The role of electrostatic potential in the translocation of triangulene across membranes.

Triangulene and its derivatives show broad application prospects in the fields of biological imaging and biosensing. However, its interaction with cell membranes is still poorly studied. In this study, classical molecular dynamics simulations were used to adjust the electrostatic potential of triangulene to observe its interactions with cell membranes. We found that electrostatic potential not only affects the behavior as it enters the cell membrane, but also spatial distribution within the cell membrane. The angle distribution of inside-0 and all-0 triangulene when penetrating the membrane is more extensive than that of ESP triangulene. However, inside-0 triangulene could cross the midline of the cell membrane and prefers to stay in the upper leaflet, while all-0 triangulene and ESP triangulene can reach the lower leaflet. These findings can help us regulate the distribution of nanoparticles in cells, so as to design functional nanoparticles that conform to the requirements.

Lanosterol reduces the aggregation propensity of ultraviolet-damaged human γD-crystallins: a molecular dynamics study.

Ultraviolet (UV) radiation-induced oxidation of tryptophan (Trp) to kynurenine (KN) (TRP > KN) in human γD-crystallins (HγD-Crys) promotes the conversion of proteins into partially unfolded species that act as important precursors for sequential large-scale aggregation. Herein, we report that lanosterol shows protective activity to the structure of the TRP > KN mutant HγD-Crys, particularly its N-terminal domain (N-td), by using all-atom molecular dynamics simulations. The Trp68 > KN mutation significantly destabilizes the originally highly stable "Tyr55-Trp68-Tyr62" cluster, thereby causing loop2, where the mutation occurs, to become very flexible. The large fluctuation of loop2 induces cracks, which appear on the protein surface, resulting in the intrusion of water molecules into the hydrophobic core of the N-td. This event eventually triggers the unfolding of the N-td. However, lanosterol can suppress the large fluctuation of loop2 to protect the structural stability of the mutant N-td, thus reducing the aggregation propensity of the TRP > KN mutant HγD-Crys. This structure protective activity of lanosterol arises from its capability to preferentially bind to the hydrophobic regions near loop2. Thus, lanosterol acts as a "water blocker" to prevent the invasion of solvent molecules into the hydrophobic core. These findings provide some valuable insights into the development of potential lanosterol-based drugs for cataract prevention and treatment.

Low-Dose X-ray-Responsive Diselenide Nanocarriers for Effective Delivery of Anticancer Agents.

X-ray-responsive nanocarriers for anticancer drug delivery have shown great promise for enhancing the efficacy of chemoradiotherapy. A critical challenge remains for development of such radiation-controlled drug delivery systems (DDSs), which is to minimize the required X-ray dose for triggering the cargo release. Herein, we design and fabricate an effective DDS based on diselenide block copolymers (as nanocarrier), which can be triggered to release their cargo with a reduced radiation dose of 2 Gy due to their sensitivity to both X-ray and the high level of reactive oxygen species (ROS) in the microenvironment of cancer cells. The underlying molecular mechanism is further illustrated by proton nuclear magnetic resonance (1H NMR) experiments and density functional theory (DFT) calculations. In vivo experiments on tumor-bearing mice validated that the loaded drugs are effectively delivered to the tumor site and exert remarkable antitumor effects (minimum tumor volume/weight) along with X-ray. Furthermore, the diselenide nanocarriers exhibit no noticeable cytotoxicity. These findings provide new insights for the de novo design of radiation-controlled DDSs for cancer chemoradiotherapy.

Investigation of the Defect Structure of Congruent and Fe-Doped LiNbO3 Powders Synthesized by the Combustion Method.

Fe-doped LiNbO3 synthesized by the combustion method to seek new multiferroic materials exhibits room-temperature ferromagnetism, as reported in our previous work [1]. In this work, the defect structure of congruent and Fe-doped LiNbO3 (0.57-3.3 mol %) powders was investigated in detail by several methods. The molar ratio of [Li]/([Li]+[Nb]) was determined by the Curie temperature (Tc) via DSC. Two peaks of Tc were observed due to phase splitting [2], and the phase at lower Tc disappears as the Fe doping concentration increases. The coexistence of two different oxidation states of Fe ions in LiNbO3 was probed by XPS and UV-Vis spectroscopy. The Raman spectra exhibit displacements along the c axis of Li and Nb ions, and a deformation of the NbO6 framework owing to Fe doping. Several doping models were applied in the Rietveld refinement of powder X-ray diffraction collected by synchrotron radiation. The fitting by the Nb vacancy model leads to an improbably distorted structure of congruent LiNbO3. In Fe-doped LiNbO3, we conjecture that Li and Nb vacancies coexist in the lattice structure; Fe+2/Fe+3 ions are substituted for Li ions at the regular Li site and may push the anti-site NbLi ion back to the regular Nb site.

Improvement of awareness, treatment and control of hypertension among chronic kidney disease patients in China from 1999 to 2005.

Controlling hypertension is important to protect renal function and prevent cardiovascular disease in chronic kidney disease (CKD) patients. However, data on hypertension awareness, treatment and control among CKD patients are limited. Two nationwide surveys were conducted in China in 1999-2000 and 2004-2005 among, respectively, 1328 and 1244 adult, non-dialysis, hypertensive CKD patients, to assess the status of hypertension awareness, treatment and control and associated factors. A standard questionnaire was adopted, and blood pressure (BP) was measured by trained staff according to a standard protocol in both surveys. Compared with the data from 1999-2000, the data from 2004-2005 showed increased awareness (87.2 vs. 75.7%, P<0.001), treatment (85.9 vs. 80.4%, P=0.001) and control (30.0 vs. 21.1%, P<0.001, by the general threshold of BP<140/90 mm Hg; 7.7 vs. 5.9%, P=0.075, by an optimal threshold of BP<130/80 mm Hg) of hypertension. The odds ratios for general BP control were 1.4 (95% confidence index (CI), 1.1-1.7) for female gender, 1.1 (95% CI, 1.0-1.1) for high estimated glomerular filtration rate, 1.3 (95% CI, 1.1-1.6) for treatment in a local hospital, 2.8 (95% CI, 2.0-3.9) for hypertension awareness and 1.7 (95% CI, 1.4-1.9) for combined treatment. General physicians from local hospitals made greater contributions to the total improvement. Lack of treatment was mainly due to patients not recognizing the necessity for it. This is the first report of hypertension awareness, treatment and control among hypertensive CKD patients from a developing country. Improvement of awareness and general control of hypertension were demonstrated. Education of both physicians and patients regarding optimal BP control should be reinforced in the future.

[Influence of angiotensin-converting enzyme gene polymorphism on the anti-proteinuria efficacy of angiotensin-converting enzyme inhibitor in Han nationality of southern Sichuan province in China].

OBJECTIVE: To investigate the association between angiotensin-converting enzyme (ACE) gene polymorphism and the reducing urinary protein efficacy of angiotensin-converting enzyme inhibitor (ACEI) in patients with primary chronic glomerulonephritis in Han nationality of southern Sichuan province. METHODS: Ninety-nine primary glomerulonephritis patients with urinary protein were enrolled in this study. They were treated with benazepril for at least 3 months. The ACE gene insertion/deletion(I/D) polymorphisms in intron 16 were determined by PCR. A comparison of the reducing urinary protein efficacy of benazepril was made between the patients with different ACE genotypes. RESULTS: Urinary protein excretion was significantly higher in patients with ACE DD genotype than that in patients with II genotype. After benazepril treatment for 3 months, the rates of urinary protein decline were observed. The rates of reduction of proteinuria in patients with DD genotype and ID genotype were obviously higher than that in patients with II genotype(P<0.05). CONCLUSION: Benazepril could decline the rate of urinary protein excretion in patients with primary chronic glomerulonephritis, and significant relationship was observed between ACE gene polymorphism and the reducing urinary protein efficacy of ACEI.