Construction of Co1-xZnxFe2xGa2-2xO4 (02 Reduction by H2O Vapour.

Solid solutions are garnering substantial attention in the realm of solar energy utilization due to their tunable electronic properties, encompassing band edge positions and charge-carrier mobilities. In this study, we designed and synthesized Co1-xZnxFe2xGa2-2xO4 (0

Sesquiterpenes from Artemisia annua and Their Cytotoxic Activities.

Artemisia annua is a well-known traditional Chinese medicine. Due to its highest antimalarial efficacy, China has a long history of cultivating A. annua, and it is used for "clearing heat and detoxicating". Several, studies have shown that the A. annua extract exerts cytotoxicity. In order to clarify the basis of the cytotoxic effect of A. annua, 18 sesquiterpenes were isolated from the herb, including 2 new sesquiterpenes and 16 known analogues. The structures of new compounds were elucidated by comprehensive spectroscopic analyses, including HR-ESI-MS, NMR experiments, single-crystal X-ray, and DP4+ and electronic circular dichroism (ECD) calculations. Cytotoxic activity screening revealed three compounds that exhibited cytotoxicity in a dose-dependent manner. Additional exploration showed that compound 5 significantly inhibited the proliferation of CT26 and HCT116 cells and induced apoptosis of HCT116 cells after 24 h. These chemical constituents contributed to elucidating the mechanism of action of the cytotoxic activity of A. annua.

Complexation of an Antimicrobial Peptide by Large-Sized Macrocycles for Decreasing Hemolysis and Improving Stability.

Traditional macrocyclic hosts have finite cavity sizes, generally 5-10 Å, which are commonly adaptive to recognize small guests rather than biological macromolecules. Here two water-soluble large-sized quaterphen[n]arenes (WQPns, n=3, 4) were designed and synthesized. These two hosts present significantly distinct recognition abilities. Specifically, they could strongly complex an antimicrobial peptide, pexiganan (PXG) with the association constants (Ka ) of (4.20±0.23)×104  M-1 for PXG/WQP3 and (2.46±0.44)×105  M-1 for PXG/WQP4. Complexation of PXG by WQP3 and WQP4 served to decrease the hemolysis of PXG in rabbit red blood cells in a statistically significant way. Furthermore, host-guest complexation was shown to substantially enhance metabolic stability of PXG in presence of proteinase K, rat plasma and liver or kidney homogenates.

Bio-Inspired Microreactors Continuously Synthesize Glucose Precursor from CO2 with an Energy Conversion Efficiency 3.3 Times of Rice.

Excessive CO2 and food shortage are two grand challenges of human society. Directly converting CO2 into food materials can simultaneously alleviate both, like what green crops do in nature. Nevertheless, natural photosynthesis has a limited energy efficiency due to low activity and specificity of key enzyme D-ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO). To enhance the efficiency, many prior studies focused on engineering the enzymes, but this study chooses to learn from the nature to design more efficient reactors. This work is original in mimicking the stacked structure of thylakoids in chloroplasts to immobilize RuBisCO in a microreactor using the layer-by-layer strategy, obtaining the continuous conversion of CO2 into glucose precursor at 1.9 nmol min-1 with enhanced activity (1.5 times), stability (≈8 times), and reusability (96% after 10 reuses) relative to the free RuBisCO. The microreactors are further scaled out from one to six in parallel and achieve the production at 15.8 nmol min-1 with an energy conversion efficiency of 3.3 times of rice, showing better performance of this artificial synthesis than NPS in terms of energy conversion efficiency. The exploration of the potential of mass production would benefit both food supply and carbon neutralization.

Metal to non-metal sites of metallic sulfides switching products from CO to CH4 for photocatalytic CO2 reduction.

The active center for the adsorption and activation of carbon dioxide plays a vital role in the conversion and product selectivity of photocatalytic CO2 reduction. Here, we find multiple metal sulfides CuInSnS4 octahedral nanocrystal with exposed (1 1 1) plane for the selectively photocatalytic CO2 reduction to methane. Still, the product is switched to carbon monoxide on the corresponding individual metal sulfides In2S3, SnS2, and Cu2S. Unlike the common metal or defects as active sites, the non-metal sulfur atom in CuInSnS4 is revealed to be the adsorption center for responding to the selectivity of CH4 products. The carbon atom of CO2 adsorbed on the electron-poor sulfur atom of CuInSnS4 is favorable for stabilizing the intermediates and thus promotes the conversion of CO2 to CH4. Both the activity and selectivity of CH4 products over the pristine CuInSnS4 nanocrystal can be further improved by the modification of with various co-catalysts to enhance the separation of the photogenerated charge carrier. This work provides a non-metal active site to determine the conversion and selectivity of photocatalytic CO2 reduction.

Structural insights into hydrolytic defluorination of difluoroacetate by microbial fluoroacetate dehalogenases.

Fluorine forms the strongest single bond to carbon with the highest bond dissociation energy among natural products. However, fluoroacetate dehalogenases (FADs) have been shown to hydrolyze this bond in fluoroacetate under mild reaction conditions. Furthermore, two recent studies demonstrated that the FAD RPA1163 from Rhodopseudomonas palustris can also accept bulkier substrates. In this study, we explored the substrate promiscuity of microbial FADs and their ability to defluorinate polyfluorinated organic acids. Enzymatic screening of eight purified dehalogenases with reported fluoroacetate defluorination activity revealed significant hydrolytic activity against difluoroacetate in three proteins. Product analysis using liquid chromatography-mass spectrometry identified glyoxylic acid as the final product of enzymatic DFA defluorination. The crystal structures of DAR3835 from Dechloromonas aromatica and NOS0089 from Nostoc sp. were determined in the apo-state along with the DAR3835 H274N glycolyl intermediate. Structure-based site-directed mutagenesis of DAR3835 demonstrated a key role for the catalytic triad and other active site residues in the defluorination of both fluoroacetate and difluoroacetate. Computational analysis of the dimer structures of DAR3835, NOS0089, and RPA1163 indicated the presence of one substrate access tunnel in each protomer. Moreover, protein-ligand docking simulations suggested similar catalytic mechanisms for the defluorination of both fluoroacetate and difluoroacetate, with difluoroacetate being defluorinated via two consecutive defluorination reactions producing glyoxylate as the final product. Thus, our findings provide molecular insights into substrate promiscuity and catalytic mechanism of FADs, which are promising biocatalysts for applications in synthetic chemistry and bioremediation of fluorochemicals.

Synergistic enhancement of the emergency treatment effect of organophosphate poisoning by a supramolecular strategy.

Poisoning by organophosphorus agents (OPs) is a serious public health issue across the world. These compounds irreversibly inhibit acetylcholinesterase (AChE), resulting in the accumulation of acetylcholine (ACh) and overstimulation of ACh receptors. A supramolecular detoxification system (SDS) has been designed with a view to deliver pyridine-2-aldoxime methochloride (PAM) with a synergistic inhibition effect on the ACh-induced hyperstimulation through host-guest encapsulation. NMR and fluorescence titration served to confirm the complexation between carboxylatopillar[6]arene (CP6A) and PAM as well as ACh with robust affinities. Patch-clamp studies proved that CP6A could exert an inhibition effect on the ACh-induced hyperstimulation of ACh receptors. Support for the feasibility of this strategy came from fluorescence imaging results. In vivo studies revealed that complexation by CP6A serves to increase the AChE reactivation efficiency of PAM. The formation of the PAM/CP6A complex contributed to enhance in a statistically significant way the ability of PAM not only to relieve symptoms of seizures but also to improve the survival ratio in paraoxon-poisoned model rats. These favorable findings are attributed to synergistic effects that PAM reactivates AChE to hydrolyze ACh and excess ACh is encapsulated in the cavity of CP6A to relieve cholinergic crisis symptoms.

Supramolecular combination chemotherapy: a pH-responsive co-encapsulation drug delivery system.

Most cancer chemotherapy regimens rely on the use of two or more chemotherapeutic agents. However, achieving the best possible dosing of the individual drugs can be challenging due to differences in metabolism, uptake, and clearance among other factors. Here we describe a supramolecular strategy for achieving drug delivery in which the loading ratio of two active components is easily defined. Specifically, we report the formation of aggregates comprised of self-assembled amphiphiles between carboxylatopillar[6]arene (CP6A) and an oxaliplatin (OX)-type Pt(iv) prodrug (PtC10). The association constant (K a) for the underlying host-guest interaction at pH 7.4 ((1.16 ± 0.03) × 104 M-1) is an order of magnitude higher than at pH 5.0 ((1.73 ± 0.15) × 103 M-1). A second chemotherapeutic, doxorubicin (DOX), may be encapsulated in the resulting vesicles (PtC10⊂CP6A) to give a supramolecular combination chemotherapeutic system DOX@PtC10⊂CP6A. Drug release studies served to confirm that PtC10 and DOX are released in acidic environments. Support for a synergistic antiproliferative effect relative to PtC10 + DOX came from cellular studies of DOX@PtC10⊂CP6A using the human liver hepatocellular carcinoma (HepG-2) cell line. In vivo studies revealed that DOX@PtC10⊂CP6A is not only able to retard tumor growth efficiently but also reduce drug-related toxic side effects in BALB/c nude mice bearing HepG-2 subcutaneous tumor xenografts. These favorable findings are attributed to the formation of a ternary complex that benefits from an enhanced permeability and retention (EPR) effect in vivo while allowing for the pH-based release of PtC10 and DOX at the tumor site.

Oligo(para-phenylenes)s-Oligoarginine Conjugates as Effective Antibacterial Agents with High Plasma Stability and Low Hemolysis.

Bacterial infections have become a global threat to human health, and the design of antibacterial agents is always an urgent task for biomedicine. Amphiphilic antibacterial agents with a different mechanism of action from traditional antibiotics have attracted researchers' attention more and more in recent years. In this work, a series of antibacterial conjugates composed of oligo(para-phenylenes)s and oligoarginine were synthesized, and their antibacterial activity was investigated. 2,2'-Biphenyl, 2,2″-terphenyl, and 2,2‴-quaterphenyl were conjugated with one or two triarginines by "click" chemical reactions to form compounds. The conjugates showed antibacterial activity against the typical Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria, relatively low cytotoxicity to L929 cell line, and hemolytic activity in a certain range of concentration. Among these conjugates, 2,2‴-quaterphenyl-triarginine conjugate (2,2‴-QP-1) showed the highest antibacterial activity against both E. coli and S. aureus. Besides, it presented better stability in plasma compared with the positive control peixiganan. The antimicrobial mechanism of 2,2‴-QP-1 was also investigated by transmission electron microscopy and confocal laser scanning microscopy, showing that 2,2‴-QP-1 could interact with the bacterial membrane and then disrupt the membrane structure. This work demonstrated a prospective approach for the design of antibacterial agents with highly effective antibacterial activity, high stability in plasma, and low cytotoxicity.

Perfusion characteristics of late radiation injury of parotid glands: quantitative evaluation with dynamic contrast-enhanced MRI.

We aimed to quantitatively investigate the alteration of parotid perfusion after irradiation using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) based on a two-compartment tracer kinetic model. This study enrolled 19 patients (53.2 +/- 14.9 years) treated by head and neck radiotherapy and 19 age-relevant and sex-matched subjects as a control group. Perfusion parameters (K ( el ), k (21) and A) of parotid glands were analyzed based on the Brix model from T1-weighted DCE-MRI. Suitability of the Brix model was evaluated via Monte Carlo simulation for the goodness-of-fit. Analysis of nonlinear goodness-of-fit showed that the Brix model is appropriate in evaluating the parotid perfusion (R(2) = 0.938 +/- 0.050). The irradiated parotid glands showed significantly lower K ( el ) (P < 0.0005) and k (21) (P < 0.05) and consequently significantly higher value of peak enhancement (P < 0.0005) and time-to-peak (P < 0.0005) compared with non-irradiated ones, suggestive of gradual and prolonged accumulation and delayed wash-out of contrast agent due to increased extracellular extravascular space and decreased vascular permeability in the irradiated glands. Linear regression analysis showed dose-dependent perfusion changes of the irradiated parotid glands. We conclude that quantitative DCE-MRI is a potential tool in investigating parotid gland perfusion changes after radiotherapy.

[Relations between alcoholism and osteoporosis or femoral head necrosis].

OBJECTIVE: To explore the relationship of alcoholism between osteoporosis or femoral head necrosis. METHODS: In this case-control study, we selected 95 eligible patients with femoral head necrosis and another 67 cases of osteoporosis as case group, together with 342 patients of fractures from the Second Hospital affiliated to Shanxi Medical College, from February to December 2010, as the control group. Questionnaire was used to collect general information of the patients. Through comparative analysis, related factors of femoral head, osteoporosis were defined. 18 patients with alcoholic femoral head necrosis, 11 patients with alcoholic osteoporosis and 20 patients with fractures were selected from the above said three groups and going through the Alcohol Use Disorders Identification Test (AUDIT) as well as the Alcohol Use Disorders Scale(ADS). Using SPSS 13.0 conducted one-way ANOVA(analysis of variance), chi-square test, categorical logistic regression analysis were used for statistical analysis. RESULTS: Results from logistic regression analysis showed that the adjusted odds ratio of those subjects who liked drinking alcohol had an incidence of femoral head necrosis or osteoporosis as 7.70 (95% CI:1.84, 32.30) and 8.44 (95% CI:1.70, 41.90), respectively. The risks of using hormone for treating femoral head necrosis or osteoporosis were 78.43 (95%CI:11.20, 149.05) and 22.75 (95%CI:2.59, 100.27) times than those without. Data from the AUDIT showed that:over-dose of alcohol drinking habit existed 100% in the femoral head necrosis group while 54.45% in the osteoporosis group, while 75 percent patients in the fractures group had normal alcohol drinking habit. Statistically significant differences appeared in the three groups (P < 0.01). RESULTS: from the ADS showed that there were statistically significant differences between the ADS scores of the three groups(F = 3.68, P = 0.03). CONCLUSION: Alcohol intake did seem to be highly correlated with the incidence rates of femoral head necrosis or osteoporosis. Alcohol-related necrosis could be viewed as alcohol-dependent diseases while alcohol-related and osteoporosis could partially be recognized as alcohol-dependent disease.