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In this paper the Stokes system in an unbounded domain is solved by the artificial boundary method. The novelty lies in an operator form of the exact Dirichlet-to-Neumann (DtN) mapping. With the help of the Chebyshev rational approximation of the square root function, we derive a highly accurate approximate DtN mapping, which can be numerically implemented without resorting to the eigen-decomposition in terms of the vectorial spherical harmonics. In addition, we develop an efficient block preconditioner for the augmented truncated saddle point problem. Numerical experiments demonstrate the effectiveness of the proposed method.

Lipid-based nanoparticles have made a breakthrough in clinical disease as delivery systems due to their biocompatibility, thermal and long-term stability, high loading ability, simplicity of preparation, inexpensive production costs, and...

Natural killer (NK) cell therapies show potential for tumor treatment but were immunologically resisted by the overexpressed immunosuppressing tumor-cell-surface glycans. To reverse this glycan-mediated immunosuppression, the surface NK-inhibitory glycan expressions need to be downregulated and NK-activating glycan levels should be elevated synchronously with optimal efficiency. Here, we design a core-shell membrane-fusogenic liposome (MFL) to simultaneously achieve the physical modification of NK-activating glycans and biological inhibition of immunosuppressing glycans on the tumor cell surface via a membrane-fusion manner. Loaded into a tumor-microenvironment-triggered-degradable thermosensitive hydrogel, MFLs could be conveniently injected and controllably released into local tumor. Through fusion with tumor cell membrane, the released MFLs could simultaneously deliver sialyltransferase-inhibitor-loaded core into cytoplasm, and anchor NK-activating-glycan-modified shell onto tumor surface. This spatially-differential distribution of core and shell in one cell ensures the effective inhibition of intracellular sialyltransferase to downregulate immunosuppressing sialic acid, and direct presentation of NK-activating Lewis X trisaccharide (LeX) on tumor surface simultaneously. Consequentially, the sialic acid-caused immunosuppression of tumor surface was reprogrammed to be LeX-induced NK activation, resulting in sensitive susceptibility to NK-cell-mediated recognition and lysis for improved tumor elimination. This MFL provides a novel platform for multiplex cell engineering and personalized regulation of intercellular interactions for enhanced cancer immunotherapy. This article is protected by copyright. All rights reserved.

Membrane fusion, a fundamental biological process of the fusion of the membrane composition between cells, is vital for cell-cell communication and cargo transport between living cells. This fusion interaction achieves the transportation of the inner content to the cellular cytosol as well as the simultaneous blending of foreign substances with the cell membrane. Inspired by this biological process, emerging membrane-fusogenic particles have been developed, opening a new area for bioengineering and biomedical applications. Especially, membrane-fusion-mediated transfer of inner cargoes can bypass endosomal entrapment to maximize the transportation efficiency, emerging as a unique cytoplasmic delivery platform distinct from those depending on conventional endocytosis-based pathways. In addition, the membrane fusion enables cell surface modification through lipid diffusion and mixing, providing a tool for direct cell membrane engineering. In this review, we focus on the development of membrane-fusogenic particles and their up-to-date progress. We briefly introduce the concept of membrane fusion, elaborate inspiring strategies of membrane-fusogenic particles, and highlight the recent advances and the promising applications of membrane-fusogenic particles as a next-generation bioengineering tool. In the end, we conclude with the present challenges and opportunities, providing insights in the future research of membrane-fusogenic particles.

This paper is concerned with a fast finite element method for the three-dimensional Poisson equation in infinite domains. Both the exterior problem and the strip-tail problem are considered. Exact Dirichlet-to-Neumann (DtN)-type artificial boundary conditions (ABCs) are derived to reduce the original infinite-domain problems to suitable truncated-domain problems. Based on the best relative Chebyshev approximation for the square-root function, a fast algorithm is developed to approximate exact ABCs. One remarkable advantage is that one need not compute the full eigensystem associated with the surface Laplacian operator on artificial boundaries. In addition, compared with the modal expansion method and the method based on Pad$\acute{\textrm{e}}$ approximation for the square-root function, the computational cost of the DtN mapping is further reduced. An error analysis is performed and numerical examples are presented to demonstrate the efficiency of the proposed method.

Immunosuppression is a key factor leading to a low therapeutic efficiency of the currently used immunotherapies. Monotherapies are unable to overcome immunosuppression because of the complex interplay of immune cells in tumors. Herein, we report a multifunctional nanomodulator (MFNM) as a carrier to deliver different types of immune modulators for comodulating multiple pathways. An MFNM has a core-shell structure, in which small-molecule drugs are encapsulated in a mesoporous silica nanoparticle (MSN) core with a pH-responsive polymer layer. Further, the polymeric shell provides active sites that are readily modifiable by multiple types of antibodies to regulate the immune-related processes. By codelivering cyclophosphamide (CTX), αPD-L1 (B7-H1), and α4-1BB (CD137L) monoclonal antibodies (mAbs) to tumors, an MFNM has been shown to regulate multiple immune pathways and enhance an antitumor immunity. As antibodies and small-molecule drugs loaded in an MFNM can be modified based on the tumor type, the MFNM provides a feasible platform for the development of advanced immunotherapies that require simultaneous modulation of multiple biological processes.

Despite the significant progress in the discovery of biomarkers and the exploitation of technologies for prostate cancer (PCa) detection and diagnosis, the initial screening of these PCa-related biomarkers using current technologies is always demanded with a bioassay or probe with high sensitivity, specificity, and noninvasiveness. Nanomaterials have emerged as novel alternative probes for PCa detection and diagnosis because of their nanoscale size, large ratio of surface area to volume, special surface chemistry, and particularly distinct physical properties. By selecting appropriate nanomaterials, a series of nanosensors or nanoprobes could be constructed for PCa bioassay with high sensitivity, selectivity, and accuracy. Meanwhile, nanosized particles also show significant potential to transport directors or contrast agents to desired sites

The numerical computation of nonlocal Schrodinger equations (SEs) on the whole real axis is considered. Based on the artificial boundary method, we first derive the exact artificial nonreflecting boundary conditions. For the numerical implementation, we employ the quadrature scheme proposed in Tian and Du (SIAM J Numer Anal 51:3458–3482, 2013) to discretize the nonlocal operator, and apply the z-transform to the discrete nonlocal system in an exterior domain, and derive an exact solution expression for the discrete system. This solution expression is referred to our exact nonreflecting boundary condition and leads us to reformulate the original infinite discrete system into an equivalent finite discrete system. Meanwhile, the trapezoidal quadrature rule is introduced to discretize the contour integral involved in exact boundary conditions. Numerical examples are finally provided to demonstrate the effectiveness of our approach.

A new type of bound states induced by PT symmetry is found which does not radiate but can be excited from the far field., Some photonic systems support bound states in the continuum (BICs) that have infinite lifetimes, although their frequencies and momenta are matched to vacuum modes. Using a prototypical system that can be treated analytically, we show that each of these BICs always splits into a pair of new type BIC and lasing threshold mode when a parity-time (PT)–symmetric perturbation is introduced. The radiation loss at the lasing threshold is exactly balanced by the net gain of the particles. These PT symmetry-induced BICs are different from ordinary BICs, as they can be excited by an external source but do not radiate, and they carry a different quality factor divergence rate from that of the ordinary BICs. While most of the attention of PT-symmetric systems is captured by the coalescence of modes at exceptional points, the splitting of ordinary BICs is a new phenomenon that illustrates the rich physics embedded in PT-symmetric systems.

Bacterial therapy, which presents a smart platform for delivering and producing therapeutic agents, as monotherapy or in combination with other therapeutic modes, has provided a breakthrough for the treatment of a range of diseases. The integration of synthetic biology technology with bacteria enables their characteristics like chemotaxis and biomolecule secretion to outperform conventional diagnostics and therapeutics, thereby facilitating their clinical applications in a range of diseases. Compared to injection-administered bacteria, orally-delivered bacteria improve patient compliance while avoiding the risk of systemic infections. However, oral administration of microbes always leads to a substantial loss of viability due to the highly acidic environment in the stomach and bile salt in the intestine. Thus, the formulation of these bacteria into microcapsules using appropriate biomaterials is a promising approach for reducing cell death during gastrointestinal passage and controlling the release of these therapeutic cells across the intestinal tract. In this review, we reveal the basic principles of oral bacterial delivery, from internal genetic engineering approaches to external encapsulation and modification, and summarize the most recent biomedical applications. Finally, we discuss future trends in oral bacterial therapy as well as current challenges that need to be resolved to advance their clinical applications.

Alzheimer's disease (AD) is a progressive and irreversible brain disorder. Recent studies revealed the pivotal role of β-amyloid (Aβ) in AD. However, there is no conclusive indication that the existing therapeutic strategies exerted any effect on the mitigation of Aβ-induced neurotoxicity and the elimination of Aβ aggregates simultaneously in vivo. Herein, we developed a novel nanocomposite that can eliminate toxic Aβ aggregates and mitigate Aβ-induced neurotoxicity in AD mice. This nanocomposite was designed to be a small-sized particle (14 ± 4 nm) with Aβ-binding peptides (KLVFF) integrated on the surface. The nanocomposite was prepared by wrapping a protein molecule with a cross-linked KLVFF-containing polymer layer synthesized by in situ polymerization. The presence of the nanocomposite remarkably changed the morphology of Aβ aggregates, which led to the formation of Aβ/nanocomposite coassembled nanoclusters instead of Aβ oligomers. With the reduction of the pathological Aβ oligomers, the nanocomposites attenuated the Aβ-induced neuron damages, regained endocranial microglia's capability to phagocytose Aβ, and eventually protected hippocampal neurons against apoptosis. Thus, we anticipate that the small-sized nanocomposite will potentially offer a feasible strategy in the development of novel AD treatments.

Understanding how attractive interactions among rigid polymers or rodlike particles influence their liquid crystal (LC) phase behavior is of fundamental and practical importance. This question has not been fully answered yet, mainly due to the shortage of model systems with “true” pairwise attractions on a single particle level while with excellent colloidal stability. Herein, we report on a well-defined rodlike system that fulfills such criteria, through covalently grafting the free end of the thermoresponsive PNIPAM block of poly(ethylene glycol)-block-poly(N-isopropylacrylamide) (PEG-b-PNIPAM) onto the classic rodlike model system—the fd or M13 virus—which is the hallmark in understanding the LC behaviors of rigid polymer or rodlike particles. Increasing temperature induces dehydration and collapse of the PNIPAM chains onto the virus surface and therefore introduces attractions among the viruses, while the outer hydrophilic PEG block offers steric stabilization to prevent interparticle aggregation, gel...

We extend the theory of global geometrical optics method, proposed originally for the linear scalar high-frequency wave-like equations in [Commun. Math. Sci., 2013, 11(1): 105-140], to the more general vector-valued Schrodinger problems in the semi-classical regime. The key ingredient in the global geometrical optics method is a moving frame technique in the phase space. The governing equation is transformed into a new equation but of the same type when expressed in any moving frame induced by the underlying Hamiltonian flow. The classical Wentzel-Kramers-Brillouin (WKB) analysis benefits from this treatment as it maintains valid for arbitrary but fixed evolutionary time. It turns out that a WKB-type function defined merely on the underlying Lagrangian submanifold can be obtained with the help of this moving frame technique, and from which a uniform first-order approximation of the wave field can be derived, even around caustics. The general theory is exemplified by two specific instances. One is the two-level Schrodinger system and the other is the periodic Schrodinger equation. Numerical tests validate the theoretical results.

The applications of nanotechnology in biomedicine have gained considerable attentions in recent years owing to the great enhancement of therapeutic efficiency. Integration of self-assembly into nanotechnology has brought tremendous convenience during the formation of nano-carriers. Based on distinctive methods of self-assembly, nano-therapeutics have been developed to an impressive stage with the ability to perform site-specific delivery with temporal and spatial control. This review focuses on the recent advances in the preparing methods for nano-therapeutics, and their applications in the treatments of diseases.

Traditionally, containers made from steel or other metals are not good for making tea, probably due to the fact that polyphenol components in tea can chelate with metal ions. A similar reason might stand behind the observations as reported herein. During the coating of well-defined metal-organic framework (MOF) crystalline particles with polydopamine (PDA) via pH-induced self-polymerization of dopamine, we found that MOF templates automatically etch off during the coating, giving rise to nonspherical PDA capsules that inherit the morphologies of the templates. Such self-etching of MOF templates is ascribed to the chelation of the metal nodes of the MOFs by the catechol moieties in the PDA layer. In addition, the self-etching of the zeolitic imidazolate framework-8 (ZIF-8) with a truncated cubic shape probably follows a crystalline facet-dependent fashion, resulting in intermediate yolk-shell structures with ZIF-8 cargos of various shapes inside a highly biocompatible PDA shell. Incubation of such intermediate hybrid particles with the cancerous HeLa cell line leads to pronounced cytotoxicity, which is tentatively connected with the cellular internalization of the ZIF@PDA nanoparticles because of the cell affinity of the PDA layer. Subsequently, the continuous release of Zn

Tumor heterogeneity has been one of the most important factors leading to the failure of conventional cancer therapies due to the accumulation of genetically distinct tumor-cell subpopulations during the tumor development process. Due to the diversity of genetic mutations during tumor growth, combining the use of multiple drugs has only achieved limited success in combating heterogeneous tumors. Herein, we report a novel antitumor strategy that effectively addresses tumor heterogeneity by using a CRISPR/Cas9-based nanoRNP carrying a combination of sgRNAs. Such nanoRNP is synthesized from Cas9 ribonucleoprotein, any combinations of required sgRNAs, and a rationally designed responsive polymer that endows nanoRNP with high circulating stability, enhanced tumor accumulation, and the efficient gene editing in targeted tumor cells eventually. By carrying a combination of sgRNAs that targets STAT3 and RUNX1, the nanoRNP exhibited efficient gene expression disruptions on a heterogeneous tumor model with two subsets of cells whose proliferations were sensitive to the reduced expression of STAT3 and RUNX1, respectively, leading to the effective growth inhibition of the heterogeneous tumor. Considering the close relationship between tumor heterogeneity and cancer progression, resistance to therapy, and recurrences, nanoRNP provides a feasible strategy to overcome tumor heterogeneity in the development of more advanced cancer therapy against malignant tumors.