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BackgroundTransmission-blocking vaccines (TBVs) have been considered an important strategy for disrupting the malaria transmission cycle, especially for Plasmodium vivax malaria, which undergoes gametocytogenesis earlier during infection. Pvs25 and Pvs28 are transmission-blocking vaccine candidates for P. vivax malaria. Assessment of genetic diversity of the vaccine candidates will provide necessary information for predicting the performance of vaccines, which will guide us during the development of malaria vaccines.ResultsWe sequenced the coding regions of pvs25 and pvs28 from 30 P. vivax isolates from Yunnan Province, identifying five amino acid haplotypes of Pvs25 and seven amino acid haplotypes of Pvs28. Among a total of four mutant residues, the predominant haplotype of Pvs25 only had the I130T substitution. For Pvs28, a total of eight amino acid substitutions were identified. The predominant haplotype of Pvs28 had two substitution at positions 52 (M52L) and 140 (T140S) with 5-6 GSGGE/D tandem repeats at the end of fourth EGF-like domain. Most amino acid substitutions were common with previous reports from South Asian isolates. Although the nucleotide diversity of pvs28 (π = 0.0034 ± 0.0012) was significantly higher than pvs25 (π = 0.0013 ± 0.0009), it was still conserved when compared with the blood stage vaccine candidates.ConclusionsGenetic analysis revealed limited genetic diversity of pvs25 and pvs28, suggesting antigenic diversity may not be a particular problem for Sal I based TBVs in most P. vivax-endemic areas of China.

4FGL J0935.3+0901 is a γ-ray source detected by the Large Area Telescope (LAT) onboard the Fermi Gamma-Ray Space Telescope. We have conducted detailed analysis of the LAT data for this source and multi-wavelength studies of the source field. Its γ-ray emission can be described with a power law (Γ = 2.0 ± 0.2) with an exponential cutoff (E c = 2.9 ± 1.6 GeV), while the flux shows significant long-term variations. From analysis of archival Neil Gehrels Swift X-ray Telescope data, we find only one Xray source in the LAT's 2σ error region. Within a 3. ′′ 7 radius error circle of the X-ray source, there is only one optical object down to r ′ ∼23 mag. Time-resolved photometry of the optical object indicates a likely 2.5 hr periodic modulation, while its spectrum shows double-peaked hydrogen and helium emission lines (similar to those seen in accretion discs in low-mass X-ray binaries). Combining these results, we conclude that we have discovered a compact X-ray emitting binary in likely association with 4FGL J0935.3+0901, i.e., a millisecond pulsar (MSP) binary. We discuss the implication of the optical spectral features: this binary could be a transitional MSP system at a subluminous disc state, although the other possibility, the binary in a rotation-powered state showing the optical emission lines due to intrabinary interaction processes, can not be excluded. Further observational studies will help determine detailed properties of this candidate MSP binary and thus clarify its current state.

Background/Aims: This study aimed to investigate the effect of Nell-1 on the osteogenic behaviors of pre-osteoblasts on titanium (Ti) surfaces and to identify the underlying signaling pathway. Methods: Nell-1 at different concentrations was added to culture medium to stimulate MC3T3-E1 subclone 14 on Ti surfaces. A CCK-8 colorimetric assay was used to detect cell proliferation. Alkaline phosphatase activity (ALP) assay and enzyme-linked immunosorbent assay (ELISA) were used to evaluate ALP activity and the osteocalcin (OCN) secretion, respectively. Indicators of osteoblastic differentiation were assessed using real-time polymerase chain reaction analysis (RT-PCR). Western blot (WB) assay was used to analyze the expression changes of the osteogenic proteins and the mitogen-activated protein kinase (MAPK) pathway. Results: Nell-1 significantly increased the osteogenic gene and protein expression levels of ALP, OCN, Runx2, osteoprotegerin (OPG), collagen type I (Col-I), and Osterix (Osx) in pre-osteoblasts on Ti surfaces. The optimal concentration of Nell-1 was 100 ng/ ml. In addition, Nell-1 activated ERK and JNK, but not P38, in MC3T3-E1 cells on the Ti surface. Except for ALP and Col-I, the promotive effects of Nell-1 on the expression of osteogenic markers were suppressed by ERK inhibitor U0126. Conclusion: Certain concentrations of Nell-1 can promote the osteogenic differentiation of pre-osteoblasts on Ti surfaces by activating the MAPK/ERK signaling pathway.

Variability is a typical observation feature of Fermi blazars, which sometimes shows quasi-periodic oscillation (QPO). In this work, we obtain 5 day binned light curves (with a time coverage of ∼12.9 yr) for S5 1044+71, based on Fermi-LAT data; apply five different methods—Date-compensated Discrete Fourier Transform, Jurkevich, Lomb–Scargle Periodogram, a Fortran 90 program, and the Weighted Wavelet Z-transform—to the γ-ray light curve; and find a possible QPO of 3.06 ± 0.43 yr at the significance level of ∼3.6σ. A binary black hole model, including an accretion model and a dual-jet model, is used to explain this quasi-periodic variability. We also estimate the Doppler factors and the apparent velocity for the two jet components. We speculate that this γ-ray quasi-periodic modulation suggests the presence of a binary supermassive black hole in S5 1044+71.

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