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Biochemical correlates of stochastic single-cell fates have been elusive, even for the well-studied mammalian cell cycle. We monitored single-cell dynamics of the ERK and Akt pathways, critical cell cycle progression hubs and anti-cancer drug targets, and paired them to division events in the same single cells using the non-transformed MCF10A epithelial line. Following growth factor treatment, in cells that divide both ERK and Akt activities are significantly higher within the S-G2 time window (~ 8.5–40 h). Such differences were much smaller in the pre-S-phase, restriction point window which is traditionally associated with ERK and Akt activity dependence, suggesting unappreciated roles for ERK and Akt in S through G2. Simple metrics of central tendency in this time window are associated with subsequent cell division fates. ERK activity was more strongly associated with division fates than Akt activity, suggesting Akt activity dynamics may contribute less to the decision driving cell division in this context. We also find that ERK and Akt activities are less correlated with each other in cells that divide. Network reconstruction experiments demonstrated that this correlation behavior was likely not due to crosstalk, as ERK and Akt do not interact in this context, in contrast to other transformed cell types. Overall, our findings support roles for ERK and Akt activity throughout the cell cycle as opposed to just before the restriction point, and suggest ERK activity dynamics may be more important than Akt activity dynamics for driving cell division in this non-transformed context.

Warming-induced drought stress leads to convergent and negative growth responses to temperature between sympatric tree species, implying an increasing interspecific competition for soil moisture. In mixed forests, sympatric tree species avoid competition by partitioning their niches according to available environment resources. We raise the hypothesis that climate warming leads to a convergence in growth responses to climate, thus increasing the competition among sympatric species in drought-prone forests. In this study, we selected a mixed forest located at ca. 3600 m a.s.l in the Baima Snow Mountains, an inner dry valley of the southeastern Tibetan Plateau. We measured width of the tree rings produced during 1910–2016 in 60 trees belonging to three sympatric species: Abies georgei, Picea likiangensis, and Betula delavayi. We analyzed the changes in radial growth and their responses to climate. We detected shifts in the responses to climate after the 1990s. The radial growth of all species was positively correlated with precipitation from 1964 to 1990, but negatively correlated with March–June temperature from 1991 to 2016. Compared to the period 1964–1990, convergent and negative growth responses to warmer temperatures in the period 1991–2016 probably reflect less available soil moisture for growing in this mixed forest. We conclude that climate warming will affect the niches of sympatric species in mixed forests subjected to seasonal drought, thus increasing competition and altering structure and composition of the stands in dry regions.

Genome-wide association studies of Systemic Lupus Erythematosus (SLE) nominate 3073 genetic variants at 91 risk loci. To systematically screen these variants for allelic transcriptional enhancer activity, we construct a massively parallel reporter assay (MPRA) library comprising 12,396 DNA oligonucleotides containing the genomic context around every allele of each SLE variant. Transfection into the Epstein-Barr virus-transformed B cell line GM12878 reveals 482 variants with enhancer activity, with 51 variants showing genotype-dependent (allelic) enhancer activity at 27 risk loci. Comparison of MPRA results in GM12878 and Jurkat T cell lines highlights shared and unique allelic transcriptional regulatory mechanisms at SLE risk loci. In-depth analysis of allelic transcription factor (TF) binding at and around allelic variants identifies one class of TFs whose DNA-binding motif tends to be directly altered by the risk variant and a second class of TFs that bind allelically without direct alteration of their motif by the variant. Collectively, our approach provides a blueprint for the discovery of allelic gene regulation at risk loci for any disease and offers insight into the transcriptional regulatory mechanisms underlying SLE., Thousands of genetic variants have been associated with lupus, but causal variants and mechanisms are unknown. Here, the authors combine a massively parallel reporter assay with genome-wide ChIP experiments to identify risk variants with allelic enhancer activity mediated through transcription factor binding.

A multi-operation laser oscillator is developed and built with multiple operation modes (OMs): injectionseeding mode, cavity-dumping mode and Q-switching mode.With the same electrical energy pumping, the multioperation laser oscillator provides different output energies and pulse durations for different OMs. In the Q-switching mode, the output coupling is optimized for different electrical energy pumping. The laser oscillator operation can be switched between different modes conveniently. The multi-operation laser sources could be operated in multiple OMs for various research and application requirements.

s Background Overexpressed PES1 promotes carcinogenesis in various types of malignant tumors. However, the biological role and clinical significance of PES1 in pancreatic cancer are still unexplored. Methods The expression level of PES1 in pancreatic cancer cell lines and pancreatic cancer patient samples was determined using Western Blotting analysis, RT-qPCR analysis, immunohistochemical (IHC) analysis of tissue microarray, and the GEPIA web tool. MTS assay, colony formation assay, and xenograft tumor assay were used to evaluate the tumor growth ability of pancreatic cancer cells. Results We established that the expression of PES1 was abnormally increased in pancreatic cancer tissues and led to poor prognosis of pancreatic cancer patients. We also found that PES1 was responsible for promoting cell growth and contributed to bromodomain and cancer cell resistance to extra-terminal (BET) inhibitors in pancreatic cancer. Furthermore, we showed that PES1 interacted with BRD4 to enhance c-Myc expression, which is the primary cause of cancer cell resistance to BET inhibitors in pancreatic cancer. Finally, CDK5 inhibitors were proven to destabilize PES1 and overcome cancer cell resistance to BET inhibitors in pancreatic cancer cells. Conclusions We have shown that PES1 could be one of the promoting factors of tumor growth and a prognosis-related protein of pancreatic cancer. Targeting PES1 with CDK5 inhibitors might help overcome cancer cell resistance to BET inhibitors in pancreatic cancer cells.

The clinical effect of laparoscopic rectal cancer curative excision with pelvic autonomic nerve preservation (PANP) was investigated. This study evaluated the frequency of urinary and sexual dysfunction of 149 male patients with middle and low rectal cancer who underwent laparoscopic or open total mesorectal excision with pelvic autonomic nerve preservation (PANP) from March 2011 to March 2013. Eighty-four patients were subjected to laparoscopic surgery, and 65 to open surgery respectively. The patients were followed up for 12 months, interviewed, and administered a standardized questionnaire about postoperative functional outcomes and quality of life. In the laparoscopic group, 13 patients (18.37%) presented transitory postoperative urinary dysfunction, and were medically treated. So did 12 patients (21.82%) in open group. Sexual desire was maintained by 52.86%, un-ability to engage in intercourse by 47.15%, and un-ability to achieve orgasm and ejaculation by 34.29% of the patients in the laparoscopic group. Sexual desire was maintained by 56.36%, un-ability to engage in intercourse by 43.63%, and un-ability to achieve orgasm and ejaculation by 33.73% of the patients in the open group. No significant differences in urinary and sexual dysfunction between the laparoscopic and open rectal resection groups were observed (P>0.05). It was concluded that laparoscopic rectal cancer radical excision with PANP did not aggravate or improve sexual and urinary dysfunction.

High-quality c-axis epitaxial Bi2Sr2CaCu2O8+δ (Bi2212) superconducting thin films prepared by the Pechini sol–gel method using nitrates as reactants have been grown on SrTiO3(100) single-crystal substrates. The precursor sol was deposited on the substrates via spin-coating method. Through the optimization of experimental parameters, 2.0 K min−1 was found to be the optimal heating rate of pre-sintering stage. Below this heating rate of pre-sintering stage, partial composition segregation occurred in the precursor films that resulted in dispersion of impurity phases in sintered thin films and caused the degradation of superconducting properties. Above this heating rate of pre-sintering stage, the surface morphology of thin films was destroyed, as the macroscopic defects, such as cracks and holes caused by excessive gas emissions during organic matter decomposition process and a sharp increase in roughness of precursor film was observed. Furthermore, through the optimization of heating rate at sintering stage, 3.5–3.0 K min−1 was found to be an optimal heating rate range at which Bi2212 thin films exhibited excellent phase purity and crystalline properties. In optimized growth condition, T c,onset rose to above 95 K. Through the optimization of heating rates of pre-sintering and sintering stages, the excellent Bi2212 superconducting thin films without macroscopic defects were prepared by Pechini sol–gel method using nitrate as reactant.

The odour emission characteristics of 22 recreational rivers in Nanjing were investigated and analysed. Eight odorous compounds (ammonia (NH3), hydrogen sulphide (H2S), sulphur dioxide (SO2), carbon disulphide (CS2), nitrobenzene (C6H5NO2), aniline (C6H5NH2), dimethylamine (C2H7N), and formaldehyde (HCHO)) were measured in odour emission samples collected using a custom-made emission flux hood chamber. The results showed that all odorants were detected in all monitoring rivers. NH3 was the main odorant, with emission rates ranging from 4.86 to 15.13 μg/min m2. The total odour emission rate of the Nan River, at 1 427.07 OU/s, was the highest of the all investigated rivers. H2S, NH3 and nitrobenzene were three key odour emission contributors according to their contributions to the total odour emission. A correlation analysis of the pollutants showed there was a significant positive correlation between the emission rate of NH3 and the concentration of ammonia nitrogen (NH4 +-N) and total nitrogen (TN). The H2S and SO2 emission rates had a significant positive correlation with sulphides (S2−) and available sulphur (AS) in the water and sediment. The content of TN, NH4 +-N, S2− and AS in the water and sediment affected the concentration of H2S, SO2 and NH3 in the emission gases. NH4 +-N, S2− and AS are suggested as the key odour control indexes for reducing odours emitted from these recreational rivers. The study provides useful information for effective pollution control, especially for odour emission control for the recreational rivers of the city. It also provides a demonstrate example to show how to monitor and assess a contaminated river when odour emission and its control need to be focused on.

GPR12, a member of the orphan G-protein-coupled receptor family, constitutively activates the Gs protein and increases intracellular cyclic AMP concentrations. GPR12 can be activated by its known ligand-sphingosylphosphorylcholine, which regulates cellular physiological activities, including proliferation, neurite extension, cell clustering, and maintenance of meiotic arrest. However, signaling pathways involved in the GPR12-mediated physiological and biochemical changes are still not clearly illustrated. In the present study, heterologous GPR12 expression was demonstrated to promote proliferation and survival in human embryonic kidney 293 cells. Immunochemical analysis showed that Ki67, a prototypic cell cycle-related nuclear protein, might participate in the regulation of GPR12-mediated cell proliferation. Activation of extracellular signal-regulated protein kinase signaling and increased total Erk1/2 and B-cell lymphoma/leukemia-2 expression were also observed in HEK293 cells overexpressing human GPR12. In addition, we found that GPR12 promoted cell survival under serum deprivation, indicating that GPR12 may play a role in cell proliferation and survival.

Tankyrase 1, which enhances telomerase access to telomeres, plays an important role in telomere maintenance. The aim of this study was to determine the expression and potential role of tankyrase 1 in gastric cancer development and progression. We examined the expression of tankyrase 1 by RT-PCR and Western blotting, and assessed telomerase activity by TRAP-ELISA method in gastric cancer and adjacent normal tissues. We found that tankyrase 1 expression was significantly up-regulated in gastric cancer tissues compared to normal corresponding tissues. Tankyrase 1 over-expression by gastric cancerous tissue was significantly associated with tumor histology differentiation and tumor stage. Moreover, tankyrase 1 expression was significantly correlation with telomerase activity. Our results indicate that tankyrase 1 over-expression may play an important role in gastric cancer development and progression. Tankyrase 1 may be used as a biomarker of gastric cancer and may serve as a target for cancer therapy.

Metal-organic-hybrid bulk chain-like, block, tubular, and plate crystals have been synthesized by a wet chemical method. Single crystal X-ray diffraction and TEM reveal that all the nano-structures are associated with their crystal motifs, which provide a successful and effective access to assemble controlled specific nano-structures from bulk crystal of which the motifs are much desired.

Isomeric polymers [Cd2(mbt)4] n and [Cd(mbt)2] n (mbt = mercaptobenzothiazole) are investigated. The complex {[Cd(μ-η2-C7H4NS2)2][Cd(μ-η2-C7H4NS2) (μ-η3-C7H4NS2)]} n is formed by the reaction of Cd(NO3)2·4H2O with 2-Hmbt in the presence of H2biim in EtOH/H2O. The complex crystallizes in the orthorhombic space group Pca2(1), where a = 21.892(2), b = 9.8994(11), c = 14.8687(15) A, α = 90, β = 90, γ = 90o, V = 3,222.3(6) A3, and Z = 4. The two Cd atoms, one exhibits a CdN2S2 tetrahedral geometry and the other exhibits a distorted CdN2S3 trigonal bipyramidal geometry, are linked by bridging–chelating mbt and bridging mbt ligands. The infinite 1D polymer chains complex {[Cd(μ-η2-C7H4N2S2)2][Cd(μ-η2-C7H4NS2) (μ3-η2-C7H4NS2)]} n is formed by the reaction of Cd(NO3)2·4H2O, 2-Hmbt in the present of H2biim, which contains a CdN2S2 tetrahedral geometry and a distorted CdN2S3 trigonal bipyramidal geometry.

Tubular metal-organic complex (C(2)H(9)N(2))(2)(C(2)H(10)N(2))(0.5)[MoO(2)(OC(6)H(4)O)(2)] has been synthesized. The title complex crystallizes in the tetragonal system, space group P4(2)/n with a = 25.214(8), c = 7.484(4) angstrom, and Z = 8. The X- ray structural analysis of the complex reveals tube-like framework which is stabilized by hydrogen bond. Chiral anions [Mo((V))O(2)(OC(6)H(4)O)(2)](3-) of the complex have two types of isomers(lambda/delta configuration). Helical nanostructure of this metal-organic complex was formed using a sonochemical method. Sonocation may lead to the transformation from the bulk tubular complex to the helical nanostructure. The as-synthesized nanohelices were all double-stranded and left-and right-handed nanohelices were both formed. The helical nanostructure is a new morphology of inorganic-organic hybrid materials on the nanoscale level and the exact formation mechanism of these helices still needs further investigation.

Metal-organic complex (H3NCH2CH2NH2)3[MoO2(OC6H4O)2] with a lamellar morphology has been synthesized. Its crystal structure was confirmed by single-crystal X-ray diffraction. The morphology of the crystal was observed by scanning electron microscopy (SEM). The metal-organic nanoparticles have been prepared by using an ultrasonic method. The morphology of the as-prepared nanoparticles was observed by transmission electron microscopy (TEM). The possible formation mechanism has also been proposed.

Quantum key distribution (QKD) is a technology with the potential capability to achieve information-theoretic security. Phasecoding is an important approach to develop practical QKD systems in fiber channel. In order to improve the phase-coding modulation rate, we proposed a new digital-modulation method in this paper and constructed a compact and robust prototype of QKD system using currently available components in our lab to demonstrate the effectiveness of the method. The system was deployed in laboratory environment over a 50 km fiber and continuously operated during 87 h without manual interaction. The quantum bit error rate (QBER) of the system was stable with an average value of 3.22% and the secure key generation rate is 8.91 kbps. Although the modulation rate of the photon in the demo system was only 200 MHz, which was limited by the Faraday- Michelson interferometer (FMI) structure, the proposed method and the field programmable gate array (FPGA) based electronics scheme have a great potential for high speed QKD systems with Giga-bits/second modulation rate.

A method was developed for the separation of imazethapyr enantiomers using capillary electrophoresis and large volume injection. Optimized buffer conditions were found using 6% hydroxypropyl-β-cyclodextrin as the chiral selector at pH 11 with an injection time of 20 s (0.5 psi). The limits of detection (LOD, S/N = 3) were 0.22 and 0.23 mg L−1 for the two imazethapyr enantiomers (imazethapyr-I and imazethapyr-II) respectively. The relative standard deviation was less than 5%. This method was successfully used in the study of enantioselective degradation of this herbicide in field soil and the results suggested that imazethapyr-I degraded at a higher rate when compared with imazethapyr-II.