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Single‐molecule localization microscopy (SMLM) based on temporal‐focusing multiphoton excitation (TFMPE) and single‐wavelength excitation is used to visualize the three‐dimensional (3D) distribution of spontaneously blinking fluorophore‐labeled subcellular structures in a thick specimen with a nanoscale‐level spatial resolution. To eliminate the photobleaching effect of unlocalized molecules in out‐of‐focus regions for improving the utilization rate of the photon budget in 3D SMLM imaging, SMLM with single‐wavelength TFMPE achieves wide‐field and axially confined two‐photon excitation (TPE) of spontaneously blinking fluorophores. TPE spectral measurement of blinking fluorophores is then conducted through TFMPE imaging at a tunable excitation wavelength, yielding the optimal TPE wavelength for increasing the number of detected photons from a single blinking event during SMLM. Subsequently, the TPE fluorescence of blinking fluorophores is recorded to obtain a two‐dimensional TFMPE‐SMLM image of the microtubules in cancer cells with a localization precision of 18±6 nm and an overall imaging resolution of approximately 51 nm, which is estimated based on the contribution of Nyquist resolution and localization precision. Combined with astigmatic imaging, the system is capable of 3D TFMPE‐SMLM imaging of brain tissue section of a 5XFAD transgenic mouse with the pathological features of Alzheimer's disease, revealing the distribution of neurotoxic amyloid‐beta peptide deposits. [ABSTRACT FROM AUTHOR]

In a recent research article published in Angewandte Chemie International Edition, Fan-Ching Chien et al. discuss a new technique called temporal-focusing multiphoton excitation for single-molecule localization microscopy. This method allows for wide-field and axially confined two-photon excitation of spontaneously blinking fluorophores, reducing photobleaching and increasing the utilization rate of the photon budget. The researchers applied this technique to study the three-dimensional morphology of fluorophore-labeled amyloid-beta fibril bundles in the brain tissues of a transgenic mouse with Alzheimer's disease. The findings have potential implications for understanding the pathology of Alzheimer's disease. [Extracted from the article]

In an article published in Angewandte Chemie, Fan-Ching Chien et al. discuss their research on single-molecule localization microscopy using temporal-focusing multiphoton excitation. This technique allows for wide-field and axially confined two-photon excitation of spontaneously blinking fluorophores, reducing photobleaching and increasing the utilization rate of the photon budget. The researchers applied this approach to study the three-dimensional morphology of fluorophore-labeled amyloid-beta fibril bundles in the brain tissues of a transgenic mouse with Alzheimer's disease. The findings have potential implications for understanding the pathology of Alzheimer's disease. [Extracted from the article]

Objectives: To explore the effects of acupoint application therapy (AAT) with TianGui Powder (TGP) on the expressions of the transforming growth factor β1 (TGF‐β1) and Smad‐2/3 signaling pathway in ovariectomized osteoporosis rats. Methods: Sixty rats were randomly divided into four groups: normal group (group A), model group (group B), TGP group (group C), and Western medicine group (group D). Group A had only the corresponding amount of adipose tissue around the ovary removed; rats in the other groups had bilateral ovariectomies. After 1 week, groups A and B were given 1 mL/100 mg normal saline solution by gavage, group C was treated with AAT with TGP on ShenQue acupoint (0.2 piece/rat, 6 h/time, 1 time/d) and group D was given calcium carbonate vitamin D3 (36 mg/kg/d) and alfacalcidol (0.05 μg/kg/d) tablet suspension. In this study, the bone mineral density (BMD) , the levels of BALP, TRAP‐5b, and BGP in serum and the changes in bone histomorphology was detected. For acquiring lumbar experimental data, the expression of TGF‐β1, Smad‐2/3 proteins and mRNA of TGF‐β1and Smad‐2/3 were assessed. After 12 weeks, the data were collected for analysis. Results: Compared with group A, the bone trabecula was thinner and significantly reduced in other groups. The result of BMD improved significantly in both groups C and D compared to group B after intervention (P < 0.05). In contrast, compared to group B, the levels of BALP, TRAP‐5b, and BGP significantly declined in both groups C and D. In group C, the results of protein expressions in TGF‐β1, Smad‐2/3 were 2.870 ± 0.270, 1.552 ± 0.111, and 1.420 ± 0.079, respectively. In groups C and D, those indications significantly declined compared to group B (P < 0.01). In group C, the level of mRNA expressions of TGF‐β1, Smad‐2/3 were 1.872 ± 0.177, 1.672 ± 0.086, and 1.790 ± 0.136, respectively. Compared with group B, those indications had significant difference in groups C and D (P < 0.05). Conclusion: Acupoint application therapy with TGP could significantly improve the BMD. The TGF‐β1 and Smad‐2/3 signaling pathway could be a therapeutic target of TGP in postmenopausal osteoporosis rats. [ABSTRACT FROM AUTHOR]

Clinical and experimental data have demonstrated that inflammation plays fundamental roles in the pathogenesis of ischemic stroke. Interleukin-16 (IL-16) is identified as a proinflammatory cytokine that is a key element in the ischemic cascade after cerebral ischemia. We aimed to examine the relationship between the IL-16 polymorphisms and the risk of ischemic stroke in a Chinese population. A total of 198 patients with ischemic stroke and 236 controls were genotyped using polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) and DNA sequencing method. We found that the rs11556218TG genotype and G allele of IL-16 were associated with significantly increased risks of ischemic stroke (TG versus TT, adjusted OR = 1.88; 95% CI, 1.15-3.07; G versus T, adjusted OR = 1.54; 95% CI, 1.05-2.27, resp.). However, there were no significant differences in the genotype and allele frequencies of IL-16 rs4778889 T/C and rs4072111 C/T polymorphisms between the two groups, even after stratification analyses by age, gender, and the presence or absence of hypertension, diabetes mellitus, hypercholesterolemia, and hypertriglyceridemia. These findings indicate that the IL-16 polymorphism may be related to the etiology of ischemic stroke in the Chinese population. [ABSTRACT FROM AUTHOR]

Cation-π interaction is comparable and as important as other main molecular interaction types, such as hydrogen bond, electrostatic interaction, van der Waals interaction, and hydrophobic interaction. Cation-π interactions frequently occur in protein structures, because six (Phe, Tyr, Trp, Arg, Lys, and His) of 20 natural amino acids and all metallic cations could be involved in cation-π interaction. Cation-π interactions arise from complex physicochemical nature and possess unique interaction behaviors, which cannot be modeled and evaluated by existing empirical equations and force field parameters that are widely used in the molecular dynamics. In this study, the authors present an empirical approach for cation-π interaction energy calculations in protein interactions. The accurate cation-π interaction energies of aromatic amino acids (Phe, Tyr, and Try) with protonated amino acids (Arg and Lys) and metallic cations (Li+, Na+, K+, and Ca2+) are calculated using B3LYP/6-311+G(d,p) method as the benchmark for the empirical formulization and parameterization. Then, the empirical equations are built and the parameters are optimized based on the benchmark calculations. The cation-π interactions are distance and orientation dependent. Correspondingly, the empirical equations of cation-π interactions are functions of two variables, the distance r and the orientation angle θ. Two types of empirical equations of cation-π interactions are proposed. One is a modified distance and orientation dependent Lennard-Jones equation. The second is a polynomial function of two variables r and θ. The amino acid-based empirical equations and parameters provide simple and useful tools for evaluations of cation-π interaction energies in protein interactions. © 2011 Wiley Periodicals, Inc. J Comput Chem , 2011 [ABSTRACT FROM AUTHOR]

Background: Adefovir dipivoxil has activity against wild-type and lamivudine-resistant hepatitis B virus (HBV) and is frequently used to manage HBV infection in transplant recipients. Calcineurin inhibitors are a central component of immunosuppressive therapy. Aims: Study GS-02-531 was an open-label, multicentre drug interaction trial to examine potential drug interactions between adefovir and tacrolimus in stable post-transplant recipients. Materials and Methods: Sixteen non-HBV-infected post-transplant recipients with median age 45.5 years (69% male, 44% Caucasian, 50% Hispanic and 6% Black) and stable hepatic and renal function on a stable daily dose of tacrolimus (2–10 mg total daily dose) were studied before (tacrolimus alone) and after co-administration of adefovir 10 mg daily for 14 days (Days 1–14). Pharmacokinetic (PK) analyses utilized non-compartmental methods. Results: The median elimination half-life of tacrolimus was 14.47 and 12.59 h for Day 0 and Day 14 respectively. The geometric mean ratios for tacrolimus on Day 14 vs Day 0 were 105.2% [90% confidence interval (90% CI): 89.8–123%] for Cmax and 106.4% (90% CI: 92.9–122%) for AUCtau. Both 90% CIs for the ratios were contained within the predefined lack of interaction bounds of 80 and 125% (i.e. within the bounds for the equivalence assessment), indicating that these PK parameters of tacrolimus are not significantly altered by co-administration of adefovir. Similarly, the observed adefovir PK parameters after 14 days of co-administration with tacrolimus were comparable to historical data in non-transplant patients receiving adefovir alone. Serum creatinine values were stable during the study period. Conclusion: There is no significant PK interaction between tacrolimus and adefovir co-administered to liver transplant recipients for 14 days. [ABSTRACT FROM AUTHOR]

Abstract: Green tea, owing to its beneficial effect on health, is becoming more and more popular worldwide. (−)-Epigallocatechin-3-gallate (EGCG), the main ingredient of green tea polyphenols, is a known protective effect on injured neurons in neurodegenerative disease, such as Alzheimer''s disease and Parkinson''s disease. Paraquat (PQ) is a widely used herbicide that possesses a similar structure to MPP+ and is toxic to mesencephalic dopaminergic neurons. In the present study, PQ-injured PC12 cells were chosen as an in vitro cell model of Parkinson''s disease and the neuroprotective effects of EGCG were investigated. The results showed that EGCG attenuated apoptosis of PC12 cells induced by PQ. The possible mechanism may be associated with maintaining mitochondrial membrane potential, inhibiting caspase-3 activity and downregulating the expression of pro-apoptotic protein Smac in cytosol. The present study supports the notion that EGCG could be used as a neuroprotective agent for treatment of neurodegenerative diseases. [Copyright &y& Elsevier]

Emtricitabine is a potent nucleoside reverse transcriptase inhibitor approved as a once-daily drug in combination with other antiretroviral agents for the treatment of HIV infection. Several phase I studies were conducted in healthy volunteers over the course of clinical development to evaluate whether pharmacokinetic drug-drug interactions exist between emtricitabine and other nucleoside antivirals that are extensively eliminated by renal excretion. Potential interactions with stavudine and famciclovir were evaluated in single-dose studies, whereas interactions with zidovudine and its major metabolite, zidovudine glucuronide, were evaluated in a multiple-dose study. Plasma pharmacokinetic profiles and, in some studies, urinary excretion data were evaluated when each drug was administered alone and in combination with emtricitabine. Safety and plasma pharmacokinetic profiles of each drug administered alone or with emtricitabine were consistent with historical data. Statistical analyses indicated that there were no significant interactions between emtricitabine and these 3 nucleoside antivirals. [ABSTRACT FROM AUTHOR]

Oxovanadium(V) complexes of N, N′-di­methyl­ethyl­enedi­amine­(salicyl­aldehyde) have been prepared and characterized. The structure of the title compound, [VO2(C11H15N2O)], reveals that the vanadium(V) centre is five-coordinate, with a distorted square-pyramidal environment. [ABSTRACT FROM AUTHOR]