Protective effect of dehydroandrographolide on obstructive cholestasis in bile duct-ligated mice

Background: Dehydroandrographolide (DA) is the main contributor to the therapeutic properties of the medicinal plant Andrographis paniculata (AP). However, it is unknown whether DA has a hepatoprotective effect on obstructive cholestasis in mice and humans. Methods: We administered DA to mice for 5 days prior to bile duct ligation (BDL) and for the 7 days. Liver function markers, liver histology and necrosis, compensatory responses of hepatocytes, liver fibrosis and the expression of hepatic fibrogenesis markers were evaluated in BDL mice and/or human LX-2 cells. Results: Mice treated with DA demonstrated lower levels of serum alanine transarninase (ALT), milder liver damage, liver necrosis and fibrosis formation than in vehicle control with carboxymethylcellulose (CMC) mice after BDL. DA treatment also enhanced the Mrp3 expression of hepatocytes but not Mrp4 following BDL. Further, DA treatment in BDL mice significantly reduced liver mRNA and/or protein expression of Tgf-β, Col1a1, α-Sma and Mmp2. This result was also supported by hydroxyproline analysis. The molecular mechanisms of DA treatment were also assessed in human hepatic stellate cell line (LX-2 cell). DA treatment significantly inhibited Tgf-β-induced Col1a1, Mmp2 and α-Sma expression in human LX-2 cells. These data suggested that DA treatment reduced liver damage through development of a hepatic adaptive response and inhibition of the activation of HSCs, which led to a reduction in liver fibrosis formation in BDL mice. Conclusions: DA treatment protected against liver damage and fibrosis following BDL and might be an effective therapy for extrahepatic cholestasis due to bile duct obstruction

3D Bioprinting: from Benches to Translational Applications

Over the last decades, the fabrication of 3D tissues has become commonplace in tissue engineering and regenerative medicine. However, conventional 3D biofabrication techniques such as scaffolding, microengineering, and fiber and cell sheet engineering are limited in their capacity to fabricate complex tissue constructs with the required precision and controllability that is needed to replicate biologically relevant tissues. To this end, 3D bioprinting offers great versatility to fabricate biomimetic, volumetric tissues that are structurally and functionally relevant. It enables precise control of the composition, spatial distribution, and architecture of resulting constructs facilitating the recapitulation of the delicate shapes and structures of targeted organs and tissues. This Review systematically covers the history of bioprinting and the most recent advances in instrumentation and methods. It then focuses on the requirements for bioinks and cells to achieve optimal fabrication of biomimetic constructs. Next, emerging evolutions and future directions of bioprinting are discussed, such as freeform, high-resolution, multimaterial, and 4D bioprinting. Finally, the translational potential of bioprinting and bioprinted tissues of various categories are presented and the Review is concluded by exemplifying commercially available bioprinting platforms

Constraints on the KS0→μ+μ−K^0_S \rightarrow \mu^+ \mu^- Branching Fraction

International audienceA search for the decay KS0→μ+μ- is performed using proton-proton collision data, corresponding to an integrated luminosity of 5.6  fb-1 and collected with the LHCb experiment during 2016, 2017, and 2018 at a center-of-mass energy of 13 TeV. The observed signal yield is consistent with zero, yielding an upper limit of B(KS0→μ+μ-)<2.2×10-10 at 90% C.L.. The limit reduces to B(KS0→μ+μ-)<2.1×10-10 at 90% C.L. once combined with the result from data taken in 2011 and 2012

Measurement of the Λb0→J/ψΛ\Lambda^0_b\rightarrow J/\psi\Lambda angular distribution and the Λb0\Lambda^0_b polarisation in pppp collisions

International audienceThis paper presents an analysis of the ${\Lambda}_b^0$→ J/ψΛ angular distribution and the transverse production polarisation of ${\Lambda}_b^0$ baryons in proton-proton collisions at centre-of-mass energies of 7, 8 and 13 TeV. The measurements are performed using data corresponding to an integrated luminosity of 4.9 fb$^{−1}$, collected with the LHCb experiment. The polarisation is determined in a fiducial region of ${\Lambda}_b^0$ transverse momentum and pseudorapidity of 1 < p$_{T}$< 20 GeV/c and 2 < η < 5, respectively. The data are consistent with ${\Lambda}_b^0$ baryons being produced unpolarised in this region. The parity-violating asymmetry parameter of the Λ → pπ$^{−}$ decay is also determined from the data and its value is found to be consistent with a recent measurement by the BES III collaboration.[graphic not available: see fulltext

Measurement of the electron reconstruction efficiency at LHCb

International audienceThe single electron track-reconstruction efficiency is determined using a sample corresponding to $1.3~\mathrm{fb}^{-1}$of $pp$ collision data recorded with the LHCb detector in 2017. This measurement exploits $B^+\to J/\psi (e^+e^-)K^+$ decays, where one of the electrons is fully reconstructed and paired with the kaon, while the other electron is reconstructed using only the information of the vertex detector. Despite this partial reconstruction, kinematic and geometric constraints allow the $B^+$-meson mass to be reconstructed and the signal to be well separated from backgrounds. This in turn allows the electron reconstruction efficiency to be measured by matching the partial track segment found in the vertex detector to tracks found by LHCb's regular reconstruction algorithms. The agreement between data and simulation is evaluated, and corrections are derived for simulated electrons in bins of kinematics. The presented method allows LHCb to measure branching fractions involving single electrons with a an electron reconstruction systematic uncertainty below $1\%$

Updated measurement of decay-time-dependent CP asymmetries in D0→K+K−D^0 \to K^+K^- and D0→π+π−D^0 \to \pi^+\pi^- decays

International audienceA search for decay-time-dependent charge-parity (CP) asymmetry in D0→K+K- and D0→π+π- decays is performed at the LHCb experiment using proton-proton collision data recorded at a center-of-mass energy of 13 TeV, and corresponding to an integrated luminosity of 5.4  fb-1. The D0 mesons are required to originate from semileptonic decays of b hadrons, such that the charge of the muon identifies the flavor of the neutral D meson at production. The asymmetries in the effective decay widths of D0 and D¯0 mesons are determined to be AΓ(K+K-)=(-4.3±3.6±0.5)×10-4 and AΓ(π+π-)=(2.2±7.0±0.8)×10-4, where the uncertainties are statistical and systematic, respectively. The results are consistent with CP symmetry and, when combined with previous LHCb results, yield AΓ(K+K-)=(-4.4±2.3±0.6)×10-4 and AΓ(π+π-)=(2.5±4.3±0.7)×10-4

Observation of a new baryon state in the Λb0π+π− {\Lambda}_{\mathrm{b}}^0{\pi}^{+}{\pi}^{-} mass spectrum

International audienceA new baryon state is observed in the ${\Lambda}_{\mathrm{b}}^0{\pi}^{+}{\pi}^{-}$ mass spectrum with high significance using a data sample of pp collisions, collected with the LHCb detector at centre-of-mass energies $\sqrt{s}$ = 7, 8 and 13 TeV, corresponding to an integrated luminosity of 9 fb$^{−1}$. The mass and natural width of the new state are measured to be${\displaystyle \begin{array}{l}m=6072.3\pm 2.9\pm 0.6\pm 0.2\ \mathrm{MeV},\\ {}\Gamma =72\pm 11\pm 2\ \mathrm{MeV},\end{array}}$where the first uncertainty is statistical and the second systematic. The third uncertainty for the mass is due to imprecise knowledge of the ${\Lambda}_{\mathrm{b}}^0$ baryon mass. The new state is consistent with the first radial excitation of the ${\Lambda}_{\mathrm{b}}^0$ baryon, the Λ$_{b}$(2S)$^{0}$ resonance. Updated measurements of the masses and the upper limits on the natural widths of the previously observed Λ$_{b}$(5912)$^{0}$ and Λ$_{b}$(5920)$^{0}$ states are also reported.[graphic not available: see fulltext

Search for A′→μ+μ−A'\to\mu^+\mu^- Decays

International audienceSearches are performed for both promptlike and long-lived dark photons, A′, produced in proton-proton collisions at a center-of-mass energy of 13 TeV. These searches look for A′→μ+μ- decays using a data sample corresponding to an integrated luminosity of 5.5  fb-1 collected with the LHCb detector. Neither search finds evidence for a signal, and 90% confidence-level exclusion limits are placed on the γ–A′ kinetic mixing strength. The promptlike A′ search explores the mass region from near the dimuon threshold up to 70 GeV and places the most stringent constraints to date on dark photons with 214<m(A′)≲740  MeV and 10.6<m(A′)≲30  GeV. The search for long-lived A′→μ+μ- decays places world-leading constraints on low-mass dark photons with lifetimes O(1)  ps

Measurement of Ξcc++\mathit{\Xi}_{cc}^{++} production in pppp collisions at s=13\sqrt{s}=13 TeV

International audienceThe production of baryons in proton-proton collisions at a centre-of-mass energy of is measured in the transverse-momentum range and the rapidity range . The data used in this measurement correspond to an integrated luminosity of , recorded by the LHCb experiment during 2016. The ratio of the production cross-section times the branching fraction of the decay relative to the prompt production cross-section is found to be , assuming the central value of the measured lifetime, where the first uncertainty is statistical and the second systematic