CD40 signal rewires fatty acid and glutamine metabolism for stimulating macrophage anti-tumorigenic functions.

Exposure of lipopolysaccharide triggers macrophage pro-inflammatory polarization accompanied by metabolic reprogramming, characterized by elevated aerobic glycolysis and a broken tricarboxylic acid cycle. However, in contrast to lipopolysaccharide, CD40 signal is able to drive pro-inflammatory and anti-tumorigenic polarization by some yet undefined metabolic programming. Here we show that CD40 activation triggers fatty acid oxidation (FAO) and glutamine metabolism to promote ATP citrate lyase-dependent epigenetic reprogramming of pro-inflammatory genes and anti-tumorigenic phenotypes in macrophages. Mechanistically, glutamine usage reinforces FAO-induced pro-inflammatory and anti-tumorigenic activation by fine-tuning the NAD <sup>+</sup> /NADH ratio via glutamine-to-lactate conversion. Genetic ablation of important metabolic enzymes involved in CD40-mediated metabolic reprogramming abolishes agonistic anti-CD40-induced antitumor responses and reeducation of tumor-associated macrophages. Together these data show that metabolic reprogramming, which includes FAO and glutamine metabolism, controls the activation of pro-inflammatory and anti-tumorigenic polarization, and highlight a therapeutic potential of metabolic preconditioning of tumor-associated macrophages before agonistic anti-CD40 treatments

The molecular systems composed of the charmed mesons in the HSˉ+h.c.H\bar{S}+h.c. doublet

We study the possible heavy molecular states composed of a pair of charm mesons in the H and S doublets. Since the P-wave charm-strange mesons $D_{s0}(2317)$ and $D_{s1}(2460)$ are extremely narrow, the future experimental observation of the possible heavy molecular states composed of $D_s/D_s^\ast$ and $D_{s0}(2317)/D_{s1}(2460)$ may be feasible if they really exist. Especially the possible $J^{PC}=1^{--}$ states may be searched for via the initial state radiation technique.Comment: 42 pages, 4 tables, 31 figures. Improved numerical results and Corrected typos

Search for jet extinction in the inclusive jet-pT spectrum from proton-proton collisions at s=8 TeV

Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published articles title, journal citation, and DOI.The first search at the LHC for the extinction of QCD jet production is presented, using data collected with the CMS detector corresponding to an integrated luminosity of 10.7  fb−1 of proton-proton collisions at a center-of-mass energy of 8 TeV. The extinction model studied in this analysis is motivated by the search for signatures of strong gravity at the TeV scale (terascale gravity) and assumes the existence of string couplings in the strong-coupling limit. In this limit, the string model predicts the suppression of all high-transverse-momentum standard model processes, including jet production, beyond a certain energy scale. To test this prediction, the measured transverse-momentum spectrum is compared to the theoretical prediction of the standard model. No significant deficit of events is found at high transverse momentum. A 95% confidence level lower limit of 3.3 TeV is set on the extinction mass scale

Searches for electroweak neutralino and chargino production in channels with Higgs, Z, and W bosons in pp collisions at 8 TeV

Searches for supersymmetry (SUSY) are presented based on the electroweak pair production of neutralinos and charginos, leading to decay channels with Higgs, Z, and W bosons and undetected lightest SUSY particles (LSPs). The data sample corresponds to an integrated luminosity of about 19.5 fb(-1) of proton-proton collisions at a center-of-mass energy of 8 TeV collected in 2012 with the CMS detector at the LHC. The main emphasis is neutralino pair production in which each neutralino decays either to a Higgs boson (h) and an LSP or to a Z boson and an LSP, leading to hh, hZ, and ZZ states with missing transverse energy (E-T(miss)). A second aspect is chargino-neutralino pair production, leading to hW states with E-T(miss). The decays of a Higgs boson to a bottom-quark pair, to a photon pair, and to final states with leptons are considered in conjunction with hadronic and leptonic decay modes of the Z and W bosons. No evidence is found for supersymmetric particles, and 95% confidence level upper limits are evaluated for the respective pair production cross sections and for neutralino and chargino mass values

Association between temperature changes and uveitis onset in mainland China

Background Some uveitis subtypes show seasonal patterns. Whether these patterns are caused by seasonally varying temperatures or by other climatic factors remains unknown. This ecological research aimed to quantify the association between climate variability and uveitis onset. Methods We combined data from the largest database of uveitis cases with surface climate data to construct panel data. We used choropleth maps to visually assess spatial uveitis variations. Results Among 12 721 reports of uveitis originating from 31 provinces of mainland China from 2006 to 2017, we found that a 1 degrees C increase in monthly temperature was associated with a rise in approximately 2 uveitis reports per 1000 individuals (95% CI 0.00059 to 0.0029). This association was present across all provinces, ranging in effect size from 0.0011 to 0.072 (95% CI 0.00037 to 0.10). A clear 0-3 months of cumulative lagging effect was noted across all types of uveitis, with the strongest effect for non-infectious uveitis (0.0067, 95% CI 0.0041 to 0.013). Stratified by age and sex, we found that men and people aged 20-50 years were more affected by temperature variations. Our model predicts that China might experience an increase in uveitis cases due to future global warming. Conclusion Our study is the largest-ever investigation of the association between uveitis and climate and, for the first time, provides evidence that rising temperature can affect large-scale uveitis onset. These results may help promote and implement policies to mitigate future temperature increases and the burden of disease caused by global warming

Association between temperature changes and uveitis onset in mainland China

Background Some uveitis subtypes show seasonal patterns. Whether these patterns are caused by seasonally varying temperatures or by other climatic factors remains unknown. This ecological research aimed to quantify the association between climate variability and uveitis onset. Methods We combined data from the largest database of uveitis cases with surface climate data to construct panel data. We used choropleth maps to visually assess spatial uveitis variations. Results Among 12 721 reports of uveitis originating from 31 provinces of mainland China from 2006 to 2017, we found that a 1 degrees C increase in monthly temperature was associated with a rise in approximately 2 uveitis reports per 1000 individuals (95% CI 0.00059 to 0.0029). This association was present across all provinces, ranging in effect size from 0.0011 to 0.072 (95% CI 0.00037 to 0.10). A clear 0-3 months of cumulative lagging effect was noted across all types of uveitis, with the strongest effect for non-infectious uveitis (0.0067, 95% CI 0.0041 to 0.013). Stratified by age and sex, we found that men and people aged 20-50 years were more affected by temperature variations. Our model predicts that China might experience an increase in uveitis cases due to future global warming. Conclusion Our study is the largest-ever investigation of the association between uveitis and climate and, for the first time, provides evidence that rising temperature can affect large-scale uveitis onset. These results may help promote and implement policies to mitigate future temperature increases and the burden of disease caused by global warming

Data-taking strategy for the precise measurement of the WW boson mass with a threshold scan at circular electron positron colliders

International audienceCircular electron positron colliders, such as the CEPC and FCC-ee, have been proposed to measure Higgs boson properties precisely, test the Standard Model, search for physics beyond the Standard Model, and so on. One of the important goals of these colliders is to measure the W boson mass with great precision by taking data around the W-pair production threshold. In this paper, the data-taking scheme is investigated to maximize the achievable precisions of the W boson mass and width with a threshold scan, when various systematic uncertainties are taken into account. The study shows that an optimal and realistic data-taking scheme is to collect data at three center-of-mass energies and that precisions of 1.0 MeV and 3.4 MeV can be achieved for the mass and width of the W boson, respectively, with a total integrated luminosity of $\mathscr {L}=3.2$ ab$^{-1}$ and several assumptions of the systematic uncertainty sources