Synthesis of Heptacyclic Compounds through C-H Bond Activation-Initiated Cascade Reactions.

Presented herein is an atom- and step-economical method enabling the precise assembly of a heptacyclic scaffold containing both azocine and indoline units through the cascade reactions of indolin-1-yl(aryl)methanimines with diazo indanediones. The formation of products involves C-H bond activation and double carbene insertion followed by intramolecular condensation, retro-[2 + 2] cycloaddition, and recyclization. This cascade reaction not only provided a concise and straightforward strategy for the synthesis of the otherwise difficult to obtain heptacyclic compounds from readily available substrates but also disclosed an unprecedented reaction mode for indoline derivatives and diazo compounds. In general, this novel synthetic protocol has advantages, such as easily obtainable substrates, structurally sophisticated products, concise synthetic procedure, good compatibility with diverse functional groups, and ready scalability. Moreover, the products thus obtained showed decent antiproliferative activity against three human cancer cell lines.

Synthesis of 1,7-Fused Indolines Tethered with Spiroindolinone Based on C-H Activation Strategy with Air as a Sustainable Oxidant.

Herein, we present an efficient synthesis of 1,7-fused indolines tethered with a spiroindolinonyl moiety through the cascade reaction of indolin-1-yl(aryl)methanimines with diazo oxindoles. To the best of our knowledge, this is the first example in which 1,7-fused indoline skeleton was constructed along with the simultaneous introduction of a spiro element initiated by the C-H bond activation of indoline. In forming the title product, the indoline substrate and the diazo coupling partner demonstrated an unprecedented reaction pattern in which the latter acts as a C1 synthon to participate in the construction of the spirocyclic scaffold through the reductive elimination of a key seven-membered Ru(II) species by using air as an effective and sustainable oxidant to regenerate the active catalyst. Moreover, studies on the cytotoxicity of selected products against several human cancer cell lines demonstrated their potential as lead compounds for the development of anticancer drugs. With notable features such as simple and economical substrates, pharmaceutically valuable products with sophisticated spirocyclic skeleton, mild reaction conditions, cost-free and sustainable oxidants, high efficiency, excellent compatibility with diverse functional groups, and scalability, this method is expected to find wide applications in related areas.

Probabilistic health risk assessment and monetization based on benzene series exposure in newly renovated teaching buildings.

To meet the needs of the rapid development of education, there have been growing investments in the issue of university infrastructures. However, few studies have paid attention to the assessment and monetization of health risks in newly renovated teaching buildings. In this study, concentrations of the benzene series (BTEX) group were measured in five areas of three newly renovated teaching buildings. A total of 135 BTEX samples were collected using passive diffusion monitors and analyzed by GC-FID. Human health risk assessments were conducted by using probabilistic methods for four types of population exposure to BTEX. The results showed that the cancer risk of benzene accounted for most of the total in each group. There was over 90% probability of excess cancer risks in the areas within the tested buildings; and the non-cancer risks were all within the acceptable level. The health risks of men were greater than those of women, and those of teachers were higher than those of students. The model calculation results of Disability-Adjusted Life Year (DALY) and Willingness to Pay (WTP) indicated that the average price that society was willing to pay to offset the health damage caused in these newly renovated teaching buildings was 381.35 yuan/year. For the first time, this study highlights the health risks of newly built teaching buildings in universities, points out the urgent need to improve the control of BTEX sources in this type of indoor environment; moreover, it provides theoretical support for the society and occupational protection departments to compensate for the health damage to professionals.

Trace Metal Lead Exposure in Typical Lip Cosmetics From Electronic Commercial Platform: Investigation, Health Risk Assessment and Blood Lead Level Analysis.

Lead (Pb) in lipstick products has become an increasing concern, which can cause safety problems to human body directly with diet. To investigate the Pb exposure and potential health risk level of typical popular lip cosmetics in Chinese e-commerce market, Python crawler was introduced to identify and select 34 typical popular lip cosmetics, including 12 lipsticks, 13 lip glosses, and 9 lip balms. And then this study used ICP-MS to determine the content of Pb. Furthermore, the ingestion health risk assessment method issued by United States Environmental Protection Agency (USEPA) and Monte Carlo simulation algorithm were applied to assess the probabilistic health risks of adults exposure. Finally, taking the possible exposure of children contacting with lip products, the health risk assessment of children blood Pb was carried out. The results showed that the concentration of Pb in lip products ranged from 0 to 0.5237 mg/kg, which was far lower than the limit set by various countries. The probabilistic non-carcinogenic risks and carcinogenic risks were 4.93 ×10-7~2.82 ×10-3 and 1.68 ×10-12~9.59 ×10-9, respectively, which were in an acceptable level. The results of blood Pb assessment suggested that the Pb content of lip cosmetics had no obvious influence on blood Pb concentration of children, and background Pb exposure is the main factor affecting children's blood Pb level (BLL). Overall, the samples of lip products are selected by Python crawler in this study, which are more objective and representative. This study focuses on deeper study of Pb, especially for the health risk assessment of blood Pb in children exposed to lip products. These results perhaps could provide useful information for the safety cosmetics usage for people in China and even the global world.

Ribosome profiling reveals translatome remodeling in cancer cells in response to zinc oxide nanoparticles.

The anticancer effect of zinc oxide nanoparticles (ZnO NPs) largely relies on cellular responses such as alteration of gene expression. Although ZnO NPs have been reported to induce transcriptional changes, the potential of ZnO NPs to affect cellular translatome remains largely unknown. Using ribosome profiling, we demonstrated that the transcription of 78 genes and the translation of 1,448 genes are affected during one hour of ZnO NPs exposure in A549 human lung cancer cells. The mitogen-activated protein kinase (MAPK) pathway is up-regulated upon ZnO NP treatment. The upstream open reading frame (uORF) plays a pervasive role in the induction of up-regulated genes, including TLNRD1 and CCNB1IP1. Knockdown of TLNRD1 or CCNB1IP1 reduces ZnO NP-induced cytotoxicity. Together, our study characterizes the landscape of translational alteration under ZnO NPs treatment and provides potential targets to augment the anticancer effect of ZnO NPs.

In Situ Electrochemical Intercalation-Induced Phase Transition to Enhance Catalytic Performance for Lithium-Sulfur Battery.

Accelerating the conversion of polysulfide to inhibit shutting effect is a promising approach to improve the performance of lithium-sulfur batteries. Herein, the hollow titanium nitride (TiN)/1T-MoS2 heterostructure nanospheres are designed with efficient electrocatalysis properties serving as a sulfur host, which is formed by in situ electrochemical intercalation from TiN/2H-MoS2 . Metallic, few-layered 1T-MoS2 nanosheets with abundant active sites decorated on TiN nanospheres enable fast electron transfer, high adsorption ability toward polysulfides, and favorable catalytic activity contributing to the conversion kinetics of polysulfides. Benefiting from the synergistic effects of these favorable features, the as-developed hollow TiN/1T-MoS2 nanospheres with advanced architecture design can achieve a high discharge capacity of 1273 mAh g-1 at 0.1 C, good rate performance with a capacity retention of 689 mAh g-1 at 2 C, and long cycling stability with a low-capacity fading rate of 0.051% per cycle at 1 C for 800 cycles. Notably, the TiN/1T-MoS2 /S cathode with a high sulfur loading of up to 7 mg cm-2 can also deliver a high capacity of 875 mAh g-1 for 50 cycles at 0.1 C. This work promotes the prospect application for TiN/1T-MoS2 in lithium-sulfur batteries.

YTHDF1-mediated translation amplifies Wnt-driven intestinal stemness.

N6-methyladenosine (m6 A) mRNA methylation has emerged as an important player in many biological processes by regulating gene expression. However, its roles in intestinal stem cell (ISC) homeostasis remain largely unknown. Here, we report that YTHDF1, an m6 A reader, is highly expressed in ISCs and its expression is upregulated by Wnt signaling at the translational level. Whereas YTHDF1 is dispensable for normal intestinal development in mice, genetic ablation of Ythdf1 dramatically blocks Wnt-driven regeneration and tumorigenesis with reduced ISC stemness. Mechanistically, YTHDF1 facilitates the translation of Wnt signaling effectors including TCF7L2/TCF4, while this process is enhanced during Wnt activation to augment ß-catenin activity. Targeting YTHDF1 in ISCs of established tumors leads to tumor shrinkage and prolonged survival. Collectively, our studies unveil YTHDF1 as an amplifier of Wnt/ß-catenin signaling at the translational level, which is required for the maintenance of ISCs during regeneration and tumorigenesis.

Faulty Feeder Identification Based on Data Analysis and Similarity Comparison for Flexible Grounding System in Electric Distribution Networks.

Reliability and safety are the most important indicators in the electric system. When a ground fault occurs, the electrical equipment and personnel will be greatly threatened. Due to the zero-sequence voltage/current sensor networks applied in the system, the fault identification and diagnosis technology are developing rapidly, including the application of ground fault suppression. A flexible grounding system (FGS) is a new technology applied to arc extinguishing in medium and high voltage electric distribution networks. Its characteristic is that when the single-phase ground fault occurs, the power-electronic-based device is put into the electric system to compensate and suppress the ground point current to be close to zero in a very short time. In order to implement the above process, the corresponding faulty feeder identification method needs to meet the requirements of rapidity and accuracy. In this article, based on the real-time sampled data from the zero-sequence current/voltage sensors, an improved faulty feeder identification method combining wavelet packet transform (WPT) and grey T-type correlation degree is proposed, which features both accuracy and rapidity. The former is used to reconstruct the transient characteristic signal, and the latter is responsible for calculating and comparing the similarity of relative variation trend. Simulation results verify the rationality and effectiveness of the proposed method and analysis.

The role of ATF3 in ZnO nanoparticle-induced genotoxicity and cytotoxicity in bronchial epithelial cells.

ZnO nanoparticle (ZnO NP) exposure causes oxidative stress in the respiratory system, leading to pulmonary damage. Activating transcription factor 3 (ATF3) participates in a variety of cellular stress responses. However, the role of ATF3 in ZnO NP genotoxicity and cytotoxicity remains to be explored. Here we reported that ZnO NP treatment dramatically induced the expression of ATF3 in human bronchial epithelial (HBE) cells, which was mediated by the nuclear factor erythroid 2-related factor 2 (Nrf2). ATF3 was required for the repair of ZnO NP-induced DNA damage as gamma foci number increased when endogenous ATF3 was silenced. Moreover, ATF3 also contributed to ZnO NP-induced cell apoptosis. Mechanistic study revealed that ATF3 interacted with the p53 protein and upregulated its expression under ZnO NP treatment. Collectively, our findings demonstrated ATF3 as an important regulator of epithelial homeostasis by promoting both DNA repair and the death of damaged cells under ZnO NP-induced genotoxic stress.

Discovery, synthesis of novel fusidic acid derivatives possessed amino-terminal groups at the 3-hydroxyl position with anticancer activity.

A series of novel fusidic acid (FA) derivatives were synthesized and screened for their in vitro cytotoxicity against the Hela, U87, KBV and MKN45 cancer cell lines. Selected FA derivatives with anti-tumor activity were firstly identified including compound 4, which exhibited good anti-proliferative activity with IC50 values in the range of 1.26-3.57 µM. Further research revealed that compound 4 induced Hela cells to undergo apoptosis by increasing the ratio of the cells in the Sub-G0/G1 phase via decreasing the neo-synthesized proteins in a dose-dependent manner from 1 to 10 µM. Compound 4 also showed good in vivo anti-tumor activity against the xenograft tumor of Hela cells and had no apparent toxicity. This study highlights the advantage of introducing the medium-length amino-terminal groups at the 3-OH position of FA to enhance its anti-tumor activity and suggests that compound 4 provides a starting point for designing more potent derivatives in the future.

Enhanced photocatalytic reduction of CO2 to CO over BiOBr assisted by phenolic resin-based activated carbon spheres.

Photocatalytic reduction of CO2 using solar energy to decrease CO2 emission is a promising clean renewable fuel production technology. Recently, Bi-based semiconductors with excellent photocatalytic activity and carbon-based carriers with large specific surface areas and strong CO2 adsorption capacity have attracted extensive attention. In this study, activated carbon spheres (ACSs) were obtained via carbonization and steam activation of phenolic resin-based carbon spheres at 850 °C synthesized by suspension polymerization. Then, the BiOBr/ACSs sample was successfully prepared via a simple impregnation method. The as-prepared samples were characterized by XRD, SEM, EDX, DRS, PL, EIS, XPS, BET, CO2 adsorption isotherm and CO2-TPD. The BiOBr and BiOBr/ACSs samples exhibited high CO selectivity for photocatalytic CO2 reduction, and BiOBr/ACSs achieved a rather higher photocatalytic activity (23.74 µmol g-1 h-1) than BiOBr (2.39 µmol g-1 h-1) under simulated sunlight irradiation. Moreover, the analysis of the obtained results indicates that in this photocatalyst system, due to their higher micropore surface area and larger micropore volume, ACSs provide enough physical adsorption sites for CO2 adsorption, and the intrinsic structure of ACSs can offer effective electron transfer ability for a fast and efficient separation of photo-induced electron-hole pairs. Finally, a possible enhanced photocatalytic mechanism of BiOBr/ACSs was investigated and proposed. Our findings should provide new and important research ideas for the construction of highly efficient photocatalyst systems for the reduction of CO2 to solar fuels and chemicals.

The emerging role of follistatin under stresses and its implications in diseases.

Follistatin (FST), a single-chain glycosylated protein, is expressed in various tissues. The essential biological function of FST is binding and neutralizing transforming growth factor ß (TGF-ß) superfamily, including activin, myostatin, and bone morphogenetic protein (BMP). Emerging evidence indicates that FST also serves as a stress responsive protein, which plays a protective role under a variety of stresses. In most cases, FST performs the protective function through its neutralization of TGF-ß superfamily. However, under certain circumstances, FST translocates into the nucleus to maintain cellular homeostasis independent of its extracellular antagonism activity. This review provides integrated insight into the most recent advances in understanding the role of FST under various stresses, and the clinical implications corresponding to these findings and discusses the mechanisms to be further studied.

Silica nanoparticle releases SIRT6-induced epigenetic silencing of follistatin.

Follistatin (FST) plays a protective role during silica nanoparticle (SiO2 NP) exposure. SiO2 NP treatment induces FST transcription with an unknown mechanism. We herein reported that SIRT6, one of the sirtuin family members, induced epigenetic silencing of FST. The expression of FST was elevated after SIRT6 knockdown while reduced after SIRT6 overexpression. Chromatin immunoprecipitation revealed a direct interaction between SIRT6 with FST promoter. Knockdown of SIRT6 increased both Ac-H3K9 level and Ac-H3K56 level at FST promoter region. SiO2 NP treatment de-stabilized SIRT6 mRNA and reduced SIRT6 expression, leading to the activation of FST transcription. Finally, over-expression of SIRT6 increased SiO2 NP-induced apoptosis. Collectively, this study provided evidence that SIRT6 is a negative regulator of FST transcription and participates in the regulation of cell survival during silica nanoparticle exposure.

Analysis of the Nonlinear Trends and Non-Stationary Oscillations of Regional Precipitation in Xinjiang, Northwestern China, Using Ensemble Empirical Mode Decomposition.

Changes in precipitation could have crucial influences on the regional water resources in arid regions such as Xinjiang. It is necessary to understand the intrinsic multi-scale variations of precipitation in different parts of Xinjiang in the context of climate change. In this study, based on precipitation data from 53 meteorological stations in Xinjiang during 1960-2012, we investigated the intrinsic multi-scale characteristics of precipitation variability using an adaptive method named ensemble empirical mode decomposition (EEMD). Obvious non-linear upward trends in precipitation were found in the north, south, east and the entire Xinjiang. Changes in precipitation in Xinjiang exhibited significant inter-annual scale (quasi-2 and quasi-6 years) and inter-decadal scale (quasi-12 and quasi-23 years). Moreover, the 2-3-year quasi-periodic fluctuation was dominant in regional precipitation and the inter-annual variation had a considerable effect on the regional-scale precipitation variation in Xinjiang. We also found that there were distinctive spatial differences in variation trends and turning points of precipitation in Xinjiang. The results of this study indicated that compared to traditional decomposition methods, the EEMD method, without using any a priori determined basis functions, could effectively extract the reliable multi-scale fluctuations and reveal the intrinsic oscillation properties of climate elements.

Protective Effect of Tetrandrine on Sodium Taurocholate-Induced Severe Acute Pancreatitis.

Tet is a type of alkaloid extracted from Stephania tetrandra, and it has recently been demonstrated that Tet can protect against inflammation and free radical injury and inhibit the release of inflammatory mediators. The present study was designed to observe the protective effect of Tet on sodium taurocholate-induced severe acute pancreatitis (SAP). The rat model of SAP was induced by retrograde bile duct injection of sodium taurocholate and then treated with Verapamil and Tet. The results showed that Tet can reduce NF-κB activation in pancreas issue, inhibit the SAP cascade, and improve SAP through inducing pancreas acinar cell apoptosis and stabilizing intracellular calcium in the pancreas, thus mitigating the damage to the pancreas. Our study revealed that Tet may reduce systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS) to protect against damage, and these roles may be mediated through the NF-κB pathway to improve the proinflammatory/anti-inflammatory imbalance.

Hygrothermal environment may cause influenza pandemics through immune suppression.

Over the past few decades, climate warming has caused profound changes in our living environment, and human diseases, including infectious diseases, have also been influenced by these changes. However, it remains unclear if a warm-wet climate can influence the infectivity of influenza and result in influenza pandemics. This study focused on observations of how the hydrothermal environment influences the infectivity of the influenza virus and the resulting immunoreactions of the infected mice. We used a manual climatic box to establish the following 3 environments with different temperatures and humidity: normal environment (T: 24 ± 1°C, RH: 50% ± 4%), wet environment (T: 24 ± 1 °C, RH: 95% ± 4%) and warm-wet environment (T: 33 ± 1 °C, RH: 95% ± 4%), and the mice were fed and maintained in these 3 different environments. After 14 days, half of the mice were infected with H1N1 (A/FM1/1/47, a lung adapted strain of the flu virus specific for the mouse lung) virus for 4 d After establishing the animal model, we observed the microstructure of the lung tissue, the Th1/Th2 T cell subsets, the Th17/Treg balance, the expression of cytokines in the peripheral blood serum and the expression of the immune recognition RLH signal pathway. The results showed that mice in different environments have different reaction. Results showed that after infection, the proportion of Th1/Th2 and Th17/Treg cells in the spleen was significantly increased, and these proportions were increased the most in the infected group kept in wet-hot conditions. After infection, the mRNA levels and protein expression of the RLH (RIG-1-like helicases) signal pathway components were up-regulated while the uninfected animals in the 3 diverse environments showed no significant change. The infected mice kept in the wet and warm-wet environments showed a slight elevation in the expression of RLH pathway components compared to infected mice maintained in the normal environment. Our study suggested that the warm-wet environment may have interfered with the immune response and balance. The mice kept in the warm-wet environment displayed immune tolerance when they were exposed to the influenza virus, and the body was not able to effectively clear the virus, leading to a persistent infection. A warm-wet climate may thus be a factor that contributes to influenza pandemics, people should focus on the warm-wet climate coming and advance prepare to vaccine manufacture.

A novel photoelectrochemical sensor based on photocathode of PbS quantum dots utilizing catalase mimetics of bio-bar-coded platinum nanoparticles/G-quadruplex/hemin for signal amplification.

Photocathode based on p-type PbS quantum dots (QDs) combing a novel signal amplification strategy utilizing catalase (CAT) mimetics was designed and utilized for sensitive photoelectrochemical (PEC) detection of DNA. The bio-bar-coded Pt nanoparticles (NPs)/G-quadruplex/hemin exhibited high CAT-like activity following the Michaelis-Menten model for decomposing H2O2 to water and oxygen, whose activity even slightly exceeded that of natural CAT. The bio-bar-code as a catalytic label was conjugated onto the surface of PbS QDs modified electrodes through the formed sandwich-type structure due to DNA hybridization. Oxygen in situ generated by the CAT mimetics of the bio-bar-code of Pt NPs/G-quadruplex/hemin acted as an efficient electron acceptor of illuminated PbS QDs, promoting charge separation and enhancing cathodic photocurrent. Under optimal conditions, the developed PEC biosensor for target DNA exhibited a dynamic range of 0.2pmol/L to 1.0nmol/L with a low detection limit of 0.08pmol/L. The high sensitivity of the method was resulted from the sensitive response of PbS QDs to oxygen and the highly efficient CAT-like catalytic activity of the bio-bar-coded Pt NPs/G-quadruplex/hemin.

A new approach to light up the application of semiconductor nanomaterials for photoelectrochemical biosensors: using self-operating photocathode as a highly selective enzyme sensor.

Due to the intrinsic hole oxidation reaction occurred on the photoanode surface, currently developed photoelectrochemical biosensors suffer from the interference from coexisting reductive species (acting as electron donor) and a novel design strategy of photoelectrode for photoelectrochemical detection is urgently required. In this paper, a self-operating photocathode based on CdS quantum dots sensitized three-dimensional (3D) nanoporous NiO was designed and created, which showed highly selective and reversible response to dissolved oxygen (acting as electron acceptor) in the electrolyte solution. Using glucose oxidase (GOD) as a biocatalyst, a novel photoelectrochemical sensor for glucose was developed. The commonly encountered interferents such as H2O2, ascorbic acid (AA), cysteine (Cys), dopamine (DA), etc., almost had no effect for the cathodic photocurrent of the 3D NiO/CdS electrode, though these substances were proved to greatly influence the photocurrent of photoanodes, which indicated greatly improved selectivity of the method. The method was applied to detect glucose in real samples including serum and glucose injections with satisfactory results. This study could provide a new train of thought on designing of self-operating photocathode in photoelectrochemical sensing, promoting the application of semiconductor nanomaterials in photoelectrochemistry.

In situ formation of p-n junction: a novel principle for photoelectrochemical sensor and its application for mercury(II) ion detection.

The discovery and development of photoelectrochemical sensors with novel principles are of great significance to realize sensitive and low-cost detection. In this paper, a new photoelectrochemial sensor based on the in situ formation of p-n junction was designed and used for the accurate determination of mercury(II) ions. Cysteine-capped ZnS quantum dots (QDs) was assembled on the surface of indium tin oxide (ITO) electrode based on the electrostatic interaction between Poly(diallyldimethylammonium chloride) (PDDA) and Cys-capped ZnS QDs. The in situ formation of HgS, a p-type semiconductor, on the surface of ZnS facilitated the charge carrier transport and promoted electron-hole separation, triggered an obviously enhanced anodic photocurrent of Cys-capped ZnS QDs. The formation of p-n junction was confirmed by P-N conductive type discriminator measurements and current-voltage (I-V) curves. The photoelectrochemical method was used for the sensing of trace mercuric (II) ions with a linear concentration of 0.01 to 10.0 µM and a detection limit of 4.6×10(-9)mol/L. It is expected that the present study can serve as a foundation to the application of p-n heterojunction to photoelectrochemical sensors and it might be easily extended to more exciting sensing systems by photoelectrochemistry.

Immunologic mechanism of Patchouli alcohol anti-H1N1 influenza virus may through regulation of the RLH signal pathway in vitro.

Patchouli alcohol (PA) is a kind of methanol extracted from traditional Chinese medicine Pogostemonis Herba. Our research aimed to observe the anti-influenza virus role of PA in vitro. 16HBE (human respiratory epithelial cell) was infected by H1N1 (A/FM1/1/47) to set the cell model. Then the 16HBE was co-cultivated with three kinds of immune cells: dendritic cells, macrophages, and monocytes, PA (the concentration is 10 µg/mL) was added as a treatment intervention for 24 h. The immune cells and the supernate were collected for RT-PCR and ELISA detection related to RLH (RIG-1-like helicases) pathway. Results showed that the IL-4 and IFN-γ in supernate were increased after H1N1 infection, and the PA treatment suppressed the expression of cytokines and the mRNA of RLH pathway. PA anti-influenza virus may through regulate the RLH singal pathway.