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Τετάρτη 18 Ιουλίου 2018

Nitrogen and sulfur co-doped highly luminescent carbon dots for sensitive detection of Cd (II) ions and living cell imaging applications

Publication date: Available online 18 July 2018

Source: Journal of Photochemistry and Photobiology B: Biology

Author(s): Dan Gu, Liu Hong, Lei Zhang, Hao Liu, Shaoming Shang

Abstract

In this work, we have developed a green, simple and fast one-pot microwave-assisted strategy for synthesis of nitrogen and sulfur co-doped fluorescent carbon dots (CDs) using scallion (SL) as the carbon source. Optical properties of the SL-CDs have been measured by UV-visible and fluorescent spectroscopy. The morphology of the prepared SL-CDs has been performed by transmission electron microscopy (TEM). Surface functionality and elemental composition of SL-CDs was analyzed by Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) spectra. The photoluminescent (PL) quantum yield of the obtained scallion carbon dots (SL-CDs) can reach as high as 18.6%. We further demonstrated that the SL-CDs can be used as fluorescent probes for detection of Cd2+ ions with a high sensitivity and an excellent selectivity. Linear relationships between the variation of the luminescent intensity of the SL-CDs before and after exposing the Cd2+ ions versus the concentration of Cd2+ ions in the range of 0.1–3.0 μM and 5.0–30.0 μM. The detection limit of Cd2+ ions can reach 15.0 nM. Moreover, the as-prepared SL-CDs exhibit negligible or extremely low cytotoxicity, which makes them be able to be used as fluorescent probes for living cell imaging. Overall, the prepared SL-CDs have promising applications in sensing of Cd2+ ions and in vivo or in vitro bioimaging.

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Sunscreen Use and Melanoma Risk Among Young Australian Adults

This population-based, case-control family study of data collected for the Australian Melanoma Family Study assesses the association of sunscreen use in childhood and early adulthood with the risk of cutaneous melanoma before age 40 years.

Spiky Skin in a Renal Transplant Recipient

A woman in her 70s with a cadaveric renal transplant presented with a 1-year history of a facial cutaneous eruption and mildly pruritic lesions, initially affecting malar cheeks and eyebrows and subsequently spreading to involve the nose, chin, upper trunk, and extremities. What is your diagnosis?

Timing of Onset of Adverse Cutaneous Reactions Associated With PD-1 Inhibitor Therapy

This observational study assesses the timing of onset of cutaneous reactions after initiation of programmed cell death protein 1 therapy in patients with metastatic melanoma or carcinoma.

A Comparison of Tanning Habits Among Gym Tanners and Other Tanners

This survey study evaluates the incidence of tanning in adults who use indoor gyms.

Effect of Stress Ball Use or Hand-holding on Anxiety During Skin Cancer Excision

This randomized clinical trial examines the effects of hand-holding vs stress ball use compared with usual care on anxiety in patients undergoing excisional removal of nonmelanoma skin cancer of the head or neck with local anesthesia.

Scabies—An Ancient Disease With Unanswered Questions in Modern Times

This Viewpoint discusses the global disease burden of scabies, as well as its diagnosis and treatment.

Predicting Fluoropyrimidine-Related Toxicity: Turning Wish to Will, The Pamm-Eortc Position



Inconsistent HIV reservoir dynamics and immune responses following anti-PD-1 therapy in cancer patients with HIV infection



Final results of a randomized phase III trial of induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in patients with stage IVA and IVB nasopharyngeal carcinoma-Taiwan Cooperative Oncology Group (TCOG) 1303 Study

Abstract
Background
Concurrent chemoradiotherapy (CCRT) is superior to radiotherapy alone for treating locoregionally advanced nasopharyngeal carcinoma (NPC). Whether adding induction chemotherapy (IC) further improves the outcome warrants investigation.
Patients and methods
This open-label multicenter phase III trial was conducted at 11 institutions in Taiwan. Patients with stage IVA or IVB NPC were randomized to receive IC followed by CCRT (I-CCRT) or CCRT alone. Patients in the I-CCRT arm received 3 cycles of mitomycin C, epirubicin, cisplatin, and 5-fluorouracil/leucovorin (MEPFL). All patients received 30 mg/m2 cisplatin weekly during radiotherapy, which was delivered as 1.8–2.2 Gy per fraction with five daily fractions per week, to a total dose of 70 Gy or greater to the primary tumor and 66–70 Gy to the involved neck. The primary endpoint was disease-free survival (DFS).
Results
In this study, 240 and 239 patients were randomized to CCRT and I-CCRT arm, respectively. The most prominent toxicities of induction were leukopenia (grade 3 and 4: 47% and 12%) and thrombocytopenia (grade 3 and 4: 24% and 3%). During radiotherapy, severe mucositis was the major side effect in both arms; an increased number of patients in the I-CCRT arm had myelosuppression; hence, discontinuation of weekly cisplatin was more common. After a median follow-up of 72.0 months, the I-CCRT arm had significantly higher DFS than that of the CCRT arm (5-year rate 61% vs 50%; hazard ratio = 0·739, 95% confidence interval (CI)= 0·565-0·965; P = 0·0264), after stratified for N3b and LDH, and adjusted for T stage.
Conclusion
Induction with MEPFL before CCRT was tolerable and significantly improved the DFS of patients with stage IVA and IVB NPC though overall survival not improved.
Clinical trial information
NCT00201396

Therapeutic advantage of genetically engineered Salmonella typhimurium carrying short hairpin RNA against inhibin alpha subunit in cancer treatment

Abstract
Background
In contrast to its well-known endocrine function, the role of inhibin in cancer development and therapeutic response is unclear. Salmonella, particularly less toxic attenuated Salmonella strains, are used to treat cancer in two ways. First, Salmonella accumulate around tumors, penetrate the cell barrier, and replicate inside the tumors. Second, Salmonella can act as a vehicle for delivering anti-cancer agents or pro-apoptotic genes to attack tumors. In this study, we aimed to develop a suitable cancer therapeutic strategy by genetically modifying attenuated Salmonella typhimurium to harbor short hairpin RNA (shRNA) expression plasmids targeting alpha subunit of inhibin (sh-INHA).
Methods
We analyzed the expression of human INHA in normal and cancer cells and tissues. We developed genetically engineered attenuated Salmonella typhimurium harboring sh-INHA (S. typhimurium/sh-INHA) and assessed its cancer therapeutic effects by using cell culture models and syngeneic mouse tumor models.
Results
INHA expression levels were markedly higher in colon cancer and melanoma cells and tissues than in their normal counterparts. Suppression of INHA expression mildly reduced cancer cell survival and induced caspase activation and downregulation of anti-apoptotic Bcl-2 and Bcl-xL expression. Although the genetically engineered S. typhimurium mildly interfered with the invasion of S. typhimurium into host colon cancer and melanoma cells, S. typhimurium/sh-INHA caused remarkable cytotoxicity in cancer compared with unmodified S. typhimurium or S. typhimurium expressing a control scrambled shRNA (S. typhimurium/sh-Cont). S. typhimurium/sh-INHA-treated mice also showed a significantly inhibited growth of colon cancers and melanomas, with a survival advantage.
Conclusion
Our results suggest that tumor-targeted therapy using S. typhimurium/sh-INHA may provide a novel cancer treatment option.

Vistusertib (dual m-TORC1/2 inhibitor) in combination with paclitaxel in patients with high grade serous ovarian and squamous non-small cell lung cancer

Abstract
Background
We have previously shown that raised p-S6K levels correlate with resistance to chemotherapy in ovarian cancer. We hypothesised that inhibiting p-S6K signalling with the dual m-TORC1/2 inhibitor in patients receiving weekly paclitaxel could improve outcomes in such patients.
Patients and Methods
In dose escalation, weekly paclitaxel (80 mg/m2) was given 6/7 weeks in combination with two intermittent schedules of vistusertib (dosing starting on the day of paclitaxel): schedule A, vistusertib dosed bd for 3 consecutive days per week (3/7days) and schedule B, vistusertib dosed bd for 2 consecutive days per week (2/7days). After establishing a recommended phase II dose (RP2D), expansion cohorts in high-grade serous ovarian cancer (HGSOC) and squamous non-small cell lung cancer (sqNSCLC) were explored in 25 and 40 patients, respectively.
Results
The dose escalation arms comprised 22 patients with advanced solid tumours. The dose-limiting toxicities were fatigue and mucositis in schedule A and rash in schedule B. Based on toxicity, pharmacokinetic (PK) and pharmacodynamic (PD) evaluations, the RP2D was established as 80 mg/m2 paclitaxel with 50 mg vistusertib bd 3/7 days for 6/7 weeks. In the HGSOC expansion RECIST and GCIG CA125 response rates were 13/25 (52%) and 16/25 (64%), respectively with median progression-free survival (mPFS) of 5.8 months (95% CI: 3.28 - 18.54). The RP2D was not well tolerated in the SqNSCLC expansion, but toxicities were manageable after the daily vistusertib dose was reduced to 25 mg bd for the following 23 patients. The RECIST response rate in this group was 8/23 (35%) and the mPFS was 5.8 months (95% CI: 2.76 - 21.25).
Discussion
In this phase I trial we report a highly active and well tolerated combination of vistusertib, administered as an intermittent schedule with weekly paclitaxel, in patients with HGSOC and SqNSCLC.
Clinical trial registration
ClinicialTrials.gov identifier: CNCT02193633

AJCC 8th Edition for Soft Tissue Sarcoma of the Extremities and Trunk



Novel therapies in urothelial carcinoma: a biomarker-driven approach

Abstract
Urothelial malignancies, including carcinomas of the bladder, ureters, and renal pelvis comprised approximately 8% of new cancer cases in the United States in 2016. In the metastatic setting, 15% of patients exhibit long-term survival following cisplatin-based chemotherapy and in patients with recurrent disease, response rates to second-line chemotherapy are generally 15-20% with a 3-month progression-free survival. However, recent advances in immunotherapy represent an opportunity to significantly improve patient outcomes. Moreover, the advent of next-generation sequencing (NGS) has resulted in both an improved understanding of the fundamental genetic changes that characterize urothelial carcinoma (UC) and identification of several candidate biomarkers of response to various therapies. Incorporation of prospective genotyping into clinical trials will allow for the identification and enrichment of patients most likely to respond to specific targeted therapies and chemotherapy. Combining different therapeutic classes to enhance outcomes is also an area of active research in UC.

Migraine and greater pain symptoms at 10-year follow-up among patients with major depressive disorder

No study has investigated the associations of migraine with pain symptoms over a ten-year period among outpatients with major depressive disorder (MDD). This study aimed to investigate this issue.

Vitamin D deficiency in patients with cluster headache: a preliminary study

Cluster headache is famous for attacks with seasonal and diurnal periodicity. This diurnal and seasonal variation might be related to sunlight and vitamin D metabolism. We investigated the serum vitamin D leve...

Increased thalamic glutamate/glutamine levels in migraineurs

Increased cortical excitability has been hypothesized to play a critical role in various neurological disorders, such as restless legs syndrome, epilepsy and migraine. Particularly for migraine, local hyperexc...

Illuminating Endocrine Evolution: The Power and Potential of Large-Scale Comparative Analyses

Abstract
Hormones are central mediators of genotype-phenotype and organism-environment interactions. Despite these important functions, the role of selection in shaping hormonal mediators of phenotype remains poorly understood. Thanks to decades of work by endocrinologists, circulating hormone levels have been measured in a diversity of organisms. Variation in other endocrine traits and mediators (e.g., receptor expression, binding globulins), and the hormonal response to standardized challenges (e.g., restraint, pharmacological challenges) are also increasingly measured in both captive and free-living populations. Large-scale comparative analyses of the multitude of available endocrine data represent a particularly promising approach to addressing the function and evolution of these key phenotypic mediators, and their potential to serve as indicators of disturbance. Several recent phylogenetic comparative analyses and meta-analyses have begun to reveal the power and potential of these approaches to address key questions in integrative biology. Here we highlight two recent developments that are facilitating such analyses: increasingly powerful and flexible phylogenetic comparative methods, and the release of two endocrine trait databases – HormoneBase (currently 474 species) and the Wildlife Endocrinology Information Network (currently 25 species) – that contain compiled measures of endocrine traits across vertebrates. Increasingly comprehensive comparative analyses of endocrine data could provide insight into many interesting questions, including how rapidly changing environments are impacting phenotypes, why endocrine traits differ so remarkably within and across populations, and the evolution of plasticity.

Non-branching personal persistence

Abstract

Given reductionism about people, personal persistence must fundamentally consist in some kind of impersonal continuity relation. Typically, these continuity relations can hold from one to many. And, if they can, the analysis of personal persistence must include a non-branching clause to avoid non-transitive identities or multiple occupancy. It is far from obvious, however, what form this clause should take. This paper argues that previous accounts are inadequate and develops a new proposal.



2-hydroxyglutarate MR Spectroscopy for Prediction of Isocitrate Dehydrogenase Mutant Glioma: A Systemic Review and Meta-analysis using Individual Patient Data

Abstract
Background
Noninvasive and accurate modality to predict Isocitrate dehydrogenase (IDH) mutant glioma may have great potential in routine clinical practice. We aimed to investigate the diagnostic performance of 2-hydroxyglutarate (2HG) magnetic resonance spectroscopy (MRS) for prediction of IDH mutant glioma and provide an optimal cut-off value for 2HG.
Methods
A systematic literature search of Ovid-MEDLINE and EMBASE was performed to identify original articles investigating the diagnostic performance of 2HG MRS up to March 20, 2018. Pooled sensitivity and specificity were calculated using a bivariate random-effects model. Subgroup analysis and meta-regression was performed to explain heterogeneity effects. An optimal cut-off value for 2HG was calculated from studies providing individual patient data.
Results
Fourteen original articles with 460 patients were included. The pooled sensitivity and specificity for the diagnostic performance of 2HG MRS for prediction of IDH mutant glioma were 95% (95% CI, 85–98%) and 91% (95% CI, 83–96%), respectively. The Higgins I2 statistic demonstrated that heterogeneity was present in the sensitivity (I2 = 50.69%), but not in the specificity (I2 = 30.37%). In the meta-regression, echo time (TE) was associated with study heterogeneity. Among the studies using point-resolved spectroscopy (PRESS), a long TE (97 ms) resulted in higher sensitivity (92%) and specificity (97%) than a short TE (30–35 ms; sensitivity of 90%, specificity of 88%; p < 0.01). The optimal 2HG cut-off value of 2HG using individual patient data was 1.76 mM.
Conclusion
2HG MRS demonstrated excellent specificity for prediction of IDH mutant glioma, with TE being associated with heterogeneity in the sensitivity.