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Notably, while TGFβ1 induced pEMT and promoted collective invasion, it abrogated self-renewal capacity of TKA organoids which correlated with the downregulation of intestinal stem cell (ISC) marker genes. Mechanistically, induction of the non-progressive pEMT required canonical TGFβ signaling mediated by Smad transcription factors (TFs), whereas the EMT master regulators Snail1 and Zeb1 were dispensable. Gene expression profiling provided further evidence for pEMT of TGFβ1-treated organoids and showed that their transcriptomes resemble those of human poor prognosis CMS4 cancers which likewise exhibit pEMT features. [https://www.selleckchem.com/products/p5091-p005091.html see more] We propose that collective invasion in colorectal carcinogenesis is triggered by microenvironmental stimuli through activation of a novel, transcription-mediated form of non-progressive pEMT independently of classical EMT regulators.Multiple myeloma (MM) is still incurable partially due to lacking effective therapeutic targets. Aberrant N6-methyladenosine (m6A) RNA modification plays a vital role in many cancers, however few researches are executed in MM. We first screened the m6A-related genes in MM patient cohorts and correlated these genes with patient outcomes. We found that YTHDF2, a well-recognized m6A reader, was increased in MM patients and associated with poor outcomes. Decreased YTHDF2 expression hampered MM cell proliferation in vitro and in vivo, while enforced YTHDF2 expression reversed those effects. The analyses of m6A-RIP-seq and RIP-PCR indicated that STAT5A was the downstream target of YTHDF2, which was binding to the m6A modification site of STAT5A to promote its mRNA degradation. ChIP-seq and PCR assays revealed that STAT5A suppressed MM cell proliferation by occupying the transcription site of MAP2K2 to decrease ERK phosphorylation. In addition, we confirmed that YTHDF2 mediated the unphosphorylated form of STAT5A to inhibit the expression of MAP2K2/p-ERK. In conclusion, our study highlights that YTHDF2/STAT5A/MAP2K2/p-ERK axis plays a key role in MM proliferation and targeting YTHDF2 may be a promising therapeutic strategy.Recent studies have shown that people engaging in joint rhythmic activity unintentionally increase their tempo. The same tempo increase does not occur when the same rhythmic activity is performed alone. This phenomenon is known as joint rushing. In two experiments, we investigated whether joint rushing is caused by correction mechanisms that facilitate sensorimotor synchronization. Because such correction mechanisms require perceptual input, joint rushing should discontinue when auditory feedback in a joint rhythmic activity is interrupted. This prediction was clearly supported in two experiments, one with musicians and one with non-musicians. Surprisingly, there was no indication that the amount of joint rushing differed between musicians and non-musicians. Furthermore, neither musicians nor non-musicians were able to return to the initially instructed tempo after feedback had been interrupted. This result indicates that joint rushing has a lasting effect on an internal timekeeper. An important question for future research is whether joint rushing is only a dysfunctional side effect of the way sensorimotor synchronization works or whether it has a function in enabling precise temporal coordination between different individuals.<br />Phthalates have been reported to alter circulating lipid concentrations in animals, and investigation of these associations in humans will provide greater understanding of potential mechanisms for health outcomes.<br />To explore associations between phthalate metabolite biomarkers and lipidomic profiles among pregnant women (n = 99) in the Puerto Rico PROTECT cohort.<br />We measured 19 urinary phthalate metabolites during 24-28 weeks of pregnancy. Lipidomic profiles were identified from plasma samples by liquid chromatography-mass spectrometry-based shotgun lipidomics. Relationships between phthalate metabolites and lipid profiles were estimated using compound-by-compound comparisons in multiple linear regression and dimension reduction techniques. We derived sums for each lipid class and sub-class (saturated, mono-unsaturated, polyunsaturated) which were then regressed on phthalate metabolites. Associations were adjusted for false discovery.<br />After controlling for multiple comparisons, 33 phthalate-lipid assoough hormone signaling, while plasmenyl-phosphatidylcholines have been implicated in membrane dynamics and important for cell-to-cell signaling. Characterization of these mechanisms are relevant for informing the etiology of maternal and children's health outcomes.<br />This study leverages emerging technology to evaluate lipidome-wide signatures of phthalate exposure during pregnancy. The greatest lipid signatures of phthalate exposure were observed for diacylglycerol 407 and plasmenyl-phosphatidylcholine 351. Polymerized glycerides are important for energy production and regulated through hormone signaling, while plasmenyl-phosphatidylcholines have been implicated in membrane dynamics and important for cell-to-cell signaling. Characterization of these mechanisms are relevant for informing the etiology of maternal and children's health outcomes.It is difficult to assess the pure impact of the type of residual astigmatism (with-the-rule; WTR, against-the-rule; ATR, and oblique astigmatism) on uncorrected distance visual acuity (UDVA) in pseudophakic eyes due to different age distribution of patients between those subgroups. We conducted the current study to investigate the association between astigmatism type and UDVA in eyes after cataract surgery with consideration for various confounding factors such as age. Data were retrospectively collected from 1535 pseudophakic eyes with corrected distance visual acuity (CDVA) of 20/20 or better, and spherical equivalent between - 0.125 D and 0.0 D. They were classified based on the pattern of residual refractive astigmatism into four groups; minimum astigmatism ( less then  0.5 D), WTR, ATR, and oblique astigmatism groups. The stepwise multivariate regression analysis showed that the magnitude of residual refractive astigmatism (standardized partial regression coefficient β = 0.559, p  less then  0.001), CDVA (β = 0.381, p  less then  0.001), minimum astigmatism group (β = - 0.188, p  less then  0.001), and WTR astigmatism group (β = - 0.058, p  less then  0.001) were significantly associated with UDVA (r2 = 0.795). Variables excluded from the multivariate regression model include age, preoperative corneal astigmatism, axial length, anterior chamber depth, intraocular lens power, and postoperative spherical equivalent. These results indicate that UDVA is significantly better in eyes with minimum and WTR astigmatism than in those with ATR and oblique astigmatism, after adjustment for confounding parameters. In pseudophakic eyes, oblique and ATR astigmatism exerts a greater impact on UDVA than WTR astigmatism does, even after controlling for age.Attributable to the Montreal Protocol, the most successful environmental treaty ever, human-made ozone-depleting substances are declining and the stratospheric Antarctic ozone layer is recovering. However, the Antarctic ozone hole continues to occur every year, with the severity of ozone loss strongly modulated by meteorological conditions. In late November and early December 2020, we measured at the northern tip of the Antarctic Peninsula the highest ultraviolet (UV) irradiances recorded in the Antarctic continent in more than two decades. On Dec. 2nd, the noon-time UV index on King George Island peaked at 14.3, very close to the largest UV index ever recorded in the continent. On Dec. 3rd, the erythemal daily dose at the same site was among the highest on Earth, only comparable to those recorded at high altitude sites in the Atacama Desert, near the Tropic of Capricorn. Here we show that, despite the Antarctic ozone recovery observed in early spring, the conditions that favor these extreme surface UV events persist in late spring, when the biologically effective UV radiation is more consequential. These conditions include long-lasting ozone holes (attributable to the polar vortex dynamics) that often bring ozone-depleted air over the Antarctic Peninsula in late spring. The fact that these conditions have been occurring at about the same frequency during the last two decades explains the persistence of extreme surface UV events in Antarctica.Toxoplasma gondii is a worldwide food-borne parasite that can infect almost all warm-blooded animals, including humans. To date, there are no effective drugs to prevent or eradicate T. gondii infection. Recent studies have shown that probiotics could influence the relationship between the microbiota and parasites in the host. Koumiss has been used to treat many diseases based on its probiotic diversity. Therefore, we explored the effect of koumiss on T. gondii infection via its effect on the host intestinal microbiota. BALB/c mice were infected with T. gondii and treated with PBS, koumiss and mares' milk. Brain cysts were counted, and long-term changes in the microbiota and the effect of koumiss on gut microbiota were investigated with high-throughput sequencing technology. The results suggested that koumiss treatment significantly decreased the cyst counts in the brain (P  less then  0.05). Moreover, T. gondii infection changed the microbiota composition, and koumiss treatment increased the relative abundance of Lachnospiraceae and Akkermansia muciniphila, which were associated with preventing T. gondii infection. Moreover, koumiss could inhibit or ameliorate T. gondii infection by increasing the abundance of certain bacteria that control unique metabolic pathways. The study not only established a close interaction among the host, intracellular pathogens and intestinal microbiota but also provided a novel focus for drug development to prevent and eradicate T. gondii infection.3D printed navigational templates have facilitated the accurate treatment of orthopaedic patients. However, during practical operation, it is found that the location hole occasionally deviates from the ideal channel. As such, there will be a security risk in clinical applications. The purpose of this study was to evaluate the influence of chemical-based sterilisation methods on the dimensional accuracy of different materials and the influence of module parameters on the degree of deformation. We found that polylactic (PLA) modules sterilised with ethylene oxide (EO) would undergo micro-deformation, and these micro-deformation characteristics depend on the building direction, i.e., the module stretches in the Z direction and shrinks in the X and Y directions. Heat-resisting polylactide (HR-PLA) has the same melting temperature (Tm) as PLA, but its glass transition temperature (Tg) is greater than the EO sterilisation temperature, so there is no obvious deformation after EO sterilisation. The layer height of the module were inversely proportional to the degree of deformation in the same sterilisation method. The deformation time of the module is concentrated within 2 h after heating. The micro-deformation of the 3D printing module depends on its Tg, sterilisation temperature, and duration of the sterilisation cycle.