Modeling Colorectal Cancer-Induced Liver Portal Vein Microthrombus on a Hepatic Lobule Chip.

Colorectal cancer is one of the most common malignant tumors. At the advanced stage of colorectal cancer, cancer cells migrate with the blood to the liver from the hepatic portal vein, eventually resulting in a portal vein tumor thrombus (PVTT). To date, the progression of the early onset of PVTT [portal vein microthrombus (PVmT) induced by tumors] is unclear. Herein, we developed an on-chip PVmT model by loading the spheroid of colorectal cancer cells into the portal vein of a hepatic lobule chip (HLC). On the HLC, the progression of PVmT was presented, and early changes in metabolites of hepatic cells and in structures of hepatic plates and sinusoids induced by PVmT were analyzed. We replicated intrahepatic angiogenesis, thickened blood vessels, an increased number of hepatocytes, disordered hepatic plates, and decreased concentrations of biomarkers of hepatic cell functions in PVmT progression on a microfluidic chip for the first time. In addition, the combined therapy of thermo-ablation and chemo-drug for PVmT was preliminarily demonstrated. This study provides a promising method for understanding PVTT evolution and offers a valuable reference for PVTT therapy.

On-Chip Label-Free Sorting of Living and Dead Cells.

With the emergence of various cutting-edge micromachining technologies, lab on a chip is growing rapidly, but it is always a challenge to realize the on-chip separation of living cells from cell samples without affecting cell activity and function. Herein, we report a novel on-chip label-free method for sorting living and dead cells by integrating the hypertonic stimulus and tilted-angle standing surface acoustic wave (T-SSAW) technologies. On a self-designed microfluidic chip, the hypertonic stimulus is used to distinguish cells by producing volume differences between living and dead cells, while T-SSAW is used to separate living and dead cells according to the cell volume difference. Under the optimized operation conditions, for the sample containing 50% of living human umbilical vein endothelial cells (HUVECs) and 50% of dead HUVECs treated with paraformaldehyde, the purity of living cells after the first separation can reach approximately 80%, while after the second separation, it can be as high as 93%; furthermore, the purity of living cells after separation increases with the initial proportion of living cells. In addition, the chip we designed is safe for cells and can robustly handle cell samples with different cell types or different causes of cell death. This work provides a new design of a microfluidic chip for label-free sorting of living and dead cells, greatly promoting the multi-functionality of lab on a chip.

Effects of zinc oxide nanoparticles transformation in sulfur-containing water on its toxicity to microalgae: Physicochemical analysis, photosynthetic efficiency and potential mechanisms.

The environmental transformation of nanomaterials will have a significant impact on their ecotoxicity. Sulfidation process is one of the most important transformation processes in the aquatic environment. Although the sulfidation of ZnO nanoparticles (ZnO NPs) has been previously reported, the transformation characteristics and the relationship between the transformation process and toxicity mechanism to aquatic organisms, especially microalgae, require further study. Therefore, we systematically investigated the transformation properties of ZnO NPs in sulfur-containing water and its impact on the toxicity to microalgae. The results showed that the transformation products of ZnO NPs mainly contained ZnS nanoparticles, and their contents increased with the increase of sulfur-zinc molar ratio in the aqueous solution. After the first week of treatment, the sulfidized ZnO NPs showed less toxicity to microalgae than the pristine ZnO NPs, and interestingly, they exhibited higher toxicity over time. The zinc ions and transformation products played a major role in different treatment periods, resulting in different toxicity. The results of photosynthetic pigments, photosynthetic efficiency, and the relative electron transport rates indicated that the sulfidation process of ZnO NPs had a remarkable influence on algal photosynthesis. These newly acquired results will help us explore the transformation characteristics of ZnO NPs and reasonably assess their potential risks in the aquatic environment.

Modeling nonalcoholic fatty liver disease on a liver lobule chip with dual blood supply.

Nonalcoholic fatty liver disease (NAFLD) has emerged as a public health concern. To date, the mechanism of NAFLD progression remains unclear, and pharmacological treatment options are scarce. Traditional animal NAFLD models are limited in helping address these problems due to interspecies differences. Liver chips are promising for modeling NAFLD. However, pre-existing liver chips cannot reproduce complex physicochemical microenvironments of the liver effectively; thus, NAFLD modeling based on these chips is incomplete. Herein, we develop a biomimetic liver lobule chip (LC) and then establish a more accurate on-chip NAFLD model. The self-developed LC achieves dual blood supply through the designed hepatic portal vein and hepatic artery and the microtissue cultured on the LC forms multiple structures similar to in vivo liver. Based on the LC, NAFLD is modeled. Steatosis is successfully induced and more importantly, changing lipid zonation in a liver lobule with the progression of NAFLD is demonstrated for the first time on a microfluidic chip. In addition, the application of the induced NAFLD model has been preliminarily demonstrated in the prevention and reversibility of promising drugs. This study provides a promising platform to understand NAFLD progression and identify drugs for treating NAFLD. STATEMENT OF SIGNIFICANCE: Liver chips are promising for modeling nonalcoholic fatty liver disease. However, on-chip replicating liver physicochemical microenvironments is still a challenge. Herein, we developed a liver lobule chip with dual blood supply, achieving self-organized liver microtissue that is similar to in vivo tissue. Based on the chip, we successfully modeled NAFLD under physiologically differentiated nutrient supplies. For the first time, the changing lipid zonation in a single liver lobule with the early-stage progression of NAFLD was demonstrated on a liver chip. This study provides a promising platform for modeling liver-related diseases.

Polyacrylamide/Chitosan-Based Conductive Double Network Hydrogels with Outstanding Electrical and Mechanical Performance at Low Temperatures.

Hydrogel-based electronics have received growing attention because of their great flexibility and stretchability. However, the fabrication of conductive hydrogels with high stretchability, excellent toughness, outstanding sensitivity, and low-temperature stability still remains a great challenge. In this study, a type of conductive hydrogels consisting of a double network (DN) structure is synthesized. The dynamically cross-linked chitosan (CS) and the flexible polyacrylamide network doped with polyaniline constitute the DN through the hydrogen bonds between the hydroxyl, amide, and aniline groups. This type of hydrogels displays excellent mechanical performance, striking conductivity, and remarkable freezing tolerance. The flexible electronic sensors based on the double-network hydrogels demonstrate superior strain sensitivity and linear response on various deformations. Additionally, the good antifreezing property of the hydrogels allows the sensors to exhibit excellent performance at -20 °C.

Multi-scale design of the chela of the hermit crab Coenobita brevimanus.

The chela of the hermit crab protects its body against the attack from predators. Yet, a deep understanding of this mechanical defense is still lacking. Here, we investigate the chela of hermit crab, Coenobita brevimanus, and establish the relationships between the microstructures, chemical compositions and mechanical properties to gain insights into its biomechanical functions. We find that the chela is a multi-layered shell composed of five different layers with distinct features of the microstructures and chemical compositions, conferring different mechanical properties. Especially, an increase of the calcium carbonate content towards the layer furthest from the exterior, unlike the chemical gradients of many crustacean exoskeletons, provides a strong resistance to deformation. Nanoindentation measurements reveal that the overall gradient of the elastic modulus and hardness in the cross-section displays a sandwich profile, i.e., a soft core clamped by two stiff surface layers. Further mechanics modeling demonstrates that the high curvature and stiff innermost sublayer enhance the structural rigidity of the chela. In conjunction with the experimental observations, dynamic finite element analysis maps the time-spatial distribution of principal stress and indicates that fiber bridging might be the major mechanism against crack propagation at microscale. The lessons gained from the study of this multiphase biological composite could provide important insights into the design and fabrication of bioinspired materials for structural applications. STATEMENT OF SIGNIFICANCE: Multiple hierarchical structures have been discovered in a variety of exoskeletons. They are naturally designed to maintain the structural integrity and act as a protective layer for the animals. However, each kind of the hierarchical structures has its unique topology, chemical gradients as well as mechanical properties. We find that the chela is multi-layered shell composed of five different layers with distinct features of the microstructures and chemical compositions, conferring different mechanical properties. Especially, a large amount of helicoidal organic fibrils form highly organized 3D woven matrix in the innermost layer, providing a strong mechanical resistance to avoid catastrophic failure. The overall gradient of the elastic modulus and hardness in the cross-section display a sandwich profile, effectively minimizing the stress concentration and deformation. The lessons gained from the multiscale design strategy of the chela provide important insights into the design and fabrication of bioinspired materials.

Optimized Hierarchical Structure and Chemical Gradients Promote the Biomechanical Functions of the Spike of Mantis Shrimps.

The tail spike of the mantis shrimp is the appendage for counteracting the enemy from behind. Here, we investigate the correlations between the chemical compositions, the microstructures, and the mechanical properties of the spike. We find that the spike is a hollow beam with a varying cross section along the length. The cross section comprises four different layers with distinct features of microstructures and chemical compositions. The local mechanical properties of these layers correlate well with the microstructures and chemical compositions, a combination of which effectively restricts the crack propagation while maximizing the release of strain energy during deformation. Finite element analysis and mechanics modeling demonstrate that the optimized structure of the spike confines the mechanical damage in the region near the tip and prevents catastrophic breakage at the base. Furthermore, we use a 3D printing technique to fabricate multiple hollow cylindrical samples consisting of biomimetic microstructures of the spike and confirm that the combination of the Bouligand structure with radially oriented parallel sheets greatly improves the toughness and strength during compression tests. The multiscale design strategy of the spike revealed here is expected to be of great interest for the development of novel bioinspired materials.

Degradation of 2, 4-dichlorophenol in aqueous solution by dielectric barrier discharge: Effects of plasma-working gases, degradation pathways and toxicity assessment.

Chlorinated phenols are a class of contaminants found in water and have been regarded as a great potential risk to environment and human health. It is thus urgent to develop effective techniques to remove chlorinated phenols in wastewater. For this purpose, we employed dielectric barrier discharge (DBD) in this work and studied the efficiency of DBD for the degradation of 2,4-dichlorophenol (2,4-DCP), one of the most typical chlorophenols in the environment. The effects of pH value, applied voltage and plasma-working gases on the dichlorophenol-removal efficiency were investigated. The results demonstrate that DBD plasma could successfully degrade 2,4-DCP, achieving efficiency of 98.16% (k = 1.09 min-1) in the Ar-DBD system, and 77.60% (k = 0.48 min-1) in the N2-DBD system, with the process following the first-order kinetics. The removal efficiency was reduced in the presence of radical scavengers, confirming that hydroxyl radicals played a key role in the degradation process, while other active substances were also found such as nitrogen radicals in the N2-DBD system, which was found to have also contribution to the degradation of 2,4-DCP. The intermediates and final products generated in the degradation process were analyzed using gas chromatography-mass spectrometry (GC-MS). Based on the identification of intermediates, the degradation pathways and mechanism were proposed and discussed. Besides, the toxicity of the DBD treated 2,4-DCP solution was also assessed using GFP-expressing recombinant Escherichia coli (E. coli) as the testing organism, showing that plasma treatment could substantially reduce the toxic effect of 2,4-DCP.

Parallel Compression Is a Fast Low-Cost Assay for the High-Throughput Screening of Mechanosensory Cytoskeletal Proteins in Cells.

Cellular mechanosensing is critical for many biological processes, including cell differentiation, proliferation, migration, and tissue morphogenesis. The actin cytoskeletal proteins play important roles in cellular mechanosensing. Many techniques have been used to investigate the mechanosensory behaviors of these proteins. However, a fast, low-cost assay for the quantitative characterization of these proteins is still lacking. Here, we demonstrate that compression assay using agarose overlay is suitable for the high throughput screening of mechanosensory proteins in live cells while requiring minimal experimental setup. We used several well-studied myosin II mutants to assess the compression assay. On the basis of elasticity theories, we simulated the mechanosensory accumulation of myosin II's and quantitatively reproduced the experimentally observed protein dynamics. Combining the compression assay with confocal microscopy, we monitored the polarization of myosin II oligomers at the subcellular level. The polarization was dependent on the ratio of the two principal strains of the cellular deformations. Finally, we demonstrated that this technique could be used on the investigation of other mechanosensory proteins.

Harmful algae blooms removal from fresh water with modified vermiculite.

Vermiculite and vermiculite modified with hydrochloric acid were investigated to evaluate their flocculation efficiencies in freshwater containing harmful algae blooms (HABs) (Microcystis aeruginosa). Scanning electron microscope, Fourier transform infrared spectroscopy, X-ray diffraction, converted fluorescence microscope, plasma-atomic emission spectrometry, and Zetasizer were used to study the flocculation mechanism of modified vermiculite. It was found that the vermiculite modified with hydrochloric acid could coagulate algae cells through charge neutralization, chemical bridging, and netting effect. The experimental results show that the efficiency of flocculation can be notably improved by modified vermiculite. Ninety-eight per cent of algae cells in algae solution could be removed within 10 min after the addition ofmodified vermiculite clay. The method that removal of HABs with modified vermiculite is economical with high efficiency, and more research is needed to assess their ecological impacts before using in practical application.

Flocculation of harmful algal blooms by modified attapulgite and its safety evaluation.

Natural attapulgite (N-AT) and modified attapulgite (M-AT) were used in this study to evaluate their flocculation efficiencies and mechanisms in freshwater containing harmful algal blooms through conventional jar test procedure. The experimental results showed that the efficiency of flocculation can be significantly improved by M-AT under appropriate conditions. It was found that the attapulgite modified by hydrochloric acid was similar to polyaluminum ferric silicate chloride (PAFSiC). The high efficiency for M-AT to flocculate Microcystis aeruginosa in freshwater was due to the mechanism of bridging and netting effect. Caenorhabditis elegans was used to detect the toxicity of N-AT and M-AT. The results showed that there was no significant toxicity on this organism. Attapulgite is a natural material, which can be readily available, abundant, and relatively inexpensive. Using modified attapulgite to remove the harmful algal blooms could have the advantages of high effectiveness, low cost, and low impact on the environment.