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A case-control study was conducted in Shandong from January to December 2017 to explore the relationship between sleep quality and the risk of active pulmonary tuberculosis (PTB). Seventy-nine patients with type 2 diabetes mellitus coincident with newly diagnosed pulmonary tuberculosis (DM-PTB) and 169 age, sex, and DM course frequency-matched controls (DM alone) were enrolled. Univariate and multivariable unconditional logistic regression analyses were conducted. We further conducted subgroup analyses to explore the relationship between sleep quality and PTB risk, including DM course (≤5 and ＞5 years), age, sex, and the presence of overweight or obesity (body mass index (BMI) ＞ 24 kg/m2). Multivariate logistic regression demonstrated that poor sleep quality had a borderline negative association with the odds of PTB (P ＝ 0.065). Subgroup multivariate analyses showed that poor sleep quality increased the risk of PTB to more than 3 times among patients with a DM course ＞ 5 years (odds ratio 3.31, 95% confidence interval: 1.08-10.13; P ＝ 0.036) after adjusting for potential confounding factors including residential area, educational level, BMI, history of contact with tuberculosis patients, smoking, alcohol consumption, physical exercise, immune status, and frequency of blood glucose monitoring. In conclusion, poor sleep quality is an independent risk factor of PTB among DM patients with a course of ＞ 5 years, which indicates significant epidemiological implications for PTB control.

Endogenous formaldehyde (FA) exists in many living cells and in inhomogeneous distribution in organelles. In particular, lysosomes play significant roles in FA generation and the biofunction of living cells. Herein, we developed a new ratiometric fluorescent nanoprobe, based on naphthalimide derivative (ND)-functionalized carbon dots (CDs), for monitoring endogenous FA in lysosomes. The fluorescence intensity (F535) of green-emitting ND at 535 nm serves as the response signal and the fluorescence intensity (F414) of blue-emitting CDs at 414 nm acts as the reference signal. The fluorescence intensity ratio (F535/F414) of the CD-ND probe is linearly correlated with FA concentration within the range of 1-40 μM in aqueous solution, and the detection limit (3σ/slope) is estimated to be 0.34 μM. As for practical application, this nanoprobe is utilized for the ratiometric fluorescence imaging of FA in live cells. Remarkably, this nanoprobe can specifically target and stain the lysosomes and detect exogenous and endogenous FA in HeLa cells. The new FA probe shows a superior lysosomal targeting ability with a Pearson's coefficient of 0.93, which is attributed to the macromolecular size and basic amine group functionalized surface of CD-ND.

Background Dictyostelid cellular slime molds (dictyostelids) are microscopic throughout their entire life cycle. The vegetative phase consists of single-celled amoeboid forms which live in the soil/leaf litter microhabitat of fields and forests along with animal dung, where they feed upon bacteria and other microbes, grow, and multiply until the available food supply is exhausted. When this happens, the amoeboid forms aggregate together in large numbers to form multi-celled pseudoplasmodia, which then give rise to fruiting bodies (sorocarps) that consist of supportive stalks and unwalled sori containing propagative spores. Results Dictyostelium purpureum var. pseudosessile, a new variant of dictyostelid, is described herein, based on morphological features and molecular data. This new variant was isolated from soil samples collected in two tropical areas of China. The complete spore-to-spore life cycle of this species, which required 50 h, including spore germination, myxamoebae, cell aggregation, pseudoplasmodium, and sorocarp formation, was documented. Descriptions and illustrations are provided for this species based on our collections. Data from ontogeny, morphology and phylogeny analyses (SSU) of D. purpureum var. pseudosessile confirm that it is a Group 4 species according to the newly proposed classification of dictyostelids. Conclusions Our results suggest that the violet sori, widens at the midpoint of sorophore and simple recurved sorophore bases represent the prominent features for the new variant D. purpureum var. pseudosessile. The latter is a Group 4 species now known from two tropical areas of China where dictyostelids remains understudied. Electronic supplementary material The online version of this article (10.1186/s12862-019-1407-2) contains supplementary material, which is available to authorized users.

Retinoblastoma is a childhood retinal tumor that develops from cone photoreceptor precursors in response to inactivating RB1 mutations and loss of functional RB protein. The cone precursor's response to RB loss involves cell type-specific signaling circuitry that helps to drive tumorigenesis. One component of the cone precursor circuitry, the thyroid hormone receptor β2 (TRβ2), enables the aberrant proliferation of diverse RB-deficient cells in part by opposing the down-regulation of S-phase kinase-associated protein 2 (SKP2) by the more widely expressed and tumor-suppressive TRβ1. However, it is unclear how TRβ2 opposes TRβ1 to enable SKP2 expression and cell proliferation. Here, we show that in human retinoblastoma cells TRβ2 mRNA encodes two TRβ2 protein isoforms: a predominantly cytoplasmic 54-kDa protein (TRβ2-54) corresponding to the well-characterized full-length murine Trβ2 and an N-terminally truncated and exclusively cytoplasmic 46-kDa protein (TRβ2-46) that starts at Met-79. Whereas TRβ2 knockdown decreased SKP2 expression and impaired retinoblastoma cell cycle progression, re-expression of TRβ2-46 but not TRβ2-54 stabilized SKP2 and restored proliferation to an extent similar to that of ectopic SKP2 restoration. We conclude that TRβ2-46 is an oncogenic thyroid hormone receptor isoform that promotes SKP2 expression and SKP2-dependent retinoblastoma cell proliferation.

Dictyostelid cellular slime molds (dictyostelids) are key components of soil microbes. The Qinghai-Tibet Plateau is characterized by unique and important forest types because of the considerable range in elevation which exists. During the period of 2012, 2013 and 2016, 12 species of dictyostelids were yielded from samples collected in this region, including two new species and three new records for China. Six other species were new records for this region. Ontogeny, morphology, ultrastructure and systematic molecular analyses (SSU & ITS) of D. minimum and D. multiforme confirm that they are Goup 4 new species. The ornamentation of the surface of dictyostelids’ spores is the first time to be observed until now. In the SSU phylogenetic tree generated in the present study, Synstelium, not assigned to order and family before, was assigned to the clade Acytosteliaceae in the Acytosteliales firstly. To our knowledge, the study reported herein is the first investigation of dictyostelid biodiversity carried out at elevations above 2000 m. Sorocarp size, sorus size, spore length, ratio of sorus and sorophore, and ratio of sorus and spore size were positively correlated with increasing elevation and no linear correlated with forest type, according to the results of linear regression analysis.

In this paper, we propose a novel peak-to-average power ratio (PAPR) reduction technique for DC-biased optical orthogonal frequency division multiplexing (DCO-OFDM)-based visible light communication (VLC) systems. The positive and negative amplitudes of DCO-OFDM are separately processed with a different linear companding transform under the emission power conservation criteria. The transfer characteristic of a commercial light-emitting diodes (LEDs) is also employed to illustrate this PAPR reduction technique's effect. The complementary cumulative distribution function simulation results indicate that the proposed scheme has the ability to improve the system performance in DCO-OFDM-based VLC systems.

In this paper, a logistic-function-based nonlinear companding transform (LNCT) is proposed to reduce the peak-to-average power ratio of asymmetrical hybrid optical orthogonal frequency division multiplexing (AHO-OFDM) signals in visible light communications (VLC). First, the positive and negative amplitudes of the bipolar AHO-OFDM signal are divided into two groups as the positive and nonnegative groups. Then, a peak detection is employed frame-by-frame to locate the group where the maximum peak occurs. Finally, the piecewise companding transform consisting of the nonlinear logistic function and a linear function is performed on the amplitude groups with and without the maximum peak, respectively. The simulation results show that the proposed LNCT scheme outperforms the classical linear nonsymmetrical transform method in terms of the complementary cumulative distribution function with a competing bit error rate performance, thus demonstrating its application potential in AHO-OFDM-based VLC systems.

The silver-deposited silicon (Si/Ag) is a successful strategy to enhance the conductivity of Si anode material. However, Ag nanoparticles can be separated from the Si due to the huge volume variation, which causes the deterioration of cycling performance. In this research, we propose a facile method of synthesizing Si/Ag particles with alloyed interface (Si/Ag2Si/Ag) by rapid thermal process to enhance the mechanical contact between Si and Ag. The reversible capacity of Si/Ag2Si/Ag still remains 1138 mAh g−1 over 100 cycles at 0.5 C (1 C = 4.2 A g−1), which is 267 mAh g−1 higher than of Si/Ag. Besides, Si/Ag2Si/Ag holds the reversible capacity of 849 mAh g−1 at 2 C.

Aiming at solving differential equations of plane problems, the algorithm of difference equation is established, and the corresponding program is compiled on BP neural network. The correctness and practicability of the difference equation algorithm are verified. A dynamic model of the parallel difference equation is constructed according to the characteristics of the parallel structure of BP neural network. By calculating examples, the continuity condition under the condition of modulus abruption is further discussed. The study shows that the two groups of differential equations are used to identify and verify the model, and the energy function satisfies both the linear embedding condition and the correct wiring. Furthermore, BP neural network is used to realize the search and routing of the maximum plane. The results show that difference equation calculations have the ability to help BP networks get rid of local minima and get better results.

Up to date, both reverse intersystem crossing (RISC) and triplet–triplet annihilation (TTA) are effective approaches to improve the internal efficiency of fluorescent OLEDs, because they can make the best of triplet excitons to generate delayed fluorescence. The energy difference between singlet and triplet excited states ( D E S-T) of special intramolecular charge transfer (CT) species is quite small, which make it posible for the participation of the CT species in RISC and TTA. When the RISC and TTA coexist in fluorescent OLEDs, the utilization of triplet excitons should be much better. The goal of this work was to demonstrate the feasibility of the coexistence. However, determining whether the coexistence happens in fluorescent OLEDs is not an easy task, because the general methods can hardly distinct the delayed fluorescence is originated from which approaches. Fortunately, both RISC and TTA are highly spin-dependent processes that can generate sizable magneto-electroluminescence (MEL) responses in OLEDs. Typically, the MEL response of RISC is a low-field effect, i.e., the MEL decreases rapid within the low-field regime ( 20 mT). Hence, the MEL can be used as a novel tool to discern RISC and TTA in fluorescent OLEDs. Following such strategy, in this work, we firstly fabricated the devices by doping different concentrations of intramolecular CT states specie 4-(Dicyanomethylene)-2-tert-butyl-6-(1,1,7,7-tetramethyljulolidin-4-yl-vinyl)-4H-pyran (DCJTB) into phosphor host material 1,3-bis(9-carbazolyl)benzene (mCP) and then measured the MEL responses of these devices at room temperature. It exhibited that the sign of low-field ( B >20 mT) but was more prominent. These results are quite similar to the theoretical MEL curves of RISC in low-field ( B >20 mT), respectively. Thus, we believe that the delayed fluorescence of DCJTB-doped devices is caused by RISC and TTA simultaneously. Moreover, the RISC and TTA rates increase as the doping concentration decreasing. Subsequently, more remarkable RISC-dominanted low-field and TTA-dominanted high-field decrease of MEL were observed with decreasing temperature from 300 to 20 K. It is attributed to the fact that low temperature can significantly enhance RISC and TTA. In summary, low doping concentration and low temperature are more favorable to the coexistence of RISC and TTA in the DCJTB-doped devices. This work has a certain reference value for the improvments of internal quantum efficiency of fluorescent OLEDs via enhancing the utilization efficiency of triplet.

A series of silicon-containing derivatives of linear alicyclic musks comprising sila-Rosamusk (3b), sila-Romandolide (5b), sila-Applelide (11b), and the corresponding dehydro derivatives was synthesized from sila-analogs of Artemone and Herbac, respectively, by means of sodium borohydride reduction and subsequent esterification with the corresponding acid chlorides in the presence of triethylamine. The olfactory properties of the new sila-odorants 3b–13b are reported in comparison with their carba-analogs 3a–13a, and quantitative threshold data allowed the generation of an improved musk olfactophore model featuring a correlation of 80.5 % with a null-cost distance of 244. This olfactophore model shows that it is likely that linear and macrocyclic musks address the same odorant receptors, and it should facilitate the design of new musks.

The radiative deexcitation processes of excitons and charge-transfer states exist simultaneously in the emitting material PFOPV. In this work, polymer light-emitting devices based on PFOPV were fabricated, the two kinds of microscopic processes were investigated via magnetic field effects (MFEs) on electroluminescence (magneto-electroluminescence, MEL) and current (magnetoconductance, MC). At room temperature, the MEL of balanced device presented negative effects, compared with the positive MEL values of the unbalanced device; at low temperatures, the sign of MEL turned from negative to positive with the increasing injection current in the balanced deice. However, under all driving voltages, the sign of MC was always negative. These dependences of MFEs on temperature and driving voltage can be attributed to the competition between the two different emission processes in devices. Analysis shows that MFEs differences of the two emission processes are caused by the combined effects of intersystem crossing and reverse intersystem crossing induced by hyperfine interaction. This study reveals that charge-transfer states are important in improving the luminous efficiency of fluorescent organic light-emitting devices.

A novel synthetic approach to (±)- Z -recifeiolide 6, a 12-membered-ring lactone which can be selectively isomerized into ( E )-recifeiolide, a natural antibiotic product isolated from fungus ( Cephalosporium recifei ) is reported. The synthesis is accomplished in five steps starting from readily available cyclooctanone and acetaldehyde based on the Lewis acid-catalyzed TMS-directed oxy-2-oxonia-Cope rearrangement. The work represents a novel strategy to assemble related macrolides.

He, Y.; Huang, L.Y.; Ding, C.; Zou, Y., and Huang, P., 2020. A correlation coupling prediction of island tourist based on multi key words of web search index: A case study of Gulang Island in Xiamen. In: Bai, X. and Zhou, H. (eds.), Advances in Water Resources, Environmental Protection, and Sustainable Development. Journal of Coastal Research, Special Issue No. 115, pp. 373-378. Coconut Creek (Florida), ISSN 0749-0208.With the rapid rise of the Internet, people rely more on the Internet to collect tourism information when traveling. This paper will make a model by Baidu search index of keywords in scenic spot, use weighted calculation and composite index, take Gulang island in Xiamen as an example to verify the feasibility of the model, and conduct heat prediction analysis of scenic spot through prediction model. Through analysis and research, it is found that the Baidu search index has a strong positive correlation with the tourist volume of scenic spots, and the tourist volume and popularity of scenic spots can be predicted by the search volume of Baidu. This conclusion is conducive to the coordination and control between the government and the scenic spots, the market analysis of tourism enterprises, and the tourists' comfortable experience of peak travel.

Although there have been many studies on atomic layer deposition of Al2O3 to improve the electrochemical performances of ternary cathode materials, few studies considered the harsh conditions such as high temperature and high voltage at the same time. In this work, the Al2O3 passivation layer is employed to coat the high nickel (Ni) LiNi0.68Co0.10Mn0.22O2 cathode through atomic layer deposition (ALD) approach. The Al2O3 coated LiNi0.68Co0.10Mn0.22O2 presents superior cycling stability and rate capability than the pristine at the cut-off voltage of 2.7–4.4 V under room temperature. Furthermore, under the harsh condition at high temperature of 60 °C or at high voltage of 2.7–4.8 V, the Al2O3 coated LiNi0.68Co0.10Mn0.22O2 also shows significantly improved performances than the pristine. The superior electrochemical performance of Al2O3 coated LiNi0.68Co0.10Mn0.22O2 could be attributed to the enhanced interfacial stability, the mitigated side reactions with electrolyte and the better maintained lithium ion diffusion kinetics. Manipulating the surface coating chemistry and evaluating the performance under harsh condition provide a useful approach for fast screening of effective surface modification technology, which might significantly advance the development of high energy density cathode materials.

Human echinococcosis has become a major public health problem in most parts of the world. The objective of this article was to study the demographics of patients with hepatic echinococcosis in Ganzi County to elucidate the main risk factors, as well as to report the concurrent prevalence of cerebral echinococcosis and pulmonary echinococcosis. We recruited 195 patients with hepatic echinococcosis from the Datongma area of Ganzi County from January 2018 to November 2018. The patients’ demographics, living environments, supported medical resources, knowledge of echinococcosis prevention and control, and hygienic practices were investigated and analyzed. The prevalence of cerebral echinococcosis and pulmonary echinococcosis were also investigated. The data were analyzed to identify risk factors for human echinococcosis. Our analysis showed that the herding Tibetan population within the 20 to 60 age group, and females, in particular, were at the highest risk of human echinococcosis infection. Having stray dogs around habitations and intimate activities with dogs and livestock were also behavioral risk factors. People with poor health literacy and low educational qualifications had possible risks of infection. In terms of hygiene, not using tap water as the drinking water source and lack of medical staff were significantly correlated with echinococcosis prevalence. Four patients were diagnosed with cerebral echinococcosis. Among them, 1 patient had both cerebral echinococcosis and pulmonary echinococcosis. Possible high-risk factors for echinococcosis were being female, herding population, in the 20 to 60 age group, having stray dogs around habitations, having activities with dogs and livestock, having poor health literacy, having low educational qualifications, and not using tap water as a drinking water source. The detection rate for brain echinococcosis in patients with hepatic echinococcosis was high (2.05%). Effective preventive strategies should be implemented in epidemic areas. Head CT scans should be applied for early detection of cerebral echinococcosis to carry out the treatment.

Dictyostelium discoideum is a specialized amoebozoan protist that can feed on, carry and disperse bacteria. However, the symbiont bacterial diversity in other species of dictyostelids and the diversity associated with essential life cycle stages are still unknown until now. Here, another species of dictyostelids, Heterostelium colligatum, a new record for tropical China, was isolated from the soil collected in Xishuangbanna Tropical Botanical Garden, Yunnan Province, China. We describe the complete life cycle of this species and illustrate details of spore-to-spore development. The symbiont bacterial diversity and relative abundance associated with life cycle stages of H. colligatum, including the aggregation, pseudoplasmodium, and sorocarp stages, were investigated by high throughput metagenomic techniques. H. colligatum appears to be capable of carrying different types of bacteria during its life history in addition to those used as a food resource. The dominant groups of those three stages in its life cycle were the Proteobacteria, Actinobacteria and Firmicutes. The relative abundance of the dominant phyla and shared OTUs were different for the aggregation, pseudoplasmodium, and sorocarp stages. A comparison of the symbiont bacterial assemblages associated with D. discoideum and H. colligatum indicated that different dictyostelid species carried different species of symbiont associated bacteria.

Oxygen vacancy (VO) is one of the most important defects and acts as the reactive sites in a variety of catalytic reactions. In this work, doping method is employed to generate controllable VO in ZnWO4 crystal and the existence of VO was validated by TEM, XPS and UV–vis absorbance spectra. A novel electrochemical sensor based on Ce-doped ZnWO4 modified carbon paste electrode (CPE) has been fabricated and the electrochemical performance of the proposed sensor is verified by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV). The as-prepared oxygen vacancy-rich ZnWO4 shows excellent electrocatalytic performance in sensing carbendazim (CBZ) compared to the virgin CPE. The results demonstrate that VO can effectively enhance electronic conductivity and narrow the band gap, leading to superior performances of 2%Ce-doped ZnWO4 in electrocatalytic reactions. Low detection limits (LOD) of CBZ is obtained to be 0.0033 μmol L−1 via DPV method (S/N = 3). The impressive detection performance is even spread to the simultaneous determination of common neurotransmitters, DA an UA, with detection limits of 0.0033 μmol L−1 and 0.17 μmol L−1 and wide linear range from 0.01 to 30 μmol L−1 and 0.5 to 100 μmol L−1 for DA and UA, respectively.

The proto-oncogene Bcl3 induces survival and proliferation in cancer cells; however, its function and regulation in ovarian cancer (OC) remain unknown. Here, we show that Bcl3 expression is increased in human OC tissues. Surprisingly, however, we found that in addition to promoting survival, proliferation, and migration of OC cells, Bcl3 promotes both constitutive and interferon-γ (IFN)-induced expression of the immune checkpoint molecule PD-L1. The Bcl3 expression in OC cells is further increased by IFN, resulting in increased PD-L1 transcription. The mechanism consists of an IFN-induced, Bcl3- and p300-dependent PD-L1 promoter occupancy by Lys-314/315 acetylated p65 NF-κB. Blocking PD-L1 by neutralizing antibody reduces proliferation of OC cells overexpressing Bcl3, suggesting that the pro-proliferative effect of Bcl3 in OC cells is partly mediated by PD-L1. Together, this work identifies PD-L1 as a novel target of Bcl3, and links Bcl3 to IFNγ signaling and PD-L1-mediated immune escape.

Background & aims: Tuberculosis (TB) patients have a significant vitamin D deficiency (VDD) endemic, which may be closely related to the onset and progress of the disease. The comorbidity of diabetes (DM) and TB has posed an increasing challenge in recent years. However, the influence of DM on TB and the possible mechanism are still uncertain. We carried out this study to identify the nutritional status of vitamin D (VD) in TB patients in a northern city in China (latitude 36° N) and investigate the possible predictors of severe vitamin D deficiency (SVDD). Methods: A cross-sectional study including 461 active TB patients (192 with and 269 without DM) were randomly selected from Qingdao Chest Hospital from June 2015 to August 2016. We measured serum 25 hydroxyvitamin D [25(OH)D], and investigated the association between sociodemographic, dietary intake, DM, body mass index (BMI), severity of initial TB signs and symptoms (TB score) and VD status. Multivariate logistic regression analysis was used to define the possible predictors of SVDD. Results: The median serum 25(OH)D concentration was 8.50 ng/mL. Of the 461 TB patients included, 383 (83.1%) had VDD [25(OH)D < 20 ng/mL], and 217 (47.1%) had SVDD [25(OH)D < 8 ng/mL]. The variables associated with serum 25(OH)D concentrations were DM, outdoor activity level, TB score and BMI (p < 0.05). Patients with severe TB score had nearly 5 fold higher risk of having SVDD compared with those in mild subgroup [OR (95% CI) = 4.919 (2.644-9.150), p < 0.001]. Low outdoor activity level also increased the odds of SVDD, while DM and high fish consumption showed protect effects. Conclusions: Severe hypovitaminosis D is prevalent in active TB patients, and the main predictors of SVDD were severe TB score, low outdoor activity, inadequate fish consumption. Lowered serum 25(OH)D may be associated with increased risk of TB in DM.

The maintenance of genomic stability in the face of endogenous and exogenous sources of DNA damage requires a robust and comprehensive cellular response. This response, appropriately deemed the DNA damage response (DDR), facilitates changes in the cellular environment promoting and coordinating cell cycle arrest, DNA repair, and cell death in cases of extreme or prolonged genomic insult. Initiation of DDR is primarily elicited by three members of the PIKK (phosphatidylinositol-3-kinase-like kinase) family: ATM (ataxia-telangiectasia mutated), ATR (ataxia-telangiectasia and Rad3-related), and DNA-PK (DNA-dependent protein kinase). While all three are required for proper genomic maintenance, DNA-PK lacks the capacity to elicit many of the effects induced by ATM or ATR. For this reason, DNA damage signaling (DDS) generally is considered to occur mainly through ATM and ATR. Recent studies, however, have implicated that DNA-PK can regulate DDS through hindrance of ATM-DDS, giving rise to an evolving view in which all three PIKK family members are essential for regulation of DDS, but not its initiation. This chapter presents a discussion of the signaling within human systems induced by DNA damage as well as an overview of the roles of DDS in promoting DDR-mediated cell cycle arrest, DNA damage repair, and changes to other cellular processes. Within this context, the roles of DDR in current and proposed chemotherapeutics will be explored.

Nucleotide excision repair (NER) in mammalian cells requires the xeroderma pigmentosum group A protein (XPA) as a core factor. Remarkably, XPA and other NER proteins have been detected by chromatin immunoprecipitation at some active promoters, and NER deficiency is reported to influence the activated transcription of selected genes. However, the global influence of XPA on transcription in human cells has not been determined. We analyzed the human transcriptome by RNA sequencing (RNA-Seq). We first confirmed that XPA is confined to the cell nucleus even in the absence of external DNA damage, in contrast to previous reports that XPA is normally resident in the cytoplasm and is imported following DNA damage. We then analyzed four genetically matched human cell line pairs deficient or proficient in XPA. Of the ∼14,000 genes transcribed in each cell line, 325 genes (2%) had a significant XPA-dependent directional change in gene expression that was common to all four pairs (with a false discovery rate of 0.05). These genes were enriched in pathways for the maintenance of mitochondria. Only 27 common genes were different by more than 1.5-fold. The most significant hits were AKR1C1 and AKR1C2, involved in steroid hormone metabolism. AKR1C2 protein was lower in all of the immortalized XPA-deficient cells. Retinoic acid treatment led to modest XPA-dependent activation of some genes with transcription-related functions. We conclude that XPA status does not globally influence human gene transcription. However, XPA significantly influences expression of a small subset of genes important for mitochondrial functions and steroid hormone metabolism. The results may help explain defects in neurological function and sterility in individuals with xeroderma pigmentosum.

Lactic acid has been used as a bio-based green solvent to study the ultrasound-assisted scale-up synthesis. We report here, for the first time, on the novel and scalable process for synthesis of pyrrole derivatives in lactic acid solvent under ultrasonic radiation. Eighteen pyrrole derivatives have been synthesized in lactic acid solvent under ultrasonic radiation and characterized by (1)H NMR, IR, ESI MS. The results show, under ultrasonic radiation, lactic acid solvent can overcome the scale-up challenges and exhibited many advantages, such as bio-based origin, shorter reaction time, lower volatility, higher yields, and ease of isolating the products.

In the presence of a Lewis acid, trimethylsilyl-substituted β,γ-unsaturated ketones and aldehydes (imines) undergo nucleophilic addition to produce zwitterionic intermediates, followed by oxy-2-oxonia(azonia)-Cope rearrangements to give homoallylic esters (amides). In the case of TMS-containing 2-vinylcycloalkanones, the process results in ring-enlargement, providing 10- to 16-membered lactones. This protocol was applied to the total synthesis of (R)-phoracantholide I.

Degeneration of the noradrenergic neurons has been reported in the brain of patients suffering from neurodegenerative diseases. However, their pathological characteristics during the neurodegenerative course and underlying mechanisms remain to be elucidated. In the present study, we used the neurotoxin camptothecin (CPT) to induce the DNA damage response in neuroblastoma SH-SY5Y cells, normal fibroblast cells, and primarily cultured locus coeruleus (LC) and raphe neurons to examine cellular responses and repair capabilities after neurotoxin exposure. To our knowledge, the present study is the first to show that noradrenergic SH-SY5Y cells are more sensitive to CPT-induced DNA damage and deficient in DNA repair, as compared to fibroblast cells. Furthermore, similar to SH-SY5Y cells, primarily cultured LC neurons are more sensitive to CPT-induced DNA damage and show a deficiency in repairing this damage. Moreover, while N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) exposure also results in DNA damage in cultured LC neurons, neither CPT nor DSP4 induce DNA damage in neuronal cultures from the raphe nuclei. Taken together, noradrenergic SH-SY5Y cells and LC neurons are sensitive to CPT-induced DNA damage and exhibit a repair deficiency, providing a mechanistic explanation for the pathological characteristics of LC degeneration when facing endogenous and environmental DNA-damaging insults in vivo.

The construction and application of a new type of composite material are achieved more and more attention. However, expected Sb2Se3/attapulgite composites aim to use the low price, and high adsorption of attapulgite in assembling Sb2Se3 is quite difficult to be acquired by a facile and benign environmental hydrothermal method. In this manuscript, we developed a new way for preparation of an emerging composite by means of Sb2O3 as a media linking Sb2Se3 and attapulgite together, and finally won an emerging composite Sb2Se3/Sb2O3@attapulgite, which presented an excellent catalytic properties for catalytic hydrogenation of p-nitrophenol. It was noted that the Sb2Se3/Sb2O3@attapulgite composites exhibited a high conversion rate for the hydrogenation of p-nitrophenol that was up to 90.7% within 15 min, which was far more than the 61.5% of Sb2Se3 sample. The excellent catalytic performance was attributed to the highly dispersion Sb2Se3 microbelts and Sb2Se3@Sb2O3@attapulgite rods, which would improve the adsorption of the reactant species and facility electronic transfer process of the catalytic hydrogenation of p-nitrophenol.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder that is caused by a point mutation in the LMNA gene, resulting in production of a truncated farnesylated-prelamin A protein (progerin). We previously reported that XPA mislocalized to the progerin-induced DNA double-strand break (DSB) sites, blocking DSB repair, which led to DSB accumulation, DNA damage responses, and early replication arrest in HGPS. In this study, the XPA mislocalization to DSBs occurred at stalled or collapsed replication forks, concurrent with a significant loss of PCNA at the forks, whereas PCNA efficiently bound to progerin. This PCNA sequestration likely exposed ds-ssDNA junctions at replication forks for XPA binding. Depletion of XPA or progerin each significantly restored PCNA at replication forks. Our results suggest that although PCNA is much more competitive than XPA in binding replication forks, PCNA sequestration by progerin may shift the equilibrium to favor XPA binding. Furthermore, we demonstrated that progerin-induced apoptosis could be rescued by XPA, suggesting that XPA-replication fork binding may prevent apoptosis in HGPS cells. Our results propose a mechanism for progerin-induced genome instability and accelerated replicative senescence in HGPS.-Hilton, B. A., Liu, J., Cartwright, B. M., Liu, Y., Breitman, M., Wang, Y., Jones, R., Tang, H., Rusinol, A., Musich, P. R., Zou, Y. Progerin sequestration of PCNA promotes replication fork collapse and mislocalization of XPA in laminopathy-related progeroid syndromes.

The sensitivity of Xeroderma pigmentosa (XP) patients to sunlight has spurred the discovery and genetic and biochemical analysis of the eight XP gene products (XPA-XPG plus XPV) responsible for this condition. These studies also have served to elucidate the nucleotide excision repair (NER) process, especially the critical role played by the XPA protein. More recent studies have shown that NER also involves numerous other proteins normally employed in DNA metabolism and cell cycle regulation. Central among these is ataxia telangiectasia and Rad3-related (ATR), a protein kinase involved in intracellular signaling in response to DNA damage, especially replicative and transcription stresses. This review summarizes recent findings on the interplay between ATR as a DNA damage signaling kinase and as a novel ligand for intrinsic cell death proteins to delay damage-induced apoptosis, and on ATR’s regulation of XPA and the NER process for repair of UV-induced DNA adducts. ATR’s regulatory role in the cytosolic-to-nuclear translocation of XPA will be discussed. In addition, recent findings elucidating a non-NER role for XPA in DNA metabolism and genome stabilization at ds-ssDNA junctions, as exemplified in prematurely aging progeroid cells, also will be reviewed.

Silicon compounds 1b–3b are sila-analogues of the galbanum odorants α-galbanone (1a), α-spirogalbanone (2a), and nor-α-galbanone (3a), respectively. Sila-α-galbanone (1b), sila-α-spirogalbanone (2b), and sila-nor-α-galbanone (3b) were synthesized in multistep syntheses in isomerically pure form, starting from Me2SiCl2, (CH2=CH)2SiCl2, and Me2(CH2=CH)SiCl, respectively. Hydroformylation of vinylsilanes, followed by either ring-closing aldol condensation or ring-closing alkene metathesis, were the key steps in these syntheses. The C/Si pairs 1a/1b, 2a/2b, and 3a/3b were studied for their olfactory properties. All compounds possess green-fruity galbanum-type odors with pineapple aspects and thus are olfactorily related. However, sila-analogues 1b–3b were found to be weaker than the corresponding parent carbon compounds 1a–3a. This effect is most pronounced for the C/Si pair 2a/2b as indicated by the odor thresholds of 0.023 ng L–1 air (2a) and 3.8 ng L–1 air (2b). However, due to their higher molecular mass, the silicon compounds are less volatile and thus more substantive in functional applications. In contrast to the stable 5-silacyclohex-1-enes 1b and 2b, the 4-silacyclopent-1-ene 3b shows a limited chemical stability. For compound 3a an extremely low odor threshold of 0.0087 ng L–1 air was measured, and the silicon analogue 3b with an odor threshold of 0.085 ng L–1 air is the sila-odorant with the lowest odor threshold measured so far.

A sequential Diels-Alder reaction/rearrangement sequence was developed for the synthesis of diverse functionalized bicyclo[2.2.1]heptanes as novel floral and woody odorants. The outcome of the rearrangement depended on the substitution pattern of the dienes. 2D NMR analysis has established the correct relative configuration of the bicyclo[2.2.1]heptanone, which was originally misassigned. Furthermore, when the initiating DA reaction was catalyzed by a chiral Lewis acid, the bicyclo[2.2.1]heptane derivatives including (+)-herbanone can be obtained in an enantiomeric ratio (er) up to 96.5:3.5.

The melanocortin 1 receptor (MC1R), which signals through cAMP, is a melanocytic transmembrane receptor involved in pigmentation, adaptive tanning, and melanoma resistance. We report MC1R-mediated or pharmacologically-induced cAMP signaling promotes nucleotide excision repair (NER) in a cAMP-dependent protein kinase A (PKA)-dependent manner. PKA directly phosphorylates ataxia telangiectasia and Rad3-related protein (ATR) at Ser435, which actively recruits the key NER protein xeroderma pigmentosum complementation group A (XPA) to sites of nuclear UV photodamage, accelerating clearance of UV-induced photolesions and reducing mutagenesis. Loss of Ser435 within ATR prevents PKA-mediated ATR phosphorylation, disrupts ATR-XPA binding, delays recruitment of XPA to UV-damaged DNA, and elevates UV-induced mutagenesis. This study mechanistically links cAMP-PKA signaling to NER and illustrates potential benefits of cAMP pharmacological rescue to reduce UV mutagenesis in MC1R-defective, melanoma-susceptible individuals.

A general method to synthesize functionalized allyl α-amino acid derivatives through an irreversible oxy-2-azonia-Cope rearrangement is reported. In the presence of AlCl3, the reaction of imino ethyl glyoxalates with various β,γ-unsaturated ketones furnished the corresponding allyl α-amino acid derivatives. The key to the success of this method is the amide bond formation, which makes the rearrangement irreversible. This reaction system constitutes a new strategy for the synthesis of unusual allyl glycine derivatives, which are valuable synthetic intermediates. An efficient and operationally simple three-component version of this reaction was also performed.

Overexpression of the pro-angiogenic chemokine IL-8 (CXCL8) is associated with a poor prognosis in several solid tumors, including epithelial ovarian cancer (EOC). Even though histone deacetylase (HDAC) inhibition has shown remarkable antitumor activity in hematological malignancies, it has been less effective in solid tumors, including EOC. Here we report results that may explain the decreased efficiency of HDAC inhibition in EOC, based on our data demonstrating that HDAC inhibition specifically induces expression of IL-8/CXCL8 in SKOV3, CAOV3, and OVCAR3 cells. Suppression or neutralization of vorinostat-induced IL-8/CXCL8 potentiates the vorinostat inhibitory effect on cell viability and proliferation. The IL-8/CXCL8 expression induced by vorinostat in EOC cells is dependent on IκB kinase (IKK) activity and associated with a gene-specific recruitment of IKKβ and IKK-dependent recruitment of p65 NFκB to the IL-8/CXCL8 promoter. In addition, HDAC inhibition induces acetylation of p65 and histone H3 and their IL-8/CXCL8 promoter occupancy. In vivo results demonstrate that combining vorinostat and the IKK inhibitor Bay 117085 significantly reduces tumor growth in nude mice compared with control untreated mice or either drug alone. Mice in the combination group had the lowest IL-8/CXCL8 tumor levels and the lowest tumor expression of the murine neutrophil [7/4] antigen, indicating reduced neutrophil infiltration. Together, our results demonstrate that HDAC inhibition specifically induces IL-8/CXCL8 expression in EOC cells and that the mechanism involves IKK, suggesting that using IKK inhibitors may increase the effectiveness of HDAC inhibitors when treating ovarian cancer and other solid tumors characterized by increased IL-8/CXCL8 expression.

Fatty acid synthase (FASN), the sole cytosolic mammalian enzyme for de novo lipid synthesis, is crucial for cancer cell survival and associates with poor prognosis. FASN overexpression has been found to cause resistance to genotoxic insults. Here we tested the hypothesis that FASN regulates DNA repair to facilitate survival against genotoxic insults and found that FASN suppresses NF-κB but increases specificity protein 1 (SP1) expression. NF-κB and SP1 bind to a composite element in the poly(ADP-ribose) polymerase 1 (PARP-1) promoter in a mutually exclusive manner and regulate PARP-1 expression. Up-regulation of PARP-1 by FASN in turn increases Ku protein recruitment and DNA repair. Furthermore, lipid deprivation suppresses SP1 expression, which is able to be rescued by palmitate supplementation. However, lipid deprivation or palmitate supplementation has no effect on NF-κB expression. Thus, FASN may regulate NF-κB and SP1 expression using different mechanisms. Altogether, we conclude that FASN regulates cellular response against genotoxic insults by up-regulating PARP-1 and DNA repair via NF-κB and SP1.

Exploration in Bayanhushu depression has been published from time to time, showing great exploration potential, but the degree is low at present. We devided Nantun formation into two third sequences through comprehensive analysis and studied on the types and distribution of sedimentary facies. The conclusion shows that Nantun formation is mainly comprised of fan delta, braid delta and lacustrine facies. The fan delta sedimentary facies mainly distribute in the western steep slope zone, while the braided river delta develops in the eastern gentle slope zone, and the lacustrine facies mainly develops in the middle trough zone and the edge of the fan delta. The sedimentary pattern has the characteristics of “east-west zoning”. From the steep slope to the gentle slope, the types of sedimentary facies gradually change from fan delta to shore-shallow lake, semi-deep lake to deep lake and then to braided river delta. The study of source-reservoir-cap assemblages and accumulation conditions shows that fan delta front and braided delta front have good physical properties and are close to high grade source. So it is easy to form inversion structural reservoirs in the steep slope break zone, while fault-lithologic reservoirs in gentle slope zone, a lithologic reservoirs near trough areas.

Asymmetrical flow field flow fractionation (AF4) combined with ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used to screen allergen protein epitopes. The selected allergen protein (tropomyosin, TM) was enzymatically digested into peptide segments and analyzed via UPLC-QTOF-MS to establish a protein-specific peptide database. The peptide segments were incubated with immunoglobulin E (IgE) for 30 min. During the incubation procedure, the specific peptide segments (with the antigen epitope) combine with IgE while the other peptide segments remain in solution. After incubation, the solution was injected into the AF4 device. The combined peptide segments flowed out of the outlet along with IgE, and the other peptide segments flowed into the waste liquid. The components of outlet were then collected, analyzed by UPLC-QTOF-MS, and the results matched with the spectra of the protein peptides. Eventually the specific peptide segments were identified to detect the antigen epitopes. This study extends the application of AF4 with a preliminary exploration of the detection of an allergen protein epitope, providing a novel research strategy for the screening of allergen epitopes.

Dopamine β-hydroxylase (DBH) and norepinephrine (NE) transporter (NET) are the noradrenergic phenotypes for their functional importance to noradrenergic neurons. It is known that in vivo N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) treatment induces degeneration of noradrenergic terminals by interacting with NET and depleting intracellular NE. However, DSP4’s precise mechanism of action remains unclear. In this study various biochemical approaches were employed to test the hypothesis that DSP4 down-regulates the expression of DBH and NET, and to determine molecular mechanisms that may be involved. The results showed that treatment of SH-SY5Y neuroblastoma cells with DSP4 significantly decreased mRNA and protein levels of DBH and NET. DSP4-induced reduction of DBH mRNA and proteins, as well as NET proteins showed a time- and concentration-dependent manner. Flow cytometric analysis demonstrated that DSP4-treated cells were arrested predominantly in the S-phase, which was reversible. The arrest was confirmed by several DNA damage response markers (phosphorylation of H2AX and p53), suggesting that DSP4 causes replication stress which triggers cell cycle arrest via the S-phase checkpoints. Moreover, the comet assay verified that DSP4 induced single-strand DNA breaks. In summary, the present study demonstrated that DSP4 down-regulates the noradrenergic phenotypes, which may be mediated by its actions on DNA replication, leading to replication stress and cell cycle arrest. These action mechanisms of DSP4 may account for its degenerative consequence after systematic administration for animal models.

The environmental arylamine mutagens are implicated in the etiology of various sporadic human cancers. Arylamine-modified dG lesions were studied in two fully paired 11-mer duplexes with a -G*CN- sequence context, in which G* is a C8-substituted dG adduct derived from fluorinated analogs of 4-aminobiphenyl (FABP), 2-aminofluorene (FAF) or 2-acetylaminofluorene (FAAF), and N is either dA or dT. The FABP and FAF lesions exist in a simple mixture of ‘stacked’ (S) and ‘B-type’ (B) conformers, whereas the N-acetylated FAAF also samples a ‘wedge’ (W) conformer. FAAF is repaired three to four times more efficiently than FABP and FAF. A simple A- to -T polarity swap in the G*CA/G*CT transition produced a dramatic increase in syn-conformation and resulted in 2- to 3-fold lower nucleotide excision repair (NER) efficiencies in Escherichia coli. These results indicate that lesion-induced DNA bending/thermodynamic destabilization is an important DNA damage recognition factor, more so than the local S/B-conformational heterogeneity that was observed previously for FAF and FAAF in certain sequence contexts. This work represents a novel 3′-next flanking sequence effect as a unique NER factor for bulky arylamine lesions in E. coli.

A new Lewis acid-catalyzed endo-selective Prins bicyclization of γ,δ-unsaturated aldehydes or ketones with a broad range of aldehydes to dioxabicyclo[2.2.2]octanes is disclosed. When using a chiral BINOL-derived N-triflylphosphoramide (NTPA) as catalyst and glyoxylate esters as substrates, the cross-dimerization afford functionalized bicyclic acetals with excellent diastereo- and enantioselectivities.

A new Lewis acid-catalyzed endo-selective Prins bicyclization of γ,δ-unsaturated aldehydes or ketones with a broad range of aldehydes to dioxabicyclo[2.2.2]octanes is disclosed. When using a chiral BINOL-derived N-triflylphosphoramide (NTPA) as catalyst and glyoxylate esters as substrates, the cross-dimerization afford functionalized bicyclic acetals with excellent diastereo- and enantioselectivities.