Most oral squamous cell carcinoma (OSCC) tumors arise from oral premalignant lesions. Oral submucous fibrosis (OSF), usually occurring in male chewers of betel quid, is a premalignant stromal disease ...characterized by a high malignant transformation rate and high prevalence. Although a relationship between the inhabited microbiome and carcinogenesis has been proposed, no detailed information regarding the oral microbiome of patients with OSF exists; the changes of the salivary microbiome during cancer formation remain unclear. This study compared the salivary microbiomes of male patients with OSCC and a predisposing OSF background (OSCC-OSF group) and those with OSF only (OSF group). The results of high-throughput sequencing of the bacterial 16S rRNA gene indicated that OSF-related carcinogenesis and smoking status significantly contributed to phylogenetic composition variations in the salivary microbiome, leading to considerable reductions in species richness and phylogenetic diversity. The microbiome profile of OSF-related malignancy was associated with increased microbial stochastic fluctuation, which dominated the salivary microbiome assembly and caused species co-occurrence network collapse. Artificial intelligence selection algorithms consistently identified 5 key species in the OSCC-OSF group: Porphyromonas catoniae, Prevotella multisaccharivorax, Prevotella sp. HMT-300, Mitsuokella sp. HMT-131, and Treponema sp. HMT-927. Robust accuracy in predicting oral carcinogenesis was obtained with our exploratory and validation data sets. In functional analysis, the microbiome of the OSCC-OSF group had greater potential for S-adenosyl-l-methionine and norspermidine synthesis but lower potential for l-ornithine and pyrimidine deoxyribonucleotide synthesis and formaldehyde metabolism. These findings indicated that the salivary microbiome plays important roles in modulating microbial metabolites during oral carcinogenesis. In conclusion, our results provided new insights into salivary microbiome alterations during the malignant transformation of OSF.
End-stage renal disease (ESRD) patients are vulnerable to Mycobacterium tuberculosis (MTB) infection, but the magnitude of the risk is uncertain. In addition, there is no reliable information on the ...MTB infection rate of patients undergoing different types of renal replacement therapy (RRT). We used the Taiwan National Health Insurance Research Database to conduct a 9-year nationwide longitudinal study. Among 49 983 ESRD patients who received three renal replacement modalities, there were 562 cases of MTB infection, corresponding to an incidence rate of 3.0 per 1000 patient-years. The risk of MTB infection relative to the general population was 4.5. Multivariate Cox regression analysis indicated that the independent risk factors for MTB infection in ESRD patients are old age (hazard ratio (HR) 1.17 per 10 years, p <0.001), male gender (HR 1.37, p <0.001), silicosis (HR 5.82, p <0.001), and chronic obstructive pulmonary disease (HR 1.68, p 0.012). Hyperlipidaemia (HR 0.71, p <0.001) and hypertension (HR 0.81, p 0.05) are associated with a lower infection rate. There was no effect of RRT modality on MTB infection rate.
We assemble a sample of 24 hydrogen-poor superluminous supernovae (SLSNe). Parameterizing the light-curve shape through rise and decline time-scales shows that the two are highly correlated. ...Magnetar-powered models can reproduce the correlation, with the diversity in rise and decline rates driven by the diffusion time-scale. Circumstellar interaction models can exhibit a similar rise–decline relation, but only for a narrow range of densities, which may be problematic for these models. We find that SLSNe are approximately 3.5 mag brighter and have light curves three times broader than SNe Ibc, but that the intrinsic shapes are similar. There are a number of SLSNe with particularly broad light curves, possibly indicating two progenitor channels, but statistical tests do not cleanly separate two populations. The general spectral evolution is also presented. Velocities measured from Fe ii are similar for SLSNe and SNe Ibc, suggesting that diffusion time differences are dominated by mass or opacity. Flat velocity evolution in most SLSNe suggests a dense shell of ejecta. If opacities in SLSNe are similar to other SNe Ibc, the average ejected mass is higher by a factor 2–3. Assuming κ = 0.1 cm2 g−1, we estimate a mean (median) SLSN ejecta mass of 10 M⊙ (6 M⊙), with a range of 3–30 M⊙. Doubling the assumed opacity brings the masses closer to normal SNe Ibc, but with a high-mass tail. The most probable mechanism for generating SLSNe seems to be the core collapse of a very massive hydrogen-poor star, forming a millisecond magnetar.
ABSTRACT We present nebular-phase imaging and spectroscopy for the hydrogen-poor superluminous supernova (SLSN) SN 2015bn, at redshift z = 0.1136, spanning +250-400 days after maximum light. The ...light curve exhibits a steepening in the decline rate from 1.4 mag (100 days)−1 to 1.7 mag (100 days)−1, suggestive of a significant decrease in the opacity. This change is accompanied by a transition from a blue continuum superposed with photospheric absorption lines to a nebular spectrum dominated by emission lines of oxygen, calcium, and magnesium. There are no obvious signatures of circumstellar interaction or large 56Ni mass. We show that the spectrum at +400 days is virtually identical to a number of energetic SNe Ic such as SN 1997dq, SN 2012au, and SN 1998bw, indicating similar core conditions and strengthening the link between "hypernovae"/long gamma-ray bursts and SLSNe. A single explosion mechanism may unify these events that span absolute magnitudes of −22 < MB < −17. Both the light curve and spectrum of SN 2015bn are consistent with an engine-driven explosion ejecting 7-30 M of oxygen-dominated ejecta (for reasonable choices in temperature and opacity). A strong and relatively narrow O i λ7774 line, seen in a number of these energetic events but not in normal supernovae, may point to an inner shell that is the signature of a central engine.
Context.
SN 2020qlb (ZTF20abobpcb) is a hydrogen-poor superluminous supernova (SLSN-I) that is among the most luminous (maximum
M
g
= −22.25 mag) and that has one of the longest rise times (77 days ...from explosion to maximum). We estimate the total radiated energy to be > 2.1 × 10
51
erg. SN 2020qlb has a well-sampled light curve that exhibits clear near and post peak undulations, a phenomenon seen in other SLSNe, whose physical origin is still unknown.
Aims.
We discuss the potential power source of this immense explosion as well as the mechanisms behind its observed light curve undulations.
Methods.
We analyze photospheric spectra and compare them to other SLSNe-I. We constructed the bolometric light curve using photometry from a large data set of observations from the
Zwicky
Transient Facility (ZTF), Liverpool Telescope (LT), and
Neil Gehrels Swift
Observatory and compare it with radioactive, circumstellar interaction and magnetar models. Model residuals and light curve polynomial fit residuals are analyzed to estimate the undulation timescale and amplitude. We also determine host galaxy properties based on imaging and spectroscopy data, including a detection of the O III
λ
4363, auroral line, allowing for a direct metallicity measurement.
Results.
We rule out the Arnett
56
Ni decay model for SN 2020qlb’s light curve due to unphysical parameter results. Our most favored power source is the magnetic dipole spin-down energy deposition of a magnetar. Two to three near peak oscillations, intriguingly similar to those of SN 2015bn, were found in the magnetar model residuals with a timescale of 32 ± 6 days and an amplitude of 6% of peak luminosity. We rule out centrally located undulation sources due to timescale considerations; and we favor the result of ejecta interactions with circumstellar material (CSM) density fluctuations as the source of the undulations.
We present a spectroscopic analysis of the most nearby Type I superluminous supernova (SLSN-I), SN 2018bsz. The photometric evolution of SN 2018bsz has several surprising features, including an ...unusual pre-peak plateau and evidence for rapid formation of dust ≳200 d post-peak. We show here that the spectroscopic and polarimetric properties of SN 2018bsz are also unique. While its spectroscopic evolution closely resembles SLSNe-I, with early O
II
absorption and C
II
P Cygni profiles followed by Ca, Mg, Fe, and other O features, a multi-component H
α
profile appearing at ∼30 d post-maximum is the most atypical. The H
α
is at first characterised by two emission components, one at ∼+3000 km s
−1
and a second at ∼ − 7500 km s
−1
, with a third, near-zero-velocity component appearing after a delay. The blue and central components can be described by Gaussian profiles of intermediate width (
FWHM
∼ 2000–6000 km s
−1
), but the red component is significantly broader (
FWHM
≳ 10 000 km s
−1
) and Lorentzian. The blue H
α
component evolves towards a lower-velocity offset before abruptly fading at ∼ + 100 d post-maximum brightness, concurrently with a light curve break. Multi-component profiles are observed in other hydrogen lines, including Pa
β
, and in lines of Ca
II
and He
I
. Spectropolarimetry obtained before (10.2 d) and after (38.4 d) the appearance of the H lines shows a large shift on the Stokes
Q
–
U
plane consistent with SN 2018bsz undergoing radical changes in its projected geometry. Assuming the supernova is almost unpolarised at 10.2 d, the continuum polarisation at 38.4 d reaches
P
∼ 1.8%, implying an aspherical configuration. We propose that the observed evolution of SN 2018bsz can be explained by highly aspherical, possibly disk-like, circumstellar material (CSM) with several emitting regions. After the supernova explosion, the CSM is quickly overtaken by the ejecta, but as the photosphere starts to recede, the different CSM regions re-emerge, producing the peculiar line profiles. Based on the first appearance of H
α
, we can constrain the distance of the CSM to be less than ∼6.5 × 10
15
cm (430 AU), or even lower (≲87 AU) if the pre-peak plateau is related to an eruption that created the CSM. The presence of CSM has been inferred previously for other SLSNe-I, both directly and indirectly. However, it is not clear whether the rare properties of SN 2018bsz can be generalised for SLSNe-I, for example in the context of pulsational pair instability, or whether they are the result of an uncommon evolutionary path, possibly involving a binary companion.
We investigated the molecular mechanisms underlying the effect of sorafenib and SC-59, a novel sorafenib derivative, on hepatocellular carcinoma (HCC). Sorafenib activated autophagy in a dose- and ...time-dependent manner in the HCC cell lines PLC5, Sk-Hep1, HepG2 and Hep3B. Sorafenib downregulated phospho-STAT3 (P-STAT3) and subsequently reduced the expression of myeloid cell leukemia-1 (Mcl-1). Inhibition of Mcl-1 by sorafenib resulted in disruption of the Beclin 1-Mcl-1 complex; however, sorafenib did not affect the amount of Beclin 1, suggesting that sorafenib treatment released Beclin 1 from binding with Mcl-1. Silencing of SHP-1 by small interference RNA (siRNA) reduced the effect of sorafenib on P-STAT3 and autophagy. Ectopic expression of Mcl-1 abolished the effect of sorafenib on autophagy. Knockdown of Beclin 1 by siRNA protected the cells from sorafenib-induced autophagy. Moreover, SC-59, a sorafenib derivative, had a more potent effect on cancer cell viability than sorafenib. SC-59 downregulated P-STAT3 and induced autophagy in all tested HCC cell lines. Furthermore, our in vivo data showed that both sorafenib and SC-59 inhibited tumor growth, downregulated P-STAT3, enhanced the activity of SHP-1 and induced autophagy in PLC5 tumors, suggesting that sorafenib and SC-59 activate autophagy in HCC. In conclusion, sorafenib and SC-59 induce autophagy in HCC through a SHP-1-STAT3-Mcl-1-Beclin 1 pathway.
Summary
Background
Acute severe ulcerative colitis (ASUC) is a potentially life‐threatening complication of ulcerative colitis.
Aim
To develop consensus statements based on a systematic review of the ...literature of the management of ASUC to improve patient outcome.
Methods
Following a literature review, the Delphi method was used to develop the consensus statements. A steering committee, based in Australia, generated the statements of interest. Three rounds of anonymous voting were carried out to achieve the final results. Acceptance of statements was pre‐determined by ≥80% votes in ‘complete agreement’ or ‘agreement with minor reservation’.
Results
Key recommendations include that patients with ASUC should be: hospitalised, undergo unprepared flexible sigmoidoscopy to assess severity and to exclude cytomegalovirus colitis, and be provided with venous thromboembolism prophylaxis and intravenous hydrocortisone 100 mg three or four times daily with close monitoring by a multidisciplinary team. Rescue therapy such as infliximab or ciclosporin should be started if insufficient response by day 3, and colectomy considered if no response to 7 days of rescue therapy or earlier if deterioration. With such an approach, it is expected that colectomy rate during admission will be below 30% and mortality less than 1% in specialist centres.
Conclusion
These evidenced‐based consensus statements on acute severe ulcerative colitis, developed by a multidisciplinary group, provide up‐to‐date best practice recommendations that improve and harmonise management as well as provide auditable quality assessments.
•Magnetic porous carbon derived from bimetallic metal–organic framework was synthesized.•The magnetic porous carbon was used as sorbent for MSPE of organochlorine pesticides from drinking and ...environmental water samples.•High extraction efficiency and good sensitivity was achieved using the developed method.
In this work, magnetic porous carbon material derived from a bimetallic metal–organic framework was explored as an adsorbent for magnetic solid-phase extraction of organochlorine pesticides (OCPs). The synthesized porous carbon possessed a high specific surface area and magnetization saturation. The OCPs in the samples were quantified using gas chromatography coupled with a triple quadrupole mass spectrometer. The experimental parameters, including the desorption solvent and conditions, amount of adsorbent, extraction time, extraction temperature, and ionic strength of the solution, were optimized. Under optimal conditions, the developed method displayed good linearity (r>0.99) within the concentration range of 2–500ngL−1. Low limits of detection (0.39–0.70ngL−1, signal-to-noise ratio=3:1) and limits of quantification (1.45–2.0ngL−1, signal-to-noise ratio=10:1) as well as good precision (relative standard deviation<10%) were also obtained. The developed method was applied in the analysis of OCPs in drinking and environmental water samples.
MicroRNAs (miRNAs) are endogenous non-coding RNAs that are known to be involved in the pathogenesis of tumors. Gastric carcinoma (GC) is a common malignancy worldwide. The aim of this study was the ...identification of the expression signature and functional roles of aberrant miRNAs in GC. Initial screening established a profile of aberrantly expressed miRNAs in tumors. miR-370 was confirmed to be overexpressed in GC tissues. Higher expression of miR-370 in GC tissues was associated with more advanced nodal metastasis and a higher clinical stage compared with controls. In addition, significantly higher level of miR-370 was noted in the plasma of GC patients compared with controls. Patients having more invasive or advanced tumors also exhibited a higher plasma level of miR-370. In vitro assays indicated that exogenous miR-370 expression enhanced the oncogenic potential of GC cells. The AGS-GFPM2 cells with exogenous miR-370 expression also exhibited enhanced abdominal metastatic dissemination in nude mice. Reporter assays confirmed that miR-370 targeted predicted sites in 3'UTR of transforming growth factor-β receptor II (TGFβ-RII) gene. The exogenous miR-370 expression decreased TGFβ-RII expression and the phosphorylation of Smad3 elicited by TGFβ1. The TGFβ1-mediated repression in cell migration was reverted by exogenous miR-370 expression. A reverse correlation between miR-370 and TGFβ-RII expression was noted in GC tissues. This study concludes that miR-370 is a miRNA that is associated with GC progression by downregulating TGFβ-RII. The miRNA expression profile described in this study should contribute to future studies on the role of miRNAs in GC.
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