No abstract

CD4þ CD25 þ regulatory T (Treg) cells engage in the maintenance of immunological self-tolerance and homeostasis by limiting aberrant or excessive inflammation. The transcription factor forkhead box P3 (FOXP3) is critical for the development and function of Treg cells. The differentiation of the Treg cell lineage is not terminal, as developmental and functional plasticity occur through the sensing of inflammatory signals in the periphery. Here, we review the recent progress in our understanding of the molecular mechanisms underlying the regulation and functional plasticity of CD4 þ CD25 þ FOXP3 þ Treg cells, through the perturbation of FOXP3 and its complex at a transcriptional, translational and post-translational level.

The High Energy X-ray telescope (HE) on-board the Hard X-ray Modulation Telescope (Insight-HXMT) can serve as a wide Field of View (FOV) gamma-ray monitor with high time resolution (μs) and large effective area (up to thousands cm2). We developed a pipeline to search for Gamma-Ray Bursts (GRBs), using the traditional signal-to-noise ratio (SNR) method for blind search and the coherent search method for targeted search. By taking into account the location and spectrum of the burst and the detector response, the targeted coherent search is more powerful to unveil weak and sub-threshold bursts, especially those in temporal coincidence with Gravitational Wave (GW) events. Based on the original method in literature, we further improved the coherent search to filter out false triggers caused by spikes in light curves, which are commonly seen in gamma-ray instruments (e.g. Fermi/GBM, POLAR). We show that our improved targeted coherent search method could eliminate almost all false triggers caused by spikes. Based on the first two years of Insight-HXMT/HE data, our targeted search recovered 40 GRBs, which were detected by either Swift/BAT or Fermi/GBM but too weak to be found in our blind search. With this coherent search pipeline, the GRB detection sensitivity of Insight-HXMT/HE is increased to about 1.5E-08 erg cm−2 (200 keV–3 MeV). We also used this targeted coherent method to search Insight-HXMT/HE data for electromagnetic (EM) counterparts of LIGO-Virgo GW events (including O2 and O3a runs). However, we did not find any significant burst associated with GW events.

XAF1 is a newly identified tumor-suppressor gene that can antagonize XIAP and sensitize cells to other cell death triggers. In this study, we utilized ZD55, a conditionally replicative adenovirus (CRAd) similar to ONYX-015 as the vector to transfer XAF1 into the tumor cells to evaluate its antitumor efficacy in vitro and in vivo. Potent and specific cytopathic effect (CPE) was observed upon infection with ZD55-XAF1 in tumor cell lines. Importantly, ZD55-XAF1 exhibited a superior suppression of tumor growth in an animal model of colorectal carcinoma in nude mice compared with Ad-XAF1 (E1-deleted replication-defective viral) and ONYX-015. Complete eradication of the established tumors was observed in four of eight mice. Our data also showed that infection with ZD55-XAF1 resulted in caspase-independent apoptosis. Although caspase-3, poly(ADP-ribose) polymerase were mildly activated in response to ZD55-XAF1 infection, pretreatment with pan-caspase inhibitor hardly influence its apoptosis-inducing activity. In summary, our study strongly suggested that ZD55-XAF1 could serve as an effective gene-virotherapy strategy and has highly potential against human cancers.

Al2O3-coated FeCo nanocapsules were synthesized by the arc-discharge method and three-dimensional wire-like macro-aggregates were self-assembled simultaneously by nanocapsules. The electromagnetic (EM) parameters (i.e. the relative permeability and permittivity) were measured at 2–18 GHz. As a consequence of the surface- and shape-anisotropy energy of the nanocapsules, a natural resonance at 6 GHz is dominant in the microwave absorption properties. A reflection loss (RL) exceeding −20 dB was obtained in the frequency range 4.2–18 GHz for absorber thicknesses of 1.3–6 mm. An optimal RL of −51 dB was found at 10.2 GHz for an absorber thickness of 2 mm. As a result, the Al2O3-coated FeCo nanocapsules show good prospects of being applied in EM wave absorptive devices.

Aberrant activation of the three-amino-acid-loop extension (TALE) homeobox gene MEIS1 shortens the latency and accelerates the onset and progression of acute leukemia, yet the molecular mechanism underlying persistent activation of the MEIS1 gene in leukemia remains poorly understood. Here we used a combined comparative genomics analysis and an in vivo transgenic zebrafish assay to identify 6 regulatory DNA elements that are able to direct GFP expression in a spatiotemporal manner during zebrafish embryonic hematopoiesis. Analysis of chromatin characteristics and regulatory signatures suggest that many of these predicted elements are potential enhancers in mammalian hematopoiesis. Strikingly, one of the enhancer elements (E9) is a frequent integration site in retroviral induced mouse acute leukemia. The genomic region corresponding to enhancer E9 is differentially marked by H3K4 mono-methylation and H3K27 acetylation, hallmarks of active enhancers, in multiple leukemia cell lines. Decreased enrichment of these histone marks is associated with downregulation of MEIS1 expression during hematopoietic differentiation. Furthermore, MEIS1/HOXA9 transactivate this enhancer via a conserved binding motif in vitro, and participate in an autoregulatory loop that modulates MEIS1 expression in vivo. Our results suggest that an intronic enhancer regulates the expression of MEIS1 in hematopoiesis and contributes to its aberrant expression in acute leukemia.

Background Minimal erythema dose (MED) has substantial inter‐ and intraindividual variations, reflecting the influence of very diverse factors. However, related studies showed little consistency probably because of their limited sample size. Objective To identify the factors associated with MED variations in a large‐scale population study. Methods The MED test was performed by following the international standard procedure on 22 146 subjects. The results were analysed in adjusted multivariable linear and logistic regression models. Results This large‐scale study revealed that lower MED was consistently associated with lighter skin [β‐coefficient = −0.33, 95% confidence interval ( CI ) −0.36 to 0.30, P = 6.41 × 10 −84 ]. Females had significantly higher MED than male (β = 0.91, 0.32–1.50, P = 2.93 × 10 −3 ). Stratified analyses showed that MED was not associated with age [female: odds ratio ( OR ) = 0.99, 0.98–1.01; male: OR = 0.99, 0.97–1.00]. MED was lower in summer than in other seasons (spring: OR = 1.08, 1.06–1.11; autumn: OR = 1.11, 1.08–1.13; winter: OR = 1.20, 1.18–1.22). Furthermore, MED was associated with air temperature (β = −0.36, −0.49 to 0.23, P = 4.81 × 10 −8 ) and air pressure (β = −0.64, −0.82 to 0.46, P = 8.01 × 10 −12 ) in summer only while not in other seasons. Conclusions This study provides unprecedented evidence that MED is associated with skin colour, sex, season and meteorological factors, but not with age.

RNA interference (RNAi) is a promising tool for cancer therapy, but its delivery strategy is a major challenge for its application. Oncolytic herpes simplex virus type 1 (HSV-1) is not only an effective antitumor drug but also an excellent vector. Herein, RNAi of oncogenes Bcl-2 and Survivin was combined with oncolytic HSV-1 (ICP34.5-/ICP6-/ICP47-/CMV-GM-CSF) and a new vector HSV010-BS was constructed. Transfected cell viability assays and animal experiments revealed that the dual silencing of Bcl-2 and Survivin improved the antitumor effect of oncolytic HSV-1 in vitro and in vivo, while the antitumor effect was correlated with the phosphorylation levels of PKR of the tumor cells. The higher the phosphorylation levels of PKR of the tumor cells, the weaker the replication ability of oncolytic HSV-1, and the more powerful HSV010-BS was than its control vectors in inhibiting the growth of the tumor cells. The results provided direct supportive proofs for a new potential cancer therapy strategy.