A Drop-and-Drain Method for Convenient and Efficient Fabrication of MOF/Fiber Composites.

The fabrication of flexible composites by integrating metal-organic frameworks (MOFs) with flexible substrates is a critical strategy for developing advanced materials with excellent feasibility and processability. These flexible MOF-based composites play a particularly important role in the separation and purification processes. However, several drawbacks remain challenge to overcome such as long processing time, high-cost, complicated processes, or harsh reaction conditions. In this paper, a convenient and efficient method is reported for fabricating MOF/fiber composites using a simple drop-and-drain (D&D) process. By exploiting the electrostatic interactions between the positively charged MOF particles and negatively charged fiber-based flexible substrates, a uniform coating of MOF on flexible fibers are achieved. This is accomplished by allowing the MOF ink to drop and drain through a substrate using a custom-made Teflon cell. Additionally, the D&D method enables the production of multiple layers of composites in a single-step process. UiO-66 and ZIF-8 submicroparticles and various substrates such as cotton-pad, cotton-fabric, nylon-fabric, PET-fabric, and filter-paper are employed to create flexible MOF/fiber composites. These composites demonstrate outstanding capacities for capturing negatively charged organic dyes, including methyl orange and indigo carmine. Furthermore, the MOF/fiber composites can be reused for dye capture after a simple washing process.

Au Octahedral Nanosponges: 3D Plasmonic Nanolenses for Near-Field Focusing.

Here, we report the synthesis of three-dimensional plasmonic nanolenses for strong near-field focusing. The nanolens exhibits a distinctive structural arrangement composed of nanoporous sponge-like networks within their interior. We denote these novel nanoparticles as "Au octahedral nanosponges" (Au Oh NSs). Employing a carefully planned multistep synthetic approach with Au octahedra serving as sacrificial templates, we successfully synthesized Au Oh NSs in solution. The porous domains resembling sponges contributed to enhanced scattering and absorption of incident light within metal ligaments. This optical energy was subsequently transferred to the nanospheres at the vertex, where near-field focusing was maximized. We named this observed enhancement a "lightning-sphere effect". Using single particle-by-particle surface-enhanced Raman scattering (SERS), we optimized the morphological dimensions of the spheres and porous domains to achieve the most effective near-field focusing. In the context of bulk SERS measurements targeting weakly adsorbing analytes (2-chloroethyl phenyl sulfide) in the gas phase, we achieved a low detection limit of 10 ppb. For nonadsorbing species (dimethyl methyl phosphonate), utilization of hybrid SERS substrates consisting of Au Oh NSs and metal-organic frameworks as gas-adsorbing intermediate layers was highly effective for successful SERS detection.

Induced Production of Atypical Naturally Nonpreferred Metal-Organic Frameworks and Their Detachment via Provoking Post-Mismatching.

The structures of metal-organic frameworks (MOFs) are typically determined by the building blocks that compose them and the conditions under which they are formed. MOFs tend to adopt a thermodynamically and/or kinetically stable structure (naturally preferred form). Thus, constructing MOFs with naturally nonpreferred structures is a challenging task, as it requires avoiding the easier pathway toward a naturally preferred MOF. Herein, an approach to construct naturally nonpreferred dicarboxylate-linked MOFs employing reaction templates is reported. This strategy relies on the registry between the surface of the template and the cell lattice of a target MOF, which reduces the effort required to form naturally nonpreferred MOFs. Reactions of p-block trivalent metal ions (Ga3+ and In3+ ) with dicarboxylic acids typically produce preferred MIL-53 or MIL-68. However, the surface of UiO-67 (and UiO-66) template exhibits the well-defined hexagonal lattice, which induce the selective formation of a naturally nonpreferred MIL-88 structure. Inductively grown MIL-88s are purely isolated from the template via provoking a post-mismatch in their lattices and weakening the interfacial interaction between product and template. It is also discovered that an appropriate template for effective induced production of naturally nonpreferred MOFs shall be properly selected based on the cell lattice of a target MOF.

Bee Venom Activates the Nrf2/HO-1 and TrkB/CREB/BDNF Pathways in Neuronal Cell Responses against Oxidative Stress Induced by Aß1-42.

Honeybee venom has recently been considered an anti-neurodegenerative agent, primarily due to its anti-inflammatory effects. The natural accumulation of amyloid-beta (Aß) in the brain is reported to be the natural cause of aging neural ability downfall, and oxidative stress is the main route by which Aß ignites its neural toxicity. Anti-neural oxidative stress is considered an effective approach for neurodegenerative therapy. To date, it is unclear how bee venom ameliorates neuronal cells in oxidative stress induced by Aß. Here, we evaluated the neuroprotective effect of bee venom on Aß-induced neural oxidative stress in both HT22 cells and an animal model. Our results indicate that bee venom protected HT22 cells against apoptosis induced by Aß1-42. This protective effect was explained by the increased nuclear translocation of nuclear factor erythroid 2-like 2 (Nrf2), consequently upregulating the production of heme oxygenase-1 (HO-1), a critical cellular instinct antioxidant enzyme that neutralizes excessive oxidative stress. Furthermore, bee venom treatment activated the tropomyosin-related kinase receptor B (TrkB)/cAMP response element-binding (CREB)/brain-derived neurotrophic factor (BDNF), which is closely related to the promotion of cellular antioxidant defense and neuronal functions. A mouse model with cognitive deficits induced by Aß1-42 intracerebroventricular (ICV) injections was also used. Bee venom enhanced animal cognitive ability and enhanced neural cell genesis in the hippocampal dentate gyrus region in a dose-dependent manner. Further analysis of animal brain tissue and serum confirmed that bee venom reduced oxidative stress, cholinergic system activity, and intercellular neurotrophic factor regulation, which were all adversely affected by Aß1-42. Our study demonstrates that bee venom exerts antioxidant and neuroprotective actions against neural oxidative stress caused by Aß1-42, thereby promoting its use as a therapeutic agent for neurodegenerative disorders.

Effects of Donepezil Treatment on Brain Metabolites, Gut Microbiota, and Gut Metabolites in an Amyloid Beta-Induced Cognitive Impairment Mouse Pilot Model.

Accumulated clinical and biomedical evidence indicates that the gut microbiota and their metabolites affect brain function and behavior in various central nervous system disorders. This study was performed to investigate the changes in brain metabolites and composition of the fecal microbial community following injection of amyloid ß (Aß) and donepezil treatment of Aß-injected mice using metataxonomics and metabolomics. Aß treatment caused cognitive dysfunction, while donepezil resulted in the successful recovery of memory impairment. The Aß + donepezil group showed a significantly higher relative abundance of Verrucomicrobia than the Aß group. The relative abundance of 12 taxa, including Blautia and Akkermansia, differed significantly between the groups. The Aß + donepezil group had higher levels of oxalate, glycerol, xylose, and palmitoleate in feces and oxalate, pyroglutamic acid, hypoxanthine, and inosine in brain tissues than the Aß group. The levels of pyroglutamic acid, glutamic acid, and phenylalanine showed similar changes in vivo and in vitro using HT-22 cells. The major metabolic pathways in the brain tissues and gut microbiota affected by Aß or donepezil treatment of Aß-injected mice were related to amino acid pathways and sugar metabolism, respectively. These findings suggest that alterations in the gut microbiota might influence the induction and amelioration of Aß-induced cognitive dysfunction via the gut-brain axis. This study could provide basic data on the effects of Aß and donepezil on gut microbiota and metabolites in an Aß-induced cognitive impairment mouse model.

Tip-To-Middle Anisotropic MOF-On-MOF Growth with a Structural Adjustment.

Well-organized construction of hybrid metal-organic frameworks (MOFs) with complicated structures or components is a great importance because of their potential usefulness. In this regard, the conjugation of more than two MOFs, which have dissimilar components and/or structures, is a smart strategy for the production of hybrid MOFs. MOF-on-MOF growth is fundamental for the conjugation of two MOFs and should be deeply understood for the finely controlled conjugation and for the formation of well-organized hybrid MOFs. Herein, we report an interesting MOF growth process for the construction of hybrid MOF particles containing heterogeneous components and cell lattices. Interestingly, even though a newly grown MOF and an MOF template have mismatched cell lattices, the anisotropic growth results in unexpectedly well-defined core-shell-type hybrid MOFs. Comprehensive monitoring of the growth process revealed a tip-to-middle MOF-on-MOF growth, which elucidates the uncommon formation of a well-defined core-shell hybrid despite the anisotropic growth. A tip-to-middle anisotropic growth process is accompanied by self-adjustment of MOF cell lattices to anchor on the template surface having mismatched cell lattices in the early reaction stage and self-reversion of cell lattices to the original comfortable configuration in the middle stage of the reaction.

Bee Venom Phospholipase A2, a Novel Foxp3+ Regulatory T Cell Inducer, Protects Dopaminergic Neurons by Modulating Neuroinflammatory Responses in a Mouse Model of Parkinson's Disease.

Foxp3-expressing CD4(+) regulatory T cells (Tregs) are vital for maintaining immune tolerance in animal models of various immune diseases. In the present study, we demonstrated that bee venom phospholipase A2 (bvPLA2) is the major BV compound capable of inducing Treg expansion and promotes the survival of dopaminergic neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. We associated this neuroprotective effect of bvPLA2 with microglial deactivation and reduction of CD4(+) T cell infiltration. Interestingly, bvPLA2 had no effect on mice depleted of Tregs by injecting anti-CD25 Ab. This finding indicated that Treg-mediated modulation of peripheral immune tolerance is strongly involved in the neuroprotective effects of bvPLA2. Furthermore, our results showed that bvPLA2 directly bound to CD206 on dendritic cells and consequently promoted the secretion of PGE2, which resulted in Treg differentiation via PGE2 (EP2) receptor signaling in Foxp3(-)CD4(+) T cells. These observations suggest that bvPLA2-CD206-PGE2-EP2 signaling promotes immune tolerance through Treg differentiation and contributes to the prevention of various neurodegenerative diseases, including Parkinson's disease.

Pyranopyran-1,8-dione, an Active Compound from Vitices Fructus, Attenuates Cigarette-Smoke Induced Lung Inflammation in Mice.

Previously, we isolated and identified pyranopyran-1,8-dione (PPY) from Viticis Fructus, as a bioactive compound possessing anti-inflammatory properties. The present study was aimed to evaluate the preventive benefit of PPY on cigarette-smoke (CS)-induced lung inflammation. C57BL/6 mice were exposed to CS for 2 weeks while PPY was administrated by oral injection 2 h before CS exposure. To validate the anti-inflammatory effects of PPY, the numbers of immune cells in the bronchoalveolar lavage fluid were counted. Proinflammatory cytokines (Tumor necrosis factor-α: TNF-α, IL-6) and keratinocyte chemokine (KC/CXCL1) were also measured. Histopathologic analysis and cellular profiles showed that inflammatory cell infiltrations were significantly decreased in peribronchial and perivascular area by PPY treatment. The alveolar destruction by CS was markedly ameliorated by PPY treatment. In addition, the TNF-α, IL-6, and KC levels were declined in the PPY groups. These observations suggest that PPY has a preventive potential for lung inflammatory diseases.

Annealing Effects of Parylene-Caulked Polydimethylsiloxane as a Substrate of Electrodes.

This paper investigates the effects of annealing of the electrodes based on parylene-caulked polydimethylsiloxane (pc-PDMS) in terms of mechanical strength and long-term electrical property. Previously, the electrodes based on pc-PDMS showed a better ability to withstand in vivo environments because of the low water absorption and beneficial mechanical properties of the substrate, compared to native PDMS. Moreover, annealing is expected to even strengthen the mechanical strength and lower the water absorption of the pc-PDMS substrate. To characterize the mechanical strength and water absorption of the annealed pc-PDMS, tensile tests were carried out and infrared (IR) spectra were measured using Fourier transform infrared spectroscopy over a month. The results showed that annealed pc-PDMS had higher mechanical strength and lower water absorption than non-annealed pc-PDMS. Then, electrochemical impedance spectroscopy was measured to evaluate the electrical stability of the electrodes based on annealed pc-PDMS in phosphate-buffered saline solution at 36.5 °C. The impedance magnitude of the electrodes on annealed pc-PDMS was twice higher than that of the electrodes on non-annealed pc-PDMS in the initial days, but the impedance magnitude of the electrodes based on two different substrates converged to a similar value after eight months, indicating that the annealing effects disappear after a certain period of time in a physiological environment.

Anti-Inflammatory Applications of Melittin, a Major Component of Bee Venom: Detailed Mechanism of Action and Adverse Effects.

Inflammation is a pervasive phenomenon triggered by the innate and adaptive immune systems to maintain homeostasis. The phenomenon normally leads to recovery from infection and healing, but when not properly phased, inflammation may cause immune disorders. Bee venom is a toxin that bees use for their protection from enemies. However, for centuries it has been used in the Orient as an anti-inflammatory medicine for the treatment of chronic inflammatory diseases. Bee venom and its major component, melittin, are potential means of reducing excessive immune responses and provide new alternatives for the control of inflammatory diseases. Recent experimental studies show that the biological functions of melittin could be applied for therapeutic use in vitro and in vivo. Reports verifying the therapeutic effects of melittin are accumulating in the literature, but the cellular mechanism(s) of the anti-inflammatory effects of melittin are not fully elucidated. In the present study, we review the current knowledge on the therapeutic effects of melittin and its detailed mechanisms of action against several inflammatory diseases including skin inflammation, neuroinflammation, atherosclerosis, arthritis and liver inflammation, its adverse effects as well as future prospects regarding the use of melittin.

Therapeutic Effects of Phytochemicals and Medicinal Herbs on Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent adverse effect of neurotoxic anticancer medicines. It leads to autonomic and somatic system dysfunction and decreases the patient's quality of life. This side effect eventually causes chemotherapy non-compliance. Patients are prompted to seek alternative treatment options since there is no conventional remedy for CIPN. A range of medicinal herbs have multifarious effects, and they have shown some evidence of efficacy in various neurological and immunological diseases. While CIPN has multiple mechanisms of neurotoxicity, these phytomedicines might offer neuronal protection or regeneration with the multiple targets in CIPN. Thus far, researchers have investigated the therapeutic benefits of several herbs, herbal formulas, and phytochemicals in preventing the onset and progress of CIPN in animals and humans. Here, we summarize current knowledge regarding the role of phytochemicals, herb extracts, and herbal formulas in alleviating CIPN.

Immunotherapy with methyl gallate, an inhibitor of Treg cell migration, enhances the anti-cancer effect of cisplatin therapy.

Foxp3(+) CD25(+)CD4(+) regulatory T (Treg) cells are crucial for the maintenance of immunological self-tolerance and are abundant in tumors. Most of these cells are chemo-attracted to tumor tissues and suppress anti-tumor responses inside the tumor. Currently, several cancer immunotherapies targeting Treg cells are being clinically tested. Cisplatin is one of the most potent chemotherapy drugs widely used for cancer treatment. While cisplatin is a powerful drug for the treatment of multiple cancers, there are obstacles that limit its use, such as renal dysfunction and the development of cisplatin-resistant cancer cells after its use. To minimize these barriers, combinatorial therapies of cisplatin with other drugs have been developed and have proven to be more effective to treat cancer. In the present study, we evaluated the eff ect of the combination therapy using methyl gallate with cisplatin in EL4 murine lymphoma bearing C57BL/6 mice. The combinatorial therapy of methyl gallate and cisplatin showed stronger anti-cancer eff ects than methyl gallate or cisplatin as single treatments. In Treg cell-depleted mice, however, the eff ect of methyl gallate vanished. It was found that methyl gallate treatment inhibited Treg cell migration into the tumor regardless of cisplatin treatment. Additionally, in both the normal and cisplatin-treated tumor-bearing mice, there was no renal toxicity attributed to methyl gallate treatment. These findings suggest that methyl gallate treatment could be useful as an adjuvant method accompanied with cisplatin therapy.

Phospholipase A2 inhibits cisplatin-induced acute kidney injury by modulating regulatory T cells by the CD206 mannose receptor.

Previously, we found that Foxp3-expressing CD4(+) regulatory T (Treg) cells attenuate cisplatin-induced acute kidney injury in mice and that bee venom and its constituent phospholipase A2 (PLA2) are capable of modulating Treg cells. Here we tested whether PLA2 could inhibit cisplatin-induced acute kidney injury. As a result of treatment with PLA2, the population of Treg cells was significantly increased, both in vivo and in vitro. PLA2-injected mice showed reduced levels of serum creatinine, blood urea nitrogen, renal tissue damage, and pro-inflammatory cytokine production upon cisplatin administration. These renoprotective effects were abolished by depletion of Treg cells. Furthermore, PLA2 bound to CD206 mannose receptors on dendritic cells, essential for the PLA2-mediated protective effects on renal dysfunction. Interestingly, PLA2 treatment increased the secretion of IL-10 in the kidney from normal mice. Foxp3(+)IL-10(+) cells and CD11c(+)IL-10(+) cells were increased by PLA2 treatment. The anticancer effects of repeated administrations of a low dose of cisplatin were not affected by PLA2 treatment in a tumor-bearing model. Thus, PLA2 may prevent inflammatory responses in cisplatin-induced acute kidney injury by modulating Treg cells and IL-10 through the CD206 mannose receptor.

Bioprinted Multi-Composition Array Mimicking Tumor Microenvironments to Evaluate Drug Efficacy with Multivariable Analysis.

Current organ-on-a-chip technologies confront limitations in effectively recapitulating the intricate in vivo microenvironments and accommodating diverse experimental conditions on a single device. Here, a novel approach for constructing a multi-composition tumor array on a single microfluidic device, mimicking complex transport phenomena within tumor microenvironments (TMEs) and allowing for simultaneous evaluation of drug efficacy across 12 distinct conditions is presented. The TME array formed by bioprinting on a microfluidic substrate consists of 36 individual TME models, each characterized by one of three different compositions and tested under four varying drug concentrations. Notably, the TME model exhibits precise compartmentalization, fostering the development of self-organized vascular endothelial barriers surrounding breast cancer spheroids affecting substance transport. Multivariable screening and analysis of diverse conditions, including model complexity, replicates, and drug concentrations, within a single microfluidic platform, highlight the synergistic potential of integrating bioprinting with microfluidics to evaluate drug responses across diverse TME conditions comprehensively.

Evaluation of Fluid Behaviors in a Pushbutton-Activated Microfluidic Device for User-Independent Flow Control.

Although numerous studies have been conducted to realize ideal point-of-care testing (POCT), the development of a user-friendly and user-independent power-free microfluidic platform is still a challenge. Among various methods, the finger-actuation method shows a promising technique that provides a user-friendly and equipment-free way of delivering fluid in a designated manner. However, the design criteria and elaborate evaluation of the fluid behavior of a pushbutton-activated microfluidic device (PAMD) remain a critical bottleneck to be widely adopted in various applications. In this study, we have evaluated the fluid behavior of the PAMD based on various parameters, such as pressing velocity and depth assisted by a press machine. We have further developed a user-friendly and portable pressing block that reduces user variation in fluid behavior based on the evaluation.

Bee venom ameliorates ovalbumin induced allergic asthma via modulating CD4+CD25+ regulatory T cells in mice.

Asthma is a potentially life-threatening inflammatory disease of the lung characterized by the presence of large numbers of CD4+ T cells. These cells produce the Th2 and Th17 cytokines that are thought to orchestrate the inflammation associated with asthma. Bee venom (BV) has traditionally been used to relieve pain and to treat chronic inflammatory diseases. Recent reports have suggested that BV might be an effective treatment for allergic diseases. However, there are still unanswered questions related to the efficacy of BV therapy in treating asthma and its therapeutic mechanism. In this study, we evaluated whether BV could inhibit asthma and whether BV inhibition of asthma could be correlated with regulatory T cells (Treg) activity. We found that BV treatment increased Treg populations and suppressed the production of Th1, Th2 and Th17-related cytokines in an in vitro culture system, including IL2, IL4, and IL17. Interestingly, production of IL10, an anti-inflammatory cytokine secreted by Tregs, was significantly augmented by BV treatment. We next evaluated the effects of BV treatment on allergic asthma in an ovalbumin (OVA)-induced mouse model of allergic asthma. Cellular profiling of the bronchoalveolar lavage (BAL) and histopathologic analysis demonstrated that peribronchial and perivascular inflammatory cell infiltrates were significantly lowered following BV treatment. BV also ameliorated airway hyperresponsiveness, a hallmark symptom of asthma. In addition, IL4 and IL13 levels in the BAL fluid were decreased in the BV treated group. Surprisingly, the beneficial effects of BV treatment on asthma were eradicated following Treg depletion by anti-CD25 antibody injection, suggesting that the major therapeutic targets of BV were Tregs. These results indicate that BV efficiently diminishes bronchial inflammation in an OVA-induced allergic asthma murine model, and that this effect might correlate with Tregs, which play an important role in maintaining immune homeostasis and suppressing the function of other T cells to limit the immune response. These results also suggest that BV has potential therapeutic value for controlling allergic asthma responses.

Curcumin attenuates lupus nephritis upon interaction with regulatory T cells in New Zealand Black/White mice.

Curcumin has been used in Asian traditional medicine for its medicinal properties. Recent studies have demonstrated that curcumin has antioxidant, anti-tumour and anti-inflammatory activities. The aim of the present study is to investigate the effects of curcumin on established lupus nephritis (LN) in New Zealand Black/White (NZB/W) F1 female mice, in particular, its interaction with regulatory T (Treg) cells. Starting at 18 weeks of age, mice were fed a standard diet or a diet containing 1 % curcumin until the end of the study. The proteinuria level and the serum levels of IgG1, IgG2a and anti-double-stranded DNA (dsDNA) IgG antibodies were measured. Additionally, IgG immune complex deposition in the glomeruli and renal inflammation were compared between curcumin-treated mice and control mice. Curcumin decreased the proteinuria level and serum levels of IgG1, IgG2a and anti-dsDNA IgG antibodies in NZB/W F1 female mice. IgG immune complex deposition in the glomeruli was reduced in curcumin-treated mice. Furthermore, renal inflammation was also decreased after curcumin treatment. Interestingly, these therapeutic effects of curcumin disappeared after Treg depletion by anti-CD25 antibody injection. Curcumin exerted a protective effect against LN in NZB/W F1 mice. We speculate that the protective effects of curcumin in LN may involve, at least in part, its interaction with Treg cells.

Prophylactic effects of Lonicera japonica extract on dextran sulphate sodium-induced colitis in a mouse model by the inhibition of the Th1/Th17 response.

Inflammatory bowel diseases (IBD) are chronically relapsing inflammatory disorders of the intestine. Although some therapeutic agents, including steroids, are available for the treatment of IBD, these agents have limited use. Therefore, dietary supplements have emerged as possible interventions for IBD. Japanese honeysuckle flower, the flower of Lonicera japonica, is a well-known dietary supplement and has been used to prevent or treat various inflammatory diseases. In the present study, we investigated the effects of L. japonica on experimental murine colitis. Colitis was induced by 5 % dextran sulphate sodium (DSS) in Balb/c mice. The water extract of L. japonica (LJE) at doses of 20, 100 or 500 mg/kg was orally administered to mice twice per day for 7 d. Body weight, colon length and a histological damage score were assessed to determine the effects on colitis. Cytokine profiles were assessed to examine the effects on helper T (Th) cell-related immunological responses. In addition, CD4⁺CD25⁺Foxp3⁺T cells were analysed in vivo and in vitro for investigating the effects on regulatory T (Treg) cells. LJE showed dose-dependent inhibitory effects against colon shortening, weight loss and histological damage. LJE down-regulated IL-1ß, TNF-α, interferon-γ, IL-6, IL-12 and IL-17. However, LJE did not show any significant effects on IL-10, IL-23, transforming growth factor-ß1 and Treg cell populations. In conclusion, LJE showed protective effects against DSS-induced colitis via the Th1/Th17 pathway and not via Treg cell-related mechanisms.

Structural Compromise Between Conflicted Spatial-Arrangements of Two Linkers in Metal-Organic Frameworks.

The structural control of metal-organic frameworks (MOFs) is essential for the development of superlative MOFs because the structural features of MOFs and their components play a critical role in determining their properties, and ultimately, their applications. The best components to endow the desired properties for MOFs are available via the appropriate choice from many existing chemicals or synthesizing new ones. However, to date, considerably less information exists regarding fine-tuning the MOF structures. Herein, a strategy for tuning MOF structures by merging two MOF structures into a single MOF, is demonstrated. Depending on the incorporated amounts and relative contributions of the two coexisting organic linkers, benzene-1,4-dicarboxylate (BDC2- ) and naphthalene-1,4-dicarboxylate (NDC2- ), which have conflicting spatial-arrangement preferences within an MOF structure, MOFs are rationally designed to have a Kagomé or rhombic lattice. In particular, MOFs with rhombic lattices are constructed to have specific lattice angles by compromising the optimal structural arrangements between the two mixed linkers. The relative contributions of the two linkers during MOF construction determine the final MOF structures, and the competitive influence between BDC2- and NDC2- is effectively regulated to produce specific MOF structures with controlled lattices.

Fabrication of a self-assembled and vascularized tumor array via bioprinting on a microfluidic chip.

A tumor microenvironment (TME) is a complex system that comprises various components, including blood vessels that play a crucial role in supplying nutrients, oxygen, and growth factors, as well as delivering chemotherapy drugs to the tumor mass through the vascular endothelial barrier. To replicate the TME in vitro, several bioprinting and microfluidic organ-on-a-chip technologies have been developed. However, these technologies have not been fully exploited in terms of potential benefits of bioprinting and microfluidics, such as precise spatial control for biological samples, construction of multiple TMEs per microfluidic device, and the ability to adjust culture environments for better biological similarity. In addition, the complex transport phenomena within the vascular endothelial barrier and the aggregated tumor mass in the TME model should be considered before applying the model to drug treatment and screening. In this study, we describe a novel integrative technology that addresses these issues by introducing a self-organized TME array bioprinted on a microfluidic chip consisting of a vascular endothelial barrier surrounding breast cancer spheroids. To integrate the TME array onto the microfluidic platform, a microfluidic substrate for extrusion bioprinting was developed for a cell culture platform, which enables diffusivity control by microstructures and establishes a perfusion culture environment inside the culture channel. We also analyzed the cellular behaviors within the TME array to investigate the influence of the diffusivity on the self-organization process required to form the vascular endothelial barrier surrounding breast cancer spheroids.