Cancer stem cells (CSCs) are inherently resistant to chemotherapy, and CSCs in chemotherapy-failed recurrent tumors are enriched; however, the cellular origin of chemotherapy-induced CSC enrichment ...remains unclear. Communication with stromal fibroblasts may induce cancer cell dedifferentiation into CSCs through secreted factors. We recently demonstrated that fibroblast-derived exosomes promote chemoresistance in colorectal cancer (CRC). Here, we report that fibroblasts confer CRC chemoresistance via exosome-induced reprogramming (dedifferentiation) of bulk CRC cells to phenotypic and functional CSCs. At the molecular level, we provided evidence that the major reprogramming regulators in fibroblast-exosomes are Wnts. Exosomal Wnts were found to increase Wnt activity and drug resistance in differentiated CRC cells, and inhibiting Wnt release diminished this effect in vitro and in vivo. Together, our results indicate that exosomal Wnts derived from fibroblasts could induce the dedifferentiation of cancer cells to promote chemoresistance in CRC, and suggest that interfering with exosomal Wnt signaling may help to improve chemosensitivity and the therapeutic window.
Double neutron star (DNS) merger events are promising candidates of short gamma-ray burst (sGRB) progenitors as well as high-frequency gravitational wave (GW) emitters. On August 17, 2017, such a ...coinciding event was detected by both the LIGO-Virgo gravitational wave detector network as GW170817 and Gamma-Ray Monitor on board NASA's Fermi Space Telescope as GRB 170817A. Here, we show that the fluence and spectral peak energy of this sGRB fall into the lower portion of the distributions of known sGRBs. Its peak isotropic luminosity is abnormally low. The estimated event rate density above this luminosity is at least Formula: see text Gpc
yr
, which is close to but still below the DNS merger event rate density. This event likely originates from a structured jet viewed from a large viewing angle. There are similar faint soft GRBs in the Fermi archival data, a small fraction of which might belong to this new population of nearby, low-luminosity sGRBs.
With the aim of gathering temporal trends on bacterial epidemiology and resistance from multiple laboratories in China, the CHINET surveillance system was organized in 2005. Antimicrobial ...susceptibility testing was carried out according to a unified protocol using the Kirby-Bauer method or automated systems. Results were analyzed according to Clinical and Laboratory Standards Institute (CLSI) 2014 definitions. Between 2005 and 2014, the number of bacterial isolates ranged between 22 774 and 84 572 annually. Rates of extended-spectrum β-lactamase production among Escherichia coli isolates were stable, between 51.7 and 55.8%. Resistance of E. coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, piperacillin/tazobactam and cefoperazone/sulbactam decreased with time. Carbapenem resistance among K. pneumoniae isolates increased from 2.4 to 13.4%. Resistance of Pseudomonas aeruginosa strains against all of antimicrobial agents tested including imipenem and meropenem decreased with time. On the contrary, resistance of Acinetobacter baumannii strains to carbapenems increased from 31 to 66.7%. A marked decrease of methicillin resistance from 69% in 2005 to 44.6% in 2014 was observed for Staphylococcus aureus. Carbapenem resistance rates in K. pneumoniae and A. baumannii in China are high. Our results indicate the importance of bacterial surveillance studies.
Nanocrystals of apatitic calcium phosphate impart the organic-inorganic nanocomposite in bone with favorable mechanical properties. So far, the factors preventing crystal growth beyond the favorable ...thickness of ca. 3 nm have not been identified. Here we show that the apatite surfaces are studded with strongly bound citrate molecules, whose signals have been identified unambiguously by multinuclear magnetic resonance (NMR) analysis. NMR reveals that bound citrate accounts for 5.5 wt% of the organic matter in bone and covers apatite at a density of about 1 molecule per (2 nm)², with its three carboxylate groups at distances of 0.3 to 0.45 nm from the apatite surface. Bound citrate is highly conserved, being found in fish, avian, and mammalian bone, which indicates its critical role in interfering with crystal thickening and stabilizing the apatite nanocrystals in bone.
Gamma-ray bursts (GRBs) are flashes of high-energy radiation arising from energetic cosmic explosions. Bursts of long (greater than two seconds) duration are produced by the core-collapse of massive ...stars
, and those of short (less than two seconds) duration by the merger of compact objects, such as two neutron stars
. A third class of events with hybrid high-energy properties was identified
, but never conclusively linked to a stellar progenitor. The lack of bright supernovae rules out typical core-collapse explosions
, but their distance scales prevent sensitive searches for direct signatures of a progenitor system. Only tentative evidence for a kilonova has been presented
. Here we report observations of the exceptionally bright GRB 211211A, which classify it as a hybrid event and constrain its distance scale to only 346 megaparsecs. Our measurements indicate that its lower-energy (from ultraviolet to near-infrared) counterpart is powered by a luminous (approximately 10
erg per second) kilonova possibly formed in the ejecta of a compact object merger.
Abstract Induced pluripotent stem cells (iPSCs) hold great promise as a cell source for regenerative medicine yet its culture, maintenance of pluripotency and induction of differentiation remain ...challenging. Conversely, graphene (G) and graphene oxide (GO) have captured tremendous interests in the fields of materials science, physics, chemistry and nanotechnology. Here we report on that G and GO can support the mouse iPSCs culture and allow for spontaneous differentiation. Intriguingly, G and GO surfaces led to distinct cell proliferation and differentiation characteristics. In comparison with the glass surface, iPSCs cultured on the G surface exhibited similar degrees of cell adhesion and proliferation while iPSCs on the GO surface adhered and proliferated at a faster rate. Moreover, G favorably maintained the iPSCs in the undifferentiated state while GO expedited the differentiation. The iPSCs cultured on both G and GO surfaces spontaneously differentiated into ectodermal and mesodermal lineages without significant disparity, but G suppressed the iPSCs differentiation towards the endodermal lineage whereas GO augmented the endodermal differentiation. These data collectively demonstrated that the different surface properties of G and GO governed the iPSCs behavior and implicate the potentials of graphene-based materials as a platform for iPSCs culture and diverse applications.
Stable isotope analysis of ancient skeletons has become a routine method and widely used to answer diverse archaeological questions related to the human (animal) diets since the initial study in ...1977. However, this study in china is underestimated and much less unknown to international circles considering the infrequent publications in English journals. In this review paper, the research history in China was overviewed shortly and then, the research progresses concerning different research themes, such as the chronological trajectory of human diets, the development and spread of agriculture, the mechanism of animal domestication, human social hierarchy, and so on, were introduced in detail, trying to draw a rough framework of human dietary evolution given the unique Chinese geography and cultures. At last, the potential research directions were also suggested for the future studies.
The +0.1‰ elevated
Fe/
Fe ratio of terrestrial basalts relative to chondrites was proposed to be a fingerprint of core-mantle segregation. However, the extent of iron isotopic fractionation between ...molten metal and silicate under high pressure-temperature conditions is poorly known. Here we show that iron forms chemical bonds of similar strengths in basaltic glasses and iron-rich alloys, even at high pressure. From the measured mean force constants of iron bonds, we calculate an equilibrium iron isotope fractionation between silicate and iron under core formation conditions in Earth of ∼0-0.02‰, which is small relative to the +0.1‰ shift of terrestrial basalts. This result is unaffected by small amounts of nickel and candidate core-forming light elements, as the isotopic shifts associated with such alloying are small. This study suggests that the variability in iron isotopic composition in planetary objects cannot be due to core formation.
Morbidity and mortality from tuberculosis (TB) are high in Taiwan. We conducted a nationwide population‐based matched cohort study using data retrieved from the Taiwan's National Health Insurance ...Research Database to determine the impact of TB after liver transplantation (LT). During 2000–2011, we identified 3202 liver transplant recipients and selected subjects from the general population matched for age, sex, and comorbidities on the same index date of recognition of LT with a 1:10 ratio. The data were analyzed using Cox proportional hazards models. Compared to the matched cohort, liver transplant patients had a higher risk for TB (adjusted HR 2.25, 95% CI 1.65–3.05, p < 0.001), and those with TB showed higher mortality (HR 2.27, 95% CI 1.30–3.97, p = 0.004). Old age (HR 2.64, 95% CI 1.25–5.54, p = 0.011) and mammalian target of rapamycin inhibitors (mTORis) (HR 3.09, 95% CI 1.68–5.69, p < 0.001) were significant risk factors for TB in LT; mTORis were also associated with mortality after adjusting for confounders (HR 2.13, 95% CI 1.73–2.62, p < 0.001). Therefore, regular surveillance of TB and treatment of latent TB infection in high‐risk patients after LT are important, especially in TB‐endemic areas.
The authors demonstrate the high risk of tuberculosis in liver transplant recipients and define old age and mammalian target of rapamycin inhibitors as risk factors for tuberculosis after liver transplantation, which provides a practical guide to selecting high‐risk liver transplant patients for regular surveillance and treatment of tuberculosis.
FeCoCrNi HEA coatings with 20% mass fraction of WC reinforcing particles were prepared by two different cladding methods, laser cladding (LC) and plasma cladding (PC). The microstructure of HEA ...matrix and WC particles of LC and PC coatings were discussed respectively. For HEA matrix, dendritic morphology was observed in both coatings. For WC particles, a few granular (Cr,W)2C carbides around WC particles in LC coatings, and a large number of crystal and fishbone Fe3W3C carbides around WC particles in PC coatings. Mechanical properties as hardness and wear resistance of the two kinds of coatings were also investigated. The interstitial solution strengthening effect of C element is stronger in PC coating, and the hardness of HEA matrix in LC coatings is twice that of in PC coating, which shows a strong retention force on WC particles. The friction coefficient of LC coating is lower and stable, with the volume wear rate of 0.7 × 10−5 mm−3/N·m, showing high wear resistance. PC coatings have poor wear resistance due to decarbonization and oxidation of WC particles and reduction of retention force of HEA matrix, with the volume wear rate of 8.29 × 10−5 mm−3/N·m. The wear mechanism of both coatings were also discussed.
•HEA/WC composite coatings were prepared by laser cladding (LC) and plasma cladding (PC) respectively.•Complex carbides around WC particles were formed in PC coatings.•The interstitial solution strengthening effect of HEA matrix is stronger in LC coatings.•LC coating is abrasive wear mechanism, showing high wear resistance.•PC coatings have poor wear resistance due to the failure of WC particles and weak retention force of HEA matrix.
PDF
