Evaluation of global ocean tide models based on tidal gravity observations in China

Previous studies show that the calculated loading effects from global ocean tide models do not match actual measurements of gravity attraction and loading effects in Southeast Asia. In this paper, taking advantage of a unique network of gravity tidal stations all over the Chinese mainland, we compare the observed and modeled tidal loading effects on the basis of the most recent global ocean tide models. The results show that the average efficiencies of the ocean tidal loading correction for O1, K1, M2 are 77%, 73% and 59%, respectively. The loading correction efficiencies using recent ocean tidal models are better than the 40 years old Schwiderskis model at coastal stations, but relative worse at stations far from ocean

Dynamic changes of gravity fields before and after the 2008 Wenchuan earthquake (Ms8.0)

The pattern evolution and dynamic mechanism of the dynamic changes of regional gravity fields occurring before and after the Wenchuan Ms8.0 earthquake are analyzed, based on five epochs of 1998–2007 mobile gravity data from the middle-south section of the north–south seismic belt, and two epochs of field research data collected after the 2008 Wenchuan earthquake in combination with GPS data, leveling observations, and geotectonic environment data. The regional dynamic gravity changes demonstrate the effects of the eastward flow of solid matter in the Qinghai-Tibetan plateau and the preparation of the 2008 Wenchuan earthquake (2–10 yr). The two most meaningful gravity indicators of the Wenchuan earthquake preparation are the positive (increasing) gravity changes occurring over many years in the southwest epicenter and the large-scale gradient zone of gravity variation, with the cumulative difference between the two sides of the gradient zone of gravity exceeding 200 μGal. The positive gravity changes may facilitate a constant energy accumulation and the gradient belt may support seismic shear breakage. Overall, the gravity changes associated with the earthquake preparation indicate a pattern of accelerating increase-decelerating increase-earthquake occurrence. The Songpan-Ganzi block generally displays a negative gravity change, providing evidence for a local upwarping of the deep crust-mantle and an interior expansion of the deep crust attributable to high temperatures. The viewpoint is consistent with the dilatant mechanism for earthquake preparation

The synergy of the XPO1 inhibitors combined with the BET inhibitor INCB057643 in high-grade B-cell lymphoma via downregulation of MYC expression

Abstract High grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL-DH) represents an uncommon B-cell lymphoma (BCL) with aggressive clinical courses and poor prognosis. Despite revolutionary therapeutic advances in BCL, there has been limited treatment progress in HGBCL-DH, thus necessitating additional therapeutic strategies for HGBCL-DH. This study demonstrated that the BET antagonist INCB057643 synergized with the XPO1 inhibitors (selinexor and eltanexor) to decrease cell viability and increase cell apoptosis in HGBCL-DH cells with or without TP53 mutations. As anticipated, the combined treatment of INCB057643 with selinexor slowed tumor growth and reduced the tumor burden in TP53-mutated HGBCL-DH xenografts. Mechanistically, MYC functional inhibition was a potential molecular mechanism underlying the synergy of the combined INCB057643 and selinexor treatment in HGBCL-DH cells independent of TP53 mutation status. In TP53 mutated HGBCL-DH cells, inducing DNA damage and impairing the DNA damage response (DDR) were involved in the therapeutic interaction of the combined regimen. In TP53 wild-type cells, the molecular mechanism was linked with upregulation of p53 levels and activation of its targeted pathways, rather than dysregulation of the DDR. Collectively, we might provide a potential promising combination therapy regimen for the management of HGBCL-DH. Clinical evaluations are warranted to confirm this conclusion

Therapeutic Interaction of Apatinib and Chidamide in T-Cell Acute Lymphoblastic Leukemia through Interference with Mitochondria Associated Biogenesis and Intrinsic Apoptosis

T-cell acute lymphoblastic leukemia (T-ALL) shows poor clinical outcome and has limited therapeutic options, indicating that new treatment approaches for this disease are urgently required. Our previous study demonstrated that apatinib, an orally selective VEGFR-2 antagonist, is highly effective in T-ALL. Additionally, chidamide, a histone deacetylase inhibitor, has proven to be cytotoxic against T-ALL in preclinical and clinical settings. However, whether the therapeutic interaction of apatinib and chidamide in T-ALL remains unknown. In this study, apatinib and chidamide acted additively to decrease cell viability and induce apoptosis in T-ALL in vitro. Notably, compared with apatinib or chidamide alone, the combinational regimen was more efficient in abrogating the leukemia burden in the spleen and bone marrow of T-ALL patient-derived xenograft (PDX) models. Mechanistically, the additive antileukemia effect of apatinib and chidamide was associated with suppression of mitochondrial respiration and downregulation of the abundance levels of several rate-limiting enzymes that are involved in the citric acid cycle and oxidative phosphorylation (OXPHOS). In addition, apatinib enhanced the antileukemia effect of chidamide on T-ALL via activation of the mitochondria-mediated apoptosis pathway and impediment of mitochondrial biogenesis. Taken together, the study provides a potential role for apatinib in combination with chidamide in the management of T-ALL and warrants further clinical evaluations of this combination in patients with T-ALL

Preclinical Studies of Chiauranib Show It Inhibits Transformed Follicular Lymphoma through the VEGFR2/ERK/STAT3 Signaling Pathway

Transformed follicular lymphoma (t-FL), for which there is no efficient treatment strategy, has a rapid progression, treatment resistance, and poor prognosis, which are the main reasons for FL treatment failure. In this study, we identified a promising therapeutic approach with chiauranib, a novel orally developed multitarget inhibitor targeting VEGFR/Aurora B/CSF-1R. We first determined the cytotoxicity of chiauranib in t-FL cell lines through CCK-8, EdU staining, flow cytometry, and transwell assays. We also determined the killing effect of chiauranib in a xenograft model. More importantly, we identified the underlying mechanism of chiauranib in t-FL tumorigenesis by immunofluorescence and Western blotting. Treatment with chiauranib significantly inhibited cell growth and migration, promoted apoptosis, induced cell cycle arrest in G2/M phase, and resulted in significant killing in vivo. Mechanistically, chiauranib suppresses the phosphorylation level of VEGFR2, which has an anti-t-FL effect by inhibiting the downstream MEK/ERK/STAT3 signaling cascade. In conclusion, chiauranib may be a potential therapy to treat t-FL, since it inhibits tumor growth and migration and induces apoptosis by altering the VEGFR2/ERK/STAT3 signaling pathway