Organic Cocrystal Alloys: From Three Primary Colors to Continuously Tunable Emission and Applications on Optical Waveguides and Displays.

Multicolor luminescence of organic fluorescent materials is an essential part of lighting and optical communication. However, the conventional construction of a multicolor luminescence system based on integrating multiple organic fluorescent materials of a single emission band remains complicated and to be improved. Herein, organic alloys (OAs) capable of full-color emission are synthesized based on charge transfer (CT) cocrystals. By adjusting the molar ratio of electron donors, the emission color of the OAs can be conveniently and continuously regulated in a wide visible range from blue (CIE: 0.187, 0.277), to green (CIE: 0.301, 0.550), and to red (CIE: 0.561, 0.435). The OAs show analogous 1D morphology with smooth surface, allowing for full-color waveguides with low optical-loss coefficient. Impressively, full-color optical displays are easily achieved through the OAs system with continuous emission, which shows promising applications in the field of optical display and promotes the development of organic photonics.

Conditional survival probability of distant-metastatic hepatocellular carcinoma: A population-based study.

BACKGROUND: The prognosis of many patients with distant metastatic hepatocellular carcinoma (HCC) improved after they survived for several months. Compared with traditional survival analysis, conditional survival (CS) which takes into account changes in survival risk could be used to describe dynamic survival probabilities. AIM: To evaluate CS of distant metastatic HCC patients. METHODS: Patients diagnosed with distant metastatic HCC between 2010 and 2015 were extracted from the Surveillance, Epidemiology and End Results database. Univariate and multivariate Cox regression analysis were used to identify risk factors for overall survival (OS), while competing risk model was used to identify risk factors for cancer-specific survival (CSS). Six-month CS was used to calculate the probability of survival for an additional 6 mo at a specific time after initial diagnosis, and standardized difference (d) was used to evaluate the survival differences between subgroups. Nomograms were constructed to predict CS. RESULTS: Positive α-fetoprotein expression, higher T stage (T3 and T4), N1 stage, non-primary site surgery, non-chemotherapy, non-radiotherapy, and lung metastasis were independent risk factors for actual OS and CSS through univariate and multivariate analysis. Actual survival rates decreased over time, while CS rates gradually increased. As for the 6-month CS, the survival difference caused by chemotherapy and radiotherapy gradually disappeared over time, and the survival difference caused by lung metastasis reversed. Moreover, the influence of age and gender on survival gradually appeared. Nomograms were fitted for patients who have lived for 2, 4 and 6 mo to predict 6-month conditional OS and CSS, respectively. The area under the curve (AUC) of nomograms for conditional OS decreased as time passed, and the AUC for conditional CSS gradually increased. CONCLUSION: CS for distant metastatic HCC patients substantially increased over time. With dynamic risk factors, nomograms constructed at a specific time could predict more accurate survival rates.

Two-stage process production of microbial lipid by co-fermentation of glucose and N-acetylglucosamine from food wastes with Cryptococcus curvatus.

Microbial lipids were produced through a two-stage process with Cryptococcus curvatus by co-fermenting rice and shrimp shells hydrolysates. In the first stage, biomass production of glucose and N-acetylglucosamine was optimized by response surface methodology with the maximum biomass yield (17.60 g/L) under optimum conditions (43.2 g/L mixed sugar concentration, pH 5.8, 200 rpm, and 28 °C). In the second stage, according to a single-factor optimization setting (43.2 g/L sugar mixture solutions, pH 5.5, and shift time of 36 h), lipid titer of 10.08 g/L with content of 55.30 % was achieved. Scaling up to a 5-L bioreactor increased lipid content to 60.07 % with 0.233 g/g yield. When Cryptococcus curvatus was cultured in the blends of rice hydrolysates and shrimp shells hydrolysate, lipid content and yield were 52.25 % and 0.204 g/g. The fatty acid compositions of lipid were similar to those of typical vegetable oils.

Systematic comparison of differential expression networks in MTB mono-, HIV mono- and MTB/HIV co-infections for drug repurposing.

The synergy between human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (MTB) could accelerate the deterioration of immunological functions. Previous studies have explored the pathogenic mechanisms of HIV mono-infection (HMI), MTB mono-infection (MMI) and MTB/HIV co-infection (MHCI), but their similarities and specificities remain to be profoundly investigated. We thus designed a computational framework named IDEN to identify gene pairs related to these states, which were then compared from different perspectives. MMI-related genes showed the highest enrichment level on a greater number of chromosomes. Genes shared by more states tended to be more evolutionarily conserved, posttranslationally modified and topologically important. At the expression level, HMI-specific gene pairs yielded higher correlations, while the overlapping pairs involved in MHCI had significantly lower correlations. The correlation changes of common gene pairs showed that MHCI shared more similarities with MMI. Moreover, MMI- and MHCI-related genes were enriched in more identical pathways and biological processes, further illustrating that MTB may play a dominant role in co-infection. Hub genes specific to each state could promote pathogen infections, while those shared by two states could enhance immune responses. Finally, we improved the network proximity measure for drug repurposing by considering the importance of gene pairs, and approximately ten drug candidates were identified for each disease state.

A Comparative Study Between Tumor Blood Vessels and Dynamic Contrast-enhanced MRI for Identifying Isocitrate Dehydrogenase Gene 1 (IDH1) Mutation Status in Glioma.

OBJECTIVE: Isocitrate dehydrogenase gene (IDH) mutations are associated with tumor angiogenesis and therefore play an important role in glioma management. This study compared the performance of tumor blood vessels counted from contrast-enhanced 3D brain volume (3D-BRAVO) sequence and dynamic contrast-enhanced (DCE) MRI in differentiating IDH1 status in gliomas. METHODS: Forty-four glioma patients [16 with IDH1 mutant-type (IDH1-MT), 28 with IDH1 wild-type (IDH1-WT)] were retrospectively analyzed. A blood vessel entering a tumor was defined as an intratumoral vessel; a blood vessel adjacent to the edge of a tumor was defined as a peritumoral vessel. Combined vessels were defined as the sum of the intratumoral and peritumoral vessels. DCE-derived metrics of tumor were normalized to the contralateral normal-appearing white matter. RESULTS: Intratumoral, peritumoral, and combined tumor blood vessels were all significantly different between IDH1-MT and IDH1-WT gliomas, and the range of area under curves (AUCs) was 0.816-0.855. For DCE-derived parameters, cerebral blood volume, cerebral blood flow, mean transit time, and volume transfer constant were significantly different between IDH1-MT and IDH1-WT gliomas, and the range of AUCs was 0.703-0.756. Combined vessels possessed the best performance for identifying IDH1 mutations in gliomas (AUC: 0.855, sensitivity: 0.857, specificity: 0.812, P<0.001). CONCLUSION: The number of tumor blood vessels has comparable diagnostic performance with DCE-derived parameters for differentiating IDH1 mutations and can serve as a potential imaging biomarker to reflect IDH1 mutations in gliomas.

Data on point cloud scanning and ground radar of composite lining in jointly constructed tunnel.

The present dataset pertains to field records of construction quality of composite lining in a jointly constructed tunnel. The dataset includes the original mining surface profile data collected by the terrestrial laser scanning (TLS) and radar information on backfill quality outside the segmental lining which was obtained by the ground-penetration radar (GPR) detection. The point cloud data of the mining surface was further processed and compared with the design tunnel model to evaluate the level of over and under- excavation. The radargram provides details on the variation of the signal waveform by which the heterogeneity of backfill can be recognized. The dataset can be used to verify that the voids are prone to occur in the outside backfill of the composite lining. Furthermore, this dataset provides a method for detecting and preventing the defects of the composite lining and also facilitates the post-construction treatment. Additional foreseeable use of this dataset includes providing modeling material for researchers interested in knowing how voids in backfill influence the behavior of composite lining. As a supplement, this dataset supports the numerical analysis outlined in the article titled "Numerical evaluation of segmental tunnel lining with voids in outside backfill" [1].

Unexpected BrdU inhibition on astrocyte-to-neuron conversion.

5-Bromo-2'-deoxyuridine (BrdU) is a halogenated pyrimidine that can be incorporated into newly synthesized DNA during the S phase of the cell cycle. BrdU is widely used in fate-mapping studies of embryonic and adult neurogenesis to identify newborn neurons, however side effects on neural stem cells and their progeny have been reported. In vivo astrocyte-to-neuron (AtN) conversion is a new approach for generating newborn neurons by directly converting endogenous astrocytes into neurons. The BrdU-labeling strategy has been used to trace astrocyte-converted neurons, but whether BrdU has any effect on the AtN conversion is unknown. Here, while conducting a NeuroD1-mediated AtN conversion study using BrdU to label dividing reactive astrocytes following ischemic injury, we accidentally discovered that BrdU inhibited AtN conversion. We initially found a gradual reduction in BrdU-labeled astrocytes during NeuroD1-mediated AtN conversion in the mouse cortex. Although most NeuroD1-infected astrocytes were converted into neurons, the number of BrdU-labeled neurons was surprisingly low. To exclude the possibility that this BrdU inhibition was caused by the ischemic injury, we conducted an in vitro AtN conversion study by overexpressing NeuroD1 in cultured cortical astrocytes in the presence or absence of BrdU. Surprisingly, we also found a significantly lower conversion rate and a smaller number of converted neurons in the BrdU-treated group compared with the untreated group. These results revealed an unexpected inhibitory effect of BrdU on AtN conversion, suggesting more caution is needed when using BrdU in AtN conversion studies and in data interpretation.

Changes in serum thyroid hormone levels in psychiatric patients treated with second-generation antipsychotics.

INTRODUCTION: The objective of the study was to evaluate changes in serum thyroid hormone levels in psychiatric patients after second-generation antipsychotic (SGA) treatment, and to determine differences between monotherapy and polytherapy with SGAs, as well as differences between patients with and without a history of antipsychotics. MATERIAL AND METHODS: A total of 71 patients with baseline thyroid hormone levels within the normal reference ranges were included in this retrospectively study. RESULTS: After SGAs treatment, the serum levels of free triiodothyronine (FT3), free thyroxine (FT4), total triiodothyronine (TT3), and total thyroxine (TT4) significantly decreased, and serum thyroid-stimulating hormone (TSH) levels significantly increased (changes from baseline: FT3: -0.31 pmol/L, p < 0.001; FT4: -2.71 pmol/L, p < 0.001; TT3: -0.05 nmol/L, p = 0.024, TT4: -12.36 nmol/L, p < 0.001; TSH: 0.46 mIU/L, p < 0.001). One (1.4%) patient had TSH levels higher than 7 mIU/L. Changes in serum levels of TSH and TT3 between patients with or without a history of antipsychotic drugs were significantly different (changes from baseline: TSH: p < 0.001 vs. p = 0.089; TT3: p = 0.013 vs. p = 0.553). Changes in serum TSH levels had a moderate positive correlation with the average daily dose of SGAs (p = 0.007, r = 0.318). CONCLUSIONS: After SGA treatment, patients seemed to have a trend of hypothyroidism, but the incidence was low. The preliminary results of this study did not show the necessity of regular monitoring of serum thyroid hormone levels in patients with baseline thyroid hormone levels within the normal reference ranges.

Application of Neurite Orientation Dispersion and Density Imaging in Assessing Glioma Grades and Cellular Proliferation.

OBJECTIVE: To explore the performance of neurite orientation dispersion and density imaging (NODDI) in grading gliomas and to evaluate the cellular proliferation. METHODS: NODDI and diffusion-weighted imaging were performed on 79 patients with histopathologically proven gliomas. Parameter maps of intracellular volume fraction (ICVF), orientation dispersion index (ODI), and apparent diffusion coefficient (ADC) were calculated. Regions of interest were placed in the most solid part of the tumor. These metrics were normalized to the contralateral normal-appearing white matter and correlated with Ki-67 expression. RESULTS: ICVF and ODI increased as tumor grades increased, whereas ADC decreased with the increase of tumor grades. Significant differences in normalized ICVF and ODI were observed between low-grade gliomas and high-grade gliomas (ICVF: 0.208 ± 0.104 vs. 0.718 ± 0.234; ODI: 0.952 ± 0.428 vs. 1.767 ± 0.636, P < 0.001, respectively) and between grades II and III (ICVF: 0.208 ± 0.104 vs. 0.603 ± 0.253; ODI: 0.952 ± 0.428 vs. 1.762 ± 0.542, P < 0.001, respectively). Normalized ICVF was also significantly different between grades III and IV (0.603 ± 0.253 vs. 0.803 ± 0.182, P = 0.004). Ki-67 labeling index was positively correlated with normalized ICVF and ODI (r = 0.755 and 0.572, P < 0.001, respectively), and negatively correlated with normalized ADC (r = -0.709, P < 0.001). CONCLUSIONS: NODDI is a promising method in grading gliomas and predicting cellular proliferation. These results may be of great significance for the clinical diagnosis and treatment of gliomas.

A modified molecular framework derived highly efficient Mn-Co-carbon cathode for a flexible Zn-air battery.

A controllable Co doping strategy is introduced to significantly activate more catalytic sites for Mn-based materials and anchor Co-Mn nanoparticles on the N-doped carbon nanotube (N-CNT) substrates. The as-synthesized CoMn2O4/N-CNTs exhibit excellent ORR catalytic performance with large limited current density and positive half-wave potential, even outperforming the Pt/C catalysts. The outstanding ORR activity allows the CoMn2O4/N-CNTs to directly serve as the cathode electrode in a liquid/solid state Zn-air battery, demonstrating large power density and robust stability.

B5, a thioredoxin reductase inhibitor, induces apoptosis in human cervical cancer cells by suppressing the thioredoxin system, disrupting mitochondrion-dependent pathways and triggering autophagy.

The synthetic curcumin analog B5 is a potent inhibitor of thioredoxin reductase (TrxR) that has potential anticancer effects. The molecular mechanism underlying B5 as an anticancer agent is not yet fully understood. In this study, we report that B5 induces apoptosis in two human cervical cancer cell lines, CaSki and SiHa, as evidenced by the downregulation of XIAP, activation of caspases and cleavage of PARP. The involvement of the mitochondrial pathway in B5-induced apoptosis was suggested by the dissipation of mitochondrial membrane potential and increased expression of pro-apoptotic Bcl-2 family proteins. In B5-treated cells, TrxR activity was markedly inhibited with concomitant accumulation of oxidized thioredoxin, increased formation of reactive oxygen species (ROS), and activation of ASK1 and its downstream regulatory target p38/JNK. B5-induced apoptosis was significantly inhibited in the presence of N-acetyl-l-cysteine. Microscopic examination of B5-treated cells revealed increased presence of cytoplasmic vacuoles. The ability of B5 to activate autophagy in cells was subsequently confirmed by cell staining with acridine orange, accumulation of LC3-II, and measurement of autophagic flux. Unlike B5-induced apoptosis, autophagy induced by B5 is not ROS-mediated but a role for the AKT and AMPK signaling pathways is implied. In SiHa cells but not CaSki cells, B5-induced apoptosis was promoted by autophagy. These data suggest that the anticarcinogenic effects of B5 is mediated by complex interplay between cellular mechanisms governing redox homeostasis, apoptosis and autophagy.

MiR-21 mediates the radiation resistance of glioblastoma cells by regulating PDCD4 and hMSH2.

The purpose of this study was to investigate the molecular mechanism by which miR-21 and its target genes mediate radiation resistance of glioblastoma cells. Real-time PCR was employed to detect miR-21 expression in normal brain tissues, glioblastoma tissues and glioblastoma cell lines (A172, T98G and U87MG). T98G cells were transfected with anti-miR-21 oligonucleotides, or plasmids containing PDCD4 or hMSH2 (PDCD4-pcDNA3 and hMSH2-pcDNA3). The survival curve was obtained to investigate the sensitivity of T98G cells to radiation. Cell apoptosis was measured by using the Caspase-3/7 kit and cell cycle by flow cytometry. Western blotting was performed to detect the expression of hMSH2 and PDCD4 in miR-21-inhibiting T98G cells. The results showed that miR-21 expression in glioblastoma cells and tissues was conversely associated with the radiation sensitivity. Over-expression of miR-21 resulted in radiation resistance, while knockdown of miR-21 led to higher sensitivity of glioblastma cells to radiation. After miR-21 knockdown, the apoptosis of T98G cells was significantly increased and the G(2) phase arrest was more significant. In addition, miR-21 knockdown increased the expression of endogenous PDCD4 and hMSH2, which contributed to the apoptosis and G(2) arrest of T98G cells. The findings suggested that miR-21 may mediate the resistance of glioblastoma cells against radiation via its target genes PDCD4 and hMSH2. MiR-21 and its target genes may be used as potential molecular targets for clinical radiotherapy sensitization in the future.

Cloning, soluble expression, rapid purification and characterization of human Cofilin1.

Cofilin1 is an actin-binding protein that plays a critical role in the regulation of actin cytoskeleton and consequently affects various physiological processes. In this study, the human Cofilin1 cDNA was cloned into the expression vector pET-28a(+) with a 6 × His tag and expressed as soluble protein in Escherichia coli BL21(DE3). Approximately 78 mg of Cofilin1, which showed high activity as determined by native PAGE, could be purified from each liter of LB medium by His-tag affinity chromatography and gel filtration. Further, high-titer IgG against Cofilin1 was positively detected after immunization in rabbits and the polyclonal antibodies were purified and identified. Together, this report provides the first protocol to efficiently obtain human Cofilin1 with high biological activity and immunogenicity using E. coli BL21 (DE3) expression system.

SNX-2112, a novel Hsp90 inhibitor, induces G2/M cell cycle arrest and apoptosis in MCF-7 cells.

SNX-2112 is a heat shock protein 90 (Hsp90) inhibitor with anticancer properties currently in clinical trials. This study investigated the effects of SNX-2112 on inhibition of cell growth, the cell cycle, and apoptosis in MCF-7 human breast cancer cells, in addition to the various molecular mechanisms. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometric analysis suggest that SNX-2112 inhibits cell growth in a time- and dose-dependent manner more potently than 17-(allylamino)-17-demethoxygeldanmycin (17-AAG), a traditional Hsp90 inhibitor, probably as a result of cell-cycle arrest at the G2/M phase and the induction of apoptosis. Downregulation of Bcl-2 and Bcl-xL, upregulation of Bax, cleavage of caspase-9 and poly (ADP-ribose) polymerase (PARP), and degradation of the breast cancer-related Hsp90 client proteins human epidermal growth factor receptor-2 (HER2), Akt, Raf-1, and nuclear factor kappa-B kinase (IKK) were observed in SNX-2112 treated cells by Western blot assay. These findings suggest that the molecular mechanisms of cell-growth inhibition by SNX-2112 involve activation of the mitochondrial apoptotic pathway and the degradation of breast cancer-related proteins.