This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

The purpose of this study was to develop novel liquid crystalline nanoparticles (LCNPs) that display improved pre-ocular residence time and ocular bioavailability and that can be used as an ophthalmic delivery system for tetrandrine (TET). The delivery system consisted of three primary components, including glyceryl monoolein, poloxamer 407, and water, and two secondary components, including Gelucire 44/14 and amphipathic octadecyl-quaternized carboxymethyl chitosan. The amount of TET, the amount of glyceryl monoolein, and the ratio of poloxamer 407 to glyceryl monoolein were selected as the factors that were used to optimize the dependent variables, which included encapsulation efficiency and drug loading. A three-factor, five-level central composite design was constructed to optimize the formulation. TET-loaded LCNPs (TET-LCNPs) were characterized to determine their particle size, zeta potential, entrapment efficiency, drug loading capacity, particle morphology, inner crystalline structure, and in vitro drug release profile. Corneal permeation in excised rabbit corneas was evaluated. Pre-ocular retention was determined using a noninvasive fluorescence imaging system. Finally, pharmacokinetic study in the aqueous humor was performed by microdialysis technique. The optimal formulation had a mean particle size of 170.0 ± 13.34 nm, a homogeneous distribution with polydispersity index of 0.166 ± 0.02, a positive surface charge with a zeta potential of 29.3 ± 1.25 mV, a high entrapment efficiency of 95.46 ± 4.13 %, and a drug loading rate of 1.63 ± 0.07 %. Transmission electron microscopy showed spherical particles that had smooth surfaces. Small-angle X-ray scattering profiles revealed an inverted hexagonal phase. The in vitro release assays showed a sustained drug release profile. A corneal permeation study showed that the apparent permeability coefficient of the optimal formulation was 2.03-fold higher than that of the TET solution. Pre-ocular retention capacity study indicated that the retention of LCNPs was significantly longer than that of the solution (p < 0.01). In addition, a pharmacokinetic study of rabbit aqueous humors demonstrated that the TET-LCNPs showed 2.65-fold higher ocular bioavailability than that of TET solution. In conclusion, a LCNP system could be a promising method for increasing the ocular bioavailability of TET by enhancing its retention time and permeation into the cornea.

Objective To investigate that whether an association between marital status and the female breast cancer risk exists. Methods The MEDLINE, EMBASE and PsycINFO databases were searched from their inception to July 2019. The Newcastle-Ottawa Scale was used to rate the methodological quality of included studies. Study data were pooled using random-effects meta-analyses to compare the breast cancer risk between unmarried, widowed, divorced or lifelong single women and married women. This study is registered with PROSPERO (number CRD42018112368). Results Forty-nine publications were included in the meta-analysis. Compared with married women, unmarried and lifelong single women had an elevated risk of breast cancer, and the pooled ORs of case-control studies were 1.20 (95% CI: 1.07 to 1.35) and 1.24 (95% CI: 1.05 to 1.45), respectively. In the subgroup analyses under these two comparisons, hospital-based estimates and multivariate-adjusted estimates demonstrated a strong association, while population-based estimates and age-adjusted estimates produced nonsignificant results. The pooled OR of cohort studies examining the effect of being a lifelong single woman was 1.10 (95% CI: 1.04 to 1.16). Heterogeneity was moderate to substantial across case-control studies (I 2 : 46% to 82%), which may be partially explained by differences in geographic

SUMMARY We present an application of the homotopy analysis method for solving the integral equations of the Lippmann–Schwinger type, which occurs frequently in acoustic and seismic scattering theory. In this method, a series solution is created which is guaranteed to converge independent of the scattering potential. This series solution differs from the conventional Born series because it contains two auxiliary parameters ϵ and h and an operator H that can be selected freely in order to control the convergence properties of the scattering series. The ϵ-parameter which controls the degree of dissipation in the reference medium (that makes the wavefield updates localized in space) is known from the so-called convergent Born series theory; but its use in conjunction with the homotopy analysis method represents a novel feature of this work. By using H = I (where I is the identity operator) and varying the convergence control parameters h and ϵ, we obtain a family of scattering series which reduces to the conventional Born series when h = −1 and ϵ = 0. By using H = γ where γ is a particular pre-conditioner and varying the convergence control parameters h and ϵ, we obtain another family of scattering series which reduces to the so-called convergent Born series when h = −1 and ϵ ≥ ϵc where ϵc is a critical dissipation parameter depending on the largest value of the scattering potential. This means that we have developed a kind of unified scattering series theory that includes the conventional and convergent Born series as special cases. By performing a series of 12 numerical experiments with a strongly scattering medium, we illustrate the effects of varying the (ϵ, h, H)-parameters on the convergence properties of the new homotopy scattering series. By using (ϵ, h, H) = (0.5, −0.8, I) we obtain a new scattering series that converges significantly faster than the convergent Born series. The use of a non-zero dissipation parameter ϵ seems to improve on the convergence properties of any scattering series, but one can now relax on the requirement ϵ ≥ ϵc from the convergent Born series theory, provided that a suitable value of the convergence control parameter h and operator H is used.

In recent years, joint inversion has been widely used for integrated geological interpretation. We extended a data‐space joint inversion algorithm of magnetotelluric, gravity and magnetic data to include first‐arrival seismic travel‐time and normalized cross‐gradient constraints. We describe the main features of the algorithm and apply it to synthetic data generated for hypothetical models. For the synthetic data, we find that the joint inversion with multiple parameters is superior to the joint inversion with two or even three parameters, which can reduce the multisolution of inversion results more effectively. Furthermore, data‐space joint inversion involves fewer memory requirements and better calculation speeds than traditional model‐space joint inversion. The normalized cross‐gradient constraints can better couple model parameters of different magnitudes compared with traditional unnormalized cross‐gradient constraints, resulting in higher levels of structural similarity among resistivity, density, magnetic susceptibility and velocity models.