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The Comprehensive Antibiotic Resistance Database (CARD; card.mcmaster.ca) combines the Antibiotic Resistance Ontology (ARO) with curated AMR gene (ARG) sequences and resistance-conferring mutations to provide an informatics framework for annotation and interpretation of resistomes. As of version 3.2.4, CARD encompasses 6627 ontology terms, 5010 reference sequences, 1933 mutations, 3004 publications, and 5057 AMR detection models that can be used by the accompanying Resistance Gene Identifier (RGI) software to annotate genomic or metagenomic sequences. Focused curation enhancements since 2020 include expanded β-lactamase curation, incorporation of likelihood-based AMR mutations for Mycobacterium tuberculosis, addition of disinfectants and antiseptics plus their associated ARGs, and systematic curation of resistance-modifying agents. This expanded curation includes 180 new AMR gene families, 15 new drug classes, 1 new resistance mechanism, and two new ontological relationships: evolutionary_variant_of and is_small_molecule_inhibitor. In silico prediction of resistomes and prevalence statistics of ARGs has been expanded to 377 pathogens, 21,079 chromosomes, 2,662 genomic islands, 41,828 plasmids and 155,606 whole-genome shotgun assemblies, resulting in collation of 322,710 unique ARG allele sequences. New features include the CARD:Live collection of community submitted isolate resistome data and the introduction of standardized 15 character CARD Short Names for ARGs to support machine learning efforts.

GRO J1008-57, as a Be/X-ray transient pulsar, is considered to have the highest magnetic field in known neutron star X-ray binary systems. Observational data of the X-ray outbursts in GRO J1008-57 from 2017 to 2020 were collected by the Insight-HXMT satellite. In this work, the spin period of the neutron star in GRO J1008-57 was determined to be about 93.28 seconds in August 2017, 93.22 seconds in February 2018, 93.25 seconds in June 2019 and 93.14 seconds in June 2020. GRO J1008-57 evolved in the spin-up process with a mean rate of − ( 2.10 ± 0.05 ) × 10−4 s/d from 2009 – 2018, and turned into a spin down process with a rate of ( 6.7 ± 0.6 ) × 10−5 s/d from Feb 2018 to June 2019. During the type II outburst of 2020, GRO J1008-57 had the spin-up torque again. During the torque reversals, the pulse profiles and continuum X-ray spectra did not change significantly, and the cyclotron resonant scattering feature around 80 keV was only detected during the outbursts in 2017 and 2020. Based on the observed mean spin-up rate, we estimated the inner accretion disk radius in GRO J1008-57 (about 1 - 2 times of the Alfven radius) by comparing different accretion torque models of magnetic neutron stars. During the spin-down process, the magnetic torque should dominate over the matter accreting inflow torque, and we constrained the surface dipole magnetic field B ≥ 6 × 10 12 G for the neutron star in GRO J1008-57, which is consistent with the magnetic field strength obtained by cyclotron line centroid energy.

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

We study the spectral evolution of the black hole candidate EXO 1846$-$031 during its 2019 outburst, in the 1--150 keV band,with the {\it {Hard X-ray Modulation Telescope}}. The continuum spectrum is well modelled with an absorbed disk-blackbody plus cutoff power-law, in the hard, intermediate and soft states. In addition, we detect an $\approx$6.6 keV Fe emission line in the hard intermediate state. Throughout the soft intermediate and soft states, the fitted inner disk radius remains almost constant; we suggest that it has settled at the innermost stable circular orbit (ISCO). However, in the hard and hard intermediate states, the apparent inner radius was unphysically small (smaller than ISCO), even after accounting for the Compton scattering of some of the disk photons by the corona in the fit. We argue that this is the result of a high hardening factor, $f_{\rm col}\approx2.0-2.7$, in the early phases of outburst evolution, well above the canonical value of 1.7 suitable to a steady disk. We suggest that the inner disk radius was close to ISCO already in the low/hard state. Furthermore, we propose that this high value of hardening factor in the relatively hard state is probably caused by the additional illuminating of the coronal irradiation onto the disk. Additionally, we estimate the spin parameter with the continuum-fitting method, over a range of plausible black hole masses and distances. We compare our results with the spin measured with the reflection-fitting method and find that the inconsistency of the two results is partly caused by the different choices of $f_{\rm col}$., Comment: 21 pages, 6 figures

The aim of this study was to investigate the effects of micro ribonucleic acid (miR)-490-5p on the proliferation and apoptosis of colon cancer cells, and to explore its potential mechanism.The mRNA expression of miR-490-5p in 30 pairs of colon cancer tissues and adjacent normal tissues was detected via reverse transcription-polymerase chain reaction (RT-PCR). Human colon cancer SW480 cell lines were cultured in vitro and divided into Control group and miR-490-5p overexpression group (miR-490-5p mimic group). The nonsense sequence and miR-490-5p mimic were transfected using liposome transfection technique into colon cancer cells in control group and miR-490-5p mimic group, respectively. Cell proliferation and apoptosis in each group were then observed. At the same time, the effect of miR-490-5p on the growth of colon cancer in vivo was explored using subcutaneous tumorigenesis assay. The protein expressions of extracellular signal-regulated kinase (ERK)1/2 signaling pathway and cyclin-dependent kinase 1 (CDK1) were determined via Western blotting. Furthermore, immunohistochemical staining was performed to verify the protein expression of CDK1 in vivo.The expression of miR-490-5p in colon cancer tissues was significantly lower than that in adjacent normal tissues (p0.05). After transfection with miR-490-5p mimic in vitro, EdU staining and colony formation assay showed that the proliferation ability of SW480 cells was significantly weakened (p0.05). Meanwhile, the number of colonies in miR-490-5p mimic group was markedly less than that in Control group (p0.05). The results of Western blotting revealed that overexpression of miR-490-5p remarkably up-regulated the Bax/Bcl-2 and C-Caspase3/T-Caspase3 ratios in cancer cells (p0.05). Subsequent results indicated that the subcutaneous tumorigenesis of colon cancer cells was markedly inhibited by overexpression of miR-490-5p (p0.05). According to the results of Western blotting, the activation of ERK signaling pathway and the protein expression of CDK1 were significantly suppressed by overexpression of miR-490-5p (p0.05). In vivo experiments further revealed that the protein expression of CDK1 in colon cancer tissues increased significantly (p0.05).MiR-490-5p was found lowly expressed in colon cancer patients. In addition, overexpression of miR-490-5p inhibited the proliferation and promoted the apoptosis of colon cancer cells via down-regulating CDK1 both in vitro and in vivo.

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

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): the National Key Research and Development Program of China Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening disease with a poor prognosis if left untreated. Pulmonary endarterectomy is the standard treatment for CTEPH, but around 40% of CTEPH patients are non-eligible for surgery. Purpose To investigate the efficacy and safety of refined balloon pulmonary angioplasty (BPA) for inoperable CTEPH in a prospective multicenter registry from China. Methods We conducted a prospective multicenter cohort study using the data from National Rare Disease Registry System of China. Total 140 consecutive patients with inoperable CTEPH who completed BPA between Jan 2016 and Dec 2020 were enrolled. The key efficacy outcomes were changes from baseline to re-evaluation in mean pulmonary arterial pressure, pulmonary vascular resistance, and six-minute walking distance. The safety outcomes were procedure-related complications. The survival outcome was all-cause mortality. Results Among the 140 patients who completed BPA, the mean age at diagnosis was 58 ± 14 years and 60.0% were female. At re-evaluation, the least-squares mean change from baseline was -18.3 mm Hg (95% confidence interval [CI], -19.9 to -16.6, P < 0.001) in mean pulmonary arterial pressure, -5.3 Wood U (95% CI, -5.9 to -4.6, P < 0.001) in pulmonary vascular resistance, and 87 meters (95% CI, 74 to 101, P < 0.001) in six-minute walking distance. BPA procedure-related complications occurred in 109 of 650 BPA sessions (16.8%), but severe complications requiring noninvasive positive pressure ventilation only occurred in 4 (0.6%) BPA sessions. During a mean follow-up time of 32 ± 14 months, 4 patients died, including 2 peri-procedural deaths, contributing to the survival rates of 97.8% (95% CI, 93.4 to 99.3) at 1 year and 96.9% (95% CI, 91.9 to 98.8) at 3 and 5 years. Conclusion Refined BPA appears to be an effective therapeutic option for inoperable CTEPH patients with acceptable safety profiles. Abstract Figure. Images of BPA Efficacy in a Patient Abstract Figure. Efficacy outcomes of BPA

We present a spectral study of the black hole candidate MAXI J1348-630 during its 2019 outburst, based on monitoring observations with Insight-HXMT and Swift. Throughout the outburst, the spectra are well fitted with power-law plus disk-blackbody components. In the soft-intermediate and soft states, we observed the canonical relation L ~ T_in^4 between disk luminosity L and peak colour temperature T_in, with a constant inner radius R_in (traditionally identified with the innermost stable circular orbit). At other stages of the outburst cycle, the behaviour is more unusual, inconsistent with the canonical outburst evolution of black hole transients. In particular, during the hard rise, the apparent inner radius is smaller than in the soft state (and increasing), and the peak colour temperature is higher (and decreasing). This anomalous behaviour is found even when we model the spectra with self-consistent Comptonization models, which take into account the up-scattering of photons from the disk component into the power-law component. To explain both those anomalous trends at the same time, we suggest that the hardening factor for the inner disk emission was larger than the canonical value of ~1.7 at the beginning of the outburst. A more physical trend of radii and temperature evolution requires a hardening factor evolving from ~3.5 at the beginning of the hard state to ~1.7 in the hard intermediate state. This could be evidence that the inner disk was in the process of condensing from the hot, optically thin medium and had not yet reached a sufficiently high optical depth for its emission spectrum to be described by the standard optically-thick disk solution., 20 pages, 10 figures, 4 tables, accepted by ApJ

A 2-year fertilization experiment was conducted to study the effect of different ratios of organic (pig) manure on wheat yield and nitrogen use efficiency (NUE). The four treatments were no nitrogen (N) (CK); 100% chemical fertilizer N (urea; T1); 70% chemical fertilizer N + 30% organic manure N (T2) and 50% chemical fertilizer N + 50% organic manure N (T3), with the same amount of applied nitrogen (120 kg/ha). The results showed the maximum grain yield (3049 kg/ha), crop nitrogen uptake (216 kg/ha), NUE (65.4%) and accumulated nitrate nitrogen (NO3−-N in 0–200 cm, 142 kg/ha) were observed in the T1 among all treatments in the first year. However, the largest grain yield (5074 kg/ha), crop nitrogen uptake (244 kg/ha) and NUE (82.5%) were under T2 treatment in the second year. Furthermore, T2 had the maximum NO3−-N content in 0–100 cm layer (116 kg/ha), especially 0–40 cm layer, and the lowest NO3−-N content in 100–200 cm (58.8 kg/ha). However, 50% organic manure N in T3 increased apparent nitrogen loss by 39.0% compared to that in T2. Therefore, 30% organic manure N application was more conducive for enhancing wheat yield and NUE and promoting environmental safety after 1-year fertilization time.

Photosystem II is sensitive to chilling stress in tropical tree species. However, the underlying mechanism is not clear. In this study, we examined the effects of chilling and light stress on activities of PSII and oxygen-evolving complex (OEC), in order to resolve the controversy of whether chilling-induced PSII photoinhibition is attributed to the excess-energy model or the two-step scheme. We determined changes in chlorophyll a fluorescence transient and energy distribution in PSII during treatment at chilling-light stress for the tropical tree species Dalbergia odorifera. At chilling temperature, the light-use efficiency was largely inhibited. During chilling treatment, the maximum quantum yield of PSII gradually decreased. Meanwhile, the relative fluorescence intensity at K-step (300 μs) significantly increased, indicating the photodamage to OEC. A tightly positive correlation was found between photodamage to OEC and PSII photoinhibition, suggesting that photodamage to OEC was a rate-limiting step for PSII photoinhibition. Furthermore, additional generation of reactive oxygen species did not aggravate PSII photoinhibition at chilling temperature. These results suggest that two-step model is responsible for chilling-induced PSII photoinhibition in the tropical tree species D. odorifera.

A new black hole X-ray binary (BHXRB) MAXI J1535-571 was discovered by MAXI during its outburst in 2017. Using observations taken by the first Chinese X-ray satellite, the Hard X-ray Modulation Telescope (dubbed as Insight-HXMT), we perform a joint spectral analysis (2-150 keV) in both energy and time domains. The energy spectra provide the essential input for probing the intrinsic Quasi-Periodic Oscillation (QPO) fractional rms spectra (FRS). Our results show that during the intermediate state, the energy spectra are in general consistent with those reported by Swift/XRT and NuSTAR. However, the QPO FRS become harder and the FRS residuals may suggest the presence of either an additional power-law component in the energy spectrum or a turn-over in the intrinsic QPO FRS at high energies.

We study the 2018 outburst of Aql X-1 via the monitor of all sky X-ray image (MAXI) data. We show that the outburst starting in February 2018 is a member of short-low class in the frame of outburst duration and the peak count rate although the outburst morphology is slightly different from the other fast-rise-exponential-decay (FRED) type outbursts with a milder rising stage. We study the partial accretion in the weak propeller stage of Aql X-1 via the MAXI data of the 2018 outburst. We report on the spectral analysis of 3 observations of Aquila X-1 obtained by Insight – hard X-ray modulation telescope (Insight-HXMT) during the late decay stage of the 2018 outburst. We discuss that the data taken by Insight-HXMT is just after the transition to the weak propeller stage. Our analysis shows the necessity of a comptonization component to take into account the existence of an electron cloud resulting photons partly up-scattered.

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.

Background Microvascular endothelial injury is recently considered playing an initial role in myocardial ischemia/reperfusion injury (MIRI). Cardiac microvascular endothelial cells (CMECs) regulate cardiomyocytes and haematocytes via secreting cytokine. MIRI jeopardize not only the barrier function but also the paracrine function of microvasculature. Resveratrol, a natural polyphenolic compound, was demonstrated to protect myocardium against MIRI and to preserve the function of endothelium. However, how the paracrine function of CMECs is regulated by MIRI and resveratrol remains to be elucidated. Purpose The study was to illuminate the alteration of cytokine profiles secreted by CMECs under hypoxia/reoxygenation (H/R) condition and its modulation by resveratrol. Methods CMECs were exposed to different concentrations of resveratrol for 30 minutes and then were subjected to H/R for 12 h/2 h. Apoptotic rates were measured to determine the optimal concentration. Protein antibody arrays were performed to find the alteration of cytokine secreted into conditioned medium by CMECs. A Gene Ontology (GO) analysis was applied to interpret the functional implication of changes in cytokine profiles. Results Resveratrol inhibited apoptosis of CMECs in a dose-dependent manner after H/R and reached its peak effect at the concentration of 100μM, which reduced apoptosis from 27.27±2.95% to 15.01±1.36% (Figure 1A and B). The results of a cluster analysis and all significantly altered factors are shown in figure 1C (fold-change >1.5; p Conclusions Resveratrol inhibited the apoptosis of CMECs and modulated the paracrine function of cardiac microvascular endothelium under ischemia/reperfusion condition. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation Figure 1Figure 2

Background The prognosis for patients with coronary artery disease (CAD) remains unfavorable despite advances in treatment. Fibrinogen (FIB) is an independent risk factor for mortality and cardiovascular events in general population. However, the relationship between FIB and long-term mortality among CAD patients undergoing PCI is less investigated, especially in individuals concomitated with diabetes mellitus (DM) and prediabetes (Pre-DM). Methods 6140 patients with CAD undergoing PCI were consecutively enrolled in our study and subsequently divided into three groups according to FIB levels (FIB-L, FIB-M, FIB-H). These patients were further grouped by glycemic metabolism state [normoglycemia (NG), Pre-DM, DM]. The primary endpoint was all-cause mortality. The secondary endpoint was cardiac mortality. Results FIB was positively associated with hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) both in CAD patients with and without DM. During a median follow-up time of 5.1 years, elevated FIB was significantly associated with long-term mortality from all-cause (adjusted HR: 1.86; 95% CI: 1.28–2.69; P=0.001) and cardiac specific (adjusted HR: 1.82; 95% CI: 1.15–2.89; P=0.011). Similarly, patients with DM but not Pre-DM had increased risk of all-cause and cardiac mortality (all P Conclusion FIB was strongly associated with long-term all-cause and cardiac mortality among CAD patients undergoing PCI, especially in persons concomitated with DM and Pre-DM, indicating FIB test may help identify high-risk individuals in this specific patient population. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Key Research and Development Program of China (No. 2016YFC1301300, 2016YFC1301301); National Natural Science Foundation of China (No. 81770365)

Background In euthyroid patients undergoing percutaneous coronary intervention (PCI), it is still unclear whether thyroxin deiodination level can predict the recurrence of cardiovascular events (CVEs). Using free triiodothyronine to free thyroxine (FT3/FT4) ratio, a marker of peripheral thyroxin deiodination, we aim to investigate its association with recurrent long-term adverse events in this population. Methods 3549 euthyroid patients with prior CVEs history undergoing PCI were consecutively enrolled in our study and subsequently divided into three FT3/FT4 ratio tertiles (T12.75, n=1181). The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), a composite of all-cause death, myocardial infarction, stroke and revascularization. The secondary endpoints were all-cause death and cardiac death. Results The median follow-up time was 5 years. The incidence of all-cause death, cardiac death and MACCE were significantly higher among patients in the lowest FT3/FT4 tertile (P Conclusions In euthyroid patients undergoing PCI, FT3/FT4 ratio, a surrogate marker of peripheral thyroxin deiodination, demonstrates a strong association with long-term recurrent cardiovascular events. Routine assessment of FT3/FT4 ratio might be a simple and effective tool for risk stratification in this specific patient population. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Key Research and Development Program of China (No. 2016YFC1301300, 2016YFC1301301); National Natural Science Foundation of China (No. 81770365)

In view of the fact that the point cloud 3D model will be interfered by environmental factors, measurement methods and other random factors in the process of data scanning and acquisition, there will be some invalid points, outliers and internal noise points. In this paper, a point cloud denoising method based on adaptive density clustering and statistical filtering is proposed to process vehicle point cloud data. which can effectively preserve vehicle features while obtaining optimal denoising effect. Compared with the existing point cloud noise processing algorithms, this algorithm can remove noise better, and has shorter time-consuming and good applicability.