K3C6N7O3·2H2O: A Multifunctional Nonlinear Optical Cyamelurate Crystal with Colossal π-Conjugated Orbitals.

The delocalized π-conjugated units are considered as an advantageous gene for improving the optical nonlinearity of acentric crystals. For the first time, we synthesized a new acentric SHG-active metal cyamelurate crystal K3C6N7O3·2H2O (I) by a facile solution method, containing a colossal planar π-conjugated (C6N7O3)3- unit. It displays a strong second-order harmonic generation (SHG) of 4 × KDP and a giant anisotropic birefringence of 0.446 at 1064 nm. The theoretical calculations reveal that such substantial improvement is contributed from the strong molecular susceptibility of (C6N7O3)3- units and their near-perfect coplanar arrangement. Moreover, I exhibits a broadband ultraviolet photoluminescence at 366 nm, suggesting its multifunctional capacity and great potential for compact highly integrated optoelectronic devices.

Radiomics models based on enhanced computed tomography to distinguish clear cell from non-clear cell renal cell carcinomas.

This study was to assess the effect of the predictive model for distinguishing clear cell RCC (ccRCC) from non-clear cell RCC (non-ccRCC) by establishing predictive radiomic models based on enhanced-computed tomography (CT) images of renal cell carcinoma (RCC). A total of 190 cases with RCC confirmed by pathology were retrospectively analyzed, with the patients being randomly divided into two groups, including the training set and testing set according to the ratio of 7:3. A total of 396 radiomic features were computationally obtained and analyzed with the Correlation between features, Univariate Logistics and Multivariate Logistics. Finally, 4 features were selected, and three machine models (Random Forest (RF), Support Vector Machine (SVM) and Logistic Regression (LR)) were established to discriminate RCC subtypes. The radiomics performance was compared with that of radiologist diagnosis. In the testing set, the RF model had an area under the curve (AUC) value of 0.909, a sensitivity of 0.956, and a specificity of 0.538. The SVM model had an AUC value of 0.841, a sensitivity of 1.0, and a specificity of 0.231, in the testing set. The LR model had an AUC value of 0.906, a sensitivity of 0.956, and a specificity of 0.692, in the testing set. The sensitivity and specificity of radiologist diagnosis to differentiate ccRCC from non-ccRCC were 0.850 and 0.581, respectively, with the AUC value of the radiologist diagnosis as 0.69. In conclusion, radiomics models based on CT imaging data show promise for augmenting radiological diagnosis in renal cancer, especially for differentiating ccRCC from non-ccRCC.

Degeneration in the Zygapophysial Joint of the Fifth Lumbar Vertebra: The V-Shaped Sign Revealed by Bone Scintigraphy.

OBJECTIVE: The aim of the study was to explore the nature of a V-shaped sign in the backbone of the fifth lumbar vertebra revealed by whole-body bone scintigraphy (WBBS). METHODS: A local single-photon emission computed tomography (SPECT) scan plus a computed tomography (CT) scan were performed on 41 patients in our department who had a V-shaped sign in the backbone of the fifth lumbar vertebra detected by WBBS. Image fusion was conducted to understand the manifestations of the changes in the V-shaped sign in the CT images in WBBS and to determine the nature of the lesion. RESULTS: All 41 patients presented with degenerative changes observed in the bilateral posterior zygapophysial joint of the fifth lumbar vertebra in the CT imaging bone window, bone hyperplasia of the articular process, joint surface hardening, and a joint gap. The vacuum sign could also be seen in some of these patients. CONCLUSION: The typical V-shaped sign in the posterior zygapophysial joint of the fifth lumbar vertebra revealed by WBBS suggests degenerative changes in the zygapophysial joint of the fifth lumbar vertebra.

Clinical relevance of lysyl oxidase-like 2 and functional mechanisms in glioma.

INTRODUCTION: Glioma is the most frequent malignancy of the adult central nervous system with high recurrence risk and poor prognosis. Understanding the biological molecular mechanisms involved in glioma progression is critical for studying oncogenic mechanisms and improving prognosis. Lysyl oxidase-like 2 (LOXL2) is a kind of lysyl oxidase catalyzing the formation of peptidyl-lysine residues and promoting intramolecular cross-linking, especially for proteins in extracellular matrix. Our study explored the expression pattern of LOXL2 in glioma for the first time and found that its high expression was associated with larger tumor size and advanced tumor grade (P<0.05). Moreover, univariate and multivariate analyses revealed LOXL2 as a novel independent prognostic factor for the overall survival of glioma patients. METHODS: To evaluate the detailed functional roles of LOXL2, we tested its oncobiology characteristics in U87-MG cells with overexpression and knockdown experiments. RESULTS: Cellular results demonstrated that LOXL2 overexpression enhanced cell proliferation and invasion, while LOXL2-siRNA attenuated cell viability. Furthermore, our data identified the participation of E-cadherin, Snail1, Src, and FAK proteins downstream of LOXL2. Notably, by using immunoprecipitation and mass spectrometry strategies, we initially verified the interaction between LOXL2 and HDAC2, indicating the existence of a protein complex containing LOXL2/Snail1/HDAC2. Additionally, the expression of HDAC2 protein was highly correlated with that of LOXL2 in clinical glioma tissues (P=0.02), further implying the synergic oncogenic roles of these 2 proteins. CONCLUSION: LOXL2 is a promising prognostic biomarker and may be further evaluated as a potential drug target for patients with glioma.

Alzheimer's disease hypothesis and related therapies.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause for dementia. There are many hypotheses about AD, including abnormal deposit of amyloid ß (Aß) protein in the extracellular spaces of neurons, formation of twisted fibers of tau proteins inside neurons, cholinergic neuron damage, inflammation, oxidative stress, etc., and many anti-AD drugs based on these hypotheses have been developed. In this review, we will discuss the existing and emerging hypothesis and related therapies.

Dynamic changes of α-melanocyte-stimulating hormone levels in the serum of patients with craniocerebral trauma.

The aim of the study was to investigate dynamic changes in α-melanocyte-stimulating hormone (α-MSH) levels in the serum of patients with craniocerebral trauma. Forty-eight patients with acute craniocerebral injury were selected between January 2015 and October 2016. The patients were divided into three groups: severe (18 cases), moderate (16 cases) and mild (14 cases), according to the Glasgow Coma Scale (GCS) score at the time of admission. At the same time, 10 adults with a similar age distribution to the patients were also selected as a control group. Venous blood was extracted from patients at 1, 3, 5 and 7 days after injury. Serum α-MSH and tumor necrosis factor (TNF)-α levels were measured using an enzyme-linked immunosorbent assay (ELISA). The correlation between α-MSH and TNF-α was analyzed using Pearson's correlation analysis. Serum α-MSH levels in patients with craniocerebral injury were lower than those in the healthy control group (P<0.05). Decreased serum α-MSH levels were usually accompanied with higher degrees of craniocerebral injury. Serum α-MSH levels initially decreased and then later increased, with the lowest α-MSH levels in the mild at 5 days, moderate at 5 days, and severe groups at 3 days after injury (P<0.05). Serum TNF-α levels in all the patient groups were higher than those in the control group at different time points after injury, with higher TNF-α serum levels accompanying higher degrees of brain injury. In all three groups, serum TNF-α levels initially increased and then decreased post-injury, with peak serum TNF-α levels found at 3-day post-injury in all the patient groups (P<0.05). A negative correlation between serum α-MSH content and serum TNF-α levels in patients with craniocerebral trauma at different time points, was noted (P<0.05). Serum α-MSH content in the survival group was higher than that in the death group (P<0.05). Serum α-MSH levels in patients with non-systemic inflammatory response syndrome (SIRS) were higher than in patients with SIRS (P<0.05). Serum α-MSH levels during the early stages after craniocerebral trauma can be used as a factor for the prediction of secondary SIRS, with constant low levels of serum α-MSH suggest poor prognosis.

Synthesis and bioassay of ß-(1,4)-D-mannans as potential agents against Alzheimer's disease.

AIM: Oligomannurarate 971 derived from a marine plant has shown neuroprotective effects. In this study we synthesized a series of truncated derivatives of the oligosaccharide, and investigated the effect of these derivatives against Aß peptide toxicity in vitro. METHODS: The sulfoxide method was applied to synthesize the derivatives. SH-SY5Y human neuroblastoma cells were treated with Aß1-40 (2 µmol/L), and the cell viability was detected using a CCK8 assay. RESULTS: A series of ß-(1,4)-D-mannosyl oligosaccharide, ranging from the disaccharide to the hexasaccharide, were synthesized. Addition of 10 µmol/L ß-(1,4)-D-mannobiose 6, ß-(1,4)-D-mannotriose 9 or ß-(1,4)-D-mannotetraose 12 in SH-SY5Y cells significantly attenuated Aß1-40-induced toxicity. The efficacies were similar to those caused by 10 µmol/L oligomannurarate 971 or alzhemed. Other oligosaccharides including oligomaltoses and oligocelluloses were less active. CONCLUSION: Synthetic homogeneous short chain ß-(1,4)-D-mannans shows neuroprotective effect against Aß peptide toxicity similar to that of heterogeneous oligomannurarate 971 and alzhemed.

The half maximum time of (99m)Tc-DTPA renography measured in healthy kidney donors, compared to (131)I-OIH.

Technetium-99m-diethylene triamine pentaacetic acid ((99m)Tc-DTPA) has been widely used after (131)I-ortho-hippurate ((131)I-OIH) for renography and to test renal function. Only a few reports refer to normal values range of (99m)Tc-DTPA renography half maximum time (HMT). We have measured the normal value range of (99m)Tc-DTPA renography HMT in our department, of 433 healthy kidney donors from 2007 to 2010, and compared these results with those of (131)I-OIH renography. There were 326 men and 107 women, 18y-69y (median age 29y), subjects were measured before the donation of their kidneys operation and their biochemical, ultrasound and renal function tests were normal. All subjects drunk at least 1 litre of tap water before renography. The (99m)Tc-DTPA dynamic scintigraphy was performed in the posterior view by injecting intravenously as a bolus 185-296MBq. Dynamic imaging was performed immediately after the injection, using a high-resolution low-energy general purpose collimator and a large field of view dual-detector gamma-camera (Hawkeye; General Electric Medical Systems, USA). Matrix was 64Χ64, the phase acquisition time of blood perfusion was 1s/frame and 30 frames were collected. Dynamic acquisition was 30s/frame and 39 frames were collected. Total acquisition time was 20min. We defined as background two regions of interest around the kidneys and the aorta, for radioactive decay correction. We also compared (99m)Tc-DTPA renography HMT values with the HMT values of (131)I-OIH, between the two kidneys, and between men and women. The findings were evaluated by using frequency distribution analysis, paired Sample Student's t-test and one sample t test, with a level of significance P<0.05. We used the SPSS 10.0 statistical software. Since values beyond a high boundary were regarded as unusual, we used the P(95), i.e. " 95% of HMT reference ranges value" to determine the medical reference range of values, as the HMT normal limit. This reference value is used especially when the data shows a skewed distribution. For the HMT (P(95) value), the normal reference values found between mean values of the left and the right kidney were: 10.76±4.14min and 10.89±4.55min, respectively and P=0.416, two tailed. For the left kidney HMT, there was no significant difference between men: 10.90±4.31min and women: 10.33±3.57min, (t=1.235, v=432, P=0.2186, two tailed), and similar findings were found between men's right kidney HMT: 11.02±4.89min and women's right kidney HMT: 10.49±3.32min, (t=1.253, v=266.59, P=0.211, two tailed). By comparing the mean value of (99m)Tc-DTPA renography HMT measured (10.76min, 10.89min) with the mean value of (131)I renography HMT that we found in the literature as referring to both left and right kidneys (4min). We found a significant difference (P=0.000, two tailed). Renography may be used to diagnose urinary tract obstruction, estimate the split renal function and is useful.

Synthesis, cytotoxic activities and cell cycle arrest profiles of naphtho[2,1-α]pyrrolo[3,4-c]carbazole-5,7(6H,12H)-dione glycosides.

Naphtho[2,1-α]pyrrolo[3,4-c]carbazole-5,7(6H,12H)-dione (NPCD) is known to be a very potent and selective cyclin D1-CDK4 inhibitors and could induce strong G1 phase arrest in breast tumor cell lines. In this work, the synthesis of five NPCD glycosides and their cytotoxic activities against eight tumor cell lines are presented, as well as the investigation of their cell cycle arrest profiles. The results showed that the introduction of a sugar moiety onto NPCD did not affect much of their cytotoxic activities, while the subtle structure of the sugar moiety affected the underlying mechanism strongly. In addition, NPCD showed distinct cell-cycle arrest profiles in BxPC3 prostate cells and MCF-7 breast cells, while NPCD glycosides shared similar cell cycle arrest profiles in MCF-7 and BxPC3 cells, which also indicated that not only the indolocarbazole framework as well known before but the sugar moiety can have a profound impact on the mechanism of action for these types of compounds.

Small molecule inhibitors of amyloid ß peptide aggregation as a potential therapeutic strategy for Alzheimer's disease.

Amyloid ß (Aß) peptides have long been viewed as a potential target for Alzheimer's disease (AD). Aggregation of Aß peptides in the brain tissue is believed to be an exclusively pathological process. Therefore, blocking the initial stages of Aß peptide aggregation with small molecules could hold considerable promise as the starting point for the development of new therapies for AD. Recent rapid progresses in our understanding of toxic amyloid assembly provide a fresh impetus for this interesting approach. Here, we discuss the problems, challenges and new concepts in targeting Aß peptides.

Negative density dependence can offset the effect of species competitive asymmetry: a niche-based mechanism for neutral-like patterns.

The debate on the role of species differences in shaping biodiversity patterns, with its two extremes of pure niche theory and neutral theory, is still ongoing. It has been demonstrated that a slight difference in competitive ability of species severely affects the predictions of the neutral model. At the same time, neutral patterns seem to be ubiquitous. Here, we model both negative density dependence (NDD) and competitive asymmetry (CA) simultaneously. Our simulation results show that an appropriate intensity of NDD can offset the negative effect of CA (modeled as fecundity difference) on species coexistence and produce a neutral-like species abundance distribution. Therefore, our model provides a plausible mechanistic explanation of neutral-like patterns, but contrary to the neutral model, a species' relative abundance is positively related to its competitive ability in our model.

MS80, a novel sulfated polysaccharide, inhibits CD40-NF-kappaB pathway via targeting RIP2.

In the previous studies, MS80 was found to be able to inhibit the pulmonary fibrosis. However, the target of MS80 remains unclear. To determine the target and the antifibrosis mechanisms of MS80, affinity column, MALDITOF-MS/MS, co-immunoprecipitation, and co-localization were used. The results showed that MS80 targeting protein was receptor interacting protein 2 (RIP2), which was further confirmed by co-immunoprecipitation and co-localization. Moreover, MS80 inhibited the CD40 ligation-induced NF-kappaB activation, and subsequently inflammatory cytokines secretion, the collagen synthesis, and the excessive proliferation of fibroblasts. Thus the detailed molecular machinery was ascribed to the involvement of MS80 in targeting CD40 signal pathway via binding and blocking RIP2, the key component of CD40 signal transduction. The findings addressed here may substantially account for the effects of MS80 in combating the pulmonary fibrosis.

[Fabrications of a poly (methyl methacrylate) (PMMA) microfluidic chip-based DNA analysis device].

A DNA analysis device based on poly(methyl methacrylate) (PMMA) microfluidic chips was developed. A PMMA chip with cross microchannels was fabricated by a simple hot embossing. Microchannels were modified with a static adsorptive coating method using 2% hydroxyethyl cellulose. A high-voltage power unit, variable in the range 0-1 800 V, was used for on-chip DNA sample injection and gel electrophoretic separation. High speed, high resolution DNA analysis was obtained with the home-built PMMA chip in a sieving matrix containing 2% hydroxyethyl cellulose with a blue intercalating dye, TO-PRO-3 (TP3), by using diode laser induced fluorescence detection based on optical fibers with a 670 nm long-pass filter. The DNA analysis device was applied for the separation of phiX-174/HaeIII DNA digest sample with 11 fragments ranging from 72 to 1 353 bp. A separation efficiency of 1.14 x 10(6) plates/m was obtained for the 603 bp fragments, while the R of 271/281 bp fragments was 1.2. The device was characterized by simple design, low cost for fabrication and operation, reusable PMMA chips, and good reproducibility. A portable microfluidic device for DNA analysis can be developed for clinical diagnosis and disease screening.

Focusing synchrotron radiation using a polycapillary half-focusing X-ray lens for imaging.

An imaging system based on a polycapillary half-focusing X-ray lens (PHFXRL) and synchrotron radiation source has been designed. The focal spot size and the gain in power density of the PHFXRL were 22 microm (FWHM) and 4648, respectively, at 14.0 keV. The spatial resolution of this new imaging system was better than 5 microm when an X-ray charge coupled device with a pixel size of 10.9 x 10.9 microm was used. A fossil of an ancient biological specimen was imaged using this system.

Static adsorptive coating of poly(methyl methacrylate) microfluidic chips for extended usage in DNA separations.

A simple and robust static adsorptive (dynamic) coating process using 2% hydroxyethylcellulose was developed for surface modification of poly(methyl methacrylate) (PMMA) microfluidic chips for DNA separations, suitable for usage over extended periods, involving hundreds of runs. The coating medium was also used as a sieving matrix for the DNA separations following the coating process. Four consecutive static treatments, by simply filling the PMMA chip channels with sieving matrix once every day, were required for obtaining a stable coating and optimum performance. The performance of the coated chips at different phases of the coating process was studied by consecutive gel electrophoretic separations with LIF detection using a PhiX-174/HaeIII DNA digest sample. The coated chip, with daily renewal of the sieving matrix, showed high stability in performance during a 25-day period of systematic study, involving more than 100 individual runs. The performance of the coated chip also remained almost the same after 3 months of continuous usage, during which over 200 separations were performed. The average precision of migration time for the 603-bp fragment was 1.31% RSD (n = 6) during the 25-day study, with a separation efficiency of 6.5 x 10(4) plates (effective separation length 5.4 cm).