Self-assembled nanoparticles of reduction-sensitive poly (lactic-co-glycolic acid)-conjugated chondroitin sulfate A for doxorubicin delivery: preparation, characterization and evaluation.

In this study, reduction-sensitive self-assembled polymer nanoparticles based on poly (lactic-co-glycolic acid) (PLGA) and chondroitin sulfate A (CSA) were developed and characterized. PLGA was conjugated with CSA via a disulfide linkage (PLGA-ss-CSA). The critical micelle concentration (CMC) of PLGA-ss-CSA conjugate is 3.5 µg/mL. The anticancer drug doxorubicin (DOX) was chosen as a model drug, and was effectively encapsulated into the nanoparticles (PLGA-ss-CSA/DOX) with high loading efficiency of 15.1%. The cumulative release of DOX from reduction-sensitive nanoparticles was only 34.8% over 96 h in phosphate buffered saline (PBS, pH 7.4). However, in the presence of 20 mM glutathione-containing PBS environment, DOX release was notably accelerated and almost complete from the reduction-sensitive nanoparticles up to 96 h. Moreover, efficient intracellular DOX release of PLGA-ss-CSA/DOX nanoparticles was confirmed by CLSM assay in A549 cells. In vitro cytotoxicity study showed that the half inhibitory concentrations of PLGA-ss-CSA/DOX nanoparticles and free DOX against A549 cells were 1.141 and 1.825 µg/mL, respectively. Therefore, PLGA-ss-CSA/DOX nanoparticles enhanced the cytotoxicity of DOX in vitro. These results suggested that PLGA-ss-CSA nanoparticles could be a promising carrier for drug delivery.

Polystyrene size-dependent impacts on microbial decomposers and nutrient cycling in streams.

The particle size of plastic is one of the most important factors influencing its ecotoxicity, but we are unclear about the effect of polystyrene (PS) particle size on microbial decomposers and consequent nutrient cycling in streams. Here, using microcosm experiments, we assessed how three PS sizes (50 nm, 1 µm, and 20 µm) influenced the process and consequences of leaf litter decomposition. Under acute exposure to 1 µm and 20 µm PS, fungal biomass significantly decreased, but microbial biomass significantly increased, indicating compensations may work between fungi and other microbial decomposers. After chronic exposure to 50 nm and 1 µm PS, the leaf decomposition rate decreased by 19.27 % and 15.22 %, respectively, due to the reduced microbial enzyme activity, fungal diversity, and dominance of Anguillospora. As a result, the regeneration of nutrients, especially phosphorus, was significantly depressed, which might influence the primary productivity of streams. Therefore, our results suggest that nanoscale PS has a greater impact on microbial activity, thus affecting their functioning in leaf litter decomposition and consequent nutrient cycling. The findings provide a data support for the risk assessment of plastic pollution in freshwater systems.

Assessing the impact of COVID-19 interventions on the hand, foot and mouth disease in Guangdong Province, China: a Bayesian modeling study.

Background: The non-pharmaceutical interventions (NPIs) against COVID-19 may have affected the transmission of hand, foot and mouth disease (HFMD). We aimed to assess the impact of the NPIs on HFMD in the high epidemic area of HFMD, Guangdong Province. Methods: The data of HFMD cases, etiological information, and meteorological factors in Guangdong from January 1, 2012, to December 31, 2021, were collected. Using a Bayesian structural time series (BSTS) model integrated counterfactual framework, we assessed the effect of NPIs on HFMD by different intervention periods, populations (gender, age, occupation), and cities. We further explored the correlation between the reduction of HFMD and socioeconomic factors in 21 cities. Results: A total of 351,217 HFMD cases were reported and 455,327 cases were averted in Guangdong Province during 2020-2021 with a reduction of 84.94% (95%CI: 81.63-87.22%) in 2020 and 29.49% (95%CI: 15.26-39.54%) in 2021. The impact of NPIs on HFMD differed by age and gender. The effects of NPIs were more remarkable for children aged 0-2 years and scattered children. We found that the relative reductions in 21 cities were related to the composition ratio of children and COVID-19 incidence. Conclusion: The reduction of HFMD incidence was significantly associated with COVID-19 NPIs, and school closure was an effective intervention to prevent HFMD outbreaks. Our findings will contribute to the development of HFMD prevention and control measures.

On-demand, remote and lossless manipulation of biofluid droplets.

The recent global outbreaks of epidemics and pandemics have shown us that we are severely under-prepared to cope with infectious agents. Exposure to infectious agents present in biofluids (e.g., blood, saliva, urine etc.) poses a severe risk to clinical laboratory personnel and healthcare workers, resulting in hundreds of millions of hospital-acquired and laboratory-acquired infections annually. Novel technologies that can minimize human exposure through remote and automated handling of infectious biofluids will mitigate such risk. In this work, we present biofluid manipulators, which allow on-demand, remote and lossless manipulation of virtually any liquid droplet. Our manipulators are designed by integrating thermo-responsive soft actuators with superomniphobic surfaces. Utilizing our manipulators, we demonstrate on-demand, remote and lossless manipulation of biofluid droplets. We envision that our biofluid manipulators will not only reduce manual operations and minimize exposure to infectious agents, but also pave the way for developing inexpensive, simple and portable robotic systems, which can allow point-of-care operations, particularly in developing nations.

Twisted-and-Coiled Actuators with Free Strokes Enable Soft Robots with Programmable Motions.

Various actuators (e.g., pneumatics, cables, dielectric elastomers, etc.) have been utilized to actuate soft robots. Besides widely used actuators, a relatively new artificial muscle-twisted-and-coiled actuators (TCAs)-is promising for actuating centimeter-scale soft robots because they are low cost, have a large work density, and can be driven by electricity. However, existing works on TCA-actuated soft robots in general can only generate simple bending motion. The reason is that TCAs fabricated with conventional methods have to be preloaded to generate a large contraction, and thus cannot actuate soft robots properly. In this work, an upgraded technique is presented to fabricate TCAs that can deliver 48% free strokes (contraction without preloading). We first compare the static performance of TCAs with free strokes with conventional TCAs, and then characterize how will the fabrication parameters influence the TCAs' stroke and force capability. After that, we demonstrate that such TCAs can actuate centimeter-scale soft robots with programmable motions (gripping, twisting, and three-dimensional bending). Finally, we combine those motions to demonstrate a soft robotic arm that can perform a pick-and-place task. We expect that TCAs with free strokes can enable miniature soft robots with rich three-dimensional motions for both locomotion and manipulation. Because TCAs are electrically driven, we can also potentially develop untethered soft robots by carrying onboard batteries and control circuits.

Preparing patterned carbonaceous nanostructures directly by overexposure of PMMA using electron-beam lithography.

The overexposure process of poly(methyl methacrylate) (PMMA) was studied in detail using electron-beam lithography. It was found that PMMA films could be directly patterned without development due to the electron-beam-induced collapse of PMMA macromolecular chains. By analyzing the evolution of surface morphologies and compositions of the overexposed PMMA films, it was also found that the transformation of PMMA from positive to negative resist was a carbonization process, so patterned carbonaceous nanostructures could be prepared directly by overexposure of PMMA using electron-beam lithography. This simple one-step process for directly obtaining patterned carbonaceous nanostructures has promising potential application as a tool to make masks and templates, nanoelectrodes, and building blocks for MEMS and nanophotonic devices.

Graphene-Based Nanomaterials: Potential Tools for Neurorepair.

Graphene, with its outstanding electrical properties, large surface area, and excellent mechanical properties, is found in a wide variety of applications in biomimetic substrates and biomedicine, with the result that there is growing interest in the effect of graphene-based nanomaterials on neural cells. This review sums up current research on the effectiveness of graphene and its derivatives on neural cells. We emphasize the biocompatibility of graphene and its derivatives, and how they affect the behavior of neural cells, including adhesion, proliferation, neurite outgrowth and differentiation. In addition, we discuss at great length the literature on graphenebased nanomaterials for drug delivery applications. While their in vivo effects on the nervous system remain to be explored, encouraging findings indicate that graphene-based nanomaterials have significant potential as novel therapies for neurodegenerative disease.

Re-entrant isotropic-nematic phase behavior in polymer-depleted amyloid fibrils.

Amyloid fibrils dispersed in water exhibit both isotropic (I) and nematic (N) phases, depending on concentration, but their coexistence, expected from the first order nature of the I - N thermodynamic transition is seldom observed. By adding a non-absorbing polymer to an amyloid fibrils suspension, we report, for the first time, an unusual closed-loop phase behavior. The phase diagrams reveal that the I + N coexistence does emerge, but only when the depleting polymer is present at intermediate concentrations. We combine depletion potentials in the dilute and semi-dilute polymer regime with the DLVO theory and the principle of equivalent law of corresponding states to calculate variations of the second virial coefficient with increasing polymer concentrations. We conclude that the decrease of the depletion potential range in the semi-dilute regime plays a pivotal role in the observed re-stabilization, leading to a closure of the I + N coexistence region.

Fabrication and characterization of nuclear localization signal-conjugated glycol chitosan micelles for improving the nuclear delivery of doxorubicin.

BACKGROUND: Supramolecular micelles as drug-delivery vehicles are generally unable to enter the nucleus of nondividing cells. In the work reported here, nuclear localization signal (NLS)-modified polymeric micelles were studied with the aim of improving nuclear drug delivery. METHODS: In this research, cholesterol-modified glycol chitosan (CHGC) was synthesized. NLS-conjugated CHGC (NCHGC) was synthesized and characterized using proton nuclear magnetic resonance spectroscopy, dynamic light scattering, and fluorescence spectroscopy. Doxorubicin (DOX), an anticancer drug with an intracellular site of action in the nucleus, was chosen as a model drug. DOX-loaded micelles were prepared by an emulsion/solvent evaporation method. The cellular uptake of different DOX formulations was analyzed by flow cytometry and confocal laser scanning microscopy. The cytotoxicity of blank micelles, free DOX, and DOX-loaded micelles in vitro was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in HeLa and HepG2 cells. RESULTS: The degree of substitution was 5.9 cholesterol and 3.8 NLS groups per 100 sugar residues of the NCHGC conjugate. The critical aggregation concentration of the NCHGC micelles in aqueous solution was 0.0209 mg/mL. The DOX-loaded NCHGC (DNCHGC) micelles were observed as being almost spherical in shape under transmission electron microscopy, and the size was determined as 248 nm by dynamic light scattering. The DOX-loading content of the DNCHGC micelles was 10.1%. The DOX-loaded micelles showed slow drug-release behavior within 72 hours in vitro. The DNCHGC micelles exhibited greater cellular uptake and higher amounts of DOX in the nuclei of HeLa cells than free DOX and DOX-loaded CHGC (DCHGC) micelles. The half maximal inhibitory concentration (IC(50)) values of free DOX, DCHGC, and DNCHGC micelles against HepG2 cells were 4.063, 0.591, and 0.171 µg/mL, respectively. Moreover, the IC(50) values of free DOX (3.210 µg/mL) and the DCHGC micelles (1.413 µg/mL) against HeLa cells were nearly 6.96- and 3.07-fold (P < 0.01), respectively, higher than the IC(50) value of the DNCHGC micelles (0.461 µg/mL). CONCLUSION: The results of this study suggest that novel NCHGC micelles could be a potential carrier for nucleus-targeting delivery.