A White Random Laser Chang, Shu-Wei; Liao, Wei-Cheng; Liao, Yu-Ming ...
Scientific reports,
02/2018, Letnik:
8, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Random laser with intrinsically uncomplicated fabrication processes, high spectral radiance, angle-free emission, and conformal onto freeform surfaces is in principle ideal for a variety of ...applications, ranging from lighting to identification systems. In this work, a white random laser (White-RL) with high-purity and high-stability is designed, fabricated, and demonstrated via the cost-effective materials (e.g., organic laser dyes) and simple methods (e.g., all-solution process and self-assembled structures). Notably, the wavelength, linewidth, and intensity of White-RL are nearly isotropic, nevertheless hard to be achieved in any conventional laser systems. Dynamically fine-tuning colour over a broad visible range is also feasible by on-chip integration of three free-standing monochromatic laser films with selective pumping scheme and appropriate colour balance. With these schematics, White-RL shows great potential and high application values in high-brightness illumination, full-field imaging, full-colour displays, visible-colour communications, and medical biosensing.
Human ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) is an evolutionarily conserved core subunit of mitochondrial respiratory chain complex III. We recently identified the ...disease-associated variants of UQCRC1 from patients with familial parkinsonism, but its function remains unclear. Here we investigate the endogenous function of UQCRC1 in the human neuronal cell line and the Drosophila nervous system. Flies with neuronal knockdown of uqcrc1 exhibit age-dependent parkinsonism-resembling defects, including dopaminergic neuron reduction and locomotor decline, and are ameliorated by UQCRC1 expression. Lethality of uqcrc1-KO is also rescued by neuronally expressing UQCRC1, but not the disease-causing variant, providing a platform to discern the pathogenicity of this mutation. Furthermore, UQCRC1 associates with the apoptosis trigger cytochrome c (cyt-c), and uqcrc1 deficiency increases cyt-c in the cytoplasmic fraction and activates the caspase cascade. Depleting cyt-c or expression of the anti-apoptotic p35 ameliorates uqcrc1-mediated neurodegeneration. Our findings identify a role for UQCRC1 in regulating cyt-c-induced apoptosis.
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•Neuronal reduction of uqcrc1, the ETC complex III subunit, causes PD-like symptoms•uqcrc1 regulates DA neuronal maintenance and locomotor activity in flies•The disease-associated uqcrc1 variant fails to bind cytochrome c, triggering apoptosis•Targeting cytochrome c, but not ROS, ameliorates uqcrc1-mediated neurodegeneration
Point mutations in human UQCRC1 associate with familial parkinsonism, but the underlying mechanisms remain unclear. Using the fruit fly as a model, Hung et al. show that the disease variant fails to retain apoptosis trigger cyt-c in mitochondria, resulting in apoptotic neurodegeneration.
Pyrophosphate ion (PPi) release after nucleotide incorporation is a necessary step for RNA polymerase II (pol II) to enter the next nucleotide addition cycle during transcription elongation. However, ...the role of pol II residues in PPi release and the mechanistic relationship between PPi release and the conformational change of the trigger loop remain unclear. In this study, we constructed a Markov state model (MSM) from extensive all-atom molecular dynamics (MD) simulations in the explicit solvent to simulate the PPi release process along the pol II secondary channel. Our results show that the trigger loop has significantly larger intrinsic motion after catalysis and formation of PPi, which in turn aids PPi release mainly through the hydrogen bonding between the trigger loop residue H1085 and the (Mg–PPi)2– group. Once PPi leaves the active site, it adopts a hopping model through several highly conserved positively charged residues such as K752 and K619 to release from the pol II pore region of the secondary channel. These positive hopping sites form favorable interactions with PPi and generate four kinetically metastable states as identified by our MSM. Furthermore, our single-mutant simulations suggest that H1085 and K752 aid PPi exit from the active site after catalysis, whereas K619 facilitates its passage through the secondary channel. Finally, we suggest that PPi release could help the opening motion of the trigger loop, even though PPi release precedes full opening of the trigger loop due to faster PPi dynamics. Our simulations provide predictions to guide future experimental tests.
Abstract
Background
We aimed to evaluate the prognostic significance of preoperative neutrophil‐to‐albumin ratio (NAR) in oral squamous cell carcinoma (OSCC).
Methods
A total of 622 patients with ...surgically treated OSCC were enrolled. NAR was defined as the absolute neutrophil count divided by the serum albumin level in peripheral blood before the radical surgery. Cox proportional hazards model were used to discover survival outcome‐associated factors.
Results
The optimal cut‐off of NAR to predict overall survival (OS) was determined to be 0.1. In Cox model, high NAR was identified as an independent negative prognosticator of OS, cancer‐specific survival, and recurrence‐free survival (adjusted hazard ratio: 1.503, 1.958, and 1.727, respectively; all
p
< 0.05). The NAR‐based nomogram accurately predicted OS (concordance index: 0.750).
Conclusion
Our study suggests that preoperative NAR is a convenient and effective prognostic marker for OSCC and NAR‐based nomogram can be a promising prognostic tool in clinical setting.
To determine the predictive factors of postoperative hospital stay and total hospital medical cost among patients who underwent total laryngectomy. A total of 213 patients who underwent total ...laryngectomy in a tertiary referral center for tumor ablation were enrolled retrospectively between January 2009 and May 2018. Statistical analyses including Pearson's chi-squared test were used to determine whether there was a significant difference between each selected clinical factors and outcomes. The outcomes of interest including postoperative length of hospital stay and inpatient total medical cost. Logistic regression analyses were performed to reveal the relationship between clinical factors and postoperative length of hospital stay or total inpatient medical cost. Preoperative radiotherapy (p = 0.007), method of wound closure (p < 0.001), postoperative serum albumin level (p = 0.025), and postoperative serum hemoglobin level (p = 0.04) were significantly associated with postoperative hospital stay in univariate analysis. Postoperative hypoalbuminemia (odds ratio OR: 2.477; 95% confidence interval CI: 1.189-5.163; p = 0.015) and previous radiotherapy history (OR 2.194; 95% CI: 1.228-3.917; p = 0.008) are independent predictors of a longer postoperative hospital stay in multiple regression analysis. With respect to total inpatient medical cost, method of wound closure (p < 0.001), preoperative serum albumin level (p = 0.04), postoperative serum albumin level (p < 0.001), and history of liver cirrhosis (p = 0.037) were significantly associated with total inpatient medical cost in univariate analysis. Postoperative hypoalbuminemia (OR: 6.671; 95% CI: 1.927-23.093; p = 0.003) and microvascular free flap reconstruction (OR: 5.011; 95% CI: 1.657-15.156; p = 0.004) were independent predictors of a higher total inpatient medical cost in multiple regression analysis. Postoperative albumin status is a significant factor in predicting prolonged postoperative hospital stay and higher inpatient medical cost among patients who undergo total laryngectomy. In this cohort, the inpatient medical cost was 48% higher and length of stay after surgery was 35% longer among hypoalbuminemia patients.
Background
For R/M HNSCC, the differences in prognosis and treatment options between distant metastasis (DM) and locoregional recurrence, especially in the DM group, remain unclear.
Methods
From the ...Taiwan Head Neck Society registry database, patients who were diagnosed with R/M HNSCC and received cetuximab‐based frontline therapy were collected for analysis.
Results
Among the enrolled patients, 59.3% (491/827) belonged to the DM group. The DM group had less primary site of oral cavity, less betel nut chewing, higher lactate dehydrogenase (LDH) levels, and higher LDH/albumin ratio compared with the non‐DM group. For the patients with primary site of oral cavity and current smokers, DM coexisted with poorer outcomes. In the DM group, EXTREME‐like regimen was more suitable for older patients, those with elevated LDH, and those with higher LDH/albumin ratio than TPExtreme‐like regimen.
Conclusion
DM coexisted with poorer prognosis in certain groups. LDH‐associated biomarkers may aid treatment options for DM patients.
Tumor multifocality and location are prognostic factors for upper tract urothelial carcinoma (UTUC). However, confounding effects can appear when these two factors are analyzed together. Therefore, ...we aimed to investigate the impact of tumor distribution on the outcomes of multifocal UTUC after radical nephroureterectomy. From the 2780 UTUC patients in the Taiwan UTUC Collaboration Group, 685 UTUC cases with multifocal tumors (defined as more than one tumor lesion in unilateral upper urinary tract) were retrospectively included and divided into three groups: multiple renal pelvic tumors, multiple ureteral tumors, and synchronous renal pelvic and ureteral tumors included 164, 152, and 369 patients, respectively. We found the prevalence of carcinoma in situ was the highest in the synchronous group. In multivariate survival analyses, tumor distribution showed no difference in cancer-specific and disease-free survival, but there was a significant difference in bladder recurrence-free survival. The synchronous group had the highest bladder recurrence rate. In summary, tumor distribution did not influence the cancer-specific outcomes of multifocal UTUC, but synchronous lesions led to a higher rate of bladder recurrence than multiple renal pelvic tumors. We believe that the distribution of tumors reflects the degree of malignant involvement within the urinary tract, but has little significance for survival or disease progression.
Abnormal DRP1 expression has been identified in a variety of human cancers. However, the prognostic potential and mechanistic role of DRP1 in head and neck cancer (HNC) are currently poorly ...understood. Here, we demonstrated a significant upregulation of DRP1 in HNC tissues, and that DRP1 expression correlates with poor survival of HNC patients. Diminished DRP1 expression suppressed tumor growth and metastasis in both in vitro and in vivo models. DRP1 expression was positively correlated with FOXM1 and MMP12 expression in HNC patient samples, suggesting pathological relevance in the context of HNC development. Moreover, DRP1 depletion affected aerobic glycolysis through the downregulation of glycolytic genes, and overexpression of MMP12 in DRP1‐depleted cells could help restore glucose consumption and lactate production. Using ChIP‐qPCR, we showed that DRP1 modulates FOXM1 expression, which can enhance MMP12 transcription by binding to its promoter. We also showed that miR‐575 could target 3’UTR of DRP1 mRNA and suppress DRP1 expression. Collectively, our study provides mechanistic insights into the role of DRP1 in HNC and highlights the potential of targeting the miR‐575/DRP1/FOXM1/MMP12 axis as a novel therapy for the prevention of HNC progression.
This study reveals that high DRP1 expression is correlated with poor survival in patients with head and neck cancer (HNC). Moreover, DRP1 modulates growth, metastasis and glycolysis of HNC cells via a FOXM1/MMP12 axis. We note that miR‐575 targets and degrades DRP1 mRNA, inhibiting DRP1‐induced aggressive phenotypes. Our work highlights DRP1 as a potential therapeutic target for patients with HNC.
Nasopharyngeal carcinoma (NPC) is known for its high metastatic potential and locoregional recurrence, although the molecular alterations that are driving NPC metastasis remain unclear at this time. ...This study aimed to examine the expression of fibulin-5 in NPC, correlate the results with clinicopathological variables and survival, and to investigate the role of fibulin-5 in human NPC cell lines.
Standard semi-quantitative-RT-PCR, quantitative-RT-PCR, immunoblotting, and immunohistochemistry were used to investigate the mRNA and protein expression profiles of fibulin-5 in normal and NPC tissues. Immunohistochemistry of fibulin-5 was correlated with clinicopathological characteristics by univariate analyses. NPC cells overexpressing fibulin-5 or fibulin-5-siRNA cells were generated by stable transfection to characterize the molecular mechanisms of fibulin-5-elicited cell growth and metastasis.
Our results demonstrated that fibulin-5 overexpression in NPC specimens and significantly correlated with advanced tumor metastasis indicating a poor 5-year overall survival. Fibulin-5 was mainly expressed in the nucleus in human NPC specimens and cell lines. Functionally, fibulin-5 overexpression yielded fast growth in NPC cells. In addition, fibulin-5 promotes cell metastasis in NPC cells through increased FLJ10540 and phosphor-AKT activity. In contrast, siRNA depletion of fibulin-5 suppressed FLJ10540 expression and phosphor-AKT activity. Suppression of either fibulin-5 or FLJ10540 can cause significant inhibition with regards to cell motility in NPC cells. Finally, immunohistochemical analysis of human aggressive NPC specimens showed a significant and positive correlation between fibulin-5 and FLJ10540 expression.
Higher fibulin-5 expression is not only an important indicator of poor survival, but also contributes to the development of new therapeutic strategies in the FLJ10540/AKT pathway for NPC treatment.
Background
The study investigates the prognostic significance of lymph node ratio (LNR) on patients with head and neck squamous cell carcinoma (HNSCC) with coexistence of multiple adverse ...pathological features.
Methods
In total, 100 patients with coexistence of perineural invasion, lymphovascular invasion, and extranodal extension of first primary HNSCC treated with radical surgery followed by adjuvant chemoradiotherapy were enrolled.
Results
The optimal LNR cut‐off value for predicting overall survival (OS) and cancer specific survival (CSS) was 7%. In Cox model, we observed that LNR ≥7% was a statistically significant unfavorable predictor of OS (HR: 2.689; 95% CI: 1.228–5.889; p = 0.013) and CSS (HR: 3.162; 95% CI: 1.234–8.102; p = 0.016).
Conclusion
For HNSCC patients with coexistence of multiple adverse pathological features, LNR is an independent survival predictor. Novel intensified treatments are needed for the subgroup of patients with a high LNR.
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