The chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) controls cellular quiescence by hyperpolarizing the cell membrane during diapause in the crustacean Artemia

Cellular quiescence, a reversible state in which growth, proliferation, and other cellular activities are arrested, is important for self-renewal, differentiation, development, regeneration, and stress resistance. However, the physiological mechanisms underlying cellular quiescence remain largely unknown. In the present study, we used embryos of the crustacean Artemia in the diapause stage, in which these embryos remain quiescent for prolonged periods, as a model to explore the relationship between cell-membrane potential (V-mem) and quiescence. We found that V-mem is hyperpolarized and that the intracellular chloride concentration is high in diapause embryos, whereas V-mem is depolarized and intracellular chloride concentration is reduced in postdiapause embryos and during further embryonic development. We identified and characterized the chloride ion channel protein cystic fibrosis transmembrane conductance regulator (CFTR) of Artemia (Ar-CFTR) and found that its expression is silenced in quiescent cells of Artemia diapause embryos but remains constant in all other embryonic stages. Ar-CFTR knockdown and GlyH-101-mediated chemical inhibition of Ar-CFTR produced diapause embryos having a high V-mem and intracellular chloride concentration, whereas control Artemia embryos released free-swimming nauplius larvae. Transcriptome analysis of embryos at different developmental stages revealed that proliferation, differentiation, and metabolism are suppressed in diapause embryos and restored in postdiapause embryos. Combined with RNA sequencing (RNA-Seq) of GlyH-101-treated MCF-7 breast cancer cells, these analyses revealed that CFTR inhibition down-regulates the Wnt and Aurora Kinase A (AURKA) signaling pathways and up-regulates the p53 signaling pathway. Our findings provide insight into CFTR-mediated regulation of cellular quiescence and V-mem in the Artemia model

Probing the R-parity violating supersymmetric effects in the exclusive c→d/sℓνℓc\to d/s\ell\nu_\ell decays

A lot of branching ratios of the exclusive $c \to d/s\ell\nu_\ell$ ($\ell=e,\mu$) decays have been quite accurately measured by CLEO-c, BELLE, BABAR, BES(I,II,III), ALEPH and MARKIII collaborations. We probe the R-parity violating supersymmetric effects in the exclusive $c \to d/s\ell\nu_\ell$ decays. From the latest experimental measurements, we obtain new upper limits on the relevant R-parity violating coupling parameters within the decays, and many upper limits are obtained for the first time. Using the constrained new parameter spaces, we predict the R-parity violating effects on the observables, which have not been measured or have not been well measured yet. We find that the R-parity violating effects due to slepton exchange could be large on the branching ratios of $D_{d/s}\to e\nu_e$ decays and the normalized forward-backward asymmetries of $D_{u/d}\to \pi/K \ell\nu_\ell$ as well as $D_s\to K \ell\nu_\ell$ decays, and all branching ratios of the relevant semileptonic $D$ decays are sensitive to squark exchange couplings. Our results in this work could be used to probe new physics effects in the leptonic decays as well as the semileptonic decays, and will correlate with searches for direct supersymmetric signals at LHC and BESIII.Comment: 26 pages, 13 figure

Two-year prognostic value of mean platelet volume in patients with diabetes and stable coronary artery disease undergoing elective percutaneous coronary intervention

Background: Mean platelet volume (MPV) is a marker of platelet size and activity, and is associated with a poor prognosis of cardiovascular disease. Studies have shown a relationship between diabetes mellitus (DM) and MPV. This study examined the relationship between admission MPV and 2-year cardiac mortality in patients with DM and stable coronary artery disease (SCAD) undergoing elective percutaneous coronary intervention (PCI). Methods: A total of 1389 patients were enrolled and divided into two groups according to MPV as fol- lows: lower MPV (n = 908, MPV ≤ 10.9 fL) and higher MPV (n = 481, MPV > 10.9 fL). Results: Body mass index, platelet distribution width, MPV/platelet and glycated hemoglobin (HbA1c) levels were significantly higher in the higher MPV group compared with the lower MPV group (all p < 0.05). The platelet count was significantly lower in the higher MPV group compared with the lower MPV group (p < 0.05). MPV was positively associated with HbA1c and fasting plasma glucose levels (r = 0.073 and 0.061, p = 0.007 and 0.023, respectively) in bivariate correlation analysis. The 2-year cardiac mortality rate was 0.7%, and was significantly lower in the lower MPV group than in the higher MPV group in Kaplan-Meier analysis (p = 0.019). Receiver operating characteristic analysis showed a good diagnostic value for MPV at predicting long-term cardiac mortality (area under the curve: 0.735, 95% confidence interval [CI]: 0.590–0.880, p = 0.01). Elevated MPV was a significant risk factor for 2-year cardiac mortality (hazard ratio: 2.091, 95% CI: 1.075–4.070, p = 0.030) in multivariable Cox regression analysis. Conclusions: Mean platelet volume is a strong, independent prognostic factor in PCI-treated patients with DM and SCAD

FAM129B, an antioxidative protein, reduces chemosensitivity by competing with Nrf2 for Keap1 binding.

BackgroundThe transcription factor Nrf2 is a master regulator of antioxidant response. While Nrf2 activation may counter increasing oxidative stress in aging, its activation in cancer can promote cancer progression and metastasis, and confer resistance to chemotherapy and radiotherapy. Thus, Nrf2 has been considered as a key pharmacological target. Unfortunately, there are no specific Nrf2 inhibitors for therapeutic application. Moreover, high Nrf2 activity in many tumors without Keap1 or Nrf2 mutations suggests that alternative mechanisms of Nrf2 regulation exist.MethodsInteraction of FAM129B with Keap1 is demonstrated by immunofluorescence, colocalization, co-immunoprecipitation and mammalian two-hybrid assay. Antioxidative function of FAM129B is analyzed by measuring ROS levels with DCF/flow cytometry, Nrf2 activation using luciferase reporter assay and determination of downstream gene expression by qPCR and wester blotting. Impact of FAM129B on in vivo chemosensitivity is examined in mice bearing breast and colon cancer xenografts. The clinical relevance of FAM129B is assessed by qPCR in breast cancer samples and data mining of publicly available databases.FindingsWe have demonstrated that FAM129B in cancer promotes Nrf2 activity by reducing its ubiquitination through competition with Nrf2 for Keap1 binding via its DLG and ETGE motifs. In addition, FAM129B reduces chemosensitivity by augmenting Nrf2 antioxidative signaling and confers poor prognosis in breast and lung cancer.InterpretationThese findings demonstrate the important role of FAM129B in Nrf2 activation and antioxidative response, and identify FMA129B as a potential therapeutic target. FUND: The Chang Gung Medical Foundation (Taiwan) and the Ministry of Science and Technology (Taiwan)

trans-Di-μ-carbonyl-bis­{carbon­yl[η5-2,3,4,5-tetra­methyl-1-(2-thien­yl)cyclo­penta­dien­yl]ruthenium(I)}(Ru—Ru)

The title compound, [Ru2(C13H15S)2(CO)4], is a centrosymmetric binuclear metal–carbonyl complex containing an Ru—Ru single bond [2.7511 (8) Å]. Each RuI atom is coordinated by two bridging carbonyl ligands, one terminal carbonyl ligand and one η5-cyclo­penta­dienyl group. The complex has a trans conformation and the two cyclo­penta­dienyl ring planes are parallel. The crystal structure involves weak C—H⋯O hydrogen bonds

Lithium diaqua­magnesium catena-borodiphosphate(V) monohydrate, LiMg(H2O)2[BP2O8]·H2O, at 173 K

The crystal structure of LiMg(H2O)2[BP2O8]·H2O consists of tubular structural units, built from tetra­hedral ∞ 1{[BP2O8]3−} borophosphate ribbons and (LiO4)n helices running along [001], which are inter­connected by MgO4(H2O)2 octa­hedra, forming a three-dimensional network structure with one-dimensional channels along [001] in which the water mol­ecules are located. The water mol­ecule in the channel is significantly displaced by up to 0.3 Å from the special position 6b (..2) to a half-occupied general position. Mg, B and one Li atom all lie on twofold axes. Of the two Li positions, one is at a special position 6b (..2), while the other is at a general position; both are only half-occupied

Mobile phone addiction and mental health: the roles of sleep quality and perceived social support

As a global phenomenon, mobile phone addiction has become an increasingly common issue among Chinese university students. Although previous research explored the link between mobile phone addiction and mental health, the possible mechanism underlying the above association is unclear. We administered a cross-sectional survey to 585 participants from two universities in Kunming, southwest China, from October 2021 to January 2022. Our results suggested that mobile phone addiction was negatively associated with mental health, and sleep quality partially mediated the relationship between mobile phone addiction and mental health. Furthermore, perceived social support positively moderated the direct effect of sleep quality on mental health, as well as the indirect effect of mobile phone addiction on mental health. These findings provide a new insight into the underlying mechanism by which mobile phone addiction affects university students’ mental health. The results emphasize a necessary task for administrators, health workers, and family members to attach importance to the overuse of mobile phones among university students

Rethinking CycleGAN: Improving Quality of GANs for Unpaired Image-to-Image Translation

An unpaired image-to-image (I2I) translation technique seeks to find a mapping between two domains of data in a fully unsupervised manner. While the initial solutions to the I2I problem were provided by the generative adversarial neural networks (GANs), currently, diffusion models (DM) hold the state-of-the-art status on the I2I translation benchmarks in terms of FID. Yet, they suffer from some limitations, such as not using data from the source domain during the training, or maintaining consistency of the source and translated images only via simple pixel-wise errors. This work revisits the classic CycleGAN model and equips it with recent advancements in model architectures and model training procedures. The revised model is shown to significantly outperform other advanced GAN- and DM-based competitors on a variety of benchmarks. In the case of Male2Female translation of CelebA, the model achieves over 40% improvement in FID score compared to the state-of-the-art results. This work also demonstrates the ineffectiveness of the pixel-wise I2I translation faithfulness metrics and suggests their revision. The code and trained models are available at https://github.com/LS4GAN/uvcgan

trans-Di-μ-carbonyl-bis­{carbon­yl[η5-2,3,4,5-tetra­methyl-1-(5-methyl-2-fur­yl)cyclo­penta­dien­yl]ruthenium(I)}(Ru—Ru)

In the crystal structure of the title compound, [Ru2(C14H17O)2(CO)4], each RuI atom is connected to one end-on and two bridging carbonyl groups and one cyclo­penta­dienyl ring. The two Ru atoms are connected into binuclear complexes via two bridging carbonyl groups, forming four-membered rings which are located on centres of inversion. The Ru—Ru distance of 2.7483 (11) Å corresponds to a single bond. The two carbonyl groups in these binuclear complexes are trans-oriented