The antitumor activity of an inhibitor of 26S proteasome bortezomib (Velcade) has been observed in various malignancies, including colon cancer, prostate cancer, breast cancer, and ovarian cancer. Bortezomib has been proposed to stimulate autophagy, but scientific observations did not always support this. Interactions between ERK activity and autophagy are complex and not completely clear. Autophagy proteins have recently been shown to regulate the functions of ERK, and ERK activation has been found to induce autophagy. On the other hand, sustained activation of ERK has also been shown to inhibit the maturation step of the autophagy process. In this study, we sought to identify the mechanism of autophagy regulation in cancer cells treated with bortezomib. Our results indicate that bortezomib blocked the autophagic flux without inhibiting the fusion of the autophagosome and lysosome. In ovarian cancer, as well as endometrial cancer and hepatocellular carcinoma cells, bortezomib inhibited protein degradation in lysosomes by suppressing cathepsins, which requires the participation of ERK phosphorylation, but not JNK or p38. Our findings that ERK phosphorylation reduced cathepsins further explain how ERK phosphorylation inhibits the autophagic flux. In conclusion, bortezomib may induce ERK phosphorylation to suppress cathepsin B and inhibit the catalytic process of autophagy in ovarian cancer and other solid tumors. The inhibition of cisplatin-induced autophagy by bortezomib can enhance chemotherapy efficacy in ovarian cancer. As we also found that bortezomib blocks the autophagic flux in other cancers, the synergistic cytotoxic effect of bortezomib by abolishing chemotherapy-related autophagy may help us develop strategies of combination therapies for multiple cancers.
The insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3) is a member of a highly conserved protein family that is expressed specifically in placenta, testis and various cancers, but is hardly detectable in normal adult tissues. IGF2BP3 has important roles in RNA stabilization and translation, especially during early stages of both human and mouse embryogenesis. Placenta is an indispensable organ in mammalian reproduction that connects developing fetus to the uterine wall, and is responsible for nutrient uptake, waste elimination and gas exchange. Fetus development in the maternal uterine cavity depends on the specialized functional trophoblast. Whether IGF2BP3 plays a role in trophoblast differentiation during placental development has never been examined. The data obtained in this study revealed that IGF2BP3 was highly expressed in human placental villi during early pregnancy, especially in cytotrophoblast cells (CTBs) and trophoblast column, but a much lower level of IGF2BP3 was detected in the third trimester placental villi. Furthermore, the expression level of IGF2BP3 in pre-eclamptic (PE) placentas was significantly lower than the gestational age-matched normal placentas. The role of IGF2BP3 in human trophoblast differentiation was shown by in vitro cell invasion and migration assays and an ex vivo explant culture model. Our data support a role of IGF2BP3 in promoting trophoblast invasion and suggest that abnormal expression of IGF2BP3 might be associated with the etiology of PE.
IGF2BP3; placenta; invasion/migration; pre-eclampsia
The potent and selective proteasome inhibitor bortezomib has shown remarkable antitumor activity and is now entering clinical trials for several cancers. However, the molecular mechanisms by which bortezomib induces cytotoxicity in ovarian cancer cells still remain unclear. In this study, we show that bortezomib induced apoptosis, which was demonstrated by the downregulation of antiapoptotic molecules (Bcl-2, Bcl-XL, p-Bad, and p-AKT) and the upregulation of proapoptotic proteins (p21, p27, and cleaved-Bid) in ovarian cancer cell lines. Moreover, bortezomib stimulates Janus kinase (JAK) phosphorylation and activates heat-shock transcription factor-1 (HSF-1) and heat-shock protein 70 (HSP70), ultimately leading to signal transducer and activator of transcription 1 (STAT1) phosphorylation. Phosphorylated STAT1 partially counteracted apoptosis induced by bortezomib in cancer cells. These findings suggest that the antitumor activity of bortezomib in ovarian cancer can be improved by inhibiting bortezomib-induced STAT1 phosphorylation. This effect can be achieved by STAT1 knockdown, HSP70 knockdown, JAK inhibition, or the addition of cisplatin, one of the most commonly used anticancer drugs. These results provide the first evidence that STAT1 phosphorylation can play a role in bortezomib resistance by exerting antiapoptotic effects. They also suggest the possibility to abolish or reduce bortezomib chemoresistance in ovarian cancer by the addition of cisplatin or JAK inhibitors.
bortezomib; ovarian cancer; cisplatin; HSP70; JAK1; STAT1
Ni nanocrystals (NCs) were embedded in BaTiO3 epitaxial films using the laser molecular beam epitaxy. The processes involving the self-organization of Ni NCs and the epitaxial growth of BaTiO3 were discussed. With the in situ monitoring of reflection high-energy electron diffraction, the nanocomposite films were engineered controllably by the fine alternation of the self-organization of Ni NCs and the epitaxial growth of BaTiO3. The transmission electron microscopy and the X-ray diffraction characterization confirmed that the composite film consists of the Ni NCs layers alternating with the (001)/(100)-oriented epitaxial BaTiO3 separation layers.
Laser molecular beam epitaxy; Nanocomposite film; Reflection high-energy electron diffraction; Self-organization; Epitaxial growth
Monodisperse FePt nanoparticles with size of 4.5 and 6.0 nm were prepared by simultaneous reduction of platinum acetylacetonate and thermal decomposition of iron pentacarbonyl in benzylether. The crystallography structure, size, and composition of the FePt nanoparticles were examined by X-ray diffraction and transmission electron microscopy. Energy dispersive X-ray spectrometry measurements of individual particles indicate a broad compositional distribution in both the 4.5 and 6 nm FePt nanoparticles. The effects of compositional distribution on the phase-transition and magnetic properties of the FePt nanoparticles were investigated.
FePt; Nanoparticles; Compositional distribution; Magnetic properties
Laccate polypores of the Ganoderma lucidum species complex are widespread white rot fungi of economic importance, but isolates cannot be identified by traditional taxonomic methods. Parsimony analysis of nucleotide sequences from the internal transcribed spacers (ITS) of the ribosomal gene (rDNA) distinguished six lineages in this species complex. Each ITS lineage may represent one or more putative species. While some isolates have identical ITS sequences, all of them could be clearly differentiated by genetic fingerprinting using random amplified polymorphic DNA (RAPD). To investigate the suitability of RAPD markers for taxonomic identification and grouping of isolates of the G. lucidum complex, RAPD fragments (RAPDs) were used as phenotypic characters in numerical and parsimony analyses. Results show that data from RAPDS do not distinguish the same clades as ITS data do. Groupings based on analysis of RAPD data were very sensitive to the choice of the grouping method used, and no consistent grouping of isolates could be proposed. However, analysis with RAPDs did resolve several robust terminal clades containing putatively conspecific isolates, suggesting that RAPDs might be helpful for systematics at the lower taxonomic levels that are unresolved by ITS sequence data. The limitations of RAPDs for systematics are briefly discussed. The conclusion of this study is that ITS sequences can be used to identify isolates of the G. lucidum complex, whereas RAPDs can be used to differentiate between isolates having identical ITS sequences. The practical implications of these results are briefly illustrated.
Isoflurane has been reported to induce caspase-3 activation, which may induce neurotoxicity and contribute to the pathogenesis of Alzheimer's disease. However, the underlying mechanism is largely unknown, especially whether or not isoflurane can induce ryanodine receptors (RyRs)-associated endoplasmic reticulum (ER) stress, leading to caspase-3 activation. We therefore assessed the effects of isoflurane on RyRs-associated ER stress.
We treated primary neurones from wild-type (C57BL/6J) mice with 1% and 2% isoflurane for 1, 3, or 6 h. We then measured levels of C/EBP homologous protein (CHOP) and caspase-12, two ER stress markers, using immunocytochemistry staining and western blotting analysis. Dantrolene (5 μM), the antagonist of RyRs, was used to investigate the role of RyRs in the isoflurane-induced ER stress and caspase-3 activation.
Isoflurane 2% for 6 h treatment increased the levels of CHOP (876% vs 100%, P=0.00009) and caspase-12 (276% vs 100%, P=0.006), and induced caspase-3 activation in the neurones. The administration of 2% isoflurane for 3 h (shorter duration), however, only increased the levels of CHOP (309% vs 100%, P=0.003) and caspase-12 (266% vs 100%, P=0.001), without causing caspase-3 activation. The isoflurane-induced ER stress (CHOP: F=16.64, P=0.0022; caspase-12: F=6.13, P=0.0383) and caspase-3 activation (F=32.06, P=0.0005) were attenuated by the dantrolene treatment.
These data imply that isoflurane might induce caspase-3 activation by causing ER stress through RyRs, and dantrolene could attenuate the isoflurane-induced ER stress and caspase-3 activation. Further investigations of the potential neurotoxicity of isoflurane are needed.
endoplasmic reticulum; inhalation anaesthetics, isoflurane; receptors, ryanodine
This meta-analysis is to determine the overall diagnostic yield of CT-guided transthoracic needle biopsy (TNB) of ground-glass opacity (GGO) lesions.
A PubMed search was performed using “ground-glass opacity” crossed with “core biopsy” and “needle biopsy”. Test performance characteristics with the use of forest plots, summary receiver operating characteristic curves and bivariate random effects models were summarized. Adverse events, if reported, were recorded.
Our search identified 52 citations, of which 6 diagnostic studies evaluated 341 patients. Pooled specificity estimates were 0.94 [95% confidence interval (CI), 0.84–0.98] and sensitivity estimates were 0.92 (95% CI, 0.88–0.95), respectively. The positive likelihood ratio was 11.27 (95% CI, 4.2–30.6), the negative likelihood ratio was 0.1 (95% CI, 0.06–0.19), the diagnostic odds ratio was 131.38 (95% CI, 39.6–436.0) and the area under the curve was 0.97.
Our data suggest that the CT-guided TNB is likely to be a useful tool for tissue diagnosis and may serve as an alternative for further patient management with GGO lesions. However, considering the limited studies and patients included, large scale studies are needed to verify these findings.
Advances in knowledge:
Some studies about CT-guided TNB of GGO lesions have been published, most have been small, single-institution case series. To our knowledge, our study is the first systematic analysis about CT-guided TNB of GGO lesions.
Obesity is a world-wide epidemic and is associated with multiple comorbidities. The mechanisms underlying the relationship between obesity and adverse health outcomes remain poorly understood. This may be due to several factors including the crude measures used to estimate adiposity, the striking heterogeneity between adipose tissue depots, and the influence of fat accumulation in multiple organs. In order to advance our understanding of fat stores and associated co-morbidities in humans, it will be necessary to image adiposity throughout the body and ultimately also assess its functionality. Large clinical studies are demonstrating the prognostic importance of adipose tissue imaging. Newer techniques capable of imaging fat metabolism and other functions of adipose tissue may provide additional prognostic utility and may be useful in guiding therapeutic interventions.
obesity; fat composition; adipose tissue imaging
OBJECTIVES: To investigate the expression and prognostic value of G-protein-coupled receptors 65 (GPR65, also known as T-cell death-associated gene 8, TDAG8) in glioblastoma patients. METHODS: We determined the expression of GPR65 using immunohistochemistry in tissue microarrays containing 102 GBM samples and 15 normal brain samples. Cumulative survival was calculated by the Kaplan-Meier method and analyzed by the log-rank test. Univariate and multivariate analyses were performed by the stepwise forward Cox regression model. RESULTS: GPR65 protein levels were significantly elevated in glioblastoma tissues compared with those of normal brain tissues for nearly 5 folds (P < 0.001). In addition to standard therapy, patients with high GPR65 protein expression had significantly shorter OS and PFS than those with low GPR65 expression (OS: 14.6 versus 22.6 months or 14.7 versus 22.6 months, p = 0.047 and 0.040, respectively; PFS: 12.5 versus 18.9 months or 12.8 versus 19.0 months, p = 0.089 and p = 0.085, respectively). In multivariate analysis, Cox regression model identified high GPR65 expression as an independent prognostic factor for OS and PFS (Hazard ration [HR] = 1.599 and 1.593; p = 0.037 and 0.034, respectively) of primary GBM patients. No adjuvant radiotherapy, small extent of resection were other three independent risk factors of poor prognosis in glioblastoma patients. CONCLUSION: High GPR65 expression occurs in a significant subset of glioblastoma patients and predicts a poorer outcome. The study identifies a potentially useful molecular marker for the categorization and targeted therapy of glioblastoma.
To evaluate the safety and feasibility of N-butyl cyanoacrylate (N-BCA) embolization of percutaneous transhepatic portal venous access tract and to establish an appropriate technique.
40 consecutive patients underwent percutaneous transhepatic portal venous intervention for various reasons. Embolization of percutaneous transhepatic portal venous access tract was performed after the procedure in all of the patients using N-BCA and Lipiodol® (Lipiodol Ultra Fluide; Laboratoire Guerbet, Aulnay-sous-Bois, France) mixture. Immediate ultrasonography and fluoroscopy were performed to evaluate perihepatic haematoma formation and unintended embolization of more than one segmental portal vein. Follow-up CT was performed, and haemoglobin and haematocrit levels were checked to evaluate the presence of bleeding.
Immediate haemostasis was achieved in all of the patients, without development of perihepatic haematoma or unintended embolization of more than one segmental portal vein. Complete embolization of percutaneous access tract was confirmed in 39 out of 40 patients by CT. Seven patients showed decreased haemoglobin and haematocrit levels. Other complications included mild pain at the site of embolization and mild fever, which resolved after conservative management. 16 patients died during the follow-up period owing to progression of the underlying disease.
Embolization of percutaneous transhepatic portal vein access tract with N-BCA is feasible and technically safe. With the appropriate technique, N-BCA can be safely used as an alternate embolic material since it is easy to use and inexpensive compared with other embolic materials.
Advances in knowledge:
This is the first study to investigate the efficacy of N-BCA for percutaneous transhepatic portal venous access tract embolization.
We examined the longitudinal association between red meat (RM) consumption and the risk of abdominal obesity in Chinese adults.
Methods and results
Our data are from 16,822 adults aged 18 to 75 in the China Health and Nutrition Survey from 1993 to 2011. We assessed RM intake with three 24-hour dietary recalls. We defined abdominal obesity as a waist circumference (WC) ≥ 85 centimeters (cm) for men and ≥ 80 cm for women. Multilevel mixed-effect regression models showed that men experienced WC increases of 0.74 cm (95% confidence interval [CI]: 0.39–1.09) from a higher total intake of fresh RM and 0.59 cm (95% CI: 0.24–0. 95) from a higher intake of fatty fresh RM but 0.14 cm (95% CI: −0.39–0.66) from a higher intake of lean fresh RM in the top versus the bottom quartile when adjusted for potential confounders. In contrast, after additional adjustment for baseline WC, the odds ratios of abdominal obesity in men were attenuated for total fresh RM (1.25 [95% CI: 1.06–1.47]) and fatty fresh RM (1.22 [95% CI: 1.03–1.44]) but were still not affected by lean fresh RM (0.95 [95% CI: 0.75–1.22]). Women also showed a positive association of fatty fresh RM intake with abdominal obesity.
Greater intake of fatty fresh RM was significantly associated with higher WC (men only) and abdominal obesity risk in Chinese adults. The gender-specific differential association of fatty versus lean fresh RM warrants further study.
fatty fresh red meat; abdominal obesity; waist circumference; Chinese
Increasing evidence has shown that microRNAs (miRNAs) can serve as oncogenes and tumour suppressors to participate in tumour development. However, the roles of miRNAs in chemoresistance of human lung adenocarcinoma (LA) remain largely undefined.
On the basis of miRNA microarray data, miR-224 was identified as the most upregulated miRNA in cisplatin (DDP; cis-diamminedichloroplatinum II)-resistant A549 cells compared with parental A549 cells. The aim of our study was to investigate the roles of miR-224 in the formation of DDP-resistant phenotype of LA cells and its possible molecular mechanisms.
Here we showed that miR-224 could promote the in vitro and in vivo DDP resistance of LA cells via regulating G1/S cell cycle transition and apoptosis. p21WAF1/CIP1, a potent cyclin-dependent kinase inhibitor, was identified as the direct and functional target gene of miR-224. Overexpression of p21WAF1/CIP1 could phenocopy the effect of miR-224 downregulation and silencing of p21WAF1/CIP1 could partially reverse the effect of miR-224 downregulation on DDP resistance of DDP-resistant LA cells. In addition, miR-224 could affect the G1/S transition of cell cycle and apoptosis in LA cells through the p21WAF1/CIP1-pRb pathway and the intrinsic mitochondrial death pathway. Furthermore, miR-224 was found to be downregulated in DDP-responding LA tissues, and its expression was inversely correlated with p21WAF1/CIP1. Multivariate analyses indicated that the status of miR-224 might be an independent prognostic factor for predicting the survival of LA patients.
Our findings shed novel light on the roles of miR-224/p21WAF1/CIP1 signalling in the DDP resistance of LA cells, and targeting it will be a potential strategic approach for reversing the DDP resistance in human LAs.
miR-224; cisplatin; chemoresistance; lung adenocarcinoma; p21WAF1/CIP1
The fermentation of sugars to alcohols by microbial systems underpins many biofuel initiatives. Short chain alcohols, like n-butanol, isobutanol and isopropanol, offer significant advantages over ethanol in terms of fuel attributes. However, production of ethanol from resistant Saccharomyces cerevisiae strains is significantly less complicated than for these alternative alcohols.
In this study, we have transplanted an n-butanol synthesis pathway largely from Clostridial sp. to the genome of an S. cerevisiae strain. Production of n-butanol is only observed when additional genetic manipulations are made to restore any redox imbalance and to drive acetyl-CoA production. We have used this butanol production strain to address a key question regarding the sensitivity of cells to short chain alcohols. In the past, we have defined specific point mutations in the translation initiation factor eIF2B based upon phenotypic resistance/sensitivity to high concentrations of exogenously added n-butanol. Here, we show that even during endogenous butanol production, a butanol resistant strain generates more butanol than a butanol sensitive strain.
These studies demonstrate that appreciable levels of n-butanol can be achieved in S. cerevisiae but that significant metabolic manipulation is required outside of the pathway converting acetyl-CoA to butanol. Furthermore, this work shows that the regulation of protein synthesis by short chain alcohols in yeast is a critical consideration if higher yields of these alcohols are to be attained.
Electronic supplementary material
The online version of this article (doi:10.1186/s13068-015-0281-4) contains supplementary material, which is available to authorized users.
Biobutanol; Saccharomyces cerevisiae; ABE pathway
There are significant challenges in developing in vitro human tissue and tumor models that can be used to support new drug development and evaluate personalized therapeutics. The challenges include: (1) working with primary cells which are often difficult to maintain ex vivo, (2) mimicking native microenvironments from which primary cells are harvested, and (3) lack of culture devices that can support these microenvironments to evaluate drug responses in a high-throughput manner. Here we report a versatile well plate-based perfusion culture device that was designed, fabricated and used to: (1) ascertain the role of perfusion in facilitating the expansion of human multiple myeloma cells and evaluate drug response of the cells, (2) preserve the physiological phenotype of primary murine osteocytes by reconstructing the 3D cellular network of osteocytes, and (3) circulate primary murine T cells through a layer of primary murine intestine epithelial cells to recapitulate the interaction of the immune cells with the epithelial cells. Through these diverse case studies, we demonstrate the device’s design features to support: (1) the convenient and spatiotemporal placement of cells and biomaterials into the culture wells of the device; (2) the replication of tissues and tumor microenvironments using perfusion, stromal cells, and/or biomaterials; (3) the circulation of non-adherent cells through the culture chambers; and (4) conventional tissue and cell characterization by plate reading, histology, and flow cytometry. Future challenges are identified and discussed from the perspective of manufacturing the device and making its operation for routine and wide use.
Enhanced susceptibility-weighted angiography (ESWAN) is a three-dimensional (3D) multi-echo gradient-echo sequence which consists of both magnitude and phase images. This study aims to demonstrate the feasibility of ESWAN for the depiction of both cerebral arteries and veins at 1.5 T by comparing with time-of-flight (TOF) MR angiography (MRA) and MR venography (MRV).
13 healthy volunteers underwent both ESWAN and 3D-TOF-MRA examinations. Among them, nine volunteers underwent an additional two-dimensional-TOF-MRV examination. With regard to the ESWAN sequence, both maximum intensity projection (MIP) and minimum intensity projection (mIP) images were reconstructed and compared with MIP reconstructions of the TOF MRA and the TOF MRV.
Concerning the depiction of the constituent segments of the Circle of Willis, as well as A1, A2, A3 (segments of the anterior cerebral artery), M1, M2 (segments of the middle cerebral artery), P1 and P2 (segments of the posterior cerebral artery), the value of the ESWAN MIP was comparable to that of the TOF MRA without regard to visualization of branches, vessel homogeneity and wall irregularities or slight stenosis. ESWAN-mIP visualized more deep cerebral veins than TOF MRV in this study.
By use of either mIP reconstruction of a long echo data set or MIP reconstruction of a short echo data set, ESWAN allows simultaneous visualization of both cerebral veins and proximal segments of intracerebral arteries at 1.5 T.
Advances in knowledge:
ESWAN acquires multiple images at different echo times corresponding to different T2* weightings, wherein a short echo TOF-MRA data set and a long echo susceptibility-weighted imaging-MRV data set are obtained simultaneously.
To illustrate characteristic features of adenomatoid odontogenic tumour (AOT) on CBCT.
The archived CBCT and panoramic radiographs of eight patients histopathologically diagnosed as AOT were analysed. The radiographic features displayed on both radiographic images were carefully described and compared.
All eight AOT cases presented as unilocular and well-demarcated lesions on both CBCT and panoramic images. CBCT images displayed three-dimensional interpretation of AOT lesions, especially the detailed intralesional radiopacities. Numerous discrete radiopaque foci scattered in the lesion with evident contrast to the radiolucent background could be considered as one of the characteristic features of AOT on CBCT.
Compared with panoramic radiography, CBCT seems to possess better potential in diagnosing AOT.
characteristic feature; adenomatoid odontogenic tumour; cone beam CT; panoramic radiograph
Quantum phase transitions play an important role in many-body systems and have been a research focus in conventional condensed-matter physics over the past few decades. Artificial atoms, such as superconducting qubits that can be individually manipulated, provide a new paradigm of realising and exploring quantum phase transitions by engineering an on-chip quantum simulator. Here we demonstrate experimentally the quantum critical behaviour in a highly controllable superconducting circuit, consisting of four qubits coupled to a common resonator mode. By off-resonantly driving the system to renormalize the critical spin-field coupling strength, we have observed a four-qubit nonequilibrium quantum phase transition in a dynamical manner; that is, we sweep the critical coupling strength over time and monitor the four-qubit scaled moments for a signature of a structural change of the system's eigenstates. Our observation of the nonequilibrium quantum phase transition, which is in good agreement with the driven Tavis–Cummings theory under decoherence, offers new experimental approaches towards exploring quantum phase transition-related science, such as scaling behaviours, parity breaking and long-range quantum correlations.
Quantum phase transitions are a discontinuous change in a property of the ground state or the structure of the excited states as a system parameter traverses a critical point. Here, the authors recreate analogous effects with laboratory-achievable light-matter coupling in an on-chip superconducting circuit
Four cycles of chemotherapy are required to assess responses of multiple myeloma (MM)
patients. We investigated whether circulating endothelial progenitor cells (cEPCs)
could be a biomarker for predicting patient response in the first cycle of
chemotherapy with bortezomib and dexamethasone, so patients might avoid ineffective
and costly treatments and reduce exposure to unwanted side effects. We measured cEPCs
and stromal cell-derived factor-1α (SDF-1α) in 46 MM patients in the first cycle of
treatment with bortezomib and dexamethasone, and investigated clinical relevance
based on patient response after four 21-day cycles. The mononuclear cell fraction was
analyzed for cEPC by FACS analysis, and SDF-1α was analyzed by ELISA. The study
population was divided into 3 groups according to the response to chemotherapy: good
responders (n=16), common responders (n=12), and non-responders (n=18). There were no
significant differences among these groups at baseline day 1 (P>0.05). cEPC levels
decreased slightly at day 21 (8.2±3.3 cEPCs/μL) vs day 1 (8.4±2.9
cEPCs/μL) in good responders (P>0.05). In contrast, cEPC levels increased
significantly in the other two groups (P<0.05). SDF-1α changes were closely
related to changes in cEPCs. These findings indicate that change in cEPCs at day 21
in the first cycle might be considered a noninvasive biomarker for predicting a later
response, and extent of change could help decide whether to continue this costly
chemotherapy. cEPCs and the SDF-1α/CXCR4 axis are potential therapeutic targets for
improved response and outcomes in MM patients.
Chemotherapy; Circulating endothelial progenitor cells; Multiple myeloma
Quantum dots are semiconductor nanocrystals that exhibit exceptional optical and electrical behaviors not found in their bulk counterparts. Following seminal work in the development of water-soluble quantum dots in the late 1990's, researchers have sought to develop interesting and novel ways of exploiting the extraordinary properties of quantum dots for biomedical applications. Since that time, over 10,000 articles have been published related to the use of quantum dots in biomedicine, many of which regard their use in detection and diagnostic bioassays. This review presents a didactic overview of fundamental physical phenomena associated with quantum dots and paradigm examples of how these phenomena can and have been readily exploited for manifold uses in nanobiotechnology with a specific focus on their implementation in in vitro diagnostic assays and biodetection.
The sub-wavelength concentration and propagation of electromagnetic energy are two complementary aspects of plasmonics that are not necessarily co-present in a single nanosystem. Here we exploit the strong nanofocusing properties of stacked optical antennas in order to highly concentrate the electromagnetic energy into a 5 nm metal-insulator-metal (MIM) cavity and convert free radiation into guided modes. The proposed nano-architecture combines the concentration properties of optical nanoantennas with the propagation capability of MIM systems, paving the way to highly miniaturized on-chip plasmonic waveguiding.
The present experiment evaluated the influence of moisture level and anaerobic fermentation on aerobic stability of total mixed ration (TMR). The dynamic changes in chemical composition and microbial population that occur after air exposure were examined, and the species of yeast associated with the deterioration process were also identified in both non-fermented and fermented TMR to deepen the understanding of aerobic deterioration. The moisture levels of TMR in this experiment were adjusted to 400 g/kg (low moisture level, LML), 450 g/kg (medium moisture level, MML), and 500 g/kg (high moisture level, HML), and both non-fermented and 56-d-fermented TMR were subjected to air exposure to determine aerobic stability. Aerobic deterioration resulted in high losses of nutritional components and largely reduced dry matter digestibility. Non-fermented TMR deteriorated during 48 h of air exposure and the HML treatment was more aerobically unstable. On dry matter (DM) basis, yeast populations significantly increased from 107 to 1010 cfu/g during air exposure, and Candida ethanolica was the predominant species during deterioration in non-fermented TMR. Fermented TMR exhibited considerable resistance to aerobic deterioration. Spoilage was only observed in the HML treatment and its yeast population increased dramatically to 109 cfu/g DM when air exposure progressed to 30 d. Zygosaccharomyces bailii was the sole yeast species isolated when spoilage occurred. These results confirmed that non-fermented and fermented TMR with a HML are more prone to spoilage, and fermented TMR has considerable resistance to aerobic deterioration. Yeasts can trigger aerobic deterioration in both non-fermented and fermented TMR. C. ethanolica may be involved in the spoilage of non-fermented TMR and the vigorous growth of Z. bailii can initiate aerobic deterioration in fermented TMR.
Total Mixed Ration; Fermentation; Moisture Level; Aerobic Stability; Yeast
Nonglycemic factors like iron deficiency (ID) or anemia may interfere with classification of diabetes and prediabetes using hemoglobin A1c (HbA1c). However, few population-based studies of diabetes in areas with endemic ID/anemia have been conducted. We aimed to determine how mutually exclusive categories of ID alone, anemia alone and iron-deficiency anemia (IDA) were each associated with prediabetes and diabetes prevalence using fasting blood glucose (FBG) versus HbA1c in a population-based study of adults with endemic ID/anemia.
We used data from the China Health and Nutrition Survey, a longitudinal, population-based study across 228 communities within nine provinces of China. This analysis included 7308 adults seen in the 2009 survey aged 18–75 years. We used descriptive and covariate-adjusted models to examine relative risk of prediabetes and diabetes using FBG alone, HbA1c alone, HbA1c and FBG, or neither (normoglycemia) by anemia alone, ID alone, IDA or normal iron/hemoglobin.
Approximately 65% of individuals with diabetes in our sample were concordantly classified with diabetes using both FBG and HbA1c, while 35% had a discordant diabetes classification: they were classified using either FBG or HbA1c, but not both. Fewer participants with ID alone versus normal iron/hemoglobin were classified with diabetes using HbA1c only. From covariate-adjusted, multinomial regression analyses, the adjusted prevalence of prediabetes using HbA1c only was 22% for men with anemia alone, but 13% for men with normal iron/hemoglobin. In contrast, the predicted prevalence of prediabetes using HbA1c only was 8% for women with ID alone, compared with 13% for women with normal iron/hemoglobin.
These findings suggest potential misclassification of diabetes using HbA1c in areas of endemic ID/anemia. Estimating diabetes prevalence using HbA1c may result in under-diagnosis in women with ID and over-diagnosis in men with anemia.