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Long-term treatment with adriamycin (ADR) is associated with higher incidences of cumulative cardiotoxicity manifest as heart failure. ADR-induced cardiomyopathy is characterized by extensive fibrosis that is caused by cardiac fibroblast activation. To date, however, no specific treatment is available to alleviate ADR-induced cardiotoxicity. Protein arginine methyltransferase 5 (PRMT5), a major enzyme responsible for methylation of arginine, regulates numerous cellular processes such as cell differentiation. In the present study we investigated the role of PRMT5 in cardiac fibrosis. Mice were administered ADR (3 mg/kg, i.p., every 2 days) for 2 weeks. We showed that aberrant PRMT5 expression was largely co-localized with α-SMA-positive activated cardiac fibroblasts in ADR-injected mice and in ADR-treated cardiac fibroblasts in vitro. PRMT5-overexpression exacerbated, whereas PRMT5 knockdown alleviated ADR-induced cardiac fibrosis in vivo and TGF-β1-induced cardiac fibroblast activation in vitro. We demonstrated that PRMT5-overexpression enhanced methylated-Smad3 levels in vivo and in vitro. Pretreatment with a specific PRMT5 inhibitor EPZ015666 (5 nM) or overexpression of a catalytically inactive mutant of PRMT5, PRMT5(E444Q), reduced PRMT5-induced methylation of Smad3, thus suppressing PRMT5-mediated cardiac fibroblast activation in vitro. Furthermore, ADR activated cardiac fibroblasts was depending on autocrine TGF-β1. Taken together, our results demonstrate that PRMT5 promotes ADR-induced cardiac fibrosis via activating cardiac fibroblasts, suggesting that it may be a potential therapeutic target of ADR-caused cardiotoxicity.

Objective To evaluate the impact of pre-operative contrast-enhanced mammography (CEM) in breast cancer patients with dense breasts. Methods We conducted a retrospective review of 232 histologically proven breast cancers in 200 women (mean age: 53.4 years ± 10.2) who underwent pre-surgical CEM imaging across two Asian institutions (Singapore and Taiwan). Majority (95.5%) of patients had dense breast tissue (BI-RADS category C or D). Surgical decision was recorded in a simulated blinded multi-disciplinary team setting on two separate scenarios: (i) pre-CEM setting with standard imaging, and clinical and histopathological results; and (ii) post-CEM setting with new imaging and corresponding histological findings from CEM. Alterations in surgical plan (if any) because of CEM imaging were recorded. Predictors CEM of patients who benefitted from surgical plan alterations were evaluated using logistic regression. Results CEM resulted in altered surgical plans in 36 (18%) of 200 patients in this study. CEM discovered clinically significant larger tumor size or extent in 24 (12%) patients and additional tumors in 12 (6%) patients. CEM also detected additional benign/false-positive lesions in 13 (6.5%) of the 200 patients. Significant predictors of patients who benefitted from surgical alterations found on multivariate analysis were pre-CEM surgical decision for upfront breast conservation (OR, 7.7; 95% CI, 1.9-32.1; p = 0.005), architectural distortion on mammograms (OR, 7.6; 95% CI, 1.3–42.9; p = .022), and tumor size of ≥ 1.5 cm (OR, 1.5; 95% CI, 1.0-2.2; p = .034). Conclusion CEM is an effective imaging technique for pre-surgical planning for Asian breast cancer patients with dense breasts. Key Points • CEM significantly altered surgical plans in 18% (nearly 1 in 5) of this Asian study cohort with dense breasts. • Significant patient and imaging predictors for surgical plan alteration include (i) patients considered for upfront breast-conserving surgery; (ii) architectural distortion lesions; and (iii) tumor size of ≥ 1.5 cm. • Additional false-positive/benign lesions detected through CEM were uncommon, affecting only 6.5% of the study cohort.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases among the elderly and it accounts for nearly 80% of all dementias. The pathogenesis of AD is complicated and enigmatic thus far. The mitochondrial cascade hypothesis assumes that mitochondrial damage may mediate, drive, or contribute to a variety of AD pathologies and may be the main factor in late-onset AD. Currently, there are no widely recognized drugs able to attenuate mitochondrial damage in AD. Notably, increasing evidence supports the efficacy of acupuncture for improving the mitochondrial structure and protecting mitochondrial functions in AD. This review reports the mechanisms by which acupuncture regulates mitochondrial dynamics, energy metabolism, calcium homeostasis and apoptosis. In conclusion, these findings suggest that AD mitochondrial dysfunction represents a reasonable therapeutic target and acupuncture could play a significant role in preventing and treating AD.

Dendritic cell (DC) vaccine is an effective strategy for cancer immunotherapy by carrying antigen into DCs and migrating these DCs to drain lymph nodes after inoculation. In this article, second near-infrared window (NIR-II) fluorescent nanoparticles have been used to uptake antigen and activate DCs. Ovalbumin (OVA), an antigen for immunization, can be loaded on the surface of these NIR-II fluorescent nanoparticles via electrostatic interaction by virtue of their functionalized poly(L-lysine) (PLL), which exhibits biocompatibility and strong selective interaction with OVA. In addition, these antigen-loaded complexes can efficiently be engulfed by immature DCs to induce DC maturation and cytokine secretion. After subcutaneous injection, highly sensitive NIR-II fluorescence signal from nanoparticles indicates that nanoparticle-labeled DCs can successfully migrate into lymph nodes in vivo, showing great promise in immunotherapy against cancer.

Background X chromosome inactivation (XCI) is that one of two chromosomes in mammalian females is silenced during early development of embryos. There has been a statistical measure for the degree of the skewness of XCI for qualitative traits. However, no method is available for such task at quantitative trait loci. Results In this article, we extend the existing statistical measure for the skewness of XCI for qualitative traits, and the likelihood ratio, Fieller’s and delta methods for constructing the corresponding confidence intervals, and make them accommodate quantitative traits. The proposed measure is a ratio of two linear regression coefficients when association exists. Noting that XCI may cause variance heterogeneity of the traits across different genotypes in females, we obtain the point estimate and confidence intervals of the measure by incorporating such information. The hypothesis testing of the proposed methods is also investigated. We conduct extensive simulation studies to assess the performance of the proposed methods. Simulation results demonstrate that the median of the point estimates of the measure is very close to the pre-specified true value. The likelihood ratio and Fieller’s methods control the size well, and have the similar test power and accurate coverage probability, which perform better than the delta method. So far, we are not aware of any association study for the X-chromosomal loci in the Minnesota Center for Twin and Family Research data. So, we apply our proposed methods to these data for their practical use and find that only the rs792959 locus, which is simultaneously associated with the illicit drug composite score and behavioral disinhibition composite score, may undergo XCI skewing. However, this needs to be confirmed by molecular genetics. Conclusions We recommend the Fieller’s method in practical use because it is a non-iterative procedure and has the similar performance to the likelihood ratio method.

A sensitive and specific assay was developed to detect bacterial leaf and flower spot disease on zinnia caused by Xanthomonas campestris pv. zinniae (Xcz). A draft genome sequence was determined for Xcz strain E4, isolated from zinnia in Jilin province, China. Comparative genomics analyses were utilized to identify a sequence specific to Xcz in the unique gene 0834. This sequence region was amplified as 1044 bp DNA fragment using designed primers 0834F and 0834R. Using this primer set, specific PCR products were only amplified from DNA from Xcz strains and not from other pathovars of X. campestris, other species of Xanthomonas, or from other genera such as Pseudomonas and Bacillus. The limit of PCR detection in pure culture suspension was approximately 1.7 × 103 CFU/ml per reaction. Specific amplification of the fragments for Xcz was sensitive relatively to the technique used, detecting as low as 0.1 pg template DNA. The PCR technique was also applied to detect the Xcz pathogen in naturally infected leaves and seeds of zinnia.

LEAF is a heavy ion experimental facility with low energy, high intensity and high charge state. It belongs to the strong current linear accelerator, and its maximum beam power can reach 10 kW. High-power beams can pose a great risk of damaging field devices in continuous beam mode due to high-power beam bombardment. In order to ensure the safe operation of field devices and key equipment, an interlocking control system for LEAF is designed by using the control board of FPGA and PLC controller. The FPGA-based interlock system mainly implements the real-time monitoring of the arc fault signals from the RFQ cavity, a few fast fault signals from LLRF system and beam diagnostic system. When a valid fault signal is detected, the system will send its protection instruction to the chopper power supply to cut off the beam rapidly. The PLC-based interlock system mainly handles the fault state detection and safety operation of field devices with a slower protective action, and the action time is in a millisecond range. The protective action time of the FPGA interlock system has been achieved within 10 µs. This system adopts two sets of control and protection logic, which are implemented in the control board of FPGA and the PLC controller. It can ensure the safety of the core devices through the double-redundant beam-cutting actions if the key equipment fails or the beam parameters are abnormal. The complete system has a simple structure. The redundant technique is used in the design of the control protection logic and data transmission path. This provides a reliable safety measure for beam commissioning and physical experiment of the LEAF facility.

The influenza epidemic is a huge burden to public health. Current influenza vaccines provide limited protection against new variants due to frequent mutation of the virus. The continual emergence of novel variants necessitates the method rapidly monitoring influenza virus infection in experimental systems. Although several replication-competent reporter viruses carrying fluorescent proteins or small luciferase have been generated in previous studies, visualizing influenza virus infection via such strategy requires reverse genetic modification for each viral strain which is usually time-consuming and inconvenient. Here, we created a novel influenza A nucleoprotein (NP) dependent reporter gene transcription activation module using NP-specific nanobodies. Our results demonstrated the modular design allowed reporter genes (mNeonGreen fluorescent protein and Gaussia luciferase) specifically expressing to detect intracellular NP protein, and therefore acts as a universal biosensor to monitor infection of various influenza A subtypes in living cells. The new system may provide a powerful tool to analyze influenza A infections at the cellular level to facilitate new antiviral drug discovery. Moreover, this approach may easily extend to develop live-cell biosensors for other viruses.

Ni-SiC composite coatings were prepared on TA15 alloy by composite electroplating technology. The friction and wear behavior of TA15 alloy, and the coating were comparatively studied at both room temperature and 600 °C using GCr15 as the counterparts. The results show that the obtained coating is relatively dense and compact, and possesses higher micro-hardness than TA15 alloy. The coating has significant friction reduction effect sliding at 600 °C, but has no obvious friction reduction effect sliding at room temperature. The coating possesses superior wear resistance than TA15 alloy, evidenced by its much lower mass losses than those of TA15 alloy sliding at both room temperature and 600 °C. The TA15 alloy and the coating showed different wear mechanisms under the given sliding conditions.

In an attempt to find single-source precursors, a series of small clusters of inorganic azides of indium (Br2InN3) n (n = 1–6) were studied using the dispersion correction density functional theory (wB97XD). The obtained (Br2InN3) n (n = 2–6) clusters have the core structures of 2n-membered ring with alternating indium and α-nitrogen atoms. The influences of cluster size (oligomerization degree n) on the structures, energies, IR spectra, and thermodynamic properties of clusters were discussed. The computed binding energies indicate the stability: 3A > 3B, 4B > 4C > 4A > 4D, 5E > 5D > 5B = 5C > 5A and 6I > 6C > 6D > 6G ≥ 6H > 6F > 6E > 6B > 6A. It is also found that (Br2InN3)2 and (Br2InN3)4 clusters possess higher stability than their neighbor sizes judged by the calculated second-order difference of energies (Δ2 E). Meanwhile, thermodynamic properties for (Br2InN3) n (n = 1–6) clusters increase with the increasing temperature and oligomerization degree n, and the oligomerizations are thermodynamically favorable at temperatures up to 800 K.

The wave method is introduced to vibration analysis of the fluid-conveying carbon nanotube. The constitutive relation of carbon nanotube on micro-scale is founded using the nonlocal elastic theory. The governing equation on micro-scale is obtained. And the first five orders of the natural frequency of the carbon nanotube conveying fluid with various speeds are calculated through the wave method. Besides, the critical flow velocity when the carbon nanotube loses stability is obtained. Meanwhile, a contrast is made between the result obtained through the wave method and that in previous researches.

Four unusual meroterpenoids, dysivillosins A–D (1–4), were isolated from an organic extract of the marine sponge Dysidea villosa collected from the South China Sea. Their planar structures were determined by 1D and 2D NMR and HRESIMS techniques, while the relative and absolute configurations were elucidated by NOESY experiments and comparison between the calculated and experimental ECD spectra. To the best of our knowledge, dysivillosins A–D are the first examples of terpene-polyketide-pyridine hybrid metabolites from the nature. Anti-allergic activity evaluation showed that compounds 1–4 potently inhibited the release of β-hexosaminidase, a marker of degranulation, in a dose-dependent manner with IC50 values of 8.2–19.9 μM. Additionally, the four meroterpenoids could downregulate the production of lipid mediator leukotrienes B4 (LTB4) and pro-inflammatory cytokine interleukin-4 (IL-4) in the antigen-stimulated RBL-2H3 mast cells. Further biological investigations revealed that dysivillosin A (1) could suppress the phosphorylation of Syk and PLCγ1 in IgE/FcɛRI/Syk signaling pathway, which resulted in the inhibition of degranulation and the downregulation of LTB4 and IL-4 production in mast cells.

Theoretical study about the magnetic properties of conjugated organic molecules containing borepin with π current density was carried out. 1-(2,4,6-Trimethylphenyl)borepin moiety is the center and other different groups are situated on the both β sides, which are named molecules 1–12 as theoretical model in order to establish the relationship between aromaticity and geometry variation of borepin. The optimized molecular structures of molecules 1–12 are almost keeping planar and the C2–C3 bond length of borepin turns longer from molecule 1 to molecule 12. Different borepin-annulated ring could change the conjugated effect of π-electron between borepin and these bore-pin-annulated rings. Moreover, the molecule presents antiaromaticity, in other words, the molecule became unstable when the C2–C3 bond length of borepin extended more than ca. 0.1417 nm. But the β position fragment and substituent groups of borepin are not affected in this case, they are still steady. However, the central borepin ring current is counteracted by symmetrical overlap of it with affiliated borepin-annulated ring current. Hence, the central borepin ring breaking would be liable to occur. These molecules have higher vertical ionization potentials(VIPs) and lower vertical electron affinities(VEAs), which suggests that these molecules could easily exist in anionic form.

Recent investigations have shown that ferrate(VI) salts oxidize organic compounds in aqueous phases with fast reaction from seconds to minutes and poor selectivity. Few studies have used ferrate(VI) in organic phases. The main issues are the poor solubility of K2FeO4 in common organic solvents and the low reaction rate. Therefore the interests to date are focused on finding a more effective catalyst in the organic oxidation. Up to now no work has been reported on acids as catalysis for the oxidative abilities of K2FeO4 in organic phases. Here we present a novel procedure for oxidizing benzyl alcohol to benzaldehyde without an overoxidation to benzoic acid by K2FeO4 in an organic phase. Using benzyl alcohol as a model, the catalytic activity of various acid solutions was measured. We found that the reactivity of K2FeO4 to the oxidation of benzyl alcohol can be highly enhanced by addition of a small amount of acid solution at room temperature. The catalytic ability of acid solutions follows the order acetic acid < oxalic acid < phosphomolybdic acid < phosphotungstic acid. On the basis of a theoretical analysis, a reaction mechanism is proposed. This method provides a new green way for oxidizing organic substances by K2FeO4 in nonaqueous media.

The red phosphorescent osmium(II) complexes [Os(LR)2(PH3)2] (L = 2-pyridyltriazole (ptz): R = H (1a), CF3 (1b), t-Bu (1c)); L = 2-pyridylpyrazole (ppz): R = H (2a), CF3 (2b), t-Bu (2c)); L = 2-phenylpyridine (ppy): R = H (3a)) were explored using density functional theory (DFT) methods. The ground- and excited-state geometries of the complexes were optimized at the B3LYP/LANL2DZ and UB3LYP/LANL2DZ levels, respectively. The absorption and phosphorescence of the complexes in CH2Cl2 media were calculated based on the optimized ground- and excited-state geometries using time-dependent density functional theory method with the polarized continuum model. The optimized geometry structural parameters of the complexes in the ground state agree well with the corresponding experimental values. The lower-lying unoccupied molecular orbitals of the complexes are dominantly localized on the L ligand, while the higher-lying occupied ones are composed of Os(II) atom and L ligand. The low-lying metal-to-ligand and intraligand charge transfer (MLCT/ILCT) transitions and high-lying ILCT transitions are red-shifted with the increase in the π-donating ability of the L ligand and the π electron-donating ability of R substituent. The calculation revealed that the phosphorescence originated from 3MLCT/3ILCT excited state. However, the complex 3a displayed different types of MLCT/ILCT excited state compared with that of 1a–2c, and the different types of transition were also found in the absorption. In addition, we found that the phosphorescence quantum efficiency of Os(II) complexes is related to the metal composition in the high-energy occupied molecular orbitals, it will be helpful to designing highly efficient phosphorescent materials.

Electronic structures and spectroscopic properties of self-assembled [Pt2M4(C≡CH)8] (M=Cu, Ag) clusters have been studied by the TD-DFT (time-dependent density functional theory) calculations with the polarizable continuum model (PCM). The ground- and excited-state structures were optimized by the DFT (density functional theory) methods. The calculated structures and spectroscopic properties are in agreement with the corresponding experimental results. The [Pt2Ag4(C≡CH)8] clusters have two stable ground state geometries (D 4 and D 4h symmetry). The calculated Pt-M distances suggest only very weak interactions. The Cu-Cu distances are larger than the van der Waals radii of two Cu atoms and the Ag-Ag distances are analogous with the sum of van der Waals radii of two Ag atoms. Upon excitation, the interaction of Pt⋯M, Ag⋯Ag is strengthened, while the Cu⋯Cu distances are shortened but they are still larger than the sum of van der Waals radii of two Cu atoms. The lowest-energy absorptions are at 450, 365 and 375 nm and the emissions are at 611, 431 and 435 nm for [Pt2Cu4(C≡CH)8], [Pt2Ag4(C≡CH)8] (A) and (B), respectively. The transitions are all perturbed by the Cu or Ag composition through the UV-Vis spectra region; therefore, there are not pure ILCT or MPtLCT characteristics (ILCT: intraligand charge transfer; MLCT: metal-to-ligand charge transfer) in absorptions of heteropolynuclear [Pt2M4(C≡CH)8] clusters. Since the emissions and the lowest-absorptions have different transition characteristics for each complex, the emissions should not come from the lowest-energy absorptions. Because the M⋯M interactions in the excited state of [Pt2Ag4(C≡CH)8] are augmented, the emissions of [Pt2Ag4(C≡CH)8] clusters bear prominent ILCT character, which is the reason why the emission wavelengths of [Pt2Ag4(C≡CH)8] have a small hypsochromic shift relative to the emission wavelength of homoleptic [Pt(C≡CH)4]2− precursor.

Osmotic coefficients and water activities for the Li2B4O7+LiCl+H2O system have been measured at T=273.15 K by the isopiestic method, using an improved apparatus. Two types of osmotic coefficients, φS and φE, were determined. φS is based on the stoichiometric molalities of the solute Li2B4O7(aq), and φE is based on equilibrium molalities from consideration of the equilibrium speciation into H3BO3,B(OH)4− and B3O3(OH)4−. The stoichiometric equilibrium constants Km for the aqueous speciation reactions were estimated. Two types of representations of the osmotic coefficients for the Li2B4O7+LiCl+H2O system are presented with ion-interaction models based on Pitzer’s equations with minor modifications: model (I) represents the φS data with six parameters based on considering the ion-interactions between three ionic species of Li+, Cl−, and B4O72−, and model (II) for represents the φE data based on considering the equilibrium speciation. The parameters of models (I) and (II) are presented. The standard deviations for the two models are 0.0152 and 0.0298, respectively. Model (I) was more satisfactory than model (II) for representing the isopiestic data.