TIPE1 (tumor necrosis factor-α-induced protein 8-like 1 or TNFAIP8L1) is a newly identified member of the TIPE (TNFAIP8) family, which play roles in regulating cell death. However, the biologic ...functions of TIPE1 in physiologic and pathologic conditions are largely unknown. Here, we report the roles of TIPE1 in hepatocellular carcinoma (HCC). Evaluated by immunohistochemical staining, HCC tissues showed significantly downregulated TIPE1 expression compared with adjacent non-tumor tissues, which positively correlated with tumor pathologic grades and patient survival. Using a homograft tumor model in Balb/c mice, we discovered that TIPE1 significantly diminished the growth and tumor weight of murine liver cancer homografts. Consistently, TIPE1 inhibited both cell growth and colony formation ability of cultured HCC cell lines, which was further identified to be due to TIPE1-inducing apoptosis in a caspase-independent, necrostatin-1 (Nec-1)-insensitive manner. Furthermore, mechanistic investigations revealed that TIPE1 interacted with Rac1, and inhibited the activation of Rac1 and its downstream p65 and c-Jun N-terminal kinase pathway. Moreover, overexpression of constitutively active Rac1 partially rescued the apoptosis induced by TIPE1, and Rac1 knockdown significantly restored the deregulated cell growth induced by TIPE1 small interfering RNA. Our findings revealed that TIPE1 induced apoptosis in HCC cells by negatively regulating Rac1 pathway, and loss of TIPE1 might be a new prognostic indicator for HCC patients.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The cross section of the e+e−→Λc+Λ¯c− process is measured with unprecedented precision using data collected with the BESIII detector at /¯s=4574.5, 4580.0, 4590.0 and 4599.5 MeV. The nonzero cross ...section near the Λc+Λ¯c− production threshold is cleared. At center-of-mass energies /¯s=4574.5 and 4599.5 MeV, the higher statistics data enable us to measure the Λc polar angle distributions. From these, the Λc electric over magnetic form-factor ratios (|GE/GM|) are measured for the first time. They are found to be 1.14±0.14±0.07 and 1.23±0.05±0.03, respectively, where the first uncertainties are statistical and the second are systematic.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
We present the methodology for a joint cosmological analysis of weak gravitational lensing from the fourth data release of the ESO Kilo-Degree Survey (KiDS-1000) and galaxy clustering from the ...partially overlapping Baryon Oscillation Spectroscopic Survey (BOSS) and the 2-degree Field Lensing Survey (2dFLenS). Cross-correlations between BOSS and 2dFLenS galaxy positions and source galaxy ellipticities have been incorporated into the analysis, necessitating the development of a hybrid model of non-linear scales that blends perturbative and non-perturbative approaches, and an assessment of signal contributions by astrophysical effects. All weak lensing signals were measured consistently via Fourier-space statistics that are insensitive to the survey mask and display low levels of mode mixing. The calibration of photometric redshift distributions and multiplicative gravitational shear bias has been updated, and a more complete tally of residual calibration uncertainties was propagated into the likelihood. A dedicated suite of more than 20 000 mocks was used to assess the performance of covariance models and to quantify the impact of survey geometry and spatial variations of survey depth on signals and their errors. The sampling distributions for the likelihood and the
χ
2
goodness-of-fit statistic have been validated, with proposed changes for calculating the effective number of degrees of freedom. The prior volume was explicitly mapped, and a more conservative, wide top-hat prior on the key structure growth parameter
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8
=
σ
8
(Ω
m
/0.3)
1/2
was introduced. The prevalent custom of reporting
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weak lensing constraints via point estimates derived from its marginal posterior is highlighted to be easily misinterpreted as yielding systematically low values of
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, and an alternative estimator and associated credible interval are proposed. Known systematic effects pertaining to weak lensing modelling and inference are shown to bias
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by no more than 0.1 standard deviations, with the caveat that no conclusive validation data exist for models of intrinsic galaxy alignments. Compared to the previous KiDS analyses,
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constraints are expected to improve by 20% for weak lensing alone and by 29% for the joint analysis.
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FMFMET, NUK, UL, UM, UPUK
The Alpha Magnetic Spectrometer (AMS) is a precision particle physics detector on the International Space Station (ISS) conducting a unique, long-duration mission of fundamental physics research in ...space. The physics objectives include the precise studies of the origin of dark matter, antimatter, and cosmic rays as well as the exploration of new phenomena. Following a 16-year period of construction and testing, and a precursor flight on the Space Shuttle, AMS was installed on the ISS on May 19, 2011. In this report we present results based on 120 billion charged cosmic ray events up to multi-TeV energies. This includes the fluxes of positrons, electrons, antiprotons, protons, and nuclei. These results provide unexpected information, which cannot be explained by the current theoretical models. The accuracy and characteristics of the data, simultaneously from many different types of cosmic rays, provide unique input to the understanding of origins, acceleration, and propagation of cosmic rays.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a ...randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0.0198) and less time required for symptoms remission (P = 0.0194) than those who received placebo. Based on chest images, both severe and critical patients treated with MSCs showed improvement by day 7 (P = 0.0099) and day 21 (P = 0.0084). MSC-treated patients had fewer adverse events. MSC infusion reduced the levels of C-reactive protein, proinflammatory cytokines, and neutrophil extracellular traps (NETs) and promoted the maintenance of SARS-CoV-2-specific antibodies. To explore how MSCs modulate the immune system, we employed single-cell RNA sequencing analysis on peripheral blood. Our analysis identified a novel subpopulation of VNN2
hematopoietic stem/progenitor-like (HSPC-like) cells expressing CSF3R and PTPRE that were mobilized following MSC infusion. Genes encoding chemotaxis factors - CX3CR1 and L-selectin - were upregulated in various immune cells. MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro. In addition, an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling. Together, our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary Background & aims Patients undergoing gastrointestinal operations are at risk of malnutrition which may increase the chance of adverse surgical outcomes. This prospective study aimed at ...correlating nutritional status of patients having gastrointestinal operations with their short-term surgical outcomes captured by a territory-wide Surgical Outcomes Monitoring and Improvement Program. Methods The preoperative malnutrition risk of Chinese adult patients undergoing elective/emergency ultra-major/major gastrointestinal operations in two surgical departments over a 12-month period were assessed by Chinese version of Malnutrition Universal Screening Tool. Their perioperative risk factors and clinical outcomes, including length of hospital stay, mortality and morbidity, were retrieved from the above mentioned program. Correlation of malnutrition risk with clinical outcomes was assessed by logistic regression analysis after controlling for known confounders. Results 943 patients (58% male; mean age 65.9 ± 14.8 years) underwent gastrointestinal operations (40.3% emergency operation; 52.7% ultra-major procedures; 66.9% bowel resections) had analyzable data. 15.8% and 17.1% of patients were at medium and high risk of malnutrition, respectively. Malnutrition risk score according to the screening tool was an independent predictor of length of hospital stay, 30-day mortality, 60-day mortality and minor medical complications. Similar correlations were found for various sub-scores of malnutrition risk. Weight loss sub-score was predictive of 30-day mortality, 60-day mortality and minor medical complications. Body mass index was predictive of mortality (30- and 60- day) whereas the acute disease sub-score was predictive of length of hospital stay. Conclusions Preoperative malnutrition was an important predictor of poor clinical outcomes in patients undergoing gastrointestinal operations in Hong Kong.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Dysphagia is a common complication in patients with oral cancer who have undergone free flap transplantation. The aim of this cluster randomized controlled trial was to evaluate the effect of ...personalized oral exercises on swallowing function in this group of patients. Eligible patients were randomly assigned to the intervention (n = 34) or control (n = 34) group. Intervention group patients received personalized oral exercises starting on day 6 after surgery. Swallowing function was evaluated on days 6 and 15, and at 1 month postoperative using the Mann Assessment of Swallowing Ability–Oral Cancer tool (MASA-OC). On day 15 and at 1 month after surgery, the total MASA-OC score (P = 0.003, P < 0.001) and the mouth opening (P = 0.001, P < 0.001) and lip seal (both P < 0.001) item scores showed a significantly greater improvement in the intervention group than in the control group. Moreover, the changes in salivation (P < 0.001) and tongue movement (P = 0.025) scores at 1 month after surgery were significantly greater in the intervention group than in the control group. There was no significant difference between the groups in the change in tongue strength scores on day 15 or at 1 month postoperative (P = 0.476, P = 0.223). Personalized oral exercises can improve swallowing function in patients with oral cancer after free flap transplantation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We report the observation of new properties of primary cosmic rays, neon (Ne), magnesium (Mg), and silicon (Si), measured in the rigidity range 2.15 GV to 3.0 TV with 1.8 × 106 Ne , 2.2 × 106 Mg , ...and 1.6 × 106 Si nuclei collected by the Alpha Magnetic Spectrometer experiment on the International Space Station. The Ne and Mg spectra have identical rigidity dependence above 3.65 GV. The three spectra have identical rigidity dependence above 86.5 GV, deviate from a single power law above 200 GV, and harden in an identical way. Unexpectedly, above 86.5 GV the rigidity dependence of primary cosmic rays Ne, Mg, and Si spectra is different from the rigidity dependence of primary cosmic rays He, C, and O. This shows that the Ne, Mg, and Si and He, C, and O are two different classes of primary cosmic rays.
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