Schematic illustration of HIV-1 gp41 and peptide fusion inhibitors.

<p>A. View of the gp41 functional regions. The residue numbers of each region correspond to their positions in gp160 of HIV-1_HXB2. FP, fusion peptide; NHR, N-terminal heptad repeat; CHR, C-terminal heptad repeat; TM, transmembrane domain. B. Sequence of CHR-derived anti-HIV-1 peptides. ABT is engineered with three amino acids different from C34 (marked in bold). The 13th residue serine (S) of C34 was changed to lysine (K) which allows a single modification by 3-maleimidopropionic acid (MPA).</p

Inhibition of ABT on HIV-1 entry and replication.

<p>A. Inhibition of HIV-1_NL4-3 Env-pseudotyped virus in single-cycle assay that demonstrates the virus-cell membrane fusion. B. Inhibition of wild-type HIV-1_NL4-3 replication. ABT shows significantly higher potency than T20 in inhibiting HIV-1_NL4-3 entry and replication. The data were derived from the results of three independent experiments and are expressed as means ± standard deviations.</p

Inhibition of ABT on subtype A, B and C HIV-1 strains^a.

a<p>The inhibitory activity of each peptide was determined in triplicate by a single-cycle infectivity assay. The data were derived from the results of three independent experiments and are expressed as means ± standard deviations.</p>b<p>Co-R: coreceptor use.</p

Biophysical characterization of ABT by CD spectroscopy.

<p>A. CD spectra of NHR and CHR-derived peptides and their complexes. B. Thermostability of the complex formed by N36 and ABT or C34. The unfolding temperature of each complex was scanned at 222 nm by CD spectroscopy, and their <i>Tm</i> values were calculated. The final concentration of each peptide in PBS is 1 µM.</p

Effect of human serum on the anti-HIV activity of ABT.

<p>The human sera were freshly isolated from a HIV-seronegative healthy volunteer. The peptide was mixed with various concentrations (5, 10, 20 and 50%) of human sera freshly isolated from a HIV-seronegative healthy volunteer and incubated for 2 h at 37°C. The mixture was then diluted with a DMEM-based complete medium supplemented with 10% FCS and subjected to the single-cycle infection assay. The percent inhibition by ABT was calculated as described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032599#s4" target="_blank">materials and method</a>. The data were derived from the results of three independent experiments and are expressed as means ± standard deviations.</p

Inhibition of ABT on CRF07_BC, CRF01_AE and B'HIV-1 variants^a.

a<p>The inhibitory activity of each peptide was determined in triplicate by a single-cycle infectivity assay. The data were derived from the results of at least three independent experiments and are expressed as means ± standard deviations.</p>b<p>HIV-1 subtypes: B/C, CRF07_BC; A/E, CRF01_AE; B′, Tai B.</p>c<p>Co-R: coreceptor use.</p

Inhibition of ABT on 6-HB formation and cell membrane fusion.

<p>A. ABT and C34 can efficiently inhibit 6-HB formation in a dose-dependent manner, but T20 has no such effect. B. Inhibition of HIV-1_HXB2 Env-mediated cell-cell membrane fusion by ABT, C34 and T20. The data were derived from the results of three independent experiments and are expressed as means ± standard deviations.</p

Inhibition of ABT on T20-resistant HIV-1 variants^a.

a<p>The data were derived from the results of three independent experiments and are expressed as means ± standard deviations.</p>b<p>HIV-1NL4-3-based pseudoviruses were constructed and used in the single-cycle infection assays except that L33S and I37V/V38T are infectious molecular clones of HIV-1NL4-3.</p>c<p>Both wild-type (WT) and D36G were used as reference viruses to calculate the resistance fold-changes.Shown in parentheses are based on the D36G as a reference.</p

Effectiveness of Teriparatide on Fracture Healing: A Systematic Review and Meta-Analysis

<div><p>Purpose</p><p>Nowadays, the efficacy of teriparatide in treating osteoporosis was widely accepted, but the discussion about using teriparatide to enhance fracture healing hasn’t come to an agreement. This meta-analysis was conducted to evaluate the effectiveness of teriparatide for fracture healing.</p><p>Methods</p><p>We searched PubMed, the Cochrane Library, and Embase in August 2016 for randomized controlled trials (RCTs) which concerned the treatment of teriparatide for fracture healing.</p><p>Results</p><p>Finally, a total of 380 patients were randomly assigned in the 5 trials included in this meta-analysis. There was a significant effectiveness with regards to function improvement in patients following fracture, however, there was no significant effectiveness with regards to time of radiographic fracture healing, fracture healing rate and reduction in pain.</p><p>Conclusions</p><p>This analysis showed that administration of teriparatide following fracture lacked the effectiveness for fracture healing. Moreover, teriparatide administration had no apparent adverse effects. These results should be interpreted with caution because of some clear limitations. If we want to confirm whether teriparatide improves fracture healing, more high-quality randomized controlled trials are needed.</p></div

Characteristics of included studies.

<p>Characteristics of included studies.</p