Molecular Motor-Driven Light-Controlled Logic-Gated K+ Channel for Cancer Cell Apoptosis.

Developing artificial ion transport systems, which process complicated information and step-wise regulate properties, is essential for deeply comprehending the subtle dynamic behaviors of natural channel proteins (NCPs). Here a photo-controlled logic-gated K+ channel based on single-chain random heteropolymers containing molecular motors, exhibiting multi-core processor-like properties to step-wise control ion transport is reported. Designed with oxygen, deoxygenation, and different wavelengths of light as input signals, complicated logical circuits comprising "YES", "AND", "OR" and "NOT" gate components are established. Implementing these logical circuits with K+ transport efficiencies as output signals, multiple state transitions including "ON", "Partially OFF" and "Totally OFF" in liposomes and cancer cells are realized, further causing step-wise anticancer treatments. Dramatic K+ efflux in the "ON" state (decrease by 50% within 7 min) significantly induces cancer cell apoptosis. This integrated logic-gated strategy will be expanded toward understanding the delicate mechanism underlying NCPs and treating cancer or other diseases is expected.

Mechanical Properties, Radiation Resistance Performances, and Mechanism Insights of Nitrile Butadiene Rubber Irradiated with High-Dose Gamma Rays.

The radiation effect of materials is very important and directly related to the safety and reliability of nuclear reactors. Polymer materials, one of the indispensable materials in nuclear power equipment, must withstand the ordeal of high-energy ionizing rays. In this work, through screening different γ-ray dose irradiation conditions, we systematically and comprehensively study the changes in the structure and properties of nitrile butadiene rubber (NBR) before and after γ-ray static irradiation at a high dose rate, and master the rule and mechanism of the γ-ray static irradiation effect of these polymer materials. The mapping relationship between the macroscopic properties, microstructure, and irradiation dose of NBR is accurately characterized. With an increase in total irradiation dose, the C=C double bond reaction occurs, and the C≡N bond, C=C, and C=O participate in the hyper crosslinking reaction. The glass transition temperature (Tg) increases with the cumulative irradiation amount. With the increased total irradiation amount, the degree of rubber cross-linking increases, causing an increased crystallinity and decomposition temperature. A growing amount of gamma irradiation causes the mechanical properties of the rubber to degrade simultaneously, increasing the shore hardness while decreasing the tensile strength and ultimate elongation at break. When the cumulative amount reaches 1 MGy, the ultimate elongation at break decreases significantly. A cumulative dose of radiation resistance of 4 MGy can be achieved by the samples. This work can provide theoretical and experimental support for the long-term stability of nitrile butadiene rubber and its derivatives in nuclear radiation fields and space radiation conditions.

Crown Ether-Based Ion Transporters in Bilayer Membranes.

Bilayer membranes that enhance the stability of the cell are essential for cell survival, separating and protecting the interior of the cell from its external environment. Membrane-based channel proteins are crucial for sustaining cellular activities. However, dysfunction of these proteins would induce serial channelopathies, which could be substituted by artificial ion channel analogs. Crown ethers (CEs) are widely studied in the area of artificial ion channels owing to their intrinsic host-guest interaction with different kinds of organic and inorganic ions. Other advantages such as lower price, chemical stability, and easier modification also make CE a research hotspot in the field of synthetic transmembrane nanopores. And numerous CEs-based membrane-active synthetic ion channels were designed and fabricated in the past decades. Herein, the recent progress of CEs-based synthetic ion transporters has been comprehensively summarized in this review, including their design principles, functional mechanisms, controllable properties, and biomedical applications. Furthermore, this review has been concluded by discussing the future opportunities and challenges facing this research field. It is anticipated that this review could offer some inspiration for the future fabrication of novel CEs-derived ion transporters with more advanced structures, properties, and practical applications.

Biomimetic Cascade Polymer Nanoreactors for Starvation and Photodynamic Cancer Therapy.

The selective disruption of nutritional supplements and the metabolic routes of cancer cells offer a promising opportunity for more efficient cancer therapeutics. Herein, a biomimetic cascade polymer nanoreactor (GOx/CAT-NC) was fabricated by encapsulating glucose oxidase (GOx) and catalase (CAT) in a porphyrin polymer nanocapsule for combined starvation and photodynamic anticancer therapy. Internalized by cancer cells, the GOx/CAT-NCs facilitate microenvironmental oxidation by catalyzing endogenous H2O2 to form O2, thereby accelerating intracellular glucose catabolism and enhancing cytotoxic singlet oxygen (1O2) production with infrared irradiation. The GOx/CAT-NCs have demonstrated synergistic advantages in long-term starvation therapy and powerful photodynamic therapy (PDT) in cancer treatment, which inhibits tumor cells at more than twice the rate of starvation therapy alone. The biomimetic polymer nanoreactor will further contribute to the advancement of complementary modes of spatiotemporal control of cancer therapy.

Injectable and fast self-healing protein hydrogels.

Injectable hydrogels are adapted to irregularities in the desired location by injection as a liquid and gelation in situ. However, traditional slow-gelling injectable hydrogels may result in loss of cargo (cells/drugs) as well as diffusion at the target site, and extremely rapid gelation may lead to undesired premature coagulation. These practical problems can be solved by using self-healing hydrogels. Herein, through the reduction of disulfide bonds in BSA protein by using a reducing agent, the disulfide bonds between the individual BSA protein molecules are re-matched to form a network structure, thereby forming a protein hydrogel. This hydrogel shows an efficient and rapid self-healing property, and the broken protein hydrogel can be fast repaired within 1-2 minutes in response to H2O2 stimulation, and the repair efficiency reached up to 100%. The hydrogel can be extruded using only a pinhole syringe, and cytotoxicity experiments have demonstrated excellent biocompatibility of the protein hydrogel. This non-toxic, injectable, fast self-healing protein hydrogel is expected to be widely used in biomedical, tissue engineering, injectable gel, 3D bioprinting, and other applications.

Biomimetic Pulsating Vesicles with Both pH-Tunable Membrane Permeability and Light-Triggered Disassembly-Re-assembly Behaviors Prepared by Supra-Amphiphilic Helices.

The reversible unfolding-refolding transition is considerably important for natural elastomeric proteins (e.g., titin) to fulfill their biological functions. It is of great importance to develop synthetic versions by borrowing their unique stretchable design principles. Herein, we present a novel pulsating vesicle by means of the aqueous self-assembly of supra-amphiphilic helices. Interestingly, this vesicle simultaneously features dynamic swelling and shrinkage movements in response to external proton triggers. Titin-like unfolding-refolding transformation of artificial helices was proved to play a crucial role in this pulsatile motion. Moreover, the vesicular membrane of this vesicle has exhibited tunable permeability during reversible expansion and contraction circulation. Meanwhile, light can also be used as a driving force to further regulate the disassembly-reassembly transformation of the pulsating vesicle. In addition, the drug delivery system was also employed as an investigating model to estimate the permeability variation and disassembly-reassembly behaviors of the pulsating vesicles, which displayed unique dual quick- and sustained-release behaviors toward anti-cancer agents. It is anticipated that this work opens an avenue for fabricating novel stretchable biomimetics by using the exclusive unfolding-refolding nature of artificial foldamers.

A remote optically controlled hydrolase model based on supramolecular assembly and disassembly of its enzyme-like active site.

A photoresponsive hydrolase model was constructed through the spatial organization of histidine/arginine-containing peptide supra-amphiphiles that are held together by cucurbit[8]uril (CB[8]) methylviologen (MV) azobenzene (Azo) ternary complexation and subsequently self-assemble into highly uniform giant vesicles. The reversible morphological transition of the vesicular structures to non-assembled peptide fragments was triggered by azobenzene photoisomerization. This enables the assembly/disassembly of its enzyme-like active site to cause a dramatic change in hydrolytic activity. The dynamic process can be directly monitored to determine the supramolecular structure-related enzymatic parameters, which may help to understand how the regulation of enzyme activity is coupled to the aggregation behaviors of natural enzymes.

A dosimetric study on the use of 3D-printed customized boluses in photon therapy: A hydrogel and silica gel study.

PURPOSE: The aim of the study was to compare the dose differences between two kinds of materials (silica gel and hydrogel) used to prepare boluses based on three-dimensional (3D) printing technologies and commercial bolus in head phantoms simulating nose, ear, and parotid gland radiotherapy. METHODS AND MATERIALS: We used 3D printing technology to make silica gel and hydrogel boluses. To evaluate the clinical feasibility, intensity modulated radiation therapy (IMRT) plans were created for head phantoms that were bolus-free or had a commercial bolus, a silica gel bolus, or a hydrogel bolus. Dosimetry differences were compared in simulating nose, ear, and parotid gland radiotherapy separately. RESULTS: The air gaps were smaller in the silica gel and hydrogel bolus than the commercial one. In nose plans, it was shown that the V95% (relative volume that is covered by at least 95% of the prescription dose) of the silica gel (99.86%) and hydrogel (99.95%) bolus were better than the commercial one (98.39%) and bolus-free (87.52%). Similarly, the homogeneity index (HI) and conformity index (CI) of the silica gel (0.06; 0.79) and hydrogel (0.058; 0.80) bolus were better than the commercial one (0.094; 0.72) and bolus-free (0.59; 0.53). The parameters of results (HI, CI, V95% ) were also better in 3D printing boluses than in the commercial bolus or without bolus in ear and parotid plans. CONCLUSIONS: Silica gel and hydrogel boluses were not only good for fit and a high level of comfort and repeatability, but also had better parameters in IMRT plans. They could replace the commercial bolus for clinical use.

Adenovirus associated with acute diarrhea: a case-control study.

BACKGROUND: Diarrhea is a major source of morbidity and mortality among young children in low-income and middle-income countries. Human adenoviruses (HAdV), particular HAdV species F (40, 41) has been recognized as important causal pathogens, however limited data exist on molecular epidemiology of other HAdV associated with acute gastroenteritis. METHODS: In the present preliminary study, we performed a case-control study involving 273 children who presented diarrheal disease and 361 healthy children matched control in Children's hospital of Hebei Province (China) to investigate the relationship between non-enteric HAdV and diarrhea. HAdV were detected and quantified using quantitative real-time PCR (qPCR) and serotyped by sequencing and phylogenetic analysis. Odds ratio (OR) was used to assess the risk factor of HAdV. RESULTS: HAdV were detected in 79 (28.94%) of 273 children with diarrhea including 7 different serotypes (HAdV 40, 41, 3, 2,1,5 and 57) with serotypes 40, 41 and 3 being the most dominant and in 26 (7.20%) of 361 healthy children containing 9 serotypes (HAdV 40, 41, 3, 2,1,5,57,6 and 31). A majority (91.14%) of HAdV positives occurred in diarrhea children and 65.38% in controls< 3 years of age. No significant difference in the viral load was found between case and control groups or between Ad41-positive patients and healthy controls. In addition to HAdV 40 and 41, HAdV 3 was also associated with diarrhea (OR = 17.301, adjusted OR = 9.205, p < 0.001). CONCLUSIONS: Our results demonstrate a high diversity of HAdV present among diarrhea and healthy children and implicate that non-enteric HAdV3 may lead to diarrhea.