The unique permselectivity of cellular membranes is of crucial importance to maintain intracellular homeostasis while adapting to microenvironmental changes. Although liposomes and polymersomes have ...been widely engineered to mimic microstructures and functions of cells, it still remains a considerable challenge to synergize the stability and permeability of artificial cells and to imitate local milieu fluctuations. Herein, we report concurrent crosslinking and permeabilizing of pH-responsive polymersomes containing Schiff base moieties within bilayer membranes via enzyme-catalyzed acid production. Notably, this synergistic crosslinking and permeabilizing strategy allows tuning of the mesh sizes of the crosslinked bilayers with subnanometer precision, showing discriminative permeability toward maltooligosaccharides with molecular sizes of ~1.4-2.6 nm. The permselectivity of bilayer membranes enables intravesicular pH oscillation, fueled by a single input of glucose. This intravesicular pH oscillation can further drive the dissipative self-assembly of pH-sensitive dipeptides. Moreover, the permeabilization of polymersomes can be regulated by intracellular pH gradient as well, enabling the controlled release of encapsulated payloads.
Abstract To emulate the ordered arrangement of monomer units found in natural macromolecules, single-unit monomer insertion (SUMI) have emerged as a potent technique for synthesizing ...sequence-controlled vinyl polymers. Specifically, numerous applications necessitate vinyl polymers encompassing both radically and cationically polymerizable monomers, posing a formidable challenge due to the distinct thiocarbonylthio end-groups required for efficient control over radical and cationic SUMIs. Herein, we present a breakthrough in the form of interconvertible radical and cationic SUMIs achieved through the manipulation of thiocarbonylthio end-groups. The transition from a trithiocarbonate (for radical SUMI) to a dithiocarbamate (for cationic SUMI) is successfully accomplished via a radical-promoted reaction with bis(thiocarbonyl) disulfide. Conversely, the reverse transformation utilizes the reaction between dithiocarbamate and bistrithiocarbonate disulfide under a cationic mechanism. Employing this strategy, we demonstrate a series of synthetic examples featuring discrete oligomers containing acrylate, maleimide, vinyl ether, and styrene, compositions unattainable through the SUMI of a single mechanism alone.
Due to the complex permittivity, it is difficult to directly clarify the transient mechanism between electromagnetic waves and Debye media. To overcome the above problem, the temporal relationship ...between the electromagnetic waves and permittivity is explicitly derived by applying the Fourier inversion and introducing the remnant displacement. With the help of the Poynting theorem and energy conservation equation, the transient power loss density is derived to describe the transient dissipation of electromagnetic field and the mechanism on phase displacement has been explicitly revealed. Besides, the unique solution can be obtained by applying the time-domain analysis method rather than involving the frequency-domain characteristics. The effectiveness of transient analysis is demonstrated by giving a comparison simulation on one-dimensional example.
At present, sequence-based models have various applications in recommendation systems; these models recommend the interested items of the user according to the user’s behavioral sequence. However, ...sequence-based models have a limitation of length. When the length of the user’s behavioral sequence exceeds the limitation of the model, the model cannot take advantage of the complete behavioral sequence of the user and cannot know the user’s holistic interests. The accuracy of the model then goes down. Meanwhile, sequence-based models only pay attention to the sequential signals of the data but do not pay attention to the spatial signals of the data, which will also affect the model’s accuracy. This paper proposes a graph sequence-based model called GSRec that combines Graph Convolutional Network (GCN) and Transformer to solve these problems. In the GCN part we designed a reverse-order graph, and in the Transformer part we introduced the user embedding. The reverse-order graph and the user embedding can make the combination of GCN and Transformer more efficient. Experiments on six datasets show that GSRec outperforms the current state-of-the-art (SOTA) models.
Background:
Aloe vera
is a medically valuable plant with anti-epileptic activity; however, its mechanism of action remains unknown. In this study, network pharmacological,
in vitro
, and
in vivo
...experiments were carried out to explore the potential anti-epileptic components and targets of
Aloe vera
.
Methods:
The main active components of
Aloe vera
were identified by searching the Traditional Chinese Medicine System Pharmacology database. Targets of
Aloe vera
were predicted using SwissTargetPrediction, whereas information about the epilepsy disease targets was obtained from Gene Cards. The protein–protein interaction network and core targets were screened according to the topological structure and CytoNCA plugin. The glutamate-induced HT22 cell line and pentylenetetrazol-induced seizure rats were used to confirm the effect of aloesone by detecting reactive oxygen species (ROS) and apoptosis, and predicting the targets.
Results:
A total of 14 core active components were selected based on the screening criteria of oral bioavailability ≥30% and drug-likeness ≥ 0.10. Four compounds, namely linoleic acid, aloesone, isoeleutherol glucosiden qt, and anthranol, demonstrated the potential ability of crossing the blood-brain barrier. A total of 153 targets associated with epilepsy were predicted for the four compounds. Moreover, after network analysis with CytoNCA, 10 targets, namely, MAPK1, SRC, MARK3, EGFR, ESR1, PTGS2, PTPN11, JAK2, PPKCA, and FYN, were selected as the core genes, and SRC, which has been predicted to be the target of aloesone and anthranol, exhibited the highest subgraph centrality value.
In vitro
experiments confirmed that aloesone treatment significantly inhibited the glutamate-induced neuronal injury by reducing the intracellular ROS content and the early phase of apoptosis. Additionally, treatment with 50 mg/kg aloesone resulted in anti-seizure effects by reducing the seizure score and prolonging the latent period in acute and chronic rats. Furthermore, aloesone treatment increased the phosphorylation of c-SRC at Y418 and reduced the phosphorylation at Y529, simultaneously activating c-SRC.
Conclusion:
Integrating network pharmacology with
in vitro
and
in vivo
experiments demonstrated that aloesone, which inhibited seizure by activating c-SRC, is a potential anti-seizure compound present in
Aloe vera
.
Inflammation serves as a natural defense mechanism to protect living organisms from infectious diseases. Nonsteroidal anti-inflammatory drugs (NSAIDs) can help relieve inflammatory reactions and are ...clinically used to treat pain, fever, and inflammation, whereas long-term use of NSAIDs may lead to severe side effects including gastrointestinal damage and cardiovascular toxicity. Therefore, it is of increasing importance to configure new dosing strategies and alleviate the side effects of NSAIDs. Towards this goal, glutathione (GSH)-responsive disulfide bonds and hydrogen peroxide (H2O2)-reactive phenylboronic ester linkages were utilized as triggering moieties in this work to design redox-responsive prodrug monomers and polyprodrug amphiphiles based on indomethacin (IND) drug. Note that IND is a widely prescribed NSAID in the clinic. Starting from three types of redox-reactive IND prodrug monomers, redox-responsive polyprodrug amphiphiles were synthesized through reversible addition-fragmentation chain transfer (RAFT) polymerizations of prodrug monomers using poly(ethylene oxide) (PEO)-based macroRAFT agent. The resultant polyprodrug amphiphiles with high IND loading contents (>33 wt%) could self-assemble into polymersomes with PEO shielding coronas and redox-responsive bilayer membranes composed of IND prodrugs. Upon incubation with GSH or H2O2, controlled release of intact IND in the active form from polyprodrug polymersomes was actuated by GSH-mediated disulfide cleavage reaction and H2O2-mediated oxidation of phenylboronic ester moieties, respectively, followed by self-immolative degradation events. Furthermore, in vitro studies at the cellular level revealed that redox-responsive polymersomes could efficiently relieve inflammatory responses induced by lipopolysaccharide (LPS) in RAW264.7 macrophage cells.
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Background
To address the lack of mental health practitioners in developing countries, the current study explored the feasibility of a newly developed self-guided digital intervention program TEA ...(training for emotional adaptation) in alleviating depressive and anxiety symptoms, as one of a few studies which adapted from theoretical models with effective intervention techniques.
Methods
The first part of this study involved 11 professional mental health practitioners giving feedback on the feasibility of the TEA; while the second part involved a mixed-method single-arm study with 32 participants recruited online, who went through the seven intervention sessions within 14 days. The questionnaires were collected before, after, 14 days after, and 30 days after intervention. Additionally, 10 participants were invited to semi-structured interviews regarding their suggestions.
Results
Practitioners thought that the TEA showed high professionalism (8.91/10) and is suitable for treating emotional symptoms (8.09/10). The generalized estimating equation model showed that the TEA significantly reduced participants' depressive and anxiety symptoms, while the effects of the intervention remained 30 days post intervention (Cohen's d > 1). Thematic analysis revealed three main themes about future improvement, including content improvement, interaction improvement, and bug-fixing.
Conclusions
To address the current needs for digital mental health intervention programs to account for the insufficient availability of mental health services in China, the current study provides preliminary evidence of the effectiveness of TEA, with the potential to address the urgent need for remote mental health services.
Trial registration
The study was registered at the Chinese Clinical Trial Register (ChiCTR), with number ChiCTR2200065944.
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•Recent advances in solid state electrolytes for lithium ion batteries are reviewed.•A novel laser annealing process of synthesizing cubic Li7La3Zr2O12 is discussed.•Cubic ...Li7La3Zr2O12 exhibits a very high Li ion conductivity of 1.0×10−4S/cm.
This paper reviews the current status of, and new progress in, the field of solid state electrolytes (SSE) for lithium ion batteries. In addition to a review of current technologies, we are also presenting our novel results on pulsed laser processing of garnet based SSEs, specifically Li7La3Zr2O12 (LLZO). LLZO powders with a tetragonal structure were prepared by a sol–gel technique, then a pulsed laser annealing process was employed to covert the powders to cubic LLZO without any loss of lithium. The tetragonal LLZO exhibited a Li ion conductivity of 1.8×10−7 S/cm, whereas the laser annealed cubic LLZO showed a Li ion conductivity of 1.0×10−4 S/cm at room temperature. A systematic study of the effect of pulsed laser annealing (PLA) on the crystal structure, morphology, composition, and ionic conductivity of LLZO was performed via X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and electrochemical impedance spectroscopy (EIS) measurements. These results demonstrate that PLA is a powerful processing technique for synthesizing the high ionic conductivity cubic phase of LLZO at relatively low temperatures, as compared to conventional methods.
The selective activation of nanovectors in pathological tissues is of crucial importance to achieve optimized therapeutic outcomes. However, conventional stimuli-responsive nanovectors lack ...sufficient sensitivity because of the slight difference between pathological and normal tissues. To this end, the development of nanovectors capable of responding to weak pathological stimuli is of increasing interest. Herein, we report the fabrication of amphiphilic polyurethane nanoparticles containing both external and built-in triggers. The activation of external triggers leads to the liberation of highly reactive primary amines, which subsequently activates the built-in triggers with the release of more primary amines in a positive feedback manner, thereby triggering the degradation of micellar nanoparticles in a cycle amplification model. The generality and versatility of the cycle amplification concept have been successfully verified using three different triggers including reductive milieu, light irradiation, and esterase. We demonstrate that these stimuli-responsive nanoparticles show self-propagating degradation performance even in the presence of trace amounts of external stimuli. Moreover, we confirm that the esterase-responsive nanoparticles can discriminate cancer cells from normal ones by amplifying the esterase stimulus that is overexpressed in cancer cells, thereby enabling the selective release of encapsulated payloads and killing cancer cells. This work presents a robust strategy to fabricate stimuli-responsive nanocarriers with highly sensitive property toward external stimuli, showing promising applications in cancer therapy with minimized side effects.
Inspired by the self-adaptive nature of living organisms, the development of stimuli-responsive polymers that can sense and respond to surrounding microenvironments has received increasing interest. ...To date, stimuli-responsive polymers have found promising applications in terms of smart coatings, actuators, photolithography, imaging and diagnosis, and so on. Notwithstanding significant progress, it remains a grand challenge to improve the sensitivity of stimuli-responsive polymers toward external stimuli, which is, however, highly desirable in practical applications when the input signals are very weak. To circumvent this problem, self-propagating polymers have been developed, which enable the amplification of input signals in a positive feedback manner, thereby exponentially elevating the sensitivity. In this minireview, we summarize the recent design strategies and potential applications of self-propagating polymers by integrating feedback signal amplification modules, which have shown promising applications ranging from fundamental research to industry.
Stimuli-responsive polymers with self-propagating degradation capacity being sensitive to acids, bases, fluoride ions, and hydrogen peroxide are reviewed, exhibiting self-accelerated degradation behavior.
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