Developing Type‐I photosensitizers is considered as an efficient approach to overcome the deficiency of traditional photodynamic therapy (PDT) for hypoxic tumors. However, it remains a challenge to ...design photosensitizers for generating reactive oxygen species by the Type‐I process. Herein, we report a series of α,β‐linked BODIPY dimers and a trimer that exclusively generate superoxide radical (O2−.) by the Type‐I process upon light irradiation. The triplet formation originates from an effective excited‐state relaxation from the initially populated singlet (S1) to triplet (T1) states via an intermediate triplet (T2) state. The low reduction potential and ultralong lifetime of the T1 state facilitate the efficient generation of O2−. by inter‐molecular charge transfer to molecular oxygen. The energy gap of T1‐S0 is smaller than that between 3O2 and 1O2 thereby precluding the generation of singlet oxygen by the Type‐II process. The trimer exhibits superior PDT performance under the hypoxic environment.
Heavy‐atom‐free boron dipyrromethene (BODIPY)‐based photosensitizers generate ROS exclusively by the Type‐I process upon near‐infrared light illumination for tumor ablation.
The preparation and transformation of heterocyclic structures have always been of great interest in organic chemistry. Electrochemical technique provides a versatile and powerful approach to the ...assembly of various heterocyclic structures. In this review, we examine the advance in relation to the electrochemical construction of heterocyclic compounds published since 2000 via intra- and intermolecular cyclization reactions.
The foundation for the development of modern compressible flow solver is based on the Riemann solution of the inviscid Euler equations. The high-order schemes are basically related to high-order ...spatial interpolation or reconstruction. In order to overcome the low-order wave interaction mechanism due to the Riemann solution, the temporal accuracy of the scheme can be improved through the Runge–Kutta method, where the dynamic deficiencies in the first-order Riemann solution is alleviated through the sub-step spatial reconstruction in the Runge–Kutta process. The close coupling between the spatial and temporal evolution in the original nonlinear governing equations seems weakened due to its spatial and temporal decoupling. Many recently developed high-order methods require a Navier–Stokes flux function under piece-wise discontinuous high-order initial reconstruction. However, the piece-wise discontinuous initial data and the hyperbolic-parabolic nature of the Navier–Stokes equations seem inconsistent mathematically, such as the divergence of the viscous and heat conducting terms due to initial discontinuity. In this paper, based on the Boltzmann equation, we are going to present a time-dependent flux function from a high-order discontinuous reconstruction. The theoretical basis for such an approach is due to the fact that the Boltzmann equation has no specific requirement on the smoothness of the initial data and the kinetic equation has the mechanism to construct a dissipative wave structure starting from an initially discontinuous flow condition on a time scale being larger than the particle collision time. The current high-order flux evaluation method is an extension of the second-order gas-kinetic BGK scheme for the Navier–Stokes equations (BGK-NS). The novelty for the easy extension from a second-order to a higher order is due to the simple particle transport and collision mechanism on the microscopic level. This paper will present a hierarchy to construct such a high-order method. The necessity to couple spatial and temporal evolution nonlinearly in the flux evaluation can be clearly observed through the numerical performance of the scheme for the viscous flow computations.
With discretized particle velocity space, a multiscale unified gas-kinetic scheme for entire Knudsen number flows is constructed based on the BGK model. The current scheme couples closely the update ...of macroscopic conservative variables with the update of microscopic gas distribution function within a time step. In comparison with many existing kinetic schemes for the Boltzmann equation, the current method has no difficulty to get accurate Navier–Stokes (NS) solutions in the continuum flow regime with a time step being much larger than the particle collision time. At the same time, the rarefied flow solution, even in the free molecule limit, can be captured accurately. The unified scheme is an extension of the gas-kinetic BGK-NS scheme from the continuum flow to the rarefied regime with the discretization of particle velocity space. The success of the method is due to the un-splitting treatment of the particle transport and collision in the evaluation of local solution of the gas distribution function. For these methods which use operator splitting technique to solve the transport and collision separately, it is usually required that the time step is less than the particle collision time. This constraint basically makes these methods useless in the continuum flow regime, especially in the high Reynolds number flow simulations. Theoretically, once the physical process of particle transport and collision is modeled statistically by the kinetic Boltzmann equation, the transport and collision become continuous operators in space and time, and their numerical discretization should be done consistently. Due to its multiscale nature of the unified scheme, in the update of macroscopic flow variables, the corresponding heat flux can be modified according to any realistic Prandtl number. Subsequently, this modification effects the equilibrium state in the next time level and the update of microscopic distribution function. Therefore, instead of modifying the collision term of the BGK model, such as ES-BGK and BGK–Shakhov, the unified scheme can achieve the same goal on the numerical level directly. Many numerical tests will be used to validate the unified method.
Novel compact ultra-wideband (UWB) bandpass filter (BPF) using stub-loaded multiple-mode resonator (MMR) is presented in this letter. The MMR is constructed by loading three open stubs in a ...uniform-impedance resonator, i.e., one stepped-impedance stub at the center and two uniform-impedance stubs at the symmetrical side locations. Five modes, including two odd modes and three even modes, could be designed within UWB band, and two transmission zeros generated by the stepped-impedance stub improve the passband selectivity greatly. The letter shows modal resonant frequencies against the step-impedance-stub-loaded parameters, which can control the even modes flexibly, while the odd modes remain the same. A compact planar UWB BPF is simulated, fabricated and measured. The simulated and measured results are in good agreement and show good in-band filtering performance and sharp selectivity.
It is a challenge to design photosensitizers to balance between the tumor‐targeting enrichment for precise treatment and efficient clearance within a reasonable timescale for reducing side effects. ...Herein, an ultra‐small nano‐photosensitizer 1a with excellent tumor‐specific accumulation and renal clearance is reported. It is formed from the self‐assembly of compound 1 bearing three triethylene glycol (TEG) arms and two pyridinium groups in water. The positively charged surface with neutral TEG coating enables 1a to efficiently target the tumor, with the signal‐to‐background ratio reaching as high as 11.5 after tail intravenous injection. The ultra‐small size of 1a with an average diameter of 5.6 nm allows its fast clearance through kidney. Self‐assembly also endows 1a with an 18.2‐fold enhancement of reactive oxygygen species generation rate compared to compound 1 in organic solution. Nano‐PS 1a manifests an excellent photodynamic therapy efficacy on tumor‐bearing mouse models. This work provides a promising design strategy of photosensitizers with renal clearable and tumor‐targeting ability.
Here, an ultra‐small nano photosensitizer is presented through a facile self‐assembly strategy that can target a disease state, boost reactive oxygen species (ROS) generation, as well as be cleared efficiently from the body in a reasonable amount of time.
The highly oxygen-dependent nature of photodynamic therapy (PDT) limits its therapeutic efficacy against hypoxic solid tumors in clinics, which is an urgent problem to be solved. Herein, we develop ...an oxygen-independent supramolecular photodynamic agent that produces hydroxyl radical (•OH) by oxidizing water in the presence of intracellularly abundant pyruvic acid under oxygen-free conditions. A fluorene-substituted BODIPY was designed as the electron donor and coassembled with perylene diimide as the electron acceptor to form the quadruple hydrogen-bonded supramolecular photodynamic agent. Detailed mechanism studies reveal that intermolecular electron transfer and charge separation upon light irradiation result in an efficient generation of radical ion pairs. Under oxygen-free conditions, the cationic radicals directly oxidize water to generate highly cytotoxic •OH, and the anionic radicals transfer electrons to pyruvic acid, realizing the catalytic cycle. Thus, this photodynamic agent exhibited superb photocytotoxicity even under severe hypoxic environments and excellent in vivo antitumor efficacy on HeLa-bearing mouse models. This work provides a strategy for constructing oxygen-independent photodynamic agents, which opens up an avenue for effective PDT against hypoxic tumors.
Given that Type-I photosensitizers (PSs) have hypoxia tolerance, developing general approaches to prepare Type-I PSs is of great importance, but remains a challenge. Here, we report a supramolecular ...strategy for the preparation of Type-I photodynamic agents, which simultaneously generate strong oxidizing cationic radicals and superoxide radicals, by introducing electron acceptors to the existing Type-II PSs. As a proof-of-concept, three electron acceptors were designed and co-assembled with a classical PS to produce quadruple hydrogen-bonded supramolecular photodynamic agents. The photo-induced electron transfer from the PS to the adjacent electron acceptor occurs efficiently, leading to the generation of a strong oxidizing PS
and an anionic radical of the acceptor, which further transfers an electron to oxygen to form O
. In addition, these photodynamic agents induce direct photocatalytic oxidation of NADH with a turnover frequency as high as 53.7 min
, which offers an oxygen-independent mechanism to damage tumors.
Biodegradable Mg‐based metals may be promising orthopedic implants for treating challenging bone diseases, attributed to their desirable mechanical and osteopromotive properties. This Review ...summarizes the current status and future research trends for Mg‐based orthopedic implants. First, the properties between Mg‐based implants and traditional orthopedic implants are compared on the following aspects: in vitro and in vivo degradation mechanisms of Mg‐based implants, peri‐implant bone responses, the fate of the degradation products, and the cellular and molecular mechanisms underlying the beneficial effects of Mg ions on osteogenesis. Then, the preclinical studies conducted at the low weight bearing sites of animals are introduced. The innovative strategies (for example, via designing Mg‐containing hybrid systems) are discussed to address the limitations of Mg‐based metals prior to their clinical applications at weight‐bearing sites. Finally, the available clinical studies are summarized and the challenges and perspectives of Mg‐based orthopedic implants are discussed. Taken together, the progress made on the development of Mg‐based implants in basic, translational, and clinical research has laid down a foundation for developing a new era in the treatment of challenging and prevalent bone diseases.
This Review summarizes the current status and future research trends for Mg‐based or containing orthopedic implants. The progress made on the development of Mg‐based or containing implants in basic, translational, and clinical research can lay down a foundation for opening a new era to improve clinical healing outcomes in the treatment of challenging bone diseases.
Rationale
Depression is a serious neuropsychiatric disorder, which is characterized by sustaining mood disorders. Loganin, a major iridoid glycoside from Corni fructus, has a variety of ...pharmacological activities, including neuroprotective effect and hypnotic effect. However, little is known about the effects of loganin on stress-induced depression.
Objective
To investigate the effects of loganin on behavioral despair of mice, and whether serotonin (5-HT) and/or noradrenaline (NE) are involved in this process.
Methods
We tested the effectiveness of loganin using tail suspension test (TST). The possible mechanism was explored using reserpine-induced ptosis and hypothermia, and 5-HTP-induced head-twitch response in mice. The changes of 5-HT and NE in the prefrontal cortex, hippocampus, and striatum were measured through high-performance liquid chromatography (HPLC) analysis. Then, we identified the effects of depleting 5-HT and NE by PCPA (p-chlorophenylalanine) and DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride) pretreatment, respectively.
Results
Loganin (12.5/50 mg/kg) induced antidepressant-like effects in mice submitted to TST. Loganin (12.5/50 mg/kg) ameliorated the reserpine-induced hypothermia and ptosis, as well as increased 5-HTP-induced head-twitch responses in mice. Loganin (50 mg/kg) significantly increased the levels of 5-HT in the prefrontal cortex, hippocampus, and striatum. Furthermore, only PCPA treatment could eliminate loganin-induced antidepressant-like effects in TST.
Conclusion
Loganin exerts antidepressant-like effect in the TST depending on 5-HT levels in the central nervous system, which provide a potential agent for depression therapy.
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