A Glucose-Responsive Cannula for Automated and Electronics-Free Insulin Delivery.

Automated delivery of insulin based on continuous glucose monitoring is revolutionizing the way insulin-dependent diabetes is treated. However, challenges remain for the widespread adoption of these systems, including the requirement of a separate glucose sensor, sophisticated electronics and algorithms, and the need for significant user input to operate these costly therapies. Herein, a user-centric glucose-responsive cannula is reported for electronics-free insulin delivery. The cannula-made from a tough, elastomer-hydrogel hybrid membrane formed through a one-pot solvent exchange method-changes permeability to release insulin rapidly upon physiologically relevant varying glucose levels, providing simple and automated insulin delivery with no additional hardware or software. Two prototypes of the cannula are evaluated in insulin-deficient diabetic mice. The first cannula-an ends-sealed, subcutaneously inserted prototype-normalizes blood glucose levels for 3 d and controls postprandial glucose levels. The second, more translational version-a cannula with the distal end sealed and the proximal end connected to a transcutaneous injection port-likewise demonstrates tight, 3-d regulation of blood glucose levels when refilled twice daily. This proof-of-concept study may aid in the development of "smart" cannulas and next-generation insulin therapies at a reduced burden-of-care toll and cost to end-users.

A Thermally Stable SO2-Releasing Mechanophore: Facile Activation, Single-Event Spectroscopy, and Molecular Dynamic Simulations.

Polymers that release small molecules in response to mechanical force are promising candidates as next-generation on-demand delivery systems. Despite advancements in the development of mechanophores for releasing diverse payloads through careful molecular design, the availability of scaffolds capable of discharging biomedically significant cargos in substantial quantities remains scarce. In this report, we detail a nonscissile mechanophore built from an 8-thiabicyclo[3.2.1]octane 8,8-dioxide (TBO) motif that releases one equivalent of sulfur dioxide (SO2) from each repeat unit. The TBO mechanophore exhibits high thermal stability but is activated mechanochemically using solution ultrasonication in either organic solvent or aqueous media with up to 63% efficiency, equating to 206 molecules of SO2 released per 143.3 kDa chain. We quantified the mechanochemical reactivity of TBO by single-molecule force spectroscopy and resolved its single-event activation. The force-coupled rate constant for TBO opening reaches ∼9.0 s-1 at ∼1520 pN, and each reaction of a single TBO domain releases a stored length of ∼0.68 nm. We investigated the mechanism of TBO activation using ab initio steered molecular dynamic simulations and rationalized the observed stereoselectivity. These comprehensive studies of the TBO mechanophore provide a mechanically coupled mechanism of multi-SO2 release from one polymer chain, facilitating the translation of polymer mechanochemistry to potential biomedical applications.

Expanding the Structural Topologies of Rare-Earth Porphyrinic Metal-Organic Frameworks through Ligand Modulation.

Expanding the structural diversity of porphyrinic metal-organic frameworks (PMOFs) is essential to develop functional materials with novel properties or enhanced performance in different applications. Herein, we establish a strategy to construct rare-earth (RE) PMOFs with unprecedented topology via rational functionalization of porphyrinic ligands. By introducing phenyl/pyridyl groups to the meso-positions of the porphyrin core, the symmetries and connectivities of the ligands are tuned, and three RE-PMOFs (BUT-224/-225/-226) with new topologies are successfully obtained. In addition, BUT-225(Co), with both the Lewis basic and acidic sites, exhibits enhanced CO2 uptake and higher catalytic activity for the cycloaddition of CO2 and epoxides under mild conditions. This work reveals that the RE-PMOFs with novel topologies can be rationally designed and constructed through ligand functionalization, which provides insights into the construction of tailored PMOFs for various applications.

A tissue-like neurotransmitter sensor for the brain and gut.

Neurotransmitters play essential roles in regulating neural circuit dynamics both in the central nervous system as well as at the peripheral, including the gastrointestinal tract1-3. Their real-time monitoring will offer critical information for understanding neural function and diagnosing disease1-3. However, bioelectronic tools to monitor the dynamics of neurotransmitters in vivo, especially in the enteric nervous systems, are underdeveloped. This is mainly owing to the limited availability of biosensing tools that are capable of examining soft, complex and actively moving organs. Here we introduce a tissue-mimicking, stretchable, neurochemical biological interface termed NeuroString, which is prepared by laser patterning of a metal-complexed polyimide into an interconnected graphene/nanoparticle network embedded in an elastomer. NeuroString sensors allow chronic in vivo real-time, multichannel and multiplexed monoamine sensing in the brain of behaving mouse, as well as measuring serotonin dynamics in the gut without undesired stimulations and perturbing peristaltic movements. The described elastic and conformable biosensing interface has broad potential for studying the impact of neurotransmitters on gut microbes, brain-gut communication and may ultimately be extended to biomolecular sensing in other soft organs across the body.

Construction and application of base-stable MOFs: a critical review.

Metal-organic frameworks (MOFs) are a new class of porous crystalline materials constructed from organic ligands and metal ions/clusters. Owing to their unique advantages, they have attracted more and more attention in recent years and numerous studies have revealed their great potential in various applications. Many important applications of MOFs inevitably involve harsh alkaline operational environments. To achieve high performance and long cycling life in these applications, high stability of MOFs against bases is necessary. Therefore, the construction of base-stable MOFs has become a critical research direction in the MOF field. This review gives a historic summary of the development of base-stable MOFs in the last few years. The key factors that can determine the robustness of MOFs under basic conditions are analyzed. We also demonstrate the exciting achievements that have been made by utilizing base-stable MOFs in different applications. In the end, we discuss major challenges for the further development of base-stable MOFs. Some possible methods to address these problems are presented.

Stable Metal-Organic Frameworks for Fluorescent Detection of Tetracycline Antibiotics.

The rapid detection of antibiotics in agricultural products is of great significance. In this work, two stable fluorescent metal-organic frameworks (MOFs), BUT-178 and BUT-179, are synthesized and used to detect tetracycline antibiotics. Among them, BUT-179 exhibits better performance in the detection of different tetracycline antibiotics in water and eggs. The limits of detection of BUT-179 toward tetracycline, aureomycin, oxytetracycline, and doxycycline all reach the nanomolar level. Furthermore, the cycling tests confirm that BUT-179 can be easily recovered and repeatedly used without an obvious performance loss. This work demonstrates the excellent application potential of MOFs for food safety, especially the fluorescence detection of antibiotics in foods.

A Hydrolytically Stable Cu(II)-Based Metal-Organic Framework with Easily Accessible Ligands for Water Harvesting.

Water scarcity is a critical issue in desert and arid regions, and atmospheric water harvesting is a potential solution. The challenge is lacking ideal adsorbents that can efficiently capture water from low-humidity air and be regenerated readily. Herein, we report a hydrolytically stable metal-organic framework (MOF), [Cu2(AD)2(SA)] (Cu-AD-SA), with excellent performance in water harvesting. More importantly, this material can be facilely prepared from two easily accessible ligands adenine (HAD) and succinic acid (H2SA). Cu-AD-SA has a three-dimensional (3D) framework structure with the crs topology and intersecting channels of ∼5 Å in diameter. The channel surface is decorated by uncoordinated aromatic N atoms, amine groups, and alkyl moieties. Interestingly, Cu-AD-SA shows a high water adsorption capacity of 0.16 g g-1 at low pressure of 0.2 P/P0 and 25 °C. Furthermore, dynamic water adsorption-desorption cycling experiments demonstrated a stable working capacity of 0.13 g g-1 for uptaking water from a low-humidity air (water partial pressure: 0.85 kPa, 20% RH at 30 °C, 5.3% RH at 55 °C) at 30 °C and desorption at 55 °C. The water adsorption mechanism was also studied by analyzing its single-crystal structure after water loading. The results indicated the existence of strong H-bonding interactions between water molecules and uncoordinated N atoms and amine groups on the framework, which should play an important role in the high adsorption at low pressure. All the above features suggest great potential of Cu-AD-SA for water harvesting in arid regions.

Organic wastewater treatment by a single-atom catalyst and electrolytically produced H2O2.

The presence of organic contaminants in wastewater poses considerable risks to the health of both humans and ecosystems. Although advanced oxidation processes that rely on highly reactive radicals to destroy organic contaminants are appealing treatment options, substantial energy and chemical inputs limit their practical applications. Here we demonstrate that Cu single atoms incorporated in graphitic carbon nitride can catalytically activate H2O2 to generate hydroxyl radicals at pH 7.0 without energy input, and show robust stability within a filtration device. We further design an electrolysis reactor for the on-site generation of H2O2 from air, water and renewable energy. Coupling the single-atom catalytic filter and the H2O2 electrolytic generator in tandem delivers a wastewater treatment system. These findings provide a promising path toward reducing the energy and chemical demands of advanced oxidation processes, as well as enabling their implementation in remote areas and isolated communities.

A Practice of Reticular Chemistry: Construction of a Robust Mesoporous Palladium Metal-Organic Framework via Metal Metathesis.

Constructing stable palladium(II)-based metal-organic frameworks (MOFs) would unlock more opportunities for MOF chemistry, particularly toward applications in catalysis. However, their availability is limited by synthetic challenges due to the inertness of the Pd-ligand coordination bond, as well as the strong tendency of the Pd(II) source to be reduced under typical solvothermal conditions. Under the guidance of reticular chemistry, herein, we present the first example of an azolate Pd-MOF, BUT-33(Pd), obtained via a deuterated solvent-assisted metal metathesis. BUT-33(Pd) retains the underlying sodalite network and mesoporosity of the template BUT-33(Ni) and shows excellent chemical stability (resistance to an 8 M NaOH aqueous solution). With rich Pd(II) sites in the atomically precise distribution, it also demonstrates good performances as a heterogeneous Pd(II) catalyst in a wide application scope, including Suzuki/Heck coupling reactions and photocatalytic CO2 reduction to CH4. This work highlights a feasible approach to reticularly construct noble metal based MOFs via metal metathesis, in which various merits, including high chemical stability, large pores, and tunable functions, have been integrated for addressing challenging tasks.

In Situ Porphyrin Substitution in a Zr(IV)-MOF for Stability Enhancement and Photocatalytic CO2 Reduction.

Despite numerous inherent merits of metal-organic frameworks (MOFs), structural fragility has imposed great restrictions on their wider involvement in many applications, such as in catalysis. Herein, a strategy for enhancing stability and enabling functionality in a labile Zr(IV)-MOF has been proposed by in situ porphyrin substitution. A size- and geometry-matched robust linear porphyrin ligand 4,4'-(porphyrin-5,15-diyl)dibenzolate (DCPP2- ) is selected to replace the 4,4'-(1,3,6,8-tetraoxobenzo[lmn][3,8]phenanthroline-2,7(1H,3H,6H,8H)-diyl)dibenzoate (NDIDB2- ) ligand in the synthesis of BUT-109(Zr), affording BUT-110 with varied porphyrin contents. Compared to BUT-109(Zr), the chemical stability of BUT-110 series is greatly improved. Metalloporphyrin incorporation endows BUT-110 MOFs with high catalytic activity in the photoreduction of CO2 , in the absence of photosensitizers. By tuning the metal species and porphyrin contents in BUT-110, the resulting BUT-110-50%-Co is demonstrated to be a good photocatalyst for selective CO2 -to-CO reduction, via balancing the chemical stability, photocatalytic efficiency, and synthetic cost. This work highlights the advantages of in situ ligand substitution for MOF modification, by which uniform distribution and high content of the incoming ligand are accessible in the resulting MOFs. More importantly, it provides a promising approach to convert unstable MOFs, which mainly constitute the vast MOF database but have always been neglected, into robust functional materials.

Boosting Interfacial Charge-Transfer Kinetics for Efficient Overall CO2 Photoreduction via Rational Design of Coordination Spheres on Metal-Organic Frameworks.

The recombination of electron-hole pairs severely detracts from the efficiency of photocatalysts. This issue could be addressed in metal-organic frameworks (MOFs) through optimization of the charge-transfer kinetics via rational design of structures at atomic level. Herein, a pyrazolyl porphyrinic Ni-MOF (PCN-601), integrating light harvesters, active catalytic sites, and high surface areas, has been demonstrated as a superior and durable photocatalyst for visible-light-driven overall CO2 reduction with H2O vapor at room temperature. Kinetic studies reveal that the robust coordination spheres of pyrazolyl groups and Ni-oxo clusters endow PCN-601 with proper energy band alignment and ultrafast ligand-to-node electron transfer. Consequently, the CO2-to-CH4 production rate of PCN-601 far exceeds those of the analogous MOFs based on carboxylate porphyrin and the classic Pt/CdS photocatalyst by more than 3- and 20-fold, respectively. The reaction avoids the use of hole scavengers and proceeds in a gaseous phase which can take full advantage of the high gas uptake of MOFs. This work demonstrates that the rational design of coordination spheres in MOF structures not only reconciles the contradiction between reactivity and stability but also greatly promotes the interfacial charge transfer to achieve optimized kinetics, providing guidance for the design of highly efficient MOF photocatalysts.

Neutralization of Interleukin-17A Attenuates Lipopolysaccharide-Induced Mastitis by Inhibiting Neutrophil Infiltration and the Inflammatory Response.

Mastitis has been recognized as a common and major disease of cows with a strong impact on dairy farming. Interleukin-17A (IL-17A) has been shown to mediate crucial crosstalk between the immune system and various epithelial tissues, initiating a series of defensive mechanisms against bacterial and fungal infections. This crosstalk is especially involved in neutrophil infiltration. To evaluate the role of IL-17A in immune defense in the mammary gland in mice, we tested the effects of depleting IL-17A on changes in pathology, neutrophil infiltration, and pro-inflammatory cytokine levels in the mammary gland stimulated by lipopolysaccharide (LPS). Further, the effects of IL-17A on the activation of the nuclear factor-κB (NF-κB) signaling pathway during mastitis induced by LPS were also studied. The results showed that the production of IL-17A was significantly elevated during mastitis induced by LPS. IL-17A blockade via an intraperitoneal antibody injection protected against LPS-induced mastitis, as indicated by decreased neutrophil infiltration, myeloperoxidase activity, pro-inflammatory cytokines levels, and NF-κB signaling pathway molecule phosphorylation in response to LPS. In conclusion, an elevated IL-17 level plays a crucial role during mastitis, and anti-IL-17A antibody blockade protects against LPS-induced mammary gland inflammation induced through the NF-κB signaling pathway, which provides a new potential treatment target for mastitis.

Upregulated expression of MNX1-AS1 long noncoding RNA predicts poor prognosis in gastric cancer.

As important regulators of gene expression long noncoding RNAs (lncRNAs) are implicated in various physiological and pathological processes, including cancer. An oncogenic role of MNX1 antisense RNA 1 (MNX1-AS1) lncRNA has been suggested in cervical cancer and glioblastoma. In this study, we investigated the clinicopathological significance and biological function of MNX1-AS1 in gastric cancer (GC). The expression of MNX1-AS1 was analyzed by qRT-PCR in 96 GC and adjacent non-tumor tissues in relation to clinicopathological features and overall survival (OS) of patients, and in five human GC cell lines compared to a normal gastric epithelial cell line. Loss-of-function experiments using small interfering RNA (siRNA) targeting MNX1-AS1 (si-MNX1-AS1) were carried out in AGS and MGC-803 GC cell lines. Cell proliferation (CCK-8 assay), migration (Transwell) and invasion (Transwell Matrigel), and protein expression of proliferating cell nuclear antigen (PCNA), E-cadherin, N-cadherin, vimentin and matrix metallopeptidase 9 (MMP-9) were analyzed in transfected GC cells. Expression of MNX1-AS1 was significantly higher in GC vs. adjacent non-tumor tissues. Higher MNX1-AS1 expression was significantly associated with tumor size, TNM stage and lymph node metastasis. Kaplan-Meier analysis showed that GC patients with higher MNX1-AS1 expression had worse OS compared to patients with lower MNX1-AS1 expression. Multivariate analysis showed that MNX1-AS1 is an independent poor prognostic factor in GC. Knockdown of MNX1-AS1 significantly inhibited proliferation, migration and invasion of AGS and MGC-803 cells, and resulted in increased E-cadherin and decreased PCNA, N-cadherin, vimentin and MMP-9 expression. Taken together, these results suggest that MNX1-AS1 has an oncogenic function in GC and potential as a molecular target in GC therapy.

Wrinkled Graphene Cages as Hosts for High-Capacity Li Metal Anodes Shown by Cryogenic Electron Microscopy.

Lithium (Li) metal has long been considered the "holy grail" of battery anode chemistry but is plagued by low efficiency and poor safety due to its high chemical reactivity and large volume fluctuation, respectively. Here we introduce a new host of wrinkled graphene cage (WGC) for Li metal. Different from recently reported amorphous carbon spheres, WGC show highly improved mechanical stability, better Li ion conductivity, and excellent solid electrolyte interphase (SEI) for continuous robust Li metal protection. At low areal capacities, Li metal is preferentially deposited inside the graphene cage. Cryogenic electron microscopy characterization shows that a uniform and stable SEI forms on the WGC surface that can shield the Li metal from direct exposure to electrolyte. With increased areal capacities, Li metal is plated densely and homogeneously into the outer pore spaces between graphene cages with no dendrite growth or volume change. As a result, a high Coulombic efficiency (CE) of ∼98.0% was achieved under 0.5 mA/cm2 and 1-10 mAh/cm2 in commercial carbonate electrolytes, and a CE of 99.1% was realized with high-concentration electrolytes under 0.5 mA/cm2 and 3 mAh/cm2. Full cells using WGC electrodes with prestored Li paired with Li iron phosphate showed greatly improved cycle lifetime. With 10 mAh/cm2 Li metal deposition, the WGC/Li composite anode was able to provide a high specific capacity of ∼2785 mAh/g. With its roll-to-roll compatible fabrication procedure, WGC serves as a highly promising material for the practical realization of Li metal anodes in next-generation high energy density secondary batteries.

Cryo-EM structures of atomic surfaces and host-guest chemistry in metal-organic frameworks.

Host-guest interactions govern the chemistry of a broad range of functional materials, but direct imaging using conventional transmission electron microscopy (TEM) has not been possible. This problem is exacerbated in metal-organic framework (MOF) materials, which are easily damaged by the electron beam. Here, we use cryogenic-electron microscopy (cryo-EM) to stabilize the host-guest structure and resolve the atomic surface of zeolitic imidazolate framework (ZIF-8) and its interaction with guest CO2 molecules. We image step-edge sites on the ZIF-8 surface that provides insight to its growth behavior. Furthermore, we observe two distinct binding sites for CO2 within the ZIF-8 pore, which are predicted by density functional theory (DFT) to be energetically favorable. This CO2 insertion induces an apparent ~3% lattice expansion along the <002> and <011> directions of the ZIF-8 unit cell. The ability to stabilize and preserve host-guest chemistry opens a rich materials space for scientific exploration and discovery using cryo-EM.

Ectopic Expression of miR-147 Inhibits Stem Cell Marker and Epithelial-Mesenchymal Transition (EMT)-Related Protein Expression in Colon Cancer Cells.

Colon cancer is one of the most common cancers in the world. Epithelial-to-mesenchymal transition (EMT) is a crucial step in tumor progression and is also involved in the acquisition of stem cell-like properties. Some miRNAs have been shown to function as either tumor suppressors or oncogenes in colon cancer. Here we investigated the role of miR-147 in the regulation of the stem cell-like traits of colon cancer cells. We observed that miR-147 was downregulated in several colon cancer cell lines, and overexpressed miR-147 decreased the expression of cancer stem cell (CSC) markers OCT4, SOX2, and NANOG in the colon cancer cell lines HCT116 and SW480. Overexpressed miR-147 inhibited EMT by increasing the expression of epithelial markers E-cadherin and α-catenin while decreasing the expression of mesenchymal markers fibronectin and vimentin. Moreover, activation of EMT by TGF-ß1 treatment significantly counteracted the inhibitive effect of miR-147 on the expression of CSC markers OCT4, SOX2, and NANOG, supporting the idea that overexpressing miR-147 inhibited stem cell-like traits by suppressing EMT in colon cancer. In addition, we found that overexpressed miR-147 downregulated the expression of ß-catenin, c-myc, and survivin, which were related to the Wnt/ß-catenin pathway. Moreover, treatment of miR-147 mimic-transfected cells with the Wnt/ß-catenin pathway activator LiCl attenuated the inhibitive effect of the miR-147 mimic on the EMT and stem cell-like traits of colon cancer cells, indicating that ectopic expression of miR-147 inhibited stem cell-like traits in colon cancer cells by suppressing EMT via the Wnt/ß-catenin pathway. In summary, our present study highlighted the crucial role of miR-147 in the inhibition of the stem cell-like traits of colon cancer cells and indicated that miR-147 could be a promising therapeutic target for colon cancer treatment.

[ARTICLE WITHDRAWN] Long Noncoding RNA LINC01296 Harbors miR-21a to Regulate Colon Carcinoma Proliferation and Invasion.

THIS ARTICLE WAS WITHDRAWN BY THE PUBLISHERS IN NOVEMBER 2020.

Tailor-Made Pyrazolide-Based Metal-Organic Frameworks for Selective Catalysis.

The predesignable porous structures in metal-organic frameworks (MOFs) render them quite attractive as a host-guest platform to address a variety of important issues at the frontiers of science. In this work, a perfluorophenylene functionalized metalloporphyrinic MOF, namely, PCN-624, has been rationally designed, synthesized, and structurally characterized. PCN-624 is constructed by 12-connected [Ni8(OH)4(H2O)2Pz12] (Pz = pyrazolide) nodes and fluorinated 5,10,15,20-tetrakis(2,3,5,6-tetrafluoro-4-(1 H-pyrazol-4-yl)phenyl)-porphyrin (TTFPPP) linker with an ftw-a topological net. Notably, PCN-624 exhibits extinguished robustness under different conditions, including organic solvents, strong acid, and base aqueous solutions. The pore surface of PCN-624 is decorated with pendant perfluorophenylene groups. These moieties fabricate densely fluorinated nanocages resulting in the selective guest capture of the material. More importantly, PCN-624 can be employed as an efficient heterogeneous catalyst for the selective synthesis of fullerene-anthracene bisadduct. Owing to the high chemical robustness of PCN-624, it can be recycled over five times without significant loss of its catalytic activity. All of these results demonstrate that MOFs can serve as a powerful platform with great flexibility for functional design to solve various synthetic problems.

Stable Metal-Organic Frameworks: Design, Synthesis, and Applications.

Metal-organic frameworks (MOFs) are an emerging class of porous materials with potential applications in gas storage, separations, catalysis, and chemical sensing. Despite numerous advantages, applications of many MOFs are ultimately limited by their stability under harsh conditions. Herein, the recent advances in the field of stable MOFs, covering the fundamental mechanisms of MOF stability, design, and synthesis of stable MOF architectures, and their latest applications are reviewed. First, key factors that affect MOF stability under certain chemical environments are introduced to guide the design of robust structures. This is followed by a short review of synthetic strategies of stable MOFs including modulated synthesis and postsynthetic modifications. Based on the fundamentals of MOF stability, stable MOFs are classified into two categories: high-valency metal-carboxylate frameworks and low-valency metal-azolate frameworks. Along this line, some representative stable MOFs are introduced, their structures are described, and their properties are briefly discussed. The expanded applications of stable MOFs in Lewis/Brønsted acid catalysis, redox catalysis, photocatalysis, electrocatalysis, gas storage, and sensing are highlighted. Overall, this review is expected to guide the design of stable MOFs by providing insights into existing structures, which could lead to the discovery and development of more advanced functional materials.

A Base-Resistant Metalloporphyrin Metal-Organic Framework for C-H Bond Halogenation.

A base-resistant porphyrin metal-organic framework (MOF), namely PCN-602 has been constructed with 12-connected [Ni8(OH)4(H2O)2Pz12] (Pz = pyrazolate) cluster and a newly designed pyrazolate-based porphyrin ligand, 5,10,15,20-tetrakis(4-(pyrazolate-4-yl)phenyl)porphyrin under the guidance of the reticular synthesis strategy. Besides its robustness in hydroxide solution, PCN-602 also shows excellent stability in aqueous solutions of F-, CO32-, and PO43- ions. Interestingly, the Mn3+-porphyrinic PCN-602, as a recyclable MOF catalyst, presents high catalytic activity for the C-H bond halogenation reaction in a basic system, significantly outperforming its homogeneous counterpart. For the first time, a porphyrinic MOF was thus used as an efficient catalyst in a basic solution with coordinating anions, to the best of our knowledge.