N-acetylcysteine alleviated tris(2-chloroisopropyl) phosphate-induced sperm motility decline and functional dysfunction in mice through reversing oxidative stress and DNA damage.

The decline in male fertility caused by environmental pollutants has attracted worldwide attention nowadays. Tris(2-chloroisopropyl) phosphate (TCPP) is a chlorine-containing organophosphorus flame retardant applied in many consumer products and has multiple side effects on health. However, whether TCPP impairs spermatogenesis remains unclear. In this study, we found that TCPP reduced the sperm motility and blastocyst formation, inhibited proliferation and induced apoptosis in mice testes and spermatocyte cell line GC-2. Moreover, TCPP induced imbalance of oxidant and anti-oxidant, DNA damage and mitochondrial dysfunction, thus induced abnormal spermatogenesis. In this process, p53 signaling pathway was activated and N-acetylcysteine treatment partially alleviated the side effects of TCPP, including decrease of sperm motility, activation of p53 signaling pathway and DNA damage. Finally, our study verified that TCPP elevated reactive oxygen species (ROS), decreased mitochondrial membrane potential and induced apoptosis in human semen samples. Overall, ROS mediated TCPP-induced germ cell proliferation inhibition and apoptosis, which finally led to the decline of sperm motility.

Identification of chalcone isomerase in the basal land plants reveals an ancient evolution of enzymatic cyclization activity for synthesis of flavonoids.

Flavonoids ubiquitously distribute to the terrestrial plants and chalcone isomerase (CHI)-catalyzed intramolecular and stereospecific cyclization of chalcones is a committed step in the production of flavonoids. However, so far the bona fide CHIs are found only in vascular plants, and their origin and evolution remains elusive. We conducted transcriptomic and/or genomic sequence search, subsequent phylogenetic analysis, and detailed biochemical and genetic characterization to explore the potential existence of CHI proteins in the basal bryophyte liverwort species and the lycophyte Selaginella moellendorffii. We found that both liverwort and Selaginella species possess canonical CHI-fold proteins that cluster with their corresponding higher plant counterparts. Among them, some members exhibited bona fide CHI activity, which catalyze stereospecific cyclization of both 6'-hydroxychalcone and 6'-deoxychalcone, yielding corresponding 5-hydroxy and 5-deoxyflavanones, resembling the typical type II CHIs currently known to be 'specific' for legume plants. Expressing those primitive bona fide CHIs in the Arabidopsis chi mutant restores the seed coat transparent testa phenotype and the accumulation of flavonoids. These findings, in contrast to our current understanding of the evolution of enzymatic CHIs, suggest that emergence of the bona fide type II CHIs is an ancient evolution event that occurred before the divergence of liverwort lineages.

[Analysis of Clinical Medication Laws for 451 Patients with HIV Infection in a Real World].

Objective To analyze clinical features and medication laws of patients with human immunodeficiency virus (HIV) infection. Methods Real world data based on Hospital Information System (HIS) were collected from 17 grade 3 hospitals across China from Jan.2006 to Dec.2011. Data of case his- tory in HIV infectors included their general information, features of AIDS, medications of Western drugs and Chinese herbs during hospitalization. Results Data of 451 patients with HIV infection were collected. A total of 261 patients had clear age record. Their age ranged between 18 and 65 [ accounting for 90. 4% (236/ 261 ) ], with an average age of 36. The ratio of male to female was 2. 8:1. They were hospitalized first at De- partment of Lemology (66. 96%), followed by Department of Respiration (8. 2%). They were admitted to hospital first at clinics (79. 6%), and accepted from Emergency Department (20. 18%). Most of them were admitted to hospital due to infectious diseases. Of them, tuberculosis occupied the top (8.29%), followed by bacterial pneumonia (6. 44%). Totally 349 patients had complete medication record. A total of 399 kinds of Western drugs and 80 kinds of Chinese patent medicines were used. The frequency of using antimicrobial drugs was the top (11. 86%), and Compound Sulfamethoxazole was mostly used in 120 cases (2. 81%). Of 80 kinds of Chinese patent medicines, heat clearing and detoxifying herbs were most often used (19. 27%), followed by antipyretics (10. 30%), tonics (8. 97%), and expectorant (7. 31%). Antimicrobial drugs combined heat clearing and detoxifying herbs were the most often seen in clinics. The 451 HIV infec- tors had steady condition after treated by Western drugs and Chinese herbs. The improvement rate reached 51. 33%. Conclusion Antimicrobial drugs were most often used in HIV patients. Heat clearing and detoxif- ying herbs were most often used in HIV patients. Antimicrobial drugs combined heat clearing and detoxif- ying herbs were most often seen in clinics for HIV patients.

Functional characterization of a Plagiochasma appendiculatum flavone synthase I showing flavanone 2-hydroxylase activity.

FNS I is a 2-oxoglutarate dependent dioxygenase (2-ODD) found mainly in species of the Apiaceae family. Here, an FNS I cDNA sequence was isolated from the liverwort Plagiochasma appendiculatum (Aytoniaceae) and characterized. The recombinant protein exhibited high FNS I activity catalyzing the conversion of naringenin to apigenin and 2-hydroxynaringenin. The critical residue for flavanone-2-hydroxylation activity was Tyr240, as identified from homology modeling and site-directed mutagenesis. The recombinant protein also showed some flavonol synthase activity, as it can convert dihydrokaempferol to kaempferol. When the Leu311 residue was mutated to Phe, the enzyme's capacity to convert dihydrokaempferol to kaempferol was substantially increased. PaFNS I represents a 2-ODD in which a hydrophobic π-stacking interaction between the key residue and the naringenin A-ring determines 2-hydroxyflavanone formation.

The function and catalysis of 2-oxoglutarate-dependent oxygenases involved in plant flavonoid biosynthesis.

Flavonoids are secondary metabolites derived from phenylalanine and acetate metabolism. They fulfil a variety of functions in plants and have health benefits for humans. During the synthesis of the tricyclic flavonoid natural products in plants, oxidative modifications to the central C ring are catalyzed by four of FeII and 2-oxoglutarate dependent (2-ODD) oxygenases, namely flavone synthase I (FNS I), flavonol synthase (FLS), anthocyanidin synthase (ANS) and flavanone 3ß-hydroxylase (FHT). FNS I, FLS and ANS are involved in desaturation of C2-C3 of flavonoids and FHT in hydroxylation of C3. FNS I, which is restricted to the Apiaceae species and in rice, is predicted to have evolved from FHT by duplication. Due to their sequence similarity and substrate specificity, FLS and ANS, which interact with the α surface of the substrate, belong to a group of dioxygenases having a broad substrate specificity, while FNS I and FHT are more selective, and interact with the naringenin ß surface. Here, we summarize recent findings regarding the function of the four 2-ODD oxygenases and the relationship between their catalytic activity, their polypeptide sequence and their tertiary structure.

Photoreversible polymer-surfactant micelles using the molecular recognition of α-cyclodextrin.

Photoreversible micelles were achieved by a combination of commercially available components sodium alginate (Alg), tetradecyltrimethylammonium bromide (TTAB), α-cyclodextrin (α-CD), and 4-(phenylazo)benzoic acid (PBA). Under visible light irradiation, α-CD interacted more favorably with PBA than with alkyl chains of TTAB. Therefore, polymer-surfactant micelles were formed by the self-assembly of Alg and TTAB through electrostatic attraction. After UV irradiation, micelles were disrupted because PBA in the cis form lost its ability to complex with α-CD, and then the latter was interacted with TTAB to prevent the association of alkyl chains of TTAB. On alternating irradiation of this quaternary system with UV and visible light, this reversible micellization process can be recycled many times.

Soluble oligomers and fibrillar species of amyloid ß-peptide differentially affect cognitive functions and hippocampal inflammatory response.

Two major active species of ß-amyloid protein (Aß), fibrillar Aß1-42 (FAß) and soluble Aß1-42 oligomers (AßO), are known to play important roles in the pathogenesis of Alzheimer's disease. However, the differences between them are largely unknown. In this study, we explored the effects of FAß and AßO on cognitive functions and hippocampal inflammatory response through a 30-days infusion of FAß or AßO (144pmol/d) into the left lateral ventricles of the rat brain. Morris water maze showed that the impairment of learning and memory functions was much more significant in the AßO-infused rats, compared to the FAß-infused rats. AßO-induced neurodegeneration and ultrastructure damage in CA1 neurons were more remarkable than those induced by FAß. Compared to FAß, AßO exerted more potent effects on the expressions of inflammatory factors toll-like receptor 4 and TNF-α and activation of NF-κB signaling. Taken together, our results from in vivo model demonstrate that AßO is more neurotoxic than FAß, and this neurotoxicity may be related to NF-κB-medicated inflammatory response.

pH-induced shape-memory polymers.

A novel pH sensitive shape-memory polymer (SMP) is prepared by cross-linking the ß-cyclodextrin modified alginate (ß-CD-Alg) and diethylenetriamine modified alginate (DETA-Alg): The pH reversible ß-CD-DETA inclusion complexes serve as a reversible phase, and the cross-linked alginate chains serve as a fixing phase. It is shown that this material can be processed into temporary shape as we needs at pH 11.5 and recover to its initial shape at pH 7. The recovery ratio and the fixity ratio were 95.7 ± 0.9% and 94.8 ± 1.1%, respectively. Furthermore, this material showed good degradability and biocompatibility. Because the shape transition pH value is quite close to that of our body fluid and this pH triggered shape-memory effect is convenient and safe to use, this material has a high potential for medical application.

Self-assembly of rod-coil polyethylenimine-poly(ethylene glycol)-α-cyclodextrin inclusion complexes into hollow spheres and rod-like particles.

This paper describes the self-assembly of rod-coil inclusion complexes, polyethylenimine-poly(ethylene glycol)-α-cyclodextrin (PEI-PEG-α-CD). It is demonstrated that α-CDs should exclusively thread on the PEG block in PEI-PEG copolymers and the resulting complexes have both rigid block (PEG-α-CD) and coil block (protonated PEI). By varying the rigid block fraction, aggregates with hollow spheres or rod-like particles could be formed simply by self-assembly in aqueous solution.