Summary Objective Disruptions of extracellular matrix (ECM) homeostasis are key events in the pathogenesis of osteoarthritis (OA). MicroRNA-140 (miRNA-140) is expressed specifically in cartilage and ...regulates ECM-degrading enzymes. Our objective in this study was to determine if intra-articular injection of miRNA-140 can attenuate OA progression in rats. Design miRNA-140 levels in human normal and OA cartilage derived chondrocytes and synovial fluid were assessed by polymerase chain reaction (PCR). After primary human chondrocytes were transfected with miRNA-140 mimic or inhibitor, PCR and western blotting were performed to quantify Collagen II, MMP-13, and ADAMTS-5 expression. An OA model was induced surgically in rats, and subsequently treated with one single intra-articular injection of miRNA-140 agomir. At 4, 8, and 12 weeks after surgery, OA progression were evaluated macroscopically, histologically, and immunohistochemically in these rats. Results miRNA-140 levels were significantly reduced in human OA cartilage derived chondrocytes and synovial fluid compared with normal chondrocytes and synovial fluid. Overexpressing miRNA-140 in primary human chondrocytes promoted Collagen II expression and inhibited MMP-13 and ADAMTS-5 expression. miRNA-140 levels in rat cartilage were significantly higher in the miRNA-140 agomir group than in the control group. Moreover, behavioural scores, chondrocyte numbers, cartilage thickness and Collagen II expression levels in cartilage were significantly higher, while pathological scores and MMP-13 and ADAMTS-5 expression levels were significantly lower in the miRNA-140 agomir group than in the control group. Conclusion Intra-articular injection of miRNA-140 can alleviate OA progression by modulating ECM homeostasis in rats, and may have potential as a new therapy for OA.
Background
This study aimed to compare sequential treatment by transcatheter arterial chemoembolization (TACE) and percutaneous radiofrequency ablation (RFA) with partial hepatectomy for ...hepatocellular carcinoma (HCC) within the Milan criteria.
Methods
In a randomized clinical trial, patients with HCC within the Milan criteria were included and randomized 1 : 1 to the partial hepatectomy group or the TACE + RFA group. The primary outcome was overall survival and the secondary outcome was recurrence‐free survival.
Results
Two hundred patients were enrolled. The 1‐, 3‐ and 5‐year overall survival rates were 97·0, 83·7 and 61·9 per cent for the partial hepatectomy group, and 96·0, 67·2 and 45·7 per cent for the TACE + RFA group (P = 0·007). The 1‐, 3‐ and 5‐year recurrence‐free survival rates were 94·0, 68·2 and 48·4 per cent, and 83·0, 44·9 and 35·5 per cent respectively (P = 0·026). On Cox proportional hazard regression analysis, HBV‐DNA (hazard ratio (HR) 1·76; P = 0·006), platelet count (HR 1·00; P = 0·017) and tumour size (HR 1·90; P < 0·001) were independent prognostic factors for recurrence‐free survival, and HBV‐DNA (HR 1·61; P = 0·036) was a risk factor for overall survival. The incidence of complications in the partial hepatectomy group was higher than in the TACE + RFA group (23·0 versus 11·0 per cent respectively; P = 0·024).
Conclusion
For patients with HCC within the Milan criteria, partial hepatectomy was associated with better overall and recurrence‐free survival than sequential treatment with TACE and RFA. Registration number: ACTRN12611000770965 (http://www.anzctr.org.au/).
Partial hepatectomy better
Sudden impulses (SIs) are an important source of ultra low frequency (ULF) wave activity throughout the Earth's magnetosphere. Most SI‐induced ULF wave events have been reported in the dayside ...magnetosphere; it is not clear when and how SIs drive ULF wave activity in the nightside plasma sheet. We examined the ULF response of the nightside plasma sheet to SIs using an ensemble of 13 SI events observed by THEMIS (Timed History of Events and Macroscale Interactions during Substorms) satellites (probes). Only three of these events resulted in ULF wave activity. The periods of the waves are found to be 3.3, 6.0, and 7.6 min. East‐west magnetic and radial electric field perturbations, which typically indicate the toroidal mode, are found to be stronger and can have phase relationships consistent with standing waves. Our results suggest that the two largest‐amplitude ULF responses to SIs in the nightside plasma sheet are tailward‐moving vortices, which have previously been reported, and the dynamic response of cross‐tail currents in the magnetotail to maintain force balance with the solar wind, which has not previously been reported as a ULF wave driver. Both mechanisms could potentially drive standing Alfvén waves (toroidal modes) observed via the field‐line resonance mechanism. Furthermore, both involve frequency selection and a preference for certain driving conditions that can explain the small number of ULF wave events associated with SIs in the nightside plasma sheet.
Key Points
In 3 of 13 SI events, steady ULF wave is induced in the nightside plasma sheet
Field perturbations are usually consistent with standing toroidal Alfven waves
Tailward moving vortices or dynamic response of tail currents may explain
A new alpha-emitting isotope U-214, produced by the fusion-evaporation reaction W-182(Ar-36,4n) U-214, was identified by employing the gas-filled recoil separator SHANS and the recoil-a correlation ...technique. More precise a-decay properties of even-even nuclei U-216,U-218 were also measured in the reactions of Ar-40, Ca-40 beams with W-180,W-182,W- 184 targets. By combining the experimental data, improved alpha-decay reduced widths delta(2) for the even-even Po-Pu nuclei in the vicinity of the magic neutron number N = 126 are deduced. Their systematic trends are discussed in terms of the N-p N-n scheme in order to study the influence of protonneutron interaction on a decay in this region of nuclei. It is strikingly found that the reduced widths of( 214,216)U are significantly enhanced by a factor of two as compared with the NpNn systematics for the 84 <= Z <= 90 and N < 126 even-even nuclei. The abnormal enhancement is interpreted by the strong monopole interaction between the valence protons and neutrons occupying the pi 1f (7/2) and nu 1f(5/2) spin-orbit partner orbits, which is supported by the large-scale shell model calculation.
Fast radio bursts (FRBs) are millisecond-duration radio transients of unknown physical origin observed at extragalactic distances
. It has long been speculated that magnetars are the engine powering ...repeating bursts from FRB sources
, but no convincing evidence has been collected so far
. Recently, the Galactic magnetar SRG 1935+2154 entered an active phase by emitting intense soft γ-ray bursts
. One FRB-like event with two peaks (FRB 200428) and a luminosity slightly lower than the faintest extragalactic FRBs was detected from the source, in association with a soft γ-ray/hard-X-ray flare
. Here we report an eight-hour targeted radio observational campaign comprising four sessions and assisted by multi-wavelength (optical and hard-X-ray) data. During the third session, 29 soft-γ-ray repeater (SGR) bursts were detected in γ-ray energies. Throughout the observing period, we detected no single dispersed pulsed emission coincident with the arrivals of SGR bursts, but unfortunately we were not observing when the FRB was detected. The non-detection places a fluence upper limit that is eight orders of magnitude lower than the fluence of FRB 200428. Our results suggest that FRB-SGR burst associations are rare. FRBs may be highly relativistic and geometrically beamed, or FRB-like events associated with SGR bursts may have narrow spectra and characteristic frequencies outside the observed band. It is also possible that the physical conditions required to achieve coherent radiation in SGR bursts are difficult to satisfy, and that only under extreme conditions could an FRB be associated with an SGR burst.
Growth performance, digestive and absorptive capacities and target of rapamycin (TOR), ribosomal protein S6 kinase 1 (S6K1) and eIF4E‐binding protein (4E‐BP) gene expression in the hepatopancreas and ...intestine of juvenile grass carp (Ctenopharyngodon idellus) fed graded ratios of dietary alpha‐linolenic acid/linoleic acid (ALA/LNA) (0.01, 0.34, 0.68, 1.03, 1.41, 1.76 and 2.15) for 60 days were investigated. The results showed that ALA/LNA ratio of 1.03 significantly improved (i) per cent weight gain (PWG) and feed efficiency, (ii) hepatopancreatic trypsin, chymotrypsin, lipase, amylase and intestinal creatine kinase (CK) activities, (iii) hepatopancreatic trypsinogen‐2 and chymotrypsinogen mRNA levels. Meanwhile, fish fed with ALA/LNA ratio of 0.68 significantly enhanced, (iv) Na+/K+‐ATPase and γ‐glutamyl transpeptidase activities in whole intestine, and alkaline phosphatase activities in the proximal intestine (PI) and distal intestine, (v) amylase, intestinal Na+/K+‐ATPase alpha‐subunit isoform 1, Na+/K+‐ATPase alpha‐subunit isoform 8 and CK mRNA abundances, (vi) TOR and S6K1 gene expression in the hepatopancreas and intestine of juvenile grass carp. Based on the quadratic regression analysis of PWG, cholecystokinin and leptin contents in the PI, optimal dietary ALA/LNA ratio of juvenile grass carp (8.78–72.00 g) was estimated to be 1.08, 1.19 and 1.05, respectively.
Summary
Background
Pemphigus is a group of rare life‐threatening mucocutaneous autoimmune diseases, presenting mainly as two subtypes: pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Inherited ...predispositions to pemphigus have long been speculated but they remain poorly understood.
Objectives
To identify common and specific nongenetic and genetic factors associated with pemphigus and its subtypes in the Chinese population.
Methods
A genome‐wide association study (GWAS) was performed in 496 unrelated patients with pemphigus (including 365 with PV and 104 with PF) and 1105 controls without pemphigus.
Results
A sex preference was observed only in PV (57·5% female) and not in PF (47·1% female). For male patients only, the mean age at diagnosis was significantly lower for PV than for PF (P < 0·001). The strongest associated single‐nucleotide polymorphisms are in the human leucocyte antigen (HLA) region: rs70993900 (PV; P = 1·5 × 10−45) and rs9469220 (PF; P = 1·1 × 10−8). HLA‐DQB1*05:03 ranks at the top (P = 4·7 × 10−40; odds ratio 12·4) in both subtypes, with significantly different risk allele frequency (RAFPV = 34·2% vs. RAFPF = 18·8% vs. RAFcontrol = 4·4%), whereas HLA‐DRB1*14:01 and HLA‐DRB1*04:06 are PV specific. HLA‐DQB1*03:03 and HLA‐DQB1*03:02 show significant subtype specificity in opposite directions. All of these associations were validated in the replication series with 147 cases of pemphigus and 604 controls. Multiple novel non‐HLA susceptibility loci were also identified in the GWAS.
Conclusions
This study represents the largest GWAS on pemphigus in the Chinese population published to date, and has allowed us to identify HLA haplotypes significantly shared between or specific to the two main subtypes of pemphigus.
What's already known about this topic?
Pemphigus is a group of autoimmune mucocutaneous diseases.
It has multiple subtypes associated with certain human leucocyte antigen (HLA) haplotypes in an ethnicity‐specific manner.
What does this study add?
This is the largest genome‐wide association study published on pemphigus to date.
We identified, for the first time, more than 100 single‐nucleotide polymorphisms (SNPs; six independent) at the HLA locus, with associations reaching genome‐wide significance.
Some of these SNPs are strongly associated with specific subtypes of pemphigus.
What is the translational message?
The identified new haplotypes can potentially serve as genetic markers to improve investigation of the epidemiology and pathogenesis of pemphigus and its specific subtypes.
Linked Comment: Geller. Br J Dermatol 2019; 180:713–714.
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Abstract
Identifying how energy transfer proceeds from macroscales down to microscales in collisionless plasmas is at the forefront of astrophysics and space physics. It provides information on the ...evolution of involved plasma systems and the generation of high-energy particles in the universe. Here we report two cross-scale energy-transfer events observed by NASA’s Magnetospheric Multiscale spacecraft in Earth’s magnetosphere. In these events, hot ions simultaneously undergo interactions with macroscale (~
$${10}^{5}$$
10
5
km) ultra-low-frequency waves and microscale (
$$\sim {10}^{3}$$
~
10
3
km) electromagnetic-ion-cyclotron (EMIC) waves. The cross-scale interactions cause energy to directly transfer from macroscales to microscales, and finally dissipate at microscales via EMIC-wave-induced ion energization. The direct measurements of the energy transfer rate in the second event confirm the efficiency of this cross-scale transfer process, whose timescale is estimated to be roughly ten EMIC-wave periods about (1 min). Therefore, these observations experimentally demonstrate that simultaneous macroscale and microscale wave-ion interactions provide an efficient mechanism for cross-scale energy transfer and plasma energization in astrophysical and space plasmas.
Whistler waves are believed to play an important role during magnetic reconnection. Here we report the near‐simultaneous occurrence of two types of the whistler‐mode waves in the magnetotail Hall ...reconnection region. The first type is observed in the magnetic pileup region of downstream and propagates away to downstream along the field lines and is possibly generated by the electron temperature anisotropy at the magnetic equator. The second type, propagating toward the X line, is found around the separatrix region and probably is generated by the electron beam‐driven whistler instability or Čerenkov emission from electron phase‐space holes. These observations of two different types of whistler waves are consistent with recent kinetic simulations and suggest that the observed whistler waves are a consequence of magnetic reconnection.
Key Points
Two types of whistler waves are observed in the reconnection diffusion region
First one is in pileup region, and second one is around separatrix
Whistlers are the consequences of magnetic reconnection
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