Triply heavy tetraquark states with the QQQˉqˉQQ\bar{Q}\bar{q} configuration

In the framework of the color-magnetic interaction, we systematically investigate the mass splittings of the $QQ\bar{Q}\bar{q}$ tetraquark states and estimated their rough masses in this work. These systems include the explicitly exotic states $cc\bar{b}\bar{q}$ and $bb\bar{c}\bar{q}$ and the hidden exotic states $cc\bar{c}\bar{q}$, $cb\bar{b}\bar{q}$, $bc\bar{c}\bar{q}$, and $bb\bar{b}\bar{q}$. If a state around the estimated mass region could be observed, its nature as a genuine tetraquark is favored. The strong decay patterns shown here will be helpful to the experimental search for these exotic states.Comment: 14 pages, 3 figures and 9 tables. Accepted by Eur. Phys. J.

Radial free forearm flap versus pectoralis major pedicled flap for reconstruction in patients with tongue cancer : assessment of quality of life

This study investigated the quality of life of Chinese patients with tongue cancer who had undergone immediate flap reconstruction surgery. In addition, we compared 2 groups of patients: those who had received radial forearm free flap (RFFF) surgery and others who had received pectoralis major myocutaneous flap (PMMF) surgery. Patients who received RFFF or PMMF reconstruction after primary tongue cancer treated with total and subtotal tongue resection were eligible for the current study. The patients? demographic data, medical history, and quality of life scores (14-item Oral Health Impact Profile (OHIP-14) and the University of Washington Quality of Life (UW-QOL) questionnaires) were collected. A total of 41 of 63 questionnaires were returned (65.08%). There were significant differences between the 2 groups in the gender (p< .05). Patients reconstructed with RFFF performed better in the shoulder domains, in addition to worse appearance domains. Using either RFFF or PMMF for reconstruction of defects after tongue cancer resection significantly influences a patient?s quality of life. Data from this study provide useful information for physicians and patients during their discussion of reconstruction modalities for tongue cancers

Systematics of the heavy flavor hadronic molecules

With a quark level interaction, we give a unified description of the loosely bound molecular systems composed of the heavy flavor hadrons $(\bar{D},\bar{D}^*)$, $(\Lambda_c, \Sigma_c, \Sigma_c^*)$, and $(\Xi_c, \Xi_c^\prime,\Xi_c^*)$. Using the $P_c$ states as inputs to fix the interaction strength of light quark-quark pairs, we reproduce the observed $P_{cs}$ and $T_{cc}^+$ states and predict another narrow $T_{cc}^{\prime+}$ state with quantum numbers $[D^*D^*]_{J=1}^{I=0}$. If we require a satisfactory description of the $T_{cc}^+$ and $P_c$ states simultaneously, our framework prefers the assignments of the $P_{c}(4440)$ and $P_{c}(4457)$ as the $[\Sigma_c\bar{D}^*]_{J=1/2}^{I=1/2}$ and $[\Sigma_c\bar{D}^*]_{J=3/2}^{I=1/2}$ states, respectively. We propose the isospin criterion to explain naturally why the experimentally observed $T_{cc}$, $P_c$, and $P_{cs}$ molecular candidates prefer the lowest isospin numbers. We also predict the loosely bound states for the bottom di-hadrons.Comment: 7 pages, 5 tables, 1 figur

Potential role for PADI-mediated histone citrullination in preimplantation development.

BACKGROUND: The peptidylarginine deiminases (PADIs) convert positively charged arginine residues to neutrally charged citrulline on protein substrates in a process that is known as citrullination or deimination. Previous reports have documented roles for histone citrullination in chromatin remodeling and gene regulation in several tissue types, however, a potential role for histone citrullination in chromatin-based activities during early embryogenesis has not been investigated. RESULTS: In the present study, we tested by laser scanning confocal indirect immunofluorescence microscopy whether specific arginine residues on the histone H3 and H4 N-terminal tails (H4R3, H3R2 + 8 + 17, and H3R26) were citrullinated in mouse oocytes and preimplantation embryos. Results showed that all of the tested residues were deiminated with each site showing a unique localization pattern during early development. Given these findings, we next tested whether inhibition of PADI activity using the PADI-specific inhibitor, Cl-amidine, may affect embryonic development. We found that treatment of pronuclear stage zygotes with Cl-amidine reduces both histone H3 and H4 tail citrullination and also potently blocks early cleavage divisions in vitro. Additionally, we found that the Cl-amidine treatment reduces acetylation at histone H3K9, H3K18, and H4K5 while having no apparent effect on the repressive histone H3K9 dimethylation modification. Lastly, we found that treatment of zygotes with trichostatin A (TSA) to induce hyperacetylation also resulted in an increase in histone citrullination at H3R2 + 8 + 17. CONCLUSIONS: Given the observed effects of Cl-amidine on embryonic development and the well documented correlation between histone acetylation and transcriptional activation, our findings suggest that histone citrullination may play an important role in facilitating gene expression in early embryos by creating a chromatin environment that is permissive for histone acetylation

Towards a surrogate system to express human lipid binding TCRs

BackgroundPreviously we reported that natural nut lipids were necessary for sensitization and that natural killer T cells (NKTs) must play a critical role in the development of food allergic responses. A major bottleneck in further understanding the interaction of nut lipids with the cells of the human immune system is the lack of well-characterized lipid responsive human cell lines.ObjectiveIn the present study, we engineered human T cell receptor (TCR) sequences TRAV10 and TRBV25 responsive to α-GalCer into a stable murine iNKT hybridoma and surrogate human T cell lines.ResultsThe murine hybridoma system has shown to be problematic. To overcome this limitation, the expression of human TCR α/β sequences has been achieved driven by a bidirectional promoter on a plasmids or a lentivirus system, employing stable DC cell lines as lipid presenting cells, and a stable T cell line as a surrogate system. Further, a commercial human Jurkat T cell line containing an inducible secreted luciferase reporter construct was shown to be functional and can be used for a transient expression of human TCRs in a lipid screening program. The transfection efficiencies were improved using the lentivirus polycistronic constructs containing the P2A sequence in a TCR αβ/γδ null cell line (Jurkat 76).ConclusionsThe results suggest that the mis-pairing of the endogenous α/β TCR during ER folding in the presence of the new human TCR sequences could be impairing the functionality of the TCR lipid receptors. The surrogate systems presented here are important first steps in the establishment of human cell-specific lipid responsive libraries for the study of natural lipid substances

Pharmacokinetic characteristics of golidocitinib, a highly selective JAK1 inhibitor, in healthy adult participants

BackgroundGolidocitinib is an orally available, potent and highly selective JAK (Janus kinase)-1 inhibitor of JAK/STAT3 signaling under clinical development for the treatment of cancer and autoimmune diseases. The objectives of the two reported studies were to investigate the pharmacokinetics (PK), safety, and tolerability of golidocitinib in healthy Chinese participants as compared to those healthy Western participants, as well as the food effect exploration.MethodsTwo phase I studies (JACKPOT2 and JACKPOT3) were conducted in USA and China, respectively. In JACKPOT2 study, participants were randomized into placebo or golidocitinib arm in single-ascending dose cohorts (5 - 150 mg) and multiple-ascending dose cohorts (25 - 100 mg, once daily) for 14 days. In the food effect cohort, golidocitinib (50 mg) was administrated shortly after a high-fat meal (fed conditions) as compared to under fasting conditions. In JACKPOT3 study conducted in China, participants were randomized to placebo or golidocitinib arm in single-ascending dose cohorts (25 - 150 mg).ResultsExposure of golidocitinib generally increased in a dose-proportional manner across a dose range of 5 mg to 150 mg (single dose) and 25 mg to 100 mg (once daily). High-fat food did not alter the PK of golidocitinib with statistical significance. Low plasma clearance and extensive volume of distribution characterizes PK of golidoctinib, and long half-life across the dose levels supported once daily dosing. The inter-ethnic difference in primary PK parameters was evaluated. The result suggested slightly higher peak plasma concentrations (Cmax) but comparable area under the plasma concentration-time curve (AUC) was observed in Asian (Chinese) subjects as compared to Caucasian and/or Black subjects, while it was not considered clinically relevant. Golidocitinib was well tolerated without Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher drug-related treatment emergent adverse events (TEAE) reported.ConclusionNo noticeable inter-ethnic difference was observed among Asian, Black, and Caucasian healthy subjects in anticipation of the favorable PK properties of golidocitinib. The effect of food on the bioavailability of golidocitinib was minor following a single oral administration of 50 mg. These data guided to use the same dose and regimen for multinational clinical development.Clinical trial registrationshttps://clinicaltrials.gov/ct2/show/NCT03728023?term=NCT03728023&amp;draw=2&amp;rank=1, identifier (NCT03728023); http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml, identifier (CTR20191011)