Possible S±S_\pm-wave superconductivity in La3_3Ni2_2O7_7

Recently, the bulk nickelate La$_3$Ni$_2$O$_7$ is reported to show signature of high-temperature superconductivity under high pressure above $14$GPa (H. Sun {\it et al.}, arXiv:2305.09586). We analyze the pairing mechanism and pairing symmetry in a bi-layer Hubbard model with two orbitals in the $E_g$ multiplet. In the weak to moderate interaction regime, our functional renormalization group calculations yield $S_\pm$-wave Cooper pairing with dominant $d_{3z^2-r^2}$-orbital content, triggered by spin fluctuations at wave vectors near $(0.84, 0)\pi$ and $(0.75, 0.75)\pi$, up to $C_{4v}$ symmetry. The gap function changes sign across the Fermi pockets. In the strong coupling limit, we develop a low-energy effective theory in terms of atomic one- and two-electron states in the $E_g$ multiplet. The effective theory predicts naturally local pairing (with anti-phase between the two orbitals due to the repulsive inter-orbital pair hopping) and strong singlet pairing on vertical inter-layer bond, where the super-exchange between $d_{3z^2-r^2}$-orbital is the strongest. The real-space structure is consistent with that from functional renormalization group, suggesting the robustness of such a pairing function. We also discuss a possible scenario for the weak insulating behavior under low pressures in terms of the tendency toward the formation of charge order in the strong coupling limit.Comment: 5 pages, 4 figure

Global and local surrogate-assisted differential evolution for expensive constrained optimization

The file attached to this record is the author's final peer reviewed version.For expensive constrained optimization problems, the computation of objective function and constraints is very time-consuming. This paper proposes a novel global and local surrogate-assisted differential evolution for solving expensive constrained optimization problems with inequality constraints. The proposed method consists of two main phases: global surrogate-assisted phase and local surrogate-assisted phase. In the global surrogate-assisted phase, differential evolution serves as the search engine to produce multiple trial vectors. Afterward, the generalized regression neural network is used to evaluate these trial vectors. In order to select the best candidate from these trial vectors, two rules are combined. The first is the feasibility rule, which at first guides the population toward the feasible region, and then toward the optimal solution. In addition, the second rule puts more emphasis on the solution with the highest predicted uncertainty, and thus alleviates the inaccuracy of the surrogates. In the local surrogate-assisted phase, the interior point method coupled with radial basis function is utilized to refine each individual in the population. During the evolution, the global surrogate-assisted phase has the capability to promptly locate the promising region and the local surrogate-assisted phase is able to speed up the convergence. Therefore, by combining these two important elements, the number of fitness evaluations can be reduced remarkably. The proposed method has been tested on numerous benchmark test functions from three test suites and two real-world cases. The experimental results demonstrate that the performance of the proposed method is better than that of other state-of-the-art methods

Multi-target siRNA based on DNMT3A/B homologous conserved region influences cell cycle and apoptosis of human prostate cancer cell line TSU-PR1

Abnormal genome hypermethylation participates in the tumorigenesis and development of prostate cancer. Prostate cancer cells highly express DNA methyltransferase 3 (DMNT3) family genes, essential for maintaining genome methylation. In the present study, multi-target siRNA, based on the homologous region of the DNMT3 family, was designed for the in vitro investigation of its effects on the proliferation, migration, and invasion of TSU-PR1 prostate cancer cells. The consequential cell-cycle derangement, through DNMT3A/B or only DNMT3B silencing, was partially efficient, without affecting apoptosis. DNMT3A silencing had absolutely no effect on changing TSU-PR1 cell biological behavior. Hence, DNMT3B alone apparently plays a key role in maintaining the unfavorable behavior of prostate-cancer cells, thereby implying its potential significance as a promising therapeutic target, with DNMT3A simply in the role of helper

Pharmacokinetics of diltiazem hydrochloride delay-onset sustained-release pellet capsules in healthy volunteers

Embora a farmacocinética (PK) do cloridrato de diltiazem nas formas de comprimidos de liberação imediata e cápsulas de liberação modificada em ensaios clínicos já tenha sido relatada, a pesquisa da PK do cloridrato de diltiazem na forma de cápsulas com peletes de liberação retardada e sustentada ainda é muito importante. Neste trabalho, propusemos avaliar a farmacocinética do cloridrato de diltiazem administrado através desta nova forma farmacêutica em voluntários chineses sadios, assim como a influência da ingestão de alimentos neste perfil farmacocinético. Foi realizado um ensaio clínico aberto, randomizado e paralelo em 36 voluntários, que receberam dose oral única de 90 mg, 180 mg ou 270 mg e dose múltiplas (90 mg/d × 6 d) pela mesma via de administração. Para avaliar o efeito da ingestão de alimentos sobre a PK do diltiazem foi realizada a administração de dose única (360 mg) em 24 voluntários chineses sadios. A concentração plasmática do diltiazem foi determinada por Cromatografia Liquida de Alta Eficiência em fase reversa (CLAE-FR) e os principais parâmetros farmacocinéticos foram analisados através do emprego do software PKSolver (Ver 2.0). O ensaio de farmacocinética clínica foi conduzido na clínica Pharmacological Center (No.JDX1999064) do Hospital de Xiangya, Central South University, China. Os parâmetros PK obtidos indicaram que a nova formulação de cápsulas de liberação retardada e sustentada de cloridrato de diltiazem possue marcantes características de liberação retardada e controlada do fármaco.The pharmacokinetics (PK) of ordinary tablets and sustained release capsules of diltiazem hydrochloride in human clinical trials had been studied. The PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules, a new dosage form, has not been reported, although it is very important to clinical use. In this paper, we investigated the PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules and the food influence in Chinese healthy volunteers. The PK parameters indicated that the diltiazem hydrochloride delay-onset sustained-release pellet capsules appeared marked characteristics of delayed and controlled release. An opened-label, randomized and parallel clinical trial was conducted in 36 Chinese healthy volunteers with single oral dose (90 mg, 180 mg or 270 mg) and a multiple oral dose (90 mg d-1×6 d) administration. The effect of food on the PK of one single oral dose (360 mg) was investigated in 24 healthy Chinese volunteers. Plasma diltiazem concentration was determined by reversed-phase high-performance liquid chromatography (RP-HPLC) and the main pharmacokinetic parameters were analyzed by PKSolver (Ver 2.0). All clinical studies were conducted in the Clinical Pharmacological Center (No. JDX1999064) of Xiangya Hospital Affiliated Central South University, China. The PK parameters suggested that the new formulation had marked characteristics of delayed and controlled release of diltiazem, and food intake did not alter significantly diltiazem pharmacokinetic parameters

Correlation-induced insulating topological phases at charge neutrality in twisted bilayer graphene

Twisted bilayer graphene (TBG) provides a unique framework to elucidate the interplay between strong correlations and topological phenomena in two-dimensional systems. The existence of multiple electronic degrees of freedom -- charge, spin, and valley -- gives rise to a plethora of possible ordered states and instabilities. Identifying which of them are realized in the regime of strong correlations is fundamental to shed light on the nature of the superconducting and correlated insulating states observed in the TBG experiments. Here, we use unbiased, sign-problem-free quantum Monte Carlo simulations to solve an effective interacting lattice model for TBG at charge neutrality. Besides the usual cluster Hubbard-like repulsion, this model also contains an assisted hopping interaction that emerges due to the non-trivial topological properties of TBG. Such a non-local interaction fundamentally alters the phase diagram at charge neutrality, gapping the Dirac cones even for infinitesimally small interaction. As the interaction strength increases, a sequence of different correlated insulating phases emerge, including a quantum valley Hall state with topological edge states, an intervalley-coherent insulator, and a valence bond solid. The charge-neutrality correlated insulating phases discovered here provide the sought-after reference states needed for a comprehensive understanding of the insulating states at integer fillings and the proximate superconducting states of TBG.Comment: 15 pages, 9 figures, 2 table

p53 Dependent Centrosome Clustering Prevents Multipolar Mitosis in Tetraploid Cells

BACKGROUND: p53 abnormality and aneuploidy often coexist in human tumors, and tetraploidy is considered as an intermediate between normal diploidy and aneuploidy. The purpose of this study was to investigate whether and how p53 influences the transformation from tetraploidy to aneuploidy. PRINCIPAL FINDINGS: Live cell imaging was performed to determine the fates and mitotic behaviors of several human and mouse tetraploid cells with different p53 status, and centrosome and spindle immunostaining was used to investigate centrosome behaviors. We found that p53 dominant-negative mutation, point mutation, or knockout led to a 2∼ 33-fold increase of multipolar mitosis in N/TERT1, 3T3 and mouse embryonic fibroblasts (MEFs), while mitotic entry and cell death were not significantly affected. In p53-/- tetraploid MEFs, the ability of centrosome clustering was compromised, while centrosome inactivation was not affected. Suppression of RhoA/ROCK activity by specific inhibitors in p53-/- tetraploid MEFs enhanced centrosome clustering, decreased multipolar mitosis from 38% to 20% and 16% for RhoA and ROCK, respectively, while expression of constitutively active RhoA in p53+/+ tetraploid 3T3 cells increased the frequency of multipolar mitosis from 15% to 35%. CONCLUSIONS: p53 could not prevent tetraploid cells entering mitosis or induce tetraploid cell death. However, p53 abnormality impaired centrosome clustering and lead to multipolar mitosis in tetraploid cells by modulating the RhoA/ROCK signaling pathway