Periodontal ligament derived stem cells (PDLSCs) are capable of differentiating into multiple cell types and inducing a promising immunomodulation for tissue regeneration and disease treatment. However, it is still challenging to develop a practical approach to activate endogenous stem cells for tissue self-healing and regeneration. In this study, transcriptome analysis reveals that resveratrol promotes PDLSC stemness through activation of stem cell, osteoprogenitor, and chondroprogenitor markers. Self-renewal and multipotent differentiation abilities are also improved in resveratrol-treated PDLSCs. In addition, immunomodulation of PDLSCs is dramatically increased after resveratrol treatment. Mechanistically, we show that resveratrol activates ERK/WNT crosstalk through elevation of olfactory and growth factor signaling pathways to upregulate the expression levels of RUNX2 and FASL for osteogenesis and immunomodulation, respectively. By using a periodontitis animal model, administration of resveratrol partially rescues bone loss through activation of endogenous somatic stem cells and inhibition of inflammatory T-cell infiltration. Taken together, our findings identify a novel pharmacological approach to achieve autotherapies for endogenous tissue regeneration.

The need to operate an rf-gun-based electron photoinjector with a beam emitted away from the cathode center can occur under various circumstances. First, in some cases the cathode can be affected by ion back-bombardment that progressively reduces the quantum efficiency (QE) in its center, making off-axis operation mandatory; second, in some cases the drive laser intensity can be sufficiently high to generate QE depletion in the cathode area illuminated by the laser, forcing off-axis operation; last, in cathodes with nonuniform QE distribution it could be convenient to operate off axis to exploit a better QE. However, operation in this mode may lead to growth of the projected transverse beam emittances due to correlations between the transverse and longitudinal degrees of freedom that are introduced within the gun and downstream rf cavities. A strategy is described to mitigate this emittance growth by allowing the beam to propagate along a carefully tuned off-axis trajectory in downstream rf cavities to remove the time-dependent rf kicks introduced in the gun. Along this trajectory, short range wakefields do not degrade the emittance, and long range wakefields degrade the emittance for very high repetition rate only.

Capecitabine is commonly used in treating breast cancer; however, therapeutic response varies among patients and there is no clinically validated model to predict individual outcomes. Here, we investigated whether drug sensitivity quantified in ex vivo patients' blood-derived cell lines can predict response to capecitabine in vivo. Lymphoblastoid cell lines (LCLs) were established from a cohort of metastatic breast cancer patients (n = 53) who were prospectively monitored during treatment with single agent capecitabine at 2000 mg/m2/day. LCLs were treated with increasing concentrations of 5'-DFUR, a major capecitabine metabolite, to assess patients' ex vivo sensitivity to this drug. Subsequently, ex vivo phenotype was compared to observed patient disease response and drug induced-toxicities. We acquired an independent cohort of breast cancer cell lines and LCLs derived from the same donors from ATCC, compared their sensitivity to 5'-DFUR. As seen in the patient population, we observed large inter-individual variability in response to 5'-DFUR treatment in patient-derived LCLs. Patients whose LCLs were more sensitive to 5'-DFUR had a significantly longer median progression free survival (9-month vs 6-month, log rank p-value = 0.017). In addition, this significant positive correlation for 5'-DFUR sensitivity was replicated in an independent cohort of 8 breast cancer cell lines and LCLs derived from the same donor. Our data suggests that at least a portion of the individual sensitivity to capecitabine is shared between germline tissue and tumor tissue. It also supports the utility of patient-derived LCLs as a predictive model for capecitabine treatment efficacy in breast cancer patients.

The CUPID-Mo experiment, located at the Laboratoire Souterrain de Modane (France), was a demonstrator experiment for CUPID. It consisted of an array of 20Li2Mo100O4 (LMO) calorimeters, each equipped with a Ge light detector for particle identification. In this work, we present the result of a search for two-neutrino and neutrinoless double-β decays of Mo100 to the first 0+ and 2+ excited states of Ru100 using the full CUPID-Mo exposure (2.71kgyr of LMO). We measure the half-life of 2νββ decay to the 01+ state as T1/22ν→01+=(7.5±0.8(stat.)-0.3+0.4(syst.))×1020yr. The bolometric technique enables measurement of the electron energies as well as the γ rays from nuclear deexcitation and this allows us to set new limits on the two-neutrino decay to the 21+ state of T1/22ν→21+>4.4×1021yr(90% c.i.) and on the neutrinoless modes of T1/20ν→21+>2.1×1023yr(90% c.i.), T1/20ν→01+>1.2×1023yr(90% c.i.). Information on the electrons' spectral shape is obtained, which allows us to make the first comparison of the single and higher state dominance 2νββ decay models for the 01+ excited state of Ru100.

The CUPID-Mo experiment to search for 0$ u\beta\beta$ decay in $^{100}$Mo has been recently completed after about 1.5 years of operation at Laboratoire Souterrain de Modane (France). It served as a demonstrator for CUPID, a next generation 0$ u\beta\beta$ decay experiment. CUPID-Mo was comprised of 20 enriched Li$_2$$^{100}$MoO$_4$ scintillating calorimeters, each with a mass of $\sim$ 0.2 kg, operated at $\sim$20 mK. We present here the final analysis with the full exposure of CUPID-Mo ($^{100}$Mo exposure of 1.47 kg$\times$yr) used to search for lepton number violation via 0$ u\beta\beta$ decay. We report on various analysis improvements since the previous result on a subset of data, reprocessing all data with these new techniques. We observe zero events in the region of interest and set a new limit on the $^{100}$Mo 0$ u\beta\beta$ decay half-life of $T^{0 u}_{1/2} > 1.8 \times 10^{24}$ year (stat.+syst.) at 90% CI. Under the light Majorana neutrino exchange mechanism this corresponds to an effective Majorana neutrino mass of $\left < (0.28$--$0.49)$ eV, dependent upon the nuclear matrix element utilized.