confirm that serum from various species, including humans, increases lysocin E antimicrobial activity, and identify apolipoprotein A-I (ApoA-I) as an enhancing factor. ApoA-I increases the antibacterial activity of lysocin E when added in vitro, and the antibiotic displays reduced activity in ApoA-I gene knockout mice. Binding of ApoA-I to lysocin E is enhanced by lipid II, a cell-wall synthesis precursor found in the bacterial membrane. Thus, the antimicrobial activity of lysocin E is potentiated through interactions with host serum proteins and microbial components.

14.
Dalton Trans ; 50(47): 17785-17791, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34821237

RESUMO

A series of microporous Ln(III)-based metal-organic frameworks (1-Ln) have been hydrothermally synthesized using 4,4',4''-nitrilotribenzoic acid (H3NTB). Single crystal X-ray diffraction analyses show that 1-Ln are isostructural and have 3D porous frameworks with remarkable stability and permanent porosity for Ar and CO2 adsorption. In addition, 1-Ln exhibit diverse photoluminescence emissions depending on the nature of lanthanide ions. More importantly, 1-Ln are further studied in the Knoevenagel reactions of benzaldehyde derivatives and malononitrile under solvent-free conditions, and it is found that 1-Tb shows the best catalytic activities (yields up to 99%), providing a unique example to differentiate the roles of Ln ions within the frameworks in catalyzing Knoevenagel reactions.

15.
EMBO Mol Med ; : e14296, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34845836

RESUMO

More than 60% of nonsmall cell lung cancer (NSCLC) patients show a positive response to the first ALK inhibitor, crizotinib, which has been used as the standard treatment for newly diagnosed patients with ALK rearrangement. However, most patients inevitably develop crizotinib resistance due to acquired secondary mutations in the ALK kinase domain, such as the gatekeeper mutation L1196M and the most refractory mutation, G1202R. Here, we develop XMU-MP-5 as a new-generation ALK inhibitor to overcome crizotinib resistance mutations, including L1196M and G1202R. XMU-MP-5 blocks ALK signaling pathways and inhibits the proliferation of cells harboring either wild-type or mutant EML4-ALK in vitro and suppresses tumor growth in xenograft mouse models in vivo. Structural analysis provides insights into the mode of action of XMU-MP-5. In addition, XMU-MP-5 induces significant regression of lung tumors in two genetically engineered mouse (GEM) models, further demonstrating its pharmacological efficacy and potential for clinical application. These preclinical data support XMU-MP-5 as a novel selective ALK inhibitor with high potency and selectivity. XMU-MP-5 holds great promise as a new therapeutic against clinically relevant secondary ALK mutations.

16.
Int J Biol Macromol ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34767882

RESUMO

Osteoporosis is a systemic metabolic bone disease with an increasing incidence rate. Chinese medicinal herbs have a long history of treating bone diseases. Polysaccharides are an important category of phytochemicals in Chinese medicinal herbs, and their health benefits have increased the interest of the public. Numerous studies have indicated that polysaccharides exhibit anti-osteoporosis effects by balancing bone resorption and bone formation, but the detailed effects and mechanism have not been systematically summarized. We performed a comprehensive review of the literature to consolidate studies for the period 2000-2021 by conducting electronic searches on the PubMed, CNKI, VIP, and Wanfang databases. In total, polysaccharides from 19 kinds of Chinese medicinal herbs in 54 studies have shown bone homeostasis protective properties. In vivo and in vitro experiments have demonstrated that polysaccharides present properties in the treatment of postmenopausal osteoporosis, senile osteoporosis, and glucocorticoid-induced secondary osteoporosis, especially postmenopausal osteoporosis. Moreover, a number of signalling pathways, such as the Wnt/ß-catenin signalling pathway, BMP/SMAD/RUNX2 signalling pathway, OPG/RANKL/RANK signalling pathway, apoptosis pathway, and transcription factors, are regulated by polysaccharides and participate in improving bone homeostasis. This review will provide a better understanding of the anti-osteoporotic effects of polysaccharides and the concomitant modulations of signalling pathways.

17.
Int J Mol Sci ; 22(21)2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34768735

RESUMO

Various factors such as ultraviolet rays can cause a continuous threat to our skin, resulting in inflammation or oxidation problems. Ferulic acid (FA), with certain antioxidant and anti-inflammatory properties, is widely used in many cosmetics, even used to treat various diseases in the clinic. In this study, the FA structural skeleton was used to search for FA derivatives. Then, molecular docking, the rule of five, and Veber rules were performed to virtually screen compounds that can bind to proteins with a good drug likeness. DPPH and ABTS were used to evaluate their antioxidant potency and an MTT assay was employed to investigate the toxicities of the compounds, while Griess Reaction System and ELISA were used to judge the concentration variations of NO and different inflammatory factors (TNF-α, IL-1ß, and IL-6). Western blotting featured nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression levels. The trend of the intracellular changes of reactive oxygen species (ROS) was detected by the DCFH-DA method and fluorescence staining. As a result, we found that the ferulic acid derivative S-52372 not only had certain scavenging effects on free radicals in biochemical experiments, but also prevented inflammation and oxidative stress in LPS-stimulated RAW264.7 cells in the cellular environment; intracellular ROS and inflammatory mediators, including iNOS, COX-2, TNF-α, and IL-6, were also suppressed. In a computer prediction, S-52372 owned better water solubility and lower toxicity than FA. This compound deserves further research to find an ideal FA derivative.

18.
Int J Cancer ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34792199

RESUMO

We compare outcomes in two large-scale contemporaneously treated HPV-positive (HPV+) oropharynx cancer (OPC) cohorts treated with definitive radiotherapy/chemoradiotherapy (RT/CRT). p16-confirmed HPV+ OPC treated between 2007 and 2015 at PMH and DAHANCA were identified. Locoregional failure (LRF), distant metastasis (DM), and overall survival (OS) were compared. Multivariable analysis (MVA) calculated adjusted-hazard-ratio (aHR) with 95% confidence interval (95% CI), adjusting for cohort, age, gender, performance status, smoking pack-years, T-category and N-category and chemotherapy. Compared to PMH (n = 701), DAHANCA (n = 1174) contained lower TNM-8T-categories (T1-T2: 77% vs 56%), N-categories (N0-N1: 77% vs 67%) and stages (stage I: 63% vs 44% (all P < .001). PMH used standard-fractionation CRT in 69% (481) while 31% (220) received hypofractionated or moderately accelerated RT-alone. All DAHANCA patients were treated with moderately accelerated RT; 96% (1129) received nimorazole (NIM) and 73% (856) concurrent weekly cisplatin. DAHANCA had shorter overall-treatment-time (P < .001), lower gross tumor (66-68 vs 70 Gy) and elective neck (50 vs 56 Gy) doses. Median follow-up was 4.8 years. DAHANCA had higher 5-year LRF (13% vs 7%, aHR = 0.47 [0.34-0.67]), comparable DM (7% vs 12%, aHR = 1.32 [0.95-1.82]), but better OS (85% vs 80%, aHR = 1.30 [1.01-1.68]). CRT patients had a lower risk of LRF (aHR 0.56 [0.39-0.82]), DM (aHR 0.70 [0.50-1.00]) and death (aHR 0.39 [0.29-0.52]) vs RT-alone. We observed exemplary outcomes for two large-scale trans-Atlantic HPV+ OPC cohorts treated in a similar manner. Concurrent chemotherapy was a strong, independent prognostic factor for all endpoints. Our findings underscore the need for a very careful approach to de-intensification of treatment for this disease.

19.
Int J Mol Sci ; 22(22)2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34830006

RESUMO

It seems quite necessary to obtain effective substances from natural products against inflammatory response (IR) as there are presently clinical problems regarding accompanying side effects and lowered quality of life. This work aimed to investigate the abilities of hyssopuside (HY), a novel phenolic glycoside isolated from Hyssopus cuspidatus (H. cuspidatus), against IR in lipopolysaccharide (LPS)-induced RAW 264.7 cells and mouse peritoneal macrophages. The results indicated that HY could reduce nitric oxide (NO) production and inhibit the production and secretion of pro-inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) in LPS-stimulated macrophages. Moreover, data from the immunofluorescence study showed that HY suppressed nuclear translocation of nuclear factor-kappa B (NF-κB) upon LPS induction. The Western blot results suggested that HY reversed the LPS-induced degradation of IκB (inhibitor of NF-κB), which is normally required for the activation of NF-κB. Meanwhile, the overexpression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) diminished significantly with the presence of HY in response to LPS stimulation. On the other hand, HY had a negligible impact on the activation of mitogen-activated protein kinase (MAPK) pathways. Moreover, an in silico study of HY against four essential proteins/enzymes revealed that COX-2 was the most efficient enzyme for the interaction, and binding of residues Phe179, Asn351, and Ser424 with HY played crucial roles in the observed activity. The structure analysis indicated the typical characterizations with phenylethanoid glycoside contributed to the anti-inflammatory effects of HY. These results indicated that HY manipulated its anti-inflammatory effects mainly through blocking the NF-κB signal transduction pathways. Collectively, we believe that HY could be a potential alternative phenolic agent for alleviating excessive inflammation in many inflammation-associated diseases.

20.
Adv Sci (Weinh) ; : e2103482, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34761562

RESUMO

Generally, growing phase pure CsPbBr3 single crystals is challenging, and CsPb2 Br5 or Cs4 PbBr6 by-products are usually formed due to the different solubilities of CsBr and PbBr2 in the single solvent. Herein, the growth of high-quality phase pure CsPbBr3 perovskite single crystals at room temperature by a humidity controlled solvent evaporation method is reported first. Meanwhile, the room temperature phase transition process from three dimensional (3D) cubic CsPbBr3 to two dimensional (2D) layered tetragonal CsPb2 Br5 and the detailed mechanism induced by humidity are revealed. Moreover, compared with the organic-inorganic perovskite, the prepared CsPbBr3 single crystals are much more stable under high humidity, which satisfies the long-term working conditions of X-ray detectors. The X-ray detectors based on CsPbBr3 single crystals show a high sensitivity and a low detection limit of 1.89 µGyair s-1 , all of which meet the needs of medical diagnosis.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...