Search

We report on the Insight-HXMT observations of the new black hole X-ray binary MAXI J1820+070 during its 2018 outburst. Detailed spectral analysis via the continuum fitting method shows an evolution of the inferred spin during its high soft sate. Moreover, the hardness ratio, the non-thermal luminosity and the reflection fraction also undergo an evolution, exactly coincident to the period when the inferred spin transition takes place. The unphysical evolution of the spin is attributed to the evolution of the inner disc, which is caused by the collapse of a hot corona due to condensation mechanism or may be related to the deceleration of a jet-like corona. The studies of the inner disc radius and the relation between the disc luminosity and the inner disc radius suggest that, only at a particular epoch, did the inner edge of the disc reach the innermost stable circular orbit and the spin measurement is reliable. We then constrain the spin of MAXI J1820+070 to be a*=0.2^{+0.2}_{-0.3}. Such a slowly spinning black hole possessing a strong jet suggests that its jet activity is driven mainly by the accretion disc rather than by the black hole spin., Comment: 14 pages, 13 figures, 5 tables, accepted for publication in MNRAS

Fast radio bursts (FRBs) are short pulses observed in radio band from cosmological distances. One class of models invoke soft gamma-ray repeaters (SGRs), or magnetars, as the sources of FRBs. Some radio pulses have been observed from some magnetars, however, no FRB-like events had been detected in association any magnetar burst, including one giant flare. Recently, a pair of FRB-like bursts (FRB 200428 hereafter) separated by milliseconds (ms) were detected from the general direction of the Galactic magnetar SGR J1935+2154. Here we report the detection of a non-thermal X-ray burst in the 1-250 keV energy band with the Insight-HXMT satellite, which we identify as emitted from SGR J1935+2154. The burst showed two hard peaks with a separation of 34 ms, broadly consistent with that of the two bursts in FRB 200428. The delay time between the double radio and X-ray peaks is about 8.57 s, fully consistent with the dispersion delay of FRB 200428. We thus identify the non-thermal X-ray burst is associated with FRB 200428 whose high energy counterpart is the two hard peaks in X-ray. Our results suggest that the non-thermal X-ray burst and FRB 200428 share the same physical origin in an explosive event from SGR J1935+2154., 24 pages, 9 figures, 6 tables; initial submission to a journal on May 9th, 2020. Significant changes include updated localization and detailed spectral evolution of the X-ray burst, and better determination of the two narrow X-ray peaks corresponding to the two radio pulses. Conclusions are strengthened. Nature Astronomy online on Feb. 18, 2021

We present a detailed timing study of the brightest persistent X-ray source Sco X-1 using the data collected by the Hard X-ray Modulation Telescope ( I n s i g h t -HXMT) from July 2017 to August 2018. A complete Z-track hardness-intensity diagram (HID) is obtained. The normal branch oscillations (NBOs) at ∼ 6 Hz in the lower part of the normal branch (NB) and the flare branch oscillations (FBOs) at ∼ 16 Hz in the beginning part of the flaring branch (FB) are found in observations with the Low Energy X-ray Telescope (LE) and the Medium Energy X-ray Telescope (ME) of I n s i g h t -HXMT, while the horizontal branch oscillations (HBOs) at ∼ 40 Hz and the kilohertz quasi-periodic oscillations (kHz QPOs) at ∼ 800 Hz are found simultaneously above 20 keV for the first time on the horizontal branch (HB) by the High Energy X-ray Telescope (HE) and ME. We find that for all types of the observed QPOs, the centroid frequencies are independent of energy, while the root mean square (rms) increases with energy; the centroid frequencies of both the HBOs and kHz QPOs increase along the Z-track from the top to the bottom of the HB; and the NBOs show soft phase lags increasing with energy. A continuous QPO transition from the FB to NB in ∼ 200 s are also detected. Our results indicate that the non-thermal emission is the origin of all types of QPOs, the innermost region of the accretion disk is non-thermal in nature, and the corona is nonhomogeneous geometrically.

The evidences for the influence of thermonuclear (type-I) X-ray bursts upon the surrounding environments in neutron star low-mass X-ray binaries (LMXB) were detected previously via spectral and timing analyses. Benefitting from a broad energy coverage of Insight-HXMT, we analyze one photospheric radius expansion (PRE) burst, and find an emission excess at soft X-rays. Our spectral analysis shows that, such an excess is not likely relevant to the disk reflection induced by the burst emission and can be attributed to an enhanced pre-burst/persistent emission. We find that the burst and enhanced persistent emissions sum up to exceed Eddington luminosity by ∼ 40 percentages. We speculate that the enhanced emission is from a region beyond the PRE radius, or through the Comptonization of the corona.

The High Energy X-ray telescope (HE) on-board the Hard X-ray Modulation Telescope (\textit{Insight}-HXMT) can serve as a wide Field of View (FOV) gamma-ray monitor with high time resolution ($\mu$s) and large effective area (up to thousands cm$^2$). 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. \textit{Fermi}/GBM, \textit{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 \textit{Insight}-HXMT/HE data, our targeted search recovered 40 GRBs, which were detected by either \textit{Swift}/BAT or \textit{Fermi}/GBM but too weak to be found in our blind search. With this coherent search pipeline, the GRB detection sensitivity of \textit{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 \textit{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., Comment: 12 pages, 14 figures, 5 tables; accepted for publication in MNRAS

We report the energy-resolved broadband timing analysis of the black hole X-ray transient MAXI J1631-479 during its 2019 outburst from February 11 to April 9, using data from the Insight-Hard X-ray Modulation Telescope (Insight-HXMT), which caught the source from its hard intermediate state to the soft state. Thanks to the large effective area of Insight-HXMT at high energies, we are able to present the energy dependence of fast variability up to ~100 keV. Type-C quasi-periodic oscillations (QPOs) with frequency varying between 4.9 Hz and 6.5 Hz are observed in the 1-100 keV energy band. While the QPO fractional rms increases with photon energy from 1 keV to ~10 keV and remains more or less constant from ~10 keV to ~100 keV, the rms of the flat-top noise first increases from 1 keV to ~8 keV then drops to less than 0.1% above ~30 keV. We suggest that the disappearance of the broadband variability above 30 keV could be caused by the non-thermal acceleration in the Comptonizing plasma. At the same time, the QPOs could be produced by the precession of either a small-scale jet or a hot inner flow model., To be published in The Astrophysical Journal

The accreting millisecond X-ray pulsar Swift J1756.9$-$2508 went into outburst in April 2018 and June 2019, 8.7 yr after the previous activity period. We investigated the temporal, timing and spectral properties of these two outbursts using data from NICER, XMM-Newton, NuSTAR, INTEGRAL, Swift and Insight-HXMT. The two outbursts exhibited similar broad-band spectra and X-ray pulse profiles. For the first time, we report the detection of the pulsed emission up to $\sim100$ keV observed by Insight-HXMT during the 2018 outburst. We also found the pulsation up to $\sim60$ keV observed by NICER and NuSTAR during the 2019 outburst. We performed a coherent timing analysis combining the data from two outbursts. The binary system is well described by a constant orbital period over a time span of $\sim12$ years. The time-averaged broad-band spectra are well fitted by an absorbed thermal Comptonization model in a slab geometry with the electron temperature $kT_{\rm e}=40$-50 keV, Thomson optical depth $\tau\sim 1.3$, blackbody seed photon temperature $kT_{\rm bb,seed}\sim $0.7-0.8 keV and hydrogen column density of $N_{\rm H}\sim 4.2\times10^{22}$ cm$^{-2}$. We searched the available data for type-I (thermonuclear) X-ray bursts, but found none, which is unsurprising given the estimated low peak accretion rate ($\approx0.05$ of the Eddington rate) and generally low expected burst rates for hydrogen-poor fuel. Based on the history of four outbursts to date, we estimate the long-term average accretion rate at roughly $5\times10^{-12}\ M_\odot\,{\rm yr}^{-1}$ for an assumed distance of 8 kpc. The expected mass transfer rate driven by gravitational radiation in the binary implies the source can be no closer than 4 kpc., Comment: Accepted for publication in A&A

In this paper, we presented a detailed timing analysis of a prominent outburst of 4U 0115+63 detected by \textit{Insight}-HXMT in 2017 August. The spin period of the neutron star was determined to be $3.61398\pm 0.00002$ s at MJD 57978. We measured the period variability and extract the orbital elements of the binary system. The angle of periastron evolved with a rate of $0.048\pm0.003$ $yr^{-1}$. The light curves are folded to sketch the pulse profiles in different energy ranges. A multi-peak structure in 1-10 keV is clearly illustrated. We introduced wavelet analysis into our data analysis procedures to study QPO signals and perform a detailed wavelet analysis in many different energy ranges. Through the wavelet spectra, we report the discovery of a QPO at the frequency $\sim 10$ mHz. In addition, the X-ray light curves showed multiple QPOs in the period of $\sim 16-32 $ s and $\sim 67- 200 $ s. We found that the $\sim100$ s QPO was significant in most of the observations and energies. There exist positive relations between X-ray luminosity and their Q-factors and S-factors, while the QPO periods have no correlation with X-ray luminosity. In wavelet phase maps, we found that the pulse phase of $\sim 67- 200 $ s QPO drifting frequently while the $\sim 16-32 $ s QPO scarcely drifting. The dissipation of oscillations from high energy to low energy was also observed. These features of QPOs in 4U 0115+63 provide new challenge to our understanding of their physical origins., 14 pages, 9 figures, and 6 tables. This work has been submitted to MNRAS after the referee's report

Based on Insight-HXMT data, we report on the pulse fraction evolution during the 2017–2018 outburst of the newly discovered first Galactic ultraluminous X-ray (ULX) source Swift J0243.6+6124. The pulse fractions of 19 observation pairs selected in the rising and fading phases with similar luminosity are investigated. The results show a general trend of the pulse fraction increasing with luminosity and energy at supercritical luminosity. However, the relative strength of the pulsation between each pair evolves strongly with luminosity. The pulse fraction in the rising phase is larger at luminosity below 7.71 × 1038 erg s−1, but smaller at above. A transition luminosity is found to be energy independent. Such a phenomenon is first confirmed by Insight-HXMT observations and we speculate that it may have relation with the radiation-pressure-dominated accretion disc.

We report on our analysis of the 2019 outburst of the X-ray accreting pulsar 4U 1901+03 observed with Insight-HXMT and NICER. Both spectra and pulse profiles evolve significantly in the decaying phase of the outburst. Dozens of flares are observed throughout the outburst. They are more frequent and brighter at the outburst peak. We find that the flares, which have a duration from tens to hundreds of seconds, are generally brighter than the persistent emission by a factor of $\sim$ 1.5. The pulse profile shape during the flares can be significantly different than that of the persistent emission. In particular, a phase shift is clearly observed in many cases. We interpret these findings as direct evidence of changes of the pulsed beam pattern, due to transitions between the sub- and super-critical accretion regimes on a short time scale. We also observe that at comparable luminosities the flares' pulse profiles are rather similar to those of the persistent emission. This indicates that the accretion on the polar cap of the neutron star is mainly determined by the luminosity, i.e., the mass accretion rate., 11 pages, 8 figures, accepted for publication in MNRAS

A link between magnetars and fast radio burst (FRB) sources has finally been established. In this context, one of the open issues is whether/which sources of extra galactic FRBs exhibit X/gamma-ray outbursts and whether it is correlated with radio activity. We aim to constrain possible X/gamma-ray burst activity from one of the nearest extragalactic FRB sources currently known over a broad energy range, by looking for bursts over a range of timescales and energies that are compatible with being powerful flares from extragalactic magnetars. We followed up the as-yet nearest extragalactic FRB source at a mere 149 Mpc distance, the periodic repeater FRB180916.J0158+65, during the active phase on February 4-7, 2020, with the Insight-Hard X-ray Modulation Telescope (HXMT). Taking advantage of the combination of broad band, large effective area, and several independent detectors available, we searched for bursts over a set of timescales from 1 ms to 1.024 s with a sensitive algorithm, that had previously been characterised and optimised. Moreover, through simulations we studied the sensitivity of our technique in the released energy-duration phase space for a set of synthetic flares and assuming different energy spectra. We constrain the possible occurrence of flares in the 1-100 keV energy band to E, 10 pages, 3 figures, accepted by A&A

We investigate the absorption and emission features in observations of GX 301-2 detected with Insight-HXMT/LE in 2017-2019. At different orbital phases, we found prominent Fe Kalpha, Kbeta and Ni Kalpha lines, as well as Compton shoulders and Fe K-shell absorption edges. These features are due to the X-ray reprocessing caused by the interaction between the radiation from the source and surrounding accretion material. According to the ratio of iron lines Kalpha and Kbeta, we infer the accretion material is in a low ionisation state. We find an orbital-dependent local absorption column density, which has a large value and strong variability around the periastron. We explain its variability as a result of inhomogeneities of the accretion environment and/or instabilities of accretion processes. In addition, the variable local column density is correlated with the equivalent width of the iron Kalpha lines throughout the orbit, which suggests that the accretion material near the neutron star is spherically distributed., Comment: 10 pages, 5 figures, 2 tables, accepted for publication in MNRAS

We report on analysis of observations of the bright transient X-ray pulsar \src obtained during its 2017-2018 giant outburst with Insight-HXMT, \emph{NuSTAR}, and \textit{Swift} observatories. We focus on the discovery of a sharp state transition of the timing and spectral properties of the source at super-Eddington accretion rates, which we associate with the transition of the accretion disk to a radiation pressure dominated (RPD) state, the first ever directly observed for magnetized neutron star. This transition occurs at slightly higher luminosity compared to already reported transition of the source from sub- to super-critical accretion regime associate with onset of an accretion column. We argue that this scenario can only be realized for comparatively weakly magnetized neutron star, not dissimilar to other ultra-luminous X-ray pulsars (ULPs), which accrete at similar rates. Further evidence for this conclusion is provided by the non-detection of the transition to the propeller state in quiescence which strongly implies compact magnetosphere and thus rules out magnetar-like fields., Submitted to MNRAS

We present a study of timing properties of the accreting pulsar 2S 1417-624 observed during its 2018 outburst, based on Swift/BAT, Fermi/GBM, Insight-HXMT and NICER observations. We report a dramatic change of the pulse profiles with luminosity. The morphology of the profile in the range 0.2-10.0keV switches from double to triple peaks at $\sim2.5$ $\rm \times 10^{37}{\it D}_{10}^2\ erg\ s^{-1}$ and from triple to quadruple peaks at $\sim7$ $\rm \times 10^{37}{\it D}_{10}^2\ erg\ s^{-1}$. The profile at high energies (25-100keV) shows significant evolutions as well. We explain this phenomenon according to existing theoretical models. We argue that the first change is related to the transition from the sub to the super-critical accretion regime, while the second to the transition of the accretion disc from the gas-dominated to the radiation pressure-dominated state. Considering the spin-up as well due to the accretion torque, this interpretation allows to estimate the magnetic field self-consistently at $\sim7\times 10^{12}$G., 7 pages, 4 figures, 1 tables, accepted for publication in MNRAS

BackgroundThe aim of the present study was to investigate relationships between the risk of chronic kidney disease (CKD) and obesity and weight changes in Asian patients with type 2 diabetes.

Upper tract urothelial cancer (UTUC) arises from the urothelial lining of the urinary tract. UTUC spreads in several different ways including direct invasion, lymphatic spread, and hematogeneous metastases. Regional lymph nodes are commonly the initial site of metastasis, followed by the liver, lung, and bone. Brain metastasis is uncommon in patients with urothelial carcinoma. Here, we report an uncommon case of kidney urothelial carcinoma with brain metastasis in a 55-year-old woman presenting with dysarthria with right side limb weakness. The patient recovered well after resection of the brain lesion without any sequelae after 1 year of follow-up.

The role of redox regulation in immune-mediated arthritis has been previously described. However, the relationship between innate immune cells, including innate lymphoid cells (ILCs) and phagocyte-derived ROS, in this process remains unclear. Here, we characterize ILCs and measure the IL-1 family cytokines along with other cytokines relevant to ILC functions and development in serum-induced arthritic joints in wild type and phagocytic NADPH oxidase (NOX2)-deficient Ncf1-/- mice. We found more severe serum-induced joint inflammation and increased NCR+ ILC3s in inflamed joints of Ncf1-/- mice. Furthermore, in vitro stimulation with IL-1β on Tbet+ ILC1s from joints facilitated their differentiation into ROR-γt+ ILC3s. Moreover, treatment with IL-1 antagonists effectively lowered the proportions of NCR+ ILC3s and IL-17A producing ILC3s in Ncf1-/- arthritic mice and ameliorated the joint inflammation. These results suggest that NOX2 is an essential regulator of ILC transdifferentiation and may mediate this process in a redox-dependent manner through IL-1β production in the inflammatory joint. Our findings shed important light on the role of ILCs in the initiation and progression in tissue inflammation and delineate a novel innate immune cell-mediated pathogenic mechanism through which redox regulation may determine the direction of immune responses in joints.

Chronic granulomatous disease (CGD) is a primary immunodeficiency disease caused by defects in the leukocyte NADP oxidase. We previously reported that sarcoplasmic/endoplasmic reticulum calcium pump (SERCA) inhibitors could be used to rescue mutant H338Y-gp91phox protein of a particular type of CGD with a CybbC1024T mutation, leading to endoplasmic reticulum (ER) retention of the mutant protein. In this study, we developed a novel mouse model with the CybbC1024T mutation on a Cybb knockout background and investigated the therapeutic effects of ER-targeted delivery of the SERCA inhibitor, curcumin, with poly(lactic-coglycolic acid) (PLGA) nanoparticles (NPs). We found that PLGA encapsulation improved the efficacy of curcumin as a SERCA inhibitor to induce ER calcium release. ER-targeting curcumin-loaded PLGA NPs reduced and delayed extracellular calcium entry and protected the cells from mitochondrial damage and apoptosis. In vivo studies showed that ER-targeting curcumin-loaded PLGA NPs treatment enhanced neutrophil gp91phox expression, ROS production and peritoneal bacterial clearance ability of the CybbC1024T transgenic Cybb−/− mice. Our findings indicate that ER-targeted delivery of curcumin not only rescues ER-retained H338Y-gp91phox protein, and hence leukocyte function, but also enhances the bioavailability and reduces cytotoxicity. Modulation of ER function by using organelle-targeted NPs may be a promising strategy to improve the therapeutic potential of curcumin as a treatment for CGD.

We present the analysis of the brightest flare that was recorded in the \emph{Insight}-HMXT data set, in a broad energy range (2$-$200 keV) from the microquasar GRS~1915+105 during an unusual low-luminosity state. This flare was detected by \emph{Insight}-HXMT among a series of flares during 2 June 2019 UTC 16:37:06 to 20:11:36, with a 2-200 keV luminosity of 3.4$-$7.27$\times10^{38}$ erg s$^{-1}$. Basing on the broad-band spectral analysis, we find that the flare spectrum shows different behaviors during bright and faint epochs. The spectrum of the flare can be fitted with a model dominated by a power-law component. Additional components show up in the bright epoch with a hard tail and in the faint epoch with an absorption line $\sim$ 6.78 keV. The reflection component of the latter is consistent with an inner disk radius $\sim$ 5 times larger than that of the former. These results on the giant flare during the "unusual" low-luminosity state of GRS~1915+105 may suggest that the source experiences a possible fast transition from a jet-dominated state to a wind-dominated state. We speculate that the evolving accretion disk and the large-scale magnetic field may play important roles in this peculiar huge flare.

Purpose To investigate the risk for psychiatric disorders in patients newly diagnosed with attention deficit hyperactive disorder (ADHD) from two longitudinal groups of children with and without ADHD. Study design In total, 1,745 children newly diagnosed with ADHD and 6,980 participants without ADHD were identified from Taiwan's National Health Insurance Research Database in 2005 and followed until 2010. Risks for psychiatric disorders in the ADHD and non-ADHD groups were compared. Results The ADHD group was 3.82 times more likely to develop psychiatric disorders than their counterparts. The ADHD group showed the highest risk for oppositional defiant disorder, followed by adult ADHD and autism spectrum disorder. Moreover, the time effects of psychiatric disorders in the ADHD group were significant. Patients with ADHD subtypes had a significant risk for psychiatric disorders compared to their counterparts. Conclusions A high risk for psychiatric disorders was revealed in this study among children with ADHD. Childhood ADHD, the duration after the ADHD diagnosis, and the ADHD subtype were associated with psychiatric disorders. Clinical relevance Various psychiatric disorders were observed in children after they had been newly diagnosed with ADHD, indicating a need for integrated care that includes medical practitioners, family members, social workers, and early intervention workers for patients newly diagnosed with ADHD to decrease the risk for comprehensive psychiatric disorders.

Western dietary patterns have been linked with kidney disease. This study investigated the association between Chinese dietary patterns and kidney disease in a Taiwanese population with type 2 diabetes and evaluated dietary fatty acid patterns, a kidney-related dietary biomarker.We recruited 838 patients with type 2 diabetes and used their dietary and renal data obtained from three repeated measures in 2008, 2009 and 2010. Diet was assessed using food-frequency questionnaires, and factor analysis was performed to identify dietary patterns. Albuminuria was defined by having an albumin-to-creatinine ratio=30 mg/g and kidney dysfunction by estimated glomerular filtration rate60 mL/min/1.73m2. Generalized estimating equation models were used to estimate ORs (95% CIs) of kidney disease adjusted for covariates. Erythrocyte fatty acids were only measured in blood samples collected in 2008.Three dietary patterns were identified: high fat-meat, traditional Chinese food-snack, and fish-vegetable. In the adjusted model, the high fat-meat and traditional Chinese food-snack diets were not associated with any kidney outcomes. The fishvegetable diet was inversely associated with kidney dysfunction (quartile 4 vs 1, OR: 0.75, 0.58-0.97), but not associated with albuminuria. A higher fish-vegetable diet factor score was associated with higher n-3 fatty acid levels.In patients with diabetes, we found greater adherence to a fish-vegetable diet to be associated with better kidney function and greater n-3 fatty acid profiles. The inclusion of repeated dietary assessments and dietary biomarker measurements in future diet-disease research, especially in patient populations, may provide more definitive risk evaluation.

We present the X-ray timing results of the new black hole candidate (BHC) MAXI J1535-571 during its 2017 outburst from Hard X-ray Modulation Telescope (\emph{Insight}-HXMT) observations taken from 2017 September 6 to 23. Following the definitions given by \citet{Belloni2010}, we find that the source exhibits state transitions from Low/Hard state (LHS) to Hard Intermediate state (HIMS) and eventually to Soft Intermediate state (SIMS). Quasi-periodic oscillations (QPOs) are found in the intermediate states, which suggest different types of QPOs. With the large effective area of \emph{Insight}-HXMT at high energies, we are able to present the energy dependence of the QPO amplitude and centroid frequency up to 100 keV which is rarely explored by previous satellites. We also find that the phase lag at the type-C QPOs centroid frequency is negative (soft lags) and strongly correlated with the centroid frequency. By assuming a geometrical origin of type-C QPOs, the source is consistent with being a high inclination system., Comment: 12 pages, 11 figures, Sumbitted to ApJ

How mass is accumulated from cloud-scale down to individual stars is a key open question in understanding high-mass star formation. Here, we present the mass accumulation process in a hub-filament cloud G22 which is composed of four supercritical filaments. Velocity gradients detected along three filaments indicate that they are collapsing with a total mass infall rate of about 440 $M_\odot$ Myr$^{-1}$, suggesting the hub mass would be doubled in six free-fall times, adding up to $ \sim2 $ Myr. A fraction of the masses in the central clumps C1 and C2 can be accounted for through large-scale filamentary collapse. Ubiquitous blue profiles in HCO$^+$ $ (3-2) $ and $^{13}$CO $ (3-2) $ spectra suggest a clump-scale collapse scenario in the most massive and densest clump C1. The estimated infall velocity and mass infall rate are 0.31 km s$^{-1}$ and $ 7.2 \times10^{-4} $ $M_\odot$ yr$^{-1}$, respectively. In clump C1, a hot molecular core (SMA1) is revealed by the SMA observations and an outflow-driving high-mass protostar is located at the center of SMA1. The mass of the protostar is estimated to be $ 11-15 $ $M_\odot$ and it is still growing with an accretion rate of $ 7\times10^{-5} $ $M_\odot$ yr$^{-1}$. The coexistent infall in filaments, clump C1, and the central hot core in G22 suggests that pre-assembled mass reservoirs (i.e., high-mass starless cores) may not be required to form high-mass stars. In the course of high-mass star formation, the central protostar, the core, and the clump can simultaneously grow in mass via core-fed/disk accretion, clump-fed accretion, and filamentary/cloud collapse., 17 pages, 16 figures 3 tables. and Accepted for publication in ApJ

Aims: To elucidate the role of reactive oxygen species (ROS) in arthritis and to identify targets of arthritis treatment in conditions with different levels of oxidant stress. Results: Through establishing an arthritis model by injecting arthritogenic serum into wild-type and NADPH oxidase 2 (NOX2)-deficient mice, we found that arthritis had a neutrophilic infiltrate and was more severe in Ncf1−/− mice, a mouse strain lacking the expression of the NCF1/p47phox component of NOX2. The levels of interleukin-1β (IL-1β) and IL-6 in inflamed joints were higher in Ncf1−/− than in controls. Antagonists of tumor necrosis factor-α (TNFα) and IL-1β were equally effective in suppressing arthritis in wild-type mice, while IL-1β blockade was more effective than TNFα blockade in Ncf1−/− mice. A treatment of caspase inhibitor and the combination treatment of a caspase inhibitor and a cathepsin inhibitor, but not a cathepsin inhibitor alone, suppressed arthritic severity in the wild-type mice, while a treatment of cathepsin inhibitor and the combination treatment of a caspase inhibitor and a cathepsin inhibitor, but not a caspase inhibitor alone, were effective in treating Ncf1−/− mice. Consistently, cathepsin B was found to proteolytically process pro-IL-1β to its active form and this activity was suppressed by ROS. Innovation: This novel mechanism of a redox-mediated immune regulation of arthritis through leukocyte-produced ROS is important for devising an optimal treatment for patients with different levels of tissue ROS. Conclusion: Our results suggest that ROS act as a negative feedback to constrain IL-1β-mediated inflammation, accounting for the more severe arthritis in the absence of NOX2. Antioxid. Redox Signal. 23, 973–984.

The bone is the most common metastatic site of breast cancer. Bone metastasis causes pain, pathologic frac- tures, and severely reduces the quality of life. Breast cancer causes osteolytic bone metastasis, which is dependent on osteo - clast-mediated bone resorption. While current treatments rely on palliative anti-resorptive agents, there is a need to develop a drug based on potential alternative therapies. This study is the first to determine that wedelolactone (WDL), a natural coumarin isolated from plants, can inhibit breast cancer- mediated osteoclastogenesis. Osteoclasts were generated from human CD14 + monocytes cultured with M-CSF/RANKL and WDL suppressed human osteoclast differentiation and activity in vitro in a dose-dependent manner. Moreover, WDL inhibited the upregulation of osteoclasts stimulated by MDA-MB-231 breast cancer cells. The activity of WDL on osteoclasts and breast cancer-mediated osteoclastogenesis was associated with the inhibition of Akt/mammalian target of the rapamycin signaling pathway (mTOR). Blocking Akt and mTOR by specific inhibitors significantly decreased osteoclast differenti - ation and bone resorption. Furthermore, WDL regulated breast cancer-enhanced interaction of osteoblasts and osteoclasts by decreasing M-CSF expression in MDA-MB-231-stimulated osteoblasts. Thus, this study suggests that WDL may be a poten - tial natural agent for preventing and treating bone destruction in patients with bone metastasis due to breast cancer.

Polyunsaturated fatty acids (PUFA) correlate with risk of dyslipidemia and cardiovascular diseases. Fatty acid desaturase (FADS) single nucleotide polymorphisms (SNPs) modulate circulating PUFA concentrations. This study examined influence of FADS1 and FADS2 genetic variants on desaturase activities and blood lipid concentrations in type 2 diabetes patients, and further assessed their interrelationships. Selected SNPs (FADS1: rs174547, rs174548, rs174550; FADS2: rs174575, rs174576, rs174583, rs498793 and rs2727270) were genotyped in 820 type 2 diabetes patients and compared with those reported in the HapMap. Patient subgroups (n = 176) without taking lipid-lowering medicine were studied to assess influence of tag SNPs including rs174547, rs174575, rs498793 and rs2727270 on delta-5 desaturase (D5D: 20:4 (n-6)/20:3 (n-6)) and delta-6 desaturase (D6D:18:3 (n-6)/18:2 (n-6)) activities, and blood lipids. FADS1 rs174547 TT/TC/CC and FADS2 rs2727270 CC/CT/TT were significantly (p for trend < 0.05) associated with reduced HDL-C, D5D and D6D activities. Upon adjustment for confounders, D5D (p = 0.006) correlated significantly and D6D marginally (p = 0.07) correlated with increased HDL-C levels, whereas rs174547 and rs2727270 polymorphisms were not associated. D6D andD5D activities may play a role in modulating HDL-C levels in type 2 diabetes. Future studies with larger sample sizes are needed to investigate how FADS genetic variations interact with desaturase activities or PUFAs in the metabolism of lipoproteins in diabetic patients.

Granulomatous inflammation causes severe tissue damage in mycobacterial infection while redox status was reported to be crucial in the granulomatous inflammation. Here, we used a NADPH oxidase 2 (NOX2)-deficient mice (Ncf1-/-) to investigate the role of leukocyte-produced reactive oxygen species (ROS) in mycobacterium-induced granulomatous inflammation. We found poorly controlled mycobacterial proliferation, significant body weight loss, and a high mortality rate after M. marinum infection in Ncf1-/- mice. Moreover, we noticed loose and neutrophilic granulomas and higher levels of interleukin (IL)-1β and neutrophil chemokines in Ncf1-/- mice when compared with those in wild type mice. The lack of ROS led to reduced production of IL-1β in macrophages, whereas neutrophil elastase (NE), an abundant product of neutrophils, may potentially exert increased inflammasome-independent protease activity and lead to higher IL-1β production. Moreover, we showed that the abundant NE and IL-1β were present in the caseous granulomatous inflammation of human TB infection. Importantly, blocking of IL-1β with either a specific antibody or a recombinant IL-1 receptor ameliorated the pulmonary inflammation. These findings revealed a novel role of ROS in the early pathogenesis of neutrophilic granulomatous inflammation and suggested a potential role of IL-1 blocking in the treatment of mycobacterial infection in the lung.

This study investigates the anticancer effect of arctigenin (ATG), a natural lignan product of Arctium lappa L., in human breast cancer MDA-MB-231 cells. Results indicate that ATG inhibits MDA-MB-231 cell growth by inducing apoptosis in vitro and in vivo. ATG triggers the mitochondrial caspase-independent pathways, as indicated by changes in Bax/Bcl-2 ratio, resulting in AIF and EndoG nuclear translocation. ATG increased cellular reactive oxygen species (ROS) production by increasing p22(phox)/NADPH oxidase 1 interaction and decreasing glutathione level. ATG clearly increases the activation of p38 MAPK, but not JNK and ERK1/2. Antioxidant EUK-8, a synthetic catalytic superoxide and hydrogen peroxide scavenger, significantly decreases ATG-mediated p38 activation and apoptosis. Blocking p38 with a specific inhibitor suppresses ATG-mediated Bcl-2 downregulation and apoptosis. Moreover, ATG activates ATF-2, a transcription factor activated by p38, and then upregulates histone H3K9 trimethylation in the Bcl-2 gene promoter region, resulting in Bcl-2 downregulation. Taken together, the results demonstrate that ATG induces apoptosis of MDA-MB-231 cells via the ROS/p38 MAPK pathway and epigenetic regulation of Bcl-2 by upregulation of histone H3K9 trimethylation.

The interaction between cancer cells and their microenvironment is a paradoxical cycle that exacerbates cancer progression and results in metastasis. Our study investigated the mechanism underlying the synergistic enhancement of release of soluble factors from tumor-associated dendritic cells and its effect on cancer development. The combination of HB-EGF (heparin-binding EGF-like growth factor) and CXCL5 (CXCL5/epithelial neutrophil-activating peptide-78) produced a strong synergistic effect on cancer proliferation, epithelial-mesenchymal transition, migration and invasion. CXCL5 not only potentiated the classical EGFR pathway and the AKT and ERK/RSK1/2 signaling pathways but also increased the phosphorylation of heat shock protein 27 (HSP27), which was slightly increased in A549 cells treated with either HB-EGF or CXCL5 only. Phosphorylated HSP27 stabilized sustained AKT activity by direct interaction, leading to enhanced tumor spheroid formation. Knockdown of HSP27 by shRNA decreased HB-EGF plus CXCL5-mediated tumor spheroid formation in a three-dimensional culture system, suggesting that AKT/HSP27 was required for HB-EGF/CXCL5-mediated cancer progression. Inhibiting RSK also reduces the modulation of c-Fos phosphorylation, Snail upregulation and cell migration by HB-EGF plus CXCL5, suggesting a synergistic effect of ERK/RSK and HB-EGF plus CXCL5 on cell migration. In mice, CXCL5 antibody synergistically enhances the efficiency of the tyrosine kinase inhibitor, gefitinib, without increasing its toxicity. These results provide evidence that elucidates potential cross-points between extracellular signals affecting lung cancer progression. Targeting CXCL5 may provide therapeutic benefits for lung cancer chemotherapy or immunotherapy.

The interaction between tumors and their microenvironments leads to a vicious cycle, which strengthens both immune suppression and cancer progression. The present study demonstrates for the first time that tumor-associated dendritic cells (TADCs) are a source of resistin, which is responsible for increasing lung cancer epithelial-to-mesenchymal transition. In addition, large amounts of resistin in the condition medium (CM) of TADCs increase cell migration and invasion, as well as the osteolytic bone metastatic properties of lung cancer cells. Neutralization of resistin from TADC-CM prevents the advanced malignancy-inducing features of TADC-CM. Significantly elevated levels of resistin have been observed in mice transplanted with lung cancer cells, tumor-infiltrating CD11c(+) DCs in human lung cancer samples and lung cancer patients' sera. Induction of lung cancer progression by TADC-derived resistin is associated with increased expression of Wolf-Hirschhorn syndrome candidate 1 (WHSC1), a histone methyltransferase. Resistin-induced WHSC1 increases the dimethylation of histone 3 at lysine 36 and decreases the trimethylation of histone 3 at lysine 27 on the promoter of Twist, resulting in an enhancement of the expression of Twist. Knockdown of WHSC1 by small interfering RNA transfection significantly decreases resistin-mediated cancer progression by decreasing the upregulation of Twist, suggesting that WHSC1 plays a critical role in the regulation of Twist by epigenetic modification. Furthermore, mice that received antiresistin antibodies showed a decreased incidence of cancer development and metastasis. These findings suggest that TADC-derived resistin may be a novel candidate in promoting the development of lung cancer.

KRAS mutations have been established as a major predictive biomarker for resistance to the treatment of metastatic colorectal cancer (mCRC) with anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR MoAbs). However, many patients with KRAS wild-type tumors still do not respond to the treatment. We conducted a systematic review with meta-analysis to assess whether BRAF mutations, PIK3CA mutations and PTEN loss can predict the outcomes of patients with KRAS wild-type mCRC treated with anti-EGFR MoAbs. Studies that explored the association of one or more of the three biomarkers with progression-free survival (PFS), overall survival (OS) and/or objective response rate (ORR) were identified through August 2012. Summary hazard ratios (HRs) and rate differences (RDs) and corresponding 95% confidence intervals (CIs) were calculated by using the random-effects model. BRAF mutations, PIK3CA exon 20 mutations and PTEN loss were all associated with shorter PFS (HR = 2.59, 95% CI 1.67–4.03; HR = 2.52, 95% CI 1.33–4.78 and HR = 1.75, 95% CI 1.19–2.56, respectively), shorter OS (HR = 2.74, 95% CI 1.79–4.19; HR = 3.29, 95% CI 1.60–6.75 and HR = 1.85, 95% CI 1.30–2.64, respectively) and lower ORR (RD = −36%, 95% CI −44 to −28%; RD = −38%, 95% CI −51 to −24% and RD = −41%, 95% CI −68 to −14%, respectively). PIK3CA exon 9 mutations were associated with none of the outcomes. Studies with relevant data consistently demonstrated a stronger predictive power of combined multiple biomarkers as compared to one alteration alone. These results suggest that BRAF mutations, PIK3CA exon 20 mutations and PTEN loss are predictive of better outcomes in KRAS wild-type mCRC treated with anti-EGFR MoAbs. However, the quality of included studies varied, and some of the meta-analyses were limited by significant between-study heterogeneity. In the future, well-designed large randomized controlled trials conducted in KRAS wild-type mCRC patients with subgroup analysis according to BRAF, PIK3CA exon 20 and PTEN status are essential to fully assess the clinical relevance of these biomarkers.

The emerging massive binary system associated with AFGL 961 signifies the latest generation of massive star and cluster formation in the Rosette Molecular Complex. We present the detection of a compact cluster of dusty cores toward the AFGL 961 region based on continuum imaging at 1.3 mm by the Submillimeter Array. The binary components of AFGL 961 are associated with the most intensive millimeter emission cores or envelopes, confirming that they are indeed in an early stage of evolution. The other massive cores, however, are found to congregate in the close vicinity of the central high-mass protostellar binary. They have no apparent infrared counterparts and are, in particular, well aligned transverse to the bipolar molecular outflows originating from AFGL 961. This provides evidence for a likely triggered origin of the massive cores. All 40 individual cores with masses ranging between 0.6 and 15 M ⊙ were detected above a 3 σ level of 3.6 mJy beam −1 (or 0.4 M ⊙ ), based on which we derive a total core mass of 107 M ⊙ in the AFGL 961 region. As compared to the stellar initial mass function, a shallow slope of 1.8 is, however, derived from the best fit to the mass spectrum of the millimeter cores with a prestellar and/or protostellar origin. The flatter core mass distribution in the AFGL 961 region is attributed here to dynamic perturbations from the massive molecular outflows that originated from the massive protostellar binary, which may have altered the otherwise more quiescent conditions of core or star formation, enhanced the formation of more massive cores and, as a result, influenced the core mass distribution in its close vicinity.

Phytoestrogens derived from plants exert estrogenic as well as antiestrogenic effects and multiple actions within breast cancer cells. Chemopreventive properties of phytoestrogens have emerged from epidemiological observations. In recent clinical research studies, phytoestrogens are safe and may even protect against breast cancer. In this brief review, the molecular mechanisms of phytoestrogens on regulation of cell cycle, apoptosis, estrogen receptors, cell signaling pathways, and epigenetic modulations in relation to breast cancer are discussed. Phytoestrogens have a preferential affinity for estrogen receptor (ER)-β, which appears to be associated with antiproliferative and anticarcinogenic effects. Moreover, while phytoestrogens not only inhibit ER-positive but also ER-negative breast cancer cells, the possibility of epigenetic modulation playing an important role is also discussed. In conclusion, as there are multiple targets and actions of phytoestrogens, extensive research is still necessary. However, due to low toxicity, low cost, and easy availability, their potent chemoprevention effects deserve further study.

Supplemental Digital Content is available in the text, There are conflicts on whether influenza vaccinated systemic lupus erythematosus (SLE) patients are associated with a decreased immunogenicity and safety, compared with healthy controls. We conducted meta-analyses to compare SLE patients with healthy controls for flu-vaccine immunogenicity, as well as for adverse events. PubMed, MEDLINE, and Cochrane Library were searched by October 15, 2015. Studies were included when they met the inclusion criteria. Two reviewers independently extracted data on study characteristics, methodological quality, and outcomes. The primary outcome was seroprotection (SP) rate after immunization. A total of 15 studies were included. There were significant differences in SP rates between the SLE patients and healthy controls, respectively, for H1N1 (RR 0.79, 95% CI 0.73–0.87) and B strain (RR 0.75, 95% CI 0.65–0.87), but not for H3N2 (RR 0.84, 95% CI 0.68–1.03). Subgroup analyses demonstrated SLE patients with immunosuppressants, corticosteroids, azathioprine and prednisone had significantly lower SP rates, compared with healthy controls. SLE patients with nonadjuvanted H1N1 vaccine had significantly lower SP rate, compared with healthy controls. SLE patients were not associated with increased adverse events (RR 1.88, 95% CI 0.94–3.77). SLE generates immunogenicity differently, compared with healthy controls in pandemic H1N1 and B strains, but same in seasonal H3N2 strain. Nonadjuvant and special kind of immunosuppressive biologics can play an important role in SLE immunogenicity to flu vaccine. There is no significant difference in adverse event rates between SLE patients and healthy controls.

Aims Interleukin-6 (IL-6), an inflammatory cytokine, is considered a candidate gene possibly involved in susceptibility to nephropathy in diabetes. This study aimed to examine whether IL-6 polymorphisms predict the progression of nephropathy in a prospective Chinese cohort of patients with type 2 diabetes. Methods A total of 568 type 2 diabetic patients with normoalbuminuria at baseline were followed up for a mean of 5.3 ± 1.5 years. Urinary albumin-to-creatinine ratio (ACR) ⩾30 mg/g in two consecutive urine tests were defined as progression to diabetic nephropathy (n = 143). Five polymorphisms of IL-6 gene, rs1800795, rs1800796, rs1524107, rs2069837, and rs2069840, were genotyped. Cox proportional hazard models were used to estimate hazard ratio (HR) and 95% CI of progression to diabetic nephropathy under different genetic models. Results Almost all patients (99.6%) carried the rs1800795 GG homozygous genotypes. In the Cox proportional models adjusted for multiple covariates, the HR under recessive model was 2.02 for rs1800796 GG (vs. CC + CG, 95% CI: 1.08–3.75, p = 0.027), 2.37 for rs2069837 GG (vs. AA + AG, 95% CI: 1.15–4.87, p = 0.019), and 2.08 for rs1524107 CC (vs. TT + TC, 95% CI: 1.12–3.89, p = 0.021). These associations remained significant for rs1800796 and rs1524107 after correction for multiple testing (α = 0.017). Overall, our results suggest that rs1800796 GG and rs1524107 CC homozygous genotypes may confer a greater risk for development of nephropathy in type 2 diabetes. Conclusions IL-6 gene polymorphisms rs1800796 and rs1524107 may serve as predictors of progression of nephropathy in Chinese patients with type 2 diabetes.

The aim of the present study was to investigate relationships between the risk of chronic kidney disease (CKD) and obesity and weight changes in Asian patients with type 2 diabetes.At baseline (2003-05), 1187 diabetic patients aged 30-70 years were recruited to the study, with follow-up surveys completed in 2008, 2009, and 2010. Chronic kidney disease was defined as an estimated glomerular filtration rate (eGFR)60 mL/min per 1.73 mOver 7 years of follow-up, obesity (RR 1.48; 95% CI 1.08-2.04; P = 0.015) and high WC (RR 1.23; 95% CI 1.00-1.52; P = 0.049) were associated with CKD after adjusting for covariates. Among participants without CKD at baseline, those who gained10% weight (RR 1.43; 95% CI 1.07-1.90; P = 0.015) and in whom WC increased15% (RR 1.37; 95% CI 1.01-1.85; P = 0.045) had a higher risk of incident CKD than those who remained stable (±5% changes in weight or WC).Diabetic patients who are obese and those with excessive central fat were more likely to have CKD. Large weight gain (10%) and increases in WC (15%) independently predicted incident CKD.

The physical mechanisms that induce the transformation of a certain mass of gas in new stars are far from being well understood. Infrared bubbles associated with HII regions have been considered to be good samples of investigating triggered star formation. In this paper we report on the investigation of the dust properties of the infrared bubble N4 around the HII region G11.898+0.747, analyzing its interaction with its surroundings and star formation histories therein, with the aim of determining the possibility of star formation triggered by the expansion of the bubble. Using Herschel PACS and SPIRE images with a wide wavelength coverage, we reveal the dust properties over the entire bubble. Meanwhile, we are able to identify six dust clumps surrounding the bubble, with a mean size of 0.50 pc, temperature of about 22 K, mean column density of 1.7 $\times10^{22}$ cm$^{-2}$, mean volume density of about 4.4 $\times10^{4}$ cm$^{-3}$, and a mean mass of 320 $M_{\odot}$. In addition, from PAH emission seen at 8 $\mu$m, free-free emission detected at 20 cm and a probability density function in special regions, we could identify clear signatures of the influence of the HII region on the surroundings. There are hints of star formation, though further investigation is required to demonstrate that N4 is the triggering source., Comment: Accepted by ApJ (16 pages, 11 figures, 9 tables)

To investigate the inhibitory activities of norcantharidin (NCTD), a demethylated analogue of cantharidin, on Hep3B cells (a human hepatoma cell line) with deficiency of p53.The survival rate of the Hep3B cells after treating with NCTD was measured by MTT assay. Cell cycle of treated cells was analyzed by flow cytometry, and DNA fragmentation was observed by electrophoresis. The influence of inhibitors for various caspases and anti-death receptors antibodies on the NCTD-induced apoptosis in the cells was determined.NCTD treatment resulted in growth inhibition of Hep3B cells in a dose- and time-dependent manner. Cell cycle analysis of the cells after treatment with NCTD for 48 h shows that NCTD induced G(2)M phase arrest occurs at low concentration ([Symbol: see text] 25 μmol/L) but G(0)G(1) phase arrest at high concentration (50 μmol/L). The addition of both caspase-3 and caspase-10 inhibitors completely inhibited DNA fragmentation. Addition of anti-TRAIL/DR5 antibody significantly inhibited DNA fragmentation.NCTD may inhibit the proliferation of Hep3B cells by arresting cell cycle at G(2)M or G(0)G(1) phase, and induce cells apoptosis via TRAIL/DR5 signal transduction through activation of caspase-3 and caspase-10 by a p53-independent pathway.

Ly6G is a glycosylphosphatidylinositol (GPI)–anchored protein of unknown function that is commonly targeted to induce experimental neutrophil depletion in mice. In the present study, we found that doses of anti-Ly6G Abs too low to produce sustained neutropenia remained capable of inhibiting experimental arthritis, leaving joint tissues free of infiltrating neutrophils. Thioglycollate-stimulated peritonitis was also attenuated. No alteration in neutrophil apoptosis was observed, implicating impaired recruitment. Indeed, Ly6G ligation abrogated neutrophil migration toward LTB4 and other chemoattractants in a transwell system. Exploring the basis for this blockade, we identified colocalization of Ly6G and β2-integrins by confocal microscopy and confirmed close association by both coimmunoprecipitation and fluorescence lifetime imaging microscopy. Anti-Ly6G Ab impaired surface expression of β2-integrins in LTB4-stimulated neutrophils and mimicked CD11a blockade in inhibiting both ICAM-1 binding and firm adhesion to activated endothelium under flow conditions. Correspondingly, migration of β2-integrin–deficient neutrophils was no longer inhibited by anti-Ly6G. These results demonstrate that experimental targeting of Ly6G has functional effects on the neutrophil population and identify a previously unappreciated role for Ly6G as a modulator of neutrophil migration to sites of inflammation via a β2-integrin–dependent mechanism.

Background Acute myeloid leukaemia (AML) is a malignant cancer of hematopoietic stem cells. The treatment of AML consists of two treatment phases: the remission induction phase to achieve a rapid, complete remission (CR) and the consolidation phase to achieve a durable molecular remission. People in CR are at risk of AML relapse, and people with relapsed AML have poor survival prospects. Thus, there is a continuous need for treatments to further improve prognosis. Interleukin-2 (IL-2), an immune-stimulatory cytokine, is an alternative to standard treatment for people with AML to maintain the efficacy after consolidation therapy. Maintenance therapy is not an integral part of the standard treatment for AML. Studies have been conducted to evaluate the efficacy of IL-2 as maintenance therapy for people with AML in first CR, but the effect of IL-2 is not yet fully established. Objectives To evaluate the efficacy and safety of IL-2 as maintenance therapy for children and adults with AML who have achieved first CR and have not relapsed. Search methods We systematically searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 8), MEDLINE (1950 to August 2015), EMBASE (1950 to August 2015), LILACS (1982 to August 2015), CBM (1978 to August 2015), relevant conference proceedings (2000 to 2015), and metaRegister of Controlled Trials (since inception to August 2015) of ongoing and unpublished trials. In addition, we screened the reference lists of relevant trials and reviews. Selection criteria Eligible studies were randomised controlled trials (RCTs) comparing IL-2 with no treatment in people with AML who had achieved first CR and had not relapsed. We did not identify studies comparing IL-2 versus best supportive care or maintenance chemotherapy or studies comparing IL-2 plus maintenance chemotherapy versus maintenance chemotherapy alone. Data collection and analysis Two review authors independently screened studies, extracted data with a predefined extraction form, and assessed risk of bias of included studies. We extracted data on the following outcomes: disease-free survival, overall survival, event-free survival, treatment-related mortality, adverse events, and quality of life. We measured the treatment effect on time-to-event outcomes and dichotomous outcomes with hazard ratio (HR) and risk ratio, respectively. We used inverse-variance method to combine HRs with fixed-effect model unless there was significant between-study heterogeneity. Main results We included nine RCTs with a total of 1665 participants, comparing IL-2 with no treatment. Six studies included adult participants, and three studies included both adults and children. However, the latter three studies did not report data for children, thus we were unable to conduct subgroup analysis of children. One Chinese study did not report any outcomes of interest for this review. We included six trials involving 1426 participants in the meta-analysis on disease-free survival, and included five trials involving 1355 participants in the meta-analysis on overall survival. There is no evidence for difference between IL-2 group and no-treatment group regarding disease-free survival (HR 0.95; 95% CI 0.86 to 1.06, P = 0.37; quality of evidence: low) or overall survival (HR 1.05; 95% CI 0.95 to 1.16, P = 0.35; quality of evidence: moderate). Based on one trial of 161 participants, IL-2 exerted no effect on event-free survival (HR 1.02; 95% CI 0.79 to 1.32, P = 0.88; quality of evidence: low). Adverse events (including thrombocytopenia, neutropenia, malaise/fatigue, and infection/fever) were more frequent in participants receiving IL-2, according to one trial of 308 participants. No mortality due to adverse events was reported. None of the included studies reported treatment-related mortality or quality of life. Authors' conclusions There is no evidence for a difference between IL-2 maintenance therapy and no treatment with respect to disease-free survival or overall survival of people with AML in first CR; however, the quality of the evidence is moderate or low, and further research is likely or very likely to have an important impact on the estimate or our confidence in the estimate. Adverse events seem to be more frequent in participants treated with IL-2, but the quality of the evidence is very low and our confidence in the estimates is very uncertain. Thus, further prospective randomised trials are needed before definitive conclusions can be drawn on these issues.