Mesenchymal stem cells (MSCs) hold great promise for the treatment of difficult diseases. As MSCs represent a rare cell population, ex vivo expansion of MSCs is indispensable to obtain sufficient ...amounts of cells for therapies and tissue engineering. However, spontaneous differentiation and aging of MSCs occur during expansion and the molecular mechanisms involved have been poorly understood.
Human MSCs in early and late passages were examined for their expression of genes involved in osteogenesis to determine their spontaneous differentiation towards osteoblasts in vitro, and of genes involved in self-renewal and proliferation for multipotent differentiation potential. In parallel, promoter DNA methylation and hostone H3 acetylation levels were determined. We found that MSCs underwent aging and spontaneous osteogenic differentiation upon regular culture expansion, with progressive downregulation of TERT and upregulation of osteogenic genes such as Runx2 and ALP. Meanwhile, the expression of genes associated with stem cell self-renewal such as Oct4 and Sox2 declined markedly. Notably, the altered expression of these genes were closely associated with epigenetic dysregulation of histone H3 acetylation in K9 and K14, but not with methylation of CpG islands in the promoter regions of most of these genes. bFGF promoted MSC proliferation and suppressed its spontaneous osteogenic differentiation, with corresponding changes in histone H3 acetylation in TERT, Oct4, Sox2, Runx2 and ALP genes.
Our results indicate that histone H3 acetylation, which can be modulated by extrinsic signals, plays a key role in regulating MSC aging and differentiation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ABSTRACT
We study the modelling of the halo occupation distribution (HOD) for the eBOSS DR16 emission line galaxies (ELGs). Motivated by previous theoretical and observational studies, we consider ...different physical effects that can change how ELGs populate haloes. We explore the shape of the average HOD, the fraction of satellite galaxies, their probability distribution function (PDF), and their density and velocity profiles. Our baseline HOD shape was fitted to a semi-analytical model of galaxy formation and evolution, with a decaying occupation of central ELGs at high halo masses. We consider Poisson and sub/super-Poissonian PDFs for satellite assignment. We model both Navarro–Frenk–White and particle profiles for satellite positions, also allowing for decreased concentrations. We model velocities with the virial theorem and particle velocity distributions. Additionally, we introduce a velocity bias and a net infall velocity. We study how these choices impact the clustering statistics while keeping the number density and bias fixed to that from eBOSS ELGs. The projected correlation function, wp, captures most of the effects from the PDF and satellites profile. The quadrupole, ξ2, captures most of the effects coming from the velocity profile. We find that the impact of the mean HOD shape is subdominant relative to the rest of choices. We fit the clustering of the eBOSS DR16 ELG data under different combinations of the above assumptions. The catalogues presented here have been analysed in companion papers, showing that eBOSS RSD+BAO measurements are insensitive to the details of galaxy physics considered here. These catalogues are made publicly available.
Abstract
The time-resolved magneto-optical (MO) Voigt effect can be utilized to study the Néel order dynamics in antiferromagnetic (AFM) materials, but it has been limited for collinear AFM spin ...configuration. Here, we have demonstrated that in Mn
3
Sn with an inverse triangular spin structure, the quench of AFM order by ultrafast laser pulses can result in a large Voigt effect modulation. The modulated Voigt angle is significantly larger than the polarization rotation due to the crystal-structure related linear dichroism effect and the modulated MO Kerr angle arising from the ferroic ordering of cluster magnetic octupole. The AFM order quench time shows negligible change with increasing temperature approaching the Néel temperature (
T
N
), in markedly contrast with the pronounced slowing-down demagnetization typically observed in conventional magnetic materials. This atypical behavior can be explained by the influence of weakened Dzyaloshinskii–Moriya interaction rather than the smaller exchange splitting on the diminished AFM order near
T
N
. The temperature-insensitive ultrafast spin manipulation can pave the way for high-speed spintronic devices either working at a wide range of temperature or demanding spin switching near
T
N
.
Neoadjuvant therapy is recommended for locally advanced esophageal cancer, but the optimal strategy remains unclear. We aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy ...(nCRT) versus neoadjuvant chemotherapy (nCT) followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal squamous cell carcinoma (ESCC).
Eligible patients staged as cT3-4aN0-1M0 ESCC were randomly assigned (1 : 1) to the nCRT or nCT group stratified by age, cN stage, and centers. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while concurrent radiotherapy was added for the nCRT group; then MIE was carried out. The primary endpoint was 3-year overall survival. This study is registered with ClinicalTrials.gov (NCT03001596).
A total of 264 patients were eligible for the intention-to-treat analysis. By 30 November 2021, 121 deaths had occurred. The median follow-up was 43.9 months (interquartile range 36.6-49.3 months). The overall survival in the intention-to-treat population was comparable between the nCRT and nCT strategies hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.58-1.18; P = 0.28, with a 3-year survival rate of 64.1% (95% CI 56.4% to 72.9%) versus 54.9% (95% CI 47.0% to 64.2%), respectively. There were also no differences in progression-free survival (HR 0.83, 95% CI 0.59-1.16; P = 0.27) and recurrence-free survival (HR 1.07, 95% CI 0.71-1.60; P = 0.75), although the pathological complete response in the nCRT group (31/112, 27.7%) was significantly higher than that in the nCT group (3/104, 2.9%; P < 0.001). Besides, a trend of lower risk of recurrence was observed in the nCRT group (P = 0.063), while the recurrence pattern was similar (P = 0.802).
NCRT followed by MIE was not associated with significantly better overall survival than nCT among patients with cT3-4aN0-1M0 ESCC. The results underscore the pending issue of the best strategy of neoadjuvant therapy for locally advanced bulky ESCC.
•The CMISG1701 trial assessed the safety and efficacy of nCRT versus nCT followed by MIE for locally advanced bulky ESCC.•The nCRT followed by MIE strategy could not improve survival significantly compared with the nCT strategy.•The best strategy of neoadjuvant therapy for locally advanced bulky ESCC remains a pending issue.
A high O3 episode with the large increases in surface ozone by 21-42 ppbv and the nocturnal surface O3 levels exceeding 70 ppbv was observed in the region between Xiamen and Quanzhou over the ...southeastern coast of China during 12-14 June 2014, before the Typhoon Hagibis landing. Variations in the surface O3, NO2, CO and meteorology during the Typhoon Hagibis event clearly suggest a substantial impact of the peripheral downdrafts in the large-scale typhoon circulation on such an O3 episode excluding the contributions of photochemical production and the horizontal transport. The influence of vertical O3 transport from the upper troposphere and lower stratosphere (UTLS) region on high surface O3 levels is further confirmed by a negative correlation between surface O3 and CO concentrations as well as dry surface air observed during the O3 episode. This study provides observational evidence of typhoon-driven intrusion of O3 from the UTLS region to surface air, revealing a significant effect of such a process of stratosphere-troposphere exchange (STE) of O3 on tropospheric O3 and ambient air quality.
Background and Purpose
Intravascular injection of mesenchymal stem cells (MSCs) has been found to cause considerable vascular obstructions which may lead to serious outcomes, particularly after ...intra-arterial injection. However, the underlying mechanisms have been poorly understood.
Methods
In this study, we fractionated MSCs that had been cultured in monolayer for six passages into small (average diameter = 17.9 μm) and large (average diameter 30.4 μm) populations according to their sizes, and examined their vascular obstructions after intra-internal carotid artery injection in rats and mice in comparison with MSCs derived from 3D spheroids which were uniformly smaller in size (average diameter 12.6 μm).
Results
We found that 3D MSCs did not cause detectable infarct in the brain as evidenced by MRI scan and TTC stain, 2D MSCs in small size caused a microinfarct in one of five animals, which was co-localized to the area of entrapped MSCs (labeled with DiI), while 2D MSCs in large size caused much larger infarcts in all five animals, and substantial amounts of DiI-positive MSCs were found in the infarct. Meanwhile, corresponding neurological defects were observed in the animals with stroke. In consistence, injection of 2D MSCs (average diameter 26.5) caused a marked loss of cortical neurons and their axons in Thy1-GFP transgenic mice and the activation of microglia in CX3CR1-GFP transgenic mice in the area with MSC entrapment.
Conclusions
Our results suggest that the size of MSCs is a significant cause of MSC caused vascular obstructions and stroke.
This article proposes doubly robust estimators for the average treatment effect on the treated (ATT) in difference-in-differences (DID) research designs. In contrast to alternative DID estimators, ...the proposed estimators are consistent if either (but not necessarily both) a propensity score or outcome regression working models are correctly specified. We also derive the semiparametric efficiency bound for the ATT in DID designs when either panel or repeated cross-section data are available, and show that our proposed estimators attain the semiparametric efficiency bound when the working models are correctly specified. Furthermore, we quantify the potential efficiency gains of having access to panel data instead of repeated cross-section data. Finally, by paying particular attention to the estimation method used to estimate the nuisance parameters, we show that one can sometimes construct doubly robust DID estimators for the ATT that are also doubly robust for inference. Simulation studies and an empirical application illustrate the desirable finite-sample performance of the proposed estimators. Open-source software for implementing the proposed policy evaluation tools is available.
Background
The impact of chemotherapy‐associated liver injury (CALI) on postoperative outcome in patients undergoing partial hepatectomy for colorectal liver metastases (CRLM) remains controversial. ...The objective of this study was to clarify the effect of CALI (sinusoidal dilatation (SD), steatosis and steatohepatitis) on postoperative morbidity and mortality by investigating a large data set from multiple international centres.
Methods
PubMed and Embase were searched for studies published between 1 January 2004 and 31 December 2013 with keywords ‘chemotherapy’, ‘liver resection’, ‘outcome’ and ‘colorectal metastases’ to identify potential collaborating centres. Univariable and multivariable analyses were performed using binary logistic regression models, with results presented as odds ratios (ORs) with 95 per cent confidence intervals.
Results
A consolidated database comprising 788 patients who underwent hepatectomy for CRLM in eight centres was obtained. In multivariable analyses, severe SD was associated with increased major morbidity (Dindo–Clavien grade III–V; OR 1·73, 95 per cent c.i. 1·02 to 2·95; P = 0·043). Severe steatosis was associated with decreased liver surgery‐specific complications (OR 0·52, 95 per cent c.i. 0·27 to 1·00; P = 0·049), whereas steatohepatitis was linked to an increase in these complications (OR 2·08, 1·18 to 3·66; P = 0·012). Subgroup analysis showed that lobular inflammation was the sole component associated with increased overall morbidity (OR 2·22, 1·48 to 3·34; P = 0·001) and liver surgery‐specific complications (OR 3·35, 2·11 to 5·32; P < 0·001). Finally, oxaliplatin treatment was linked to severe SD (OR 2·74, 1·67 to 4·49; P < 0·001).
Conclusion
An increase in postoperative major morbidity and liver surgery‐specific complications was observed after partial hepatectomy in patients with severe SD and steatohepatitis. Postoperative liver failure occurred more often in patients with severe SD.
Increased complications in severe sinusoidal dilatation and steatohepatitis
Background
The aim of this study was to evaluate whether adjuvant chemotherapy is associated with improved survival in patients with resectable gastric neuroendocrine carcinomas (G‐NECs) or mixed ...adenoneuroendocrine carcinomas (G‐MANECs).
Methods
The study included patients with G‐NECs or G‐MANECs who underwent surgery in one of 21 centres in China between 2004 and 2016. Propensity score matching analysis was used to reduce selection bias, and overall survival (OS) in different treatment groups was estimated by the Kaplan–Meier method.
Results
In total, 804 patients with resectable G‐NECs or G‐MANECs were included, of whom 490 (60·9 per cent) received adjuvant chemotherapy. After propensity score matching, OS in the chemotherapy group was similar to that in the no‐chemotherapy group. Among patients with G‐NECs, survival in the fluorouracil (5‐FU)‐based chemotherapy group and the non‐5‐FU‐based chemotherapy group was similar to that in the no‐chemotherapy group. Similarly, etoposide plus cisplatin or irinotecan plus cisplatin was not associated with better OS in patients with G‐NECs. Among patients with G‐MANECs, OS in the non‐5‐FU‐based chemotherapy group was worse than that in the no‐chemotherapy group. Patients with G‐MANECs did not have better OS when platinum‐based chemotherapy was
used.
Conclusion
There was no survival benefit in patients who received adjuvant chemotherapy for G‐NECs or G‐MANECs.
Antecedentes
El objetivo de este estudio fue evaluar si la quimioterapia adyuvante mejoraba la supervivencia en pacientes con carcinomas gástricos resecables neuroendocrinos (gastric neuroendocrine carcinomas, G‐NECs) y carcinomas adenoneuroendocrinos mixtos (mixed adenoneuroendocrine carcinomas, G‐MANECs).
Métodos
Se incluyeron pacientes con G‐NECs y G‐MANECs tratados quirúrgicamente en 21 centros en China entre 2004 y 2016. Se utilizó un análisis de emparejamiento por puntaje de propensión para reducir el sesgo de selección y el método de Kaplan‐Meier para estimar la supervivencia global (overall survival, OS) de los pacientes en los diferentes grupos de tratamiento.
Resultados
En total, se incluyeron en el estudio 804 pacientes con G‐NECs y G‐MANECs resecables y 490 pacientes (60,9%) recibieron quimioterapia adyuvante. Después del emparejamiento por puntaje de propensión, la OS del grupo con quimioterapia fue similar a la del grupo sin quimioterapia. En los pacientes con G‐NECs, la supervivencia en los grupos con quimioterapia basada en 5‐FU (fluorouracilo) y de quimioterapia sin 5‐FU fue similar a la del grupo sin quimioterapia. Asimismo, la combinación de etopósido y cisplatino o de irinotecán y cisplatino no se asoció con una mejor OS en pacientes con G‐NECs. En pacientes con G‐MANECs, la OS del grupo con quimioterapia sin 5‐FU fue peor que la del grupo sin quimioterapia. Los pacientes con G‐MANECs no presentaron una mejor OS cuando se administró quimioterapia basada en platinos.
Conclusión
La administración de quimioterapia adyuvante en pacientes con G‐NECs y G‐MANECs no mejoró la supervivencia.
This multicentre study enrolled 804 patients with resectable gastric neuroendocrine carcinomas and gastric mixed adenoneuroendocrine carcinomas. In propensity score matching analysis, there were no associations between the use of adjuvant chemotherapy and improved overall survival. Similar results were obtained in stratified analysis according to different chemotherapy regimens.
No benefit
Polariton lasing is the coherent emission arising from a macroscopic polariton condensate first proposed in 1996. Over the past two decades, polariton lasing has been demonstrated in a few inorganic ...and organic semiconductors in both low and room temperatures. Polariton lasing in inorganic materials significantly relies on sophisticated epitaxial growth of crystalline gain medium layers sandwiched by two distributed Bragg reflectors in which combating the built-in strain and mismatched thermal properties is nontrivial. On the other hand, organic active media usually suffer from large threshold density and weak nonlinearity due to the Frenkel exciton nature. Further development of polariton lasing toward technologically significant applications demand more accessible materials, ease of device fabrication, and broadly tunable emission at room temperature. Herein, we report the experimental realization of room-temperature polariton lasing based on an epitaxy-free all-inorganic cesium lead chloride perovskite nanoplatelet microcavity. Polariton lasing is unambiguously evidenced by a superlinear power dependence, macroscopic ground-state occupation, blueshift of the ground-state emission, narrowing of the line width and the buildup of long-range spatial coherence. Our work suggests considerable promise of lead halide perovskites toward large-area, low-cost, high-performance room-temperature polariton devices and coherent light sources extending from the ultraviolet to near-infrared range.
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