Modulation of photonic skyrmions in a thin metal film structure.

Photonic skyrmions have been a hot topic in recent years. However, modulating the spin distributions of the skyrmions is still a challenging topic. In this paper, we investigate the detailed spin distributions of photonic skyrmions in thin metal film sandwiched by different dielectrics. We find that the ratios of different spin components can be adjusted by the thickness of the metal film, while the absolute value of total spin can be controlled by the frequency of the light source. Therefore, by choosing proper metal thickness in the preparation process and certain beam frequency in actual experiment, we can get the exact type of spin distribution we prefer. In addition, when the dielectric layers are arranged asymmetrically, the spin distributions can also be modulated significantly by adjustig the ratio of the dielectric constants of the upper and lower dielectric layers. Our results provide a new pathway for the modulation of photonic skyrmions.

SMAD4 regulates the progression of cholangiocarcinoma by modulating the expression of STING1.

SMAD4 is a tumour suppressor and an important regulator of tumour immune scape which is downregulated in cholangiocarcinoma (CCA). STING1 is a vital sensing factor of abnormal DNA; however, the correlation between SMAD4 and STING1 and the role of the SMAD4-STING1 interaction in the progression of CCA have not yet been evaluated. Public database was analysed to reveal the expression of SMAD4 and STING1. A cohort comprising 50 iCCA, 113 pCCA and 119 dCCA patients was assembled for the study. Immunohistochemistry was employed to evaluate the expression levels of STING1 and SMAD4. In vitro transwell and CCK8 assays, along with luciferase reporter assay, were conducted to analyse the potential regulatory mechanisms of SMAD4 on the expression of STING1. Expression of SMAD4 and STING1 were downregulated in CCA tumours and STING1 expression correlated with SMAD4 expression. The overexpression of SMAD4 was found to suppress the migration, invasion and proliferation capabilities of CCA cells; whereas, the knockdown of SMAD4 enhanced these abilities. Furthermore, it was observed that SMAD4 translocated into the nucleus following TGF-ß1 stimulation. Knockdown of SMAD4 resulted in the inhibition of STING1 transcriptional activity, whereas the overexpression of SMAD4 promoted the transcriptional activity of STING1. Clinically, low STING1 and SMAD4 expression indicated poor prognosis in CCA, and simultaneously low expression of STING1 and SMAD4 predicts poorer patient survival. SMAD4 regulates the expression of STING1 through its transcription regulating function. Dual low expression of STING1 and SMAD4 had more power in predicting patient survival. These results indicate that SMAD4-silenced CCA may downregulate its STING1 expression to adapt to the immune system.

Battery Capacity of Energy-Storing Quantum Systems.

The quantum battery capacity is introduced in this Letter as a figure of merit that expresses the potential of a quantum system to store and supply energy. It is defined as the difference between the highest and the lowest energy that can be reached by means of the unitary evolution of the system. This function is closely connected to the ergotropy, but it does not depend on the temporary level of energy of the system. The capacity of a quantum battery can be directly linked with the entropy of the battery state, as well as with measures of coherence and entanglement.

Synthesis of 10-Membered Azecines through Pd-Catalyzed Formal [6+4] Cycloaddition and Their Transannular Reaction to Polycyclic Compounds.

Azecine fragments are frequently presented in natural products and bioactive compounds. However, minor efforts have been devoted to these 10-membered N-heterocycles, and their synthesis is still challenging. Reported herein is the first catalytic formal [6+4] cycloaddition for the synthesis of 10-membered azecines. Under palladium catalysis, the reaction of δ-vinylvalerolactones and benzofuran-derived azadienes proceeds smoothly to afford benzofuran-fused azecines with high diastereoselectivity in moderate to good yields. A unique transannular reaction of these 10-membered azecines for the construction of polycyclic compounds is also demonstrated.

Divergent Reaction of Indoline-derived Azadienes with α-Bromohydroxamates: Synthesis of Spiro-indolinepyrrolidinones and Indoline-fused Diazepinones.

A divergent reaction of indoline-derived azadienes with α-bromohydroxamates for the selective synthesis of spiro-indolinepyrrolidinones and indoline-fused diazepinones was disclosed. This reaction sequence involved an initial formation of five-membered spirocyclic products followed by an intramolecular ring-opening and ring expansion to produce seven-membered diazepinones. We demonstrated that controlling the reaction time could modulate the reaction pathway for formation of different molecular frameworks for the same set of substrates. Based on the experimental results, the reaction mechanism was also discussed and proposed to explain the phenomena observed in the process.

Copper-Catalyzed Cascade Annulation of o-Hydroxyphenyl Propargylamines with Pyrazolin-5-ones to Access Pyrano[2,3-c]pyrazoles.

An efficient copper-catalyzed cascade annulation of o-hydroxyphenyl propargylamines and pyrazolin-5-ones is described. This methodology leads to the rapid assembly of a series of valuable pyrano[2,3-c]pyrazoles with good yields across a wide range of substrates in a simple fashion. This novel reaction involves the formation of alkynyl ortho-quinone methides, a 1,4-conjugate addition, and a subsequent 6-endo cyclization process. The mechanistic elucidation is well supported by control experiment and literature precedents.

Access to 4-Alkenylated Coumarins via Ruthenium-Catalyzed Olefinic C-H Alkenylation of Coumarins with Modifiable and Removable Directing Groups.

The ruthenium-catalyzed activation of the C4 position of coumarins for coupling with acrylates was described using modifiable ketone as a directing group. The alkenylation reaction provided a direct approach to prepare previously inaccessible 4-alkenylated coumarins with operational simplicity and high atom-economy. This protocol also worked well with coumarin-3-carboxylic acids to unveil a rare instance of a tandem alkenylation/decarboxylation reaction. The potential value of this approach was further highlighted by the efficient synthesis of several heterocyclic fused coumarin derivatives.

One-Pot Synthesis of Aza-Morita-Baylis-Hillman Adducts via Zinc-Mediated Allylation of 4-Bromocrotonates and Imines.

An approach to the synthetically valuable ß-substituted aza-Morita-Baylis-Hillman (MBH) type products, through zinc-mediated allylation of imines with 4-bromocrotonates followed by subsequent isomerization of the double bond, was developed. Complementary to classical MBH reaction, this reaction utilizes easily available 4-bromocrotonates as the reaction partners, providing a rapid alternative to the traditional use of α,ß-unsaturated carbonyl compounds. The short reaction time, one-pot operation, broad substrate scopes, gram-scale synthesis, and synthetic application exemplified the utility and practicability of this method.

Diastereoselective Construction of Spiro-furo[3,2- c]benzopyranoxindoles through a Cu(OTf)2/AcOH Cooperative Promoted Bicyclization Reaction.

We disclose herein a highly diastereoselective approach for the Cu(OTf)2/AcOH cooperative promoted bicyclization reaction of 3-cinnamyl-3-hydroxy-2-oxindoles and ortho-quinonemethides ( o-QMs) generated in situ from salicylaldehydes for the synthesis of spiro-furo[3,2- c]benzopyranoxindoles. The reaction has the advantages of readily available starting materials, simple operation, and high bond-forming efficiency, which not only provides an efficient access to spiro-furo[3,2- c]benzopyranoxindoles but also enriches the research contents of o-QMs-involved reactions. The synthetic applications of the products such as amide reduction are also demonstrated.

Facile way to obtain multiple interface modes in a photonic crystal heterostructure.

A very facile way to obtain multiple interface modes in a one-dimensional photonic crystal heterostructure is proposed in this Letter. We found that the interface modes can be generated by introducing the interfaces, and the number of interface modes equals the number of introduced interfaces. All these interface modes originating from a different geometric Zak phase can create two band branches governed by the two different interfaces. We further find that the two band branches can be renormalized into one band branch with discrete energy levels in the form of sinusoidal function. We believe that these findings can be used to provide direct guidance for practical application and can also make the estimation of practical samples more convenient.

General way to obtain multiple defect modes in multiple photonic quantum-well structures.

We introduce a method to obtain and describe the multiple defect modes in the multiple photonic quantum-well structure [(AB)mC]n(AB)m. It is found that the relationship between structural parameters and defect modes can be obtained by analytically solving the dispersion relationship for the photonic crystal with its periodic unit [(AB)mC], and a laconic and unifying expression can be used to describe the energy levels of both the interface modes and defect modes. The internal mechanism to determine the related parameters is revealed. We believe that these findings can be used to provide direct guidance for practical application.

Zinc-mediated α-regioselective Barbier-type cinnamylation reactions of aldehydes, ketones and esters.

We report a simple, efficient, and general method for the zinc-mediated regioselective cinnamylation of aldehydes and ketones under Barbier-type conditions in a one-pot synthesis affording the corresponding α-cinnamylated alcohols in moderate to excellent yields. Compared to the literature procedures, this approach is operationally simple, uses simple reactants, and provides direct access to linear α-cinnamylated alcohols with excellent regioselectivity. Experimental results suggest that the reactions proceed through the radical pathway. In addition, the reaction was found to be scalable to the gram-scale and the one-pot protocol is also applicable to less reactive esters leading to bishomoallylic alcohols which were valuable intermediates for desymmetrizing intramolecular Heck cyclization, allowing for the elaboration to functionalized building blocks.

Zinc-Mediated C-3 α-Prenylation of Isatins with Prenyl Bromide: Access to 3-Prenyl-3-hydroxy-2-oxindoles and Its Application.

A convenient and highly α-regioselective strategy for the synthesis of 3-prenyl-3-hydroxy-2-oxindoles has been developed starting from isatins and prenylzinc with good to excellent yields. This protocol provides a straightforward and practical way to introduce an α-prenyl moiety into the C-3 position of isatins. The advantages of this reaction are use of the cheap and readily available reagents, operational simplicity, and wide substrate scope. Furthermore, this transformation was applied to the synthesis of several oxindole-containing natural products, which further demonstrated the synthetic utility of this methodology.

One-pot synthesis of 1,4-dihydroxy-2-((E)-1-hydroxy-4-phenylbut-3-enyl)anthracene-9,10-diones as novel shikonin analogs and evaluation of their antiproliferative activities.

A series of shikonin analogs have been synthesized in a one-pot reaction of quinizarin with ß,γ-unsaturated aldehydes in MeOH under mild conditions and investigated for their cytotoxicity against four cancer cell lines and one normal cell line. The synthesized compounds were found to be cytotoxic against HeLa cells with no apparent toxicity against normal cell line. Further modification led to the discovery of a novel tetracyclic anthraquinone (4b/4b') with potent cytotoxic activities against cervical, breast and pancreatic cancer cell lines with no significant effect on the growth of the control mammary epithelial cell line MCF-10. The good cytotoxicity and selectivity of compound 4b/4b' suggest that it could be a promising lead for further optimization.

A new Suzuki synthesis of triphenylethylenes that inhibit aromatase and bind to estrogen receptors α and ß.

The design and synthesis of dual aromatase inhibitors/selective estrogen receptor modulators (AI/SERMs) is an attractive strategy for the discovery of new breast cancer therapeutic agents. Previous efforts led to the preparation of norendoxifen (4) derivatives with dual aromatase inhibitory activity and estrogen receptor binding activity. In the present study, some of the structural features of the potent AI letrozole were incorporated into the lead compound (norendoxifen) to afford a series of new dual AI/SERM agents based on a symmetrical diphenylmethylene substructure that eliminates the problem of E,Z isomerization encountered with norendoxifen-based AI/SERMs. Compound 12d had good aromatase inhibitory activity (IC50=62.2nM) while also exhibiting good binding activity to both ER-α (EC50=72.1nM) and ER-ß (EC50=70.8nM). In addition, a new synthesis was devised for the preparation of norendoxifen and its analogues through a bis-Suzuki coupling strategy.

Synthesis of Furo[3,2-c]benzopyrans via an Intramolecular [4 + 2] Cycloaddition Reaction of o-Quinonemethides.

An intramolecular [4 + 2] cycloaddition reaction of o-quinonemethides generated from salicylaldehydes and α-prenylated alcohols is described. In the presence of a catalytic amount of benzenesulfonic acid (BSA), the reaction proceeded smoothly in EtOH to afford furo[3,2-c]benzopyrans through a three-bond forming process in moderate to excellent yields with high diastereoselectivity. This reaction provides a simple and straightforward protocol to efficiently construct furo[3,2-c]benzopyran skeletons. A possible mechanism involving hemiacetal formation/hetero-Diels-Alder reaction is proposed to rationalize the observed results.

Quantitative assessment of pulmonary perfusion using dynamic contrast-enhanced CT in patients with chronic obstructive pulmonary disease: correlations with pulmonary function test and CT volumetric parameters.

BACKGROUND: Pulmonary function test (PFT) is commonly used to help diagnose chronic obstructive pulmonary disease (COPD) and other lung diseases. However, it cannot be used to evaluate regional function and morphological abnormalities. PURPOSE: To quantitatively evaluate pulmonary perfusion imaging using dynamic contrast-enhanced (DCE) computed tomography (CT) and observe its correlations with PFT and CT volumetric parameters in COPD patients. MATERIAL AND METHODS: PFT and CT pulmonary perfusion examination were performed in 63 COPD patients. Perfusion defects were quantitated by calculating the CT value ratio (RHU) between perfusion defects (HUdefect) and normal lung (HUnormal). Volumetric CT data were used to calculate emphysema index (EI), total lung volume (TLV), and total emphysema volume (TEV). Emphysematous parenchyma was defined as the threshold of lung area lower than -950 HU. Correlations between RHU and TLV, TEV, EI, and PFT were assessed using Spearman correlation analysis. RESULTS: The positive rate of perfusion defects on CT perfusion images was higher than that of emphysema on CT mask images (χ(2) = 17.027, P < 0.001). The Spearman correlation test showed that RHU was positively correlated with FEV1 (R = 0.59, P < 0.001), FEV1% Predicted (R = 0.61, P < 0.001), FVC (R = 0.47, P = 0.002), and FEV1/FVC (R = 0.65, P < 0.001), and negatively correlated with EI (R = -0.67, P < 0.001). CONCLUSION: CT perfusion imaging is more sensitive in detecting emphysema that is inconspicuous on CT images. RHU is correlated with PFT and CT volumetric parameters, suggesting that it is more sensitive in detecting early COPD changes and may prove to be a potential predictor of focal lung function.

Knockdown of UbcH10 enhances the chemosensitivity of dual drug resistant breast cancer cells to epirubicin and docetaxel.

Breast cancer is one of the most common and lethal cancers in women. As a hub gene involved in a diversity of tumors, the ubiquitin-conjugating enzyme H10 (UbcH10), may also play some roles in the genesis and development of breast cancer. In the current study, we found that the expression of UbcH10 was up-regulated in some breast cancer tissues and five cell lines. We established a dual drug resistant cell line MCF-7/EPB (epirubicin)/TXT (docetaxel) and a lentiviral system expressing UbcH10 shRNA to investigate the effects of UbcH10 knockdown on the chemosensitivity of MCF-7/EPB/TXT cells to epirubicin and docetaxel. The knockdown of UbcH10 inhibited the proliferation of both MCF-7 and MCF-7/EPB/TXT cells, due to the G1 phase arrest in cell cycle. Furthermore, UbcH10 knockdown increased the sensitivity of MCF-7/EPB/TXT cells to epirubicin and docetaxel and promoted the apoptosis induced by these two drugs. Protein detection showed that, in addition to inhibiting the expression of Ki67 and cyclin D1, UbcH10 RNAi also impaired the increased BCL-2 and MDR-1 expression levels in MCF-7/EPB/TXT cells, which may contribute to abating the drug resistance in the breast cancer cells. Our research in the current study demonstrated that up-regulation of UbcH10 was involved in breast cancer and its knockdown can inhibit the growth of cancer cells and increase the chemosensitivity of the dual drug resistant breast cancer cells to epirubicin and docetaxel, suggesting that UbcH10 may be a promising target for the therapy of breast cancer.

Dynamic contrast enhanced magnetic resonance perfusion imaging in high-risk smokers and smoking-related COPD: correlations with pulmonary function tests and quantitative computed tomography.

The study aimed to prospectively evaluate correlations between dynamic contrast-enhanced (DCE) MR perfusion imaging, pulmonary function tests (PFT) and volume quantitative CT in smokers with or without chronic obstructive pulmonary disease (COPD) and to determine the value of DCE-MR perfusion imaging and CT volumetric imaging on the assessment of smokers. According to the ATS/ERS guidelines, 51 male smokers were categorized into five groups: At risk for COPD (n = 8), mild COPD (n = 9), moderate COPD (n = 12), severe COPD (n = 10), and very severe COPD (n = 12). Maximum slope of increase (MSI), positive enhancement integral (PEI), etc. were obtained from MR perfusion data. The signal intensity ratio (RSI) of the PDs and normal lung was calculated (RSI = SIPD/SInormal). Total lung volume (TLV), total emphysema volume (TEV) and emphysema index (EI) were obtained from volumetric CT data. For "at risk for COPD," the positive rate of PDs on MR perfusion images was higher than that of abnormal changes on non-enhanced CT images (p < 0.05). Moderate-to-strong positive correlations were found between all the PFT parameters and SIPD, or RSI (r range 0.445∼0.683, p ≤ 0.001). TEV and EI were negatively correlated better with FEV1/FVC than other PFT parameters (r range -0.48 --0.63, p < 0.001). There were significant differences in RSI and SIPD between "at risk for COPD" and "very severe COPD," and between "mild COPD" and "very severe COPD". Thus, MR perfusion imaging may be a good approach to identify early evidence of COPD and may have potential to assist in classification of COPD.

[Clinical value of MRI united-sequences examination in diagnosis and differentiation of morphological sub-type of hilar and extrahepatic big bile duct cholangiocarcinoma].

OBJECTIVE: To investigate MRI features and associated histological and pathological changes of hilar and extrahepatic big bile duct cholangiocarcinoma with different morphological sub-types, and its value in differentiating between nodular cholangiocarcinoma (NCC) and intraductal growing cholangiocarcinoma (IDCC). METHODS: Imaging data of 152 patients with pathologically confirmed hilar and extrahepatic big bile duct cholangiocarcinoma were reviewed, which included 86 periductal infiltrating cholangiocarcinoma (PDCC), 55 NCC, and 11 IDCC. Imaging features of the three morphological sub-types were compared. RESULTS: Each of the subtypes demonstrated its unique imaging features. Significant differences (P < 0.05) were found between NCC and IDCC in tumor shape, dynamic enhanced pattern, enhancement degree during equilibrium phase, multiplicity or singleness of tumor, changes in wall and lumen of bile duct at the tumor-bearing segment, dilatation of tumor upstream or downstream bile duct, and invasion of adjacent organs. CONCLUSION: Imaging features reveal tumor growth patterns of hilar and extrahepatic big bile duct cholangiocarcinoma. MRI united-sequences examination can accurately describe those imaging features for differentiation diagnosis.