Accelerating Anhydrous Proton Transport in Covalent Organic Frameworks: Pore Chemistry and Its Impacts.

Proton conduction is important in both fundamental research and technological development. Here we report designed synthesis of crystalline porous covalent organic frameworks as a new platform for high-rate anhydrous proton conduction. By developing nanochannels with different topologies as proton pathways and loading neat phosphoric acid to construct robust proton carrier networks in the pores, we found that pore topology is crucial for proton conduction. Its effect on increasing proton conductivity is in an exponential mode other than linear fashion, endowing the materials with exceptional proton conductivities exceeding 10-2 S cm-1 over a broad range of temperature and a low activation energy barrier down to 0.24 eV. Remarkably, the pore size controls conduction mechanism, where mesopores promote proton conduction via a fast-hopping mechanism, while micropores follow a sluggish vehicle process. Notably, decreasing phosphoric acid loading content drastically reduces proton conductivity and greatly increases activation energy barrier, emphasizing the pivotal role of well-developed proton carrier network in proton transport. These findings and insights unveil a new general and transformative guidance for designing porous framework materials and systems for high-rate ion conduction, energy storage, and energy conversion.

Exceptional Anhydrous Proton Conduction in Covalent Organic Frameworks.

Covalent organic frameworks (COFs) offer an irreplaceable platform for mass transport, as they provide aligned one-dimensional channels as pathways. Especially, proton conduction is of great scientific interest and technological importance. However, unlike proton conduction under humidity, anhydrous proton conduction remains a challenge, as it requires robust materials and proceeds under harsh conditions. Here, we report exceptional anhydrous proton conduction in stable crystalline porous COFs by integrating neat phosphoric acid into the channels to form extended hydrogen-bonding networks. The phosphoric acid networks in the pores are stabilized by hierarchical multipoint and multichain hydrogen-bonding interactions with the 3D channel walls. We synthesized five hexagonal COFs that possess different pore sizes, which are gradually tuned from micropores to mesopores. Remarkably, mesoporous COFs with a high pore volume exhibit an exceptional anhydrous proton conductivity of 0.31 S cm-1, which marks the highest conductivity among all examples reported for COFs. We observed that the proton conductivity is dependent on the pore volume, pore size, and content of phosphoric acid. Increasing the pore volume improves the proton conductivity in an exponential fashion. Remarkably, changing the pore volume from 0.41 to 1.60 cm3 g-1 increases the proton conductivity by 1150-fold. Interestingly, as the pore size increases, the activation energy barrier of proton conduction decreases in linear mode. The mesopores enable fast proton hopping across the channels, while the micropores follow sluggish vehicle conduction. Experiments on tuning phosphoric acid loading contents revealed that a well-developed hydrogen-bonding phosphoric acid network in the pores is critical for proton conduction.

Light-Gating Crystalline Porous Covalent Organic Frameworks.

We report light gating in synthetic one-dimensional nanochannels of stable crystalline porous covalent organic frameworks. The frameworks consist of 2D hexagonal skeletons that are extended over the x-y plane and stacked along the z-direction to create dense yet aligned 1D mesoporous channels. The pores are designed to be photoadaptable by covalently integrating tetrafluoro-substituted azobenzene units onto edges, which protrude from walls and offer light-gating machinery confined in the channels. The implanted tetrafluoroazobenzene units are thermally stable yet highly sensitive to visible light to induce photoisomerization between the E and Z forms. Remarkably, photoisomerization induces drastic changes in intrapore polarity as well as pore shape and size, which exert profound effects on the molecular adsorption of a broad spectrum of compounds, ranging from inorganic iodine to organic dyes, drugs, and enzymes. Unexpectedly, the systems respond rapidly to visible lights to gate the molecular release of drugs and enzymes. Photoadaptable covalent organic frameworks with reversibly convertible pores offer a platform for constructing light-gating porous materials and tailorable delivery systems, remotely controlled by visible lights.

Covalent Organic Frameworks: Linkage Chemistry and Its Critical Role in The Evolution of π Electronic Structures and Functions.

Covalent organic frameworks (COFs) provide a molecular platform for designing a novel class of functional materials with well-defined structures. A crucial structural parameter is the linkage, which dictates how knot and linker units are connected to form two-dimensional polymers and layer frameworks, shaping ordered π-array and porous architectures. However, the roles of linkage in the development of ordered π electronic structures and functions remain fundamental yet unresolved issues. Here we report the designed synthesis of COFs featuring four representative linkages: hydrazone, imine, azine, and C=C bonds, to elucidate their impacts on the evolution of π electronic structures and functions. Our observations revealed that the hydrazone linkage provides a non-conjugated connection, while imine and azine allow partial π conjugation, and the C=C bond permits full π-conjugation. Importantly, the linkage profoundly influences the control of π electronic structures and functions, unraveling its pivotal role in determining key electronic properties such as band gap, frontier energy levels, light absorption, luminescence, carrier density and mobility, and magnetic permeability. These findings highlight the significance of linkage chemistry in COFs and offer a general and transformative guidance for designing framework materials to achieve electronic functions.

Photoresponsive Covalent Organic Frameworks: Visible-Light Controlled Conversion of Porous Structures and Its Impacts.

Covalent organic frameworks are a novel class of crystalline porous polymers that enable molecular design of extended polygonal skeletons to attain well-defined porous structures. However, construction of a framework that allows remote control of pores remains a challenge. Here we report a strategy that merges covalent, noncovalent, and photo chemistries to design photoresponsive frameworks with reversibly and remotely controllable pores. We developed a topology-guided multicomponent polycondensation system that integrates protruded tetrafluoroazobenzene units as photoresponsive sites on pore walls at predesigned densities, so that a series of crystalline porous frameworks with the same backbone can be constructed to develop a broad spectrum of pores ranging from mesopores to micropores. Distinct from conventional azobenzene-based systems, the tetrafluoroazobenzene frameworks are highly sensitive to visible lights to undergo high-rate isomerization. The photoisomerization exerts profound effects on pore size, shape, number, and environment, as well as molecular uptake and release, rendering the system able to convert and switch pores reversibly and remotely with visible lights. Our results open a way to a novel class of smart porous materials with pore structures and functions that are convertible and manageable with visible lights.

Crystalline, Porous Helicene Covalent Organic Frameworks.

Helicenes are a class of fascinating chiral helical molecules with rich chemistry developed continuously over the past 100 years. Their helical, conjugated, and twisted structures make them attractive for constructing molecular systems. However, studies over the past century are mainly focused on synthesizing helicenes with increased numbers of aromatic rings and complex heterostructures, while research on inorganic, organic, and polymeric helicene materials is still embryonic. Herein, we report the first examples of helicene covalent organic frameworks, i.e., [7]Helicene sp2 c-COF-1, by condensing [7]Helicene dialdehyde with trimethyl triazine via the C=C bond formation reaction under solvothermal conditions. The resultant [7]Helicene sp2 c-COF-1 exhibits prominent X-ray diffraction peaks and assumes a highly ordered 2D lattice structure originated from the twisted configuration of [7]Helicene unit. The C=C linked [7]Helicene sp2 c-COF-1 materials exhibited extended π conjugation and broadly tuned their absorption, emission, redox activity, photoconductivity, and light-emitting activity, demonstrating rich multifunctionalities and great potentials in developing various applications. This work opens a way to a new family of COFs as well as helicene materials, enabling the exploration of unprecedented π architectures and properties.

Covalent Organic Frameworks: Reversible 3D Coalesce via Interlocked Skeleton-Pore Actions and Impacts on π Electronic Structures.

Covalent organic frameworks (COFs) create extended two-dimensional (2D) skeletons and aligned one-dimensional (1D) channels, constituting a class of novel π architectures with predesignable structural ordering. A distinct feature is that stacks of π building units in skeletons shape the pore walls, onto which a diversity of different units can be assembled to form various pore interfaces, opening a great potential to trigger a strong structural correlation between the skeleton and the pore. However, such a possibility has not yet been explored. Herein, we report reversible three-dimensional (3D) coalescence and interlocked actions between the skeleton and pore in COFs by controlling hydrogen-bonding networks in the pores. Introducing carboxylic acid units to the pore walls develops COFs that can confine water molecular networks, which are locked by the surface carboxylic acid units on the pore walls via multipoint, multichain, and multidirectional hydrogen-bonding interactions. As a result, the skeleton undergoes an interlocked action with pores to shrink over the x-y plane and to stack closer along the z direction upon water uptake. Remarkably, this interlocked action between the skeleton and pore is reversibly driven by water adsorption and desorption and triggers profound effects on π electronic structures and functions, including band gap, light absorption, and emission.

Knockdown of KLF5 ameliorates renal fibrosis in MRL/lpr mice via inhibition of MX1 transcription.

OBJECTIVE: This study aims to elucidate the role of Kruppel-like factor (KLF5) and myxovirus resistance 1 (MX1) in the progression of renal fibrosis in lupus nephritis (LN). METHODS: First, the expression of KLF5 and MX1 was assessed in the peripheral blood of LN patients and healthy participants. Next, the pathological changes in renal tissues were evaluated and compared in BALB/c and MRL/lpr mice, by detecting the expression of fibrosis marker proteins (transforming growth factor-ß [TGF-ß] and CTGF) and α-SMA, the content of urine protein, and the levels of serum creatinine, blood urea nitrogen, and serum double-stranded DNA antibody. In TGF-ß1-induced HK-2 cells, the messenger RNA levels of KLF5 and MX1 were tested by qRT-PCR, and the protein expression of α-SMA, type I collagen (Col I), fibronectin (FN), and matrix metalloproteinase 9 (MMP9) was measured by western blot analysis. Moreover, the relationship between KLF5 and MX1 was predicted and verified. RESULTS: In renal tissues of MRL/lpr mice and the peripheral blood of LN patients, KLF5 and MX1 were highly expressed. Pearson analysis revealed that KLF5 was positively correlated with MX1. Furthermore, KLF5 bound to MX1 promoter and promoted its transcription level. MRL/lpr mice showed substantial renal injury, accompanied by increased expression of α-SMA, TGF-ß, CTGF, Col I, FN, and MMP9. Injection of sh-KLF5 or sh-MX1 alone in MRL/lpr mice reduced renal fibrosis in LN, while simultaneous injection of sh-KLF5 and ad-MX1 exacerbated renal injury and fibrosis. Furthermore, we obtained the same results in TGF-ß1-induced HK-2 cells. CONCLUSION: Knockdown of KLF5 alleviated renal fibrosis in LN through repressing the transcription of MX1.

Intravitreal conbercept for diabetic macular oedema: 2-year results from a randomised controlled trial and open-label extension study.

BACKGROUND: To demonstrate the efficacy and safety of intravitreal injections of conbercept versus laser photocoagulation in the treatment of diabetic macular oedema (DME). METHODS: A 12-month multicentre, randomised, double-masked, double-sham, parallel controlled, phase III trial (Sailing Study), followed by a 12-month open-label extension study. Patients with centre-involved DME were randomly assigned to receive either laser photocoagulation followed by pro re nata (PRN) sham intravitreal injections (laser/sham) or sham laser photocoagulation followed by PRN 0.5 mg conbercept intravitreal injections (sham/conbercept). Patients who entered the extension study received PRN conbercept treatment. The primary endpoint was the changes in best-corrected visual acuity (BCVA) from baseline. RESULTS: A total of 248 eyes were included in the full analysis set and 157 eyes continued in the extension study. Significant improvement in mean change in BCVA from baseline to month 12 was observed in the sham/conbercept group (8.2±9.5 letters), whereas no improvement was observed in the laser/sham group (0.3±12.0 letters). Patients in the laser/sham group showed a marked improvement in BCVA after the switch to conbercept in the extension study, and there was no difference in BCVA between the two groups at the end of the extension study. CONCLUSION: The use of a conbercept PRN intravitreal injection regimen improved the BCVA of patients with DME, and its efficacy was better than that of laser photocoagulations, and the same efficacy was observed when the eyes treated with laser alone were switched to conbercept. TRIAL REGISTRATION NUMBER: NCT02194634.

Haemolymph metabolomic differences in silkworms (Bombyx mori L.) under mulberry leaf and two artificial diet rearing methods.

The new technology of silkworm (Bombyx mori L.) artificial feed breeding has many characteristics and advantages. This study assessed silkworm rearing with mulberry leaf at all instars (MF) as the control, and used metabolomics to explore the differences in haemolymph metabolism of fifth instar silkworms under two modes of rearing with an artificial diet at all instars (AF) and rearing with an artificial diet during first to third instars and mulberry leaf during the fourth and fifth instars (AMF). The results show that, compared with silkworms of the MF group, the amount and fold change of various metabolites were higher in the haemolymph of AF group silkworms, and the metabolism of amino acids and uric acid, carbohydrates, lipids, and vitamins were changed. These changes may be the reasons for the poor performance of the AF silkworms. However, the amount and fold change of the various metabolites of silkworms in the AMF group were lower, and some metabolic pathways were more active. The amount of material and energy supply were greater. These changes could explain the high efficiency growth of body weight of silkworms after the conversion from artificial diet rearing to mulberry leaf rearing. These findings provide an important theoretical basis for the optimisation of artificial diet rearing technology for silkworms.

Water cluster in hydrophobic crystalline porous covalent organic frameworks.

Progress over the past decades in water confinement has generated a variety of polymers and porous materials. However, most studies are based on a preconception that small hydrophobic pores eventually repulse water molecules, which precludes the exploration of hydrophobic microporous materials for water confinement. Here, we demonstrate water confinement across hydrophobic microporous channels in crystalline covalent organic frameworks. The frameworks are designed to constitute dense, aligned and one-dimensional polygonal channels that are open and accessible to water molecules. The hydrophobic microporous frameworks achieve full occupation of pores by water via synergistic nucleation and capillary condensation and deliver quick water exchange at low pressures. Water confinement experiments with large-pore frameworks pinpoint thresholds of pore size where confinement becomes dominated by high uptake pressure and large exchange hysteresis. Our results reveal a platform based on microporous hydrophobic covalent organic frameworks for water confinement.

Hydroxide Anion Transport in Covalent Organic Frameworks.

Hydroxide anion transport is essential for alkaline fuel cells, but hydroxide anion has an inherently low conductivity owing to its small diffusion coefficient and high mass. Ordered open channels found in covalent organic frameworks are promising as pathways to enable hydroxide anion transport, but this remains to be explored. Here we report designed synthesis of anionic covalent organic frameworks that promote hydroxide anion transport across the one-dimensional channels. Engineering cationic chains with imidazolium termini onto the pore walls self-assembles a supramolecular interface of single-file hydroxide anion chains in the channels. The frameworks facilitate hydroxide anion transport to achieve an exceptional conductivity of 1.53 × 10-2 S cm-1 at 80 °C, which is 2-6 orders of magnitude higher than those of linear polymers and other porous frameworks. Impedance spectroscopy at different temperatures and studies on deuterated samples reveal that hydroxide anions transport via a proton-exchange hopping mechanism. These results open a way to design framework materials for energy conversions via engineering an anionic interface.

Efficacy and safety of mycophenolate mofetil in the treatment for IgA nephropathy: a meta-analysis of randomized controlled trials.

AIM: IgA nephropathy is virtually known as the most common glomerulopathy to end-stage renal failure in the world. Mycophenolate mofetil is a selective immunosuppressant widely used in organ transplantation, yet its tolerance and effectiveness in IgAN is controversial. METHODS: This is a systematic review and random-effects meta-analysis, searching PubMed, Embase, Te Cochrane Library, Science Citation Index, Ovid evidence-based medicine, Chinese Biomedical Literature and Chinese Science and Technology Periodicals. Screen out randomized controlled trials on patients with biopsy-proven IgA nephropathy and analysis mycophenolate mofetil treatment regimens used for therapy of IgA nephropathy. Complete remission and partial remission, doubling of creatinine level, proteinuria, incidence of end-stage kidney disease, infection, Cushing syndrome, diabetes, hepatic dysfunction or gastrointestinal symptoms, neurologic or visual ambiguity, acne, and alopecia were observed. RESULTS: Nine relevant trials were conducted with 587 patients enrolled. In Mycophenolate mofetil or plus medium/low-dose steroid comparing full-dose steroid alone or placebo, there was no significant difference. The risk of Cushing syndrome and diabetes had been significantly lowered with Mycophenolate mofetil-treated patients, while the risk of infection had been increased. CONCLUSIONS: Mycophenolate mofetil therapy did not differ in reducing proteinuria and Scr in patients with IgAN who had persistent proteinuria, while having fewer Cushing syndrome and diabetes risk and more infection risk. However, larger randomized studies are needed to reveal these results.

Ultrafast and Stable Proton Conduction in Polybenzimidazole Covalent Organic Frameworks via Confinement and Activation.

Polybenzimidazoles are engineering plastics with superb thermal stability and this specificity has sparked a wide-ranging research to explore proton-conducting materials. Nevertheless, such materials encounter challenging issues owing to phosphoric acid proton carrier leakage and slow proton transport. We report a strategy for designing porous polybenzimidazole frameworks to address these key fundamental issues. The built-in channels are designed to be one-dimensionally extended, unidirectionally aligned, and fully occupied by neat phosphoric acid, while the benzimidazole walls trigger multipoint, multichain, and multitype interactions to spatially confine a phosphoric acid network in pores and facilitate proton conduction via deprotonation. The materials exhibit ultrafast and stable proton conduction for low proton carrier content and activation energy-a set of features highly desired for proton transport. Our results offer a design strategy for the fabrication of porous polybenzimidazoles for use in energy conversion applications.

Optimized timing of using infliximab in perianal fistulizing Crohn's disease.

Infliximab (IFX), as a drug of first-line therapy, can alter the natural progression of Crohn's disease (CD), promote mucosal healing and reduce complications, hospitalizations, and the incidence of surgery. Perianal fistulas are responsible for the refractoriness of CD and represent a more aggressive disease. IFX has been demonstrated as the most effective drug for the treatment of perianal fistulizing CD. Unfortunately, a significant proportion of patients only partially respond to IFX, and optimization of the therapeutic strategy may increase clinical remission. There is a significant association between serum drug concentrations and the rates of fistula healing. Higher IFX levels during induction are associated with a complete fistula response in these patients. Given the apparent relapse of perianal fistulizing CD, maintenance therapy with IFX over a longer period seems to be more beneficial. It appears that patients without deep remission are at an increased risk of relapse after stopping anti-tumor necrosis factor agents. Thus, only patients in prolonged clinical remission should be considered for withdrawal of IFX treatment when biomarker and endoscopic remission is demonstrated, especially when the hyperintense signals of fistulas on T2-weighed images have disappeared on magnetic resonance imaging. Fundamentally, the optimal timing of IFX use is highly individualized and should be determined by a multidisciplinary team.

One-Year Effectiveness Study of Intravitreously Administered Conbercept® Monotherapy in Diabetic Macular Degeneration: A Systematic Review and Meta-Analysis.

INTRODUCTION: The evidence on efficacy of intravitreously administered Conbercept (IVC) monotherapy for diabetic macular degeneration was still limited. METHODS: A systematic review was conducted in November 2019 to summarize the current evidence on visual acuity (VA) changes with IVC monotherapy in the treatment of diabetic macular edema (DME) from Pubmed, ClinicalTrials.gov, EMbase, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chin VIP Information (VIP), and Chinese Biomedical Database (CBM). Retrospective or prospective clinical studies which used IVC injection for the treatment of DME were included. Outcomes included in the analysis were change in best-corrected visual acuity (BCVA) and central macular thickness (CMT). A meta-regression was conducted to assess 1-year BCVA and CMT changes against numbers of injections. RESULTS: A total of 20 studies were included in current study. At 12-month follow-up, an overall increase of 0.67 logarithm of the minimum angle of resolution (logMAR) BCVA score [95% confidence interval (CI) 0.24-1.11; P = 0.003] and 1.03 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (95% CI 0.69-1.38; P < 0.001) was shown with IVC injection compared to baseline. Decrease in CMT was 142.79 µm (95% CI 112.71-172.87; P < 0.001) compared to baseline. The meta-regression showed a significant increase in effect size between number of injections and 12-month logMAR BCVA scale change as well as CMT. CONCLUSION: Our findings suggest improved VA and CMT outcomes during 1-year follow-up in patients with DME who underwent IVC monotherapy. Increased injection frequency demonstrates a significant trend with improved outcomes at 12 months.

Confining H3PO4 network in covalent organic frameworks enables proton super flow.

Development of porous materials combining stability and high performance has remained a challenge. This is particularly true for proton-transporting materials essential for applications in sensing, catalysis and energy conversion and storage. Here we report the topology guided synthesis of an imine-bonded (C=N) dually stable covalent organic framework to construct dense yet aligned one-dimensional nanochannels, in which the linkers induce hyperconjugation and inductive effects to stabilize the pore structure and the nitrogen sites on pore walls confine and stabilize the H3PO4 network in the channels via hydrogen-bonding interactions. The resulting materials enable proton super flow to enhance rates by 2-8 orders of magnitude compared to other analogues. Temperature profile and molecular dynamics reveal proton hopping at low activation and reorganization energies with greatly enhanced mobility.

Covalent Organic Frameworks: Design, Synthesis, and Functions.

Covalent organic frameworks (COFs) are a class of crystalline porous organic polymers with permanent porosity and highly ordered structures. Unlike other polymers, a significant feature of COFs is that they are structurally predesignable, synthetically controllable, and functionally manageable. In principle, the topological design diagram offers geometric guidance for the structural tiling of extended porous polygons, and the polycondensation reactions provide synthetic ways to construct the predesigned primary and high-order structures. Progress over the past decade in the chemistry of these two aspects undoubtedly established the base of the COF field. By virtue of the availability of organic units and the diversity of topologies and linkages, COFs have emerged as a new field of organic materials that offer a powerful molecular platform for complex structural design and tailor-made functional development. Here we target a comprehensive review of the COF field, provide a historic overview of the chemistry of the COF field, survey the advances in the topology design and synthetic reactions, illustrate the structural features and diversities, scrutinize the development and potential of various functions through elucidating structure-function correlations based on interactions with photons, electrons, holes, spins, ions, and molecules, discuss the key fundamental and challenging issues that need to be addressed, and predict the future directions from chemistry, physics, and materials perspectives.

Designing Covalent Organic Frameworks with a Tailored Ionic Interface for Ion Transport across One-Dimensional Channels.

A strategy based on covalent organic frameworks for ultrafast ion transport involves designing an ionic interface to mediate ion motion. Electrolyte chains were integrated onto the walls of one-dimensional channels to construct ionic frameworks via pore surface engineering, so that the ionic interface can be systematically tuned at the desired composition and density. This strategy enables a quantitative correlation between interface and ion transport and unveils a full picture of managing ionic interface to achieve high-rate ion transport. Moreover, the effect of interfaces was scaled on ion transport; ion mobility is increased in an exponential mode with the ionic interface. This strategy not only sets a benchmark system but also offers a general guidance for designing ionic interface that is key to systems for energy conversion and storage.

Covalent Organic Frameworks: Chemical Approaches to Designer Structures and Built-In Functions.

A new approach has been developed to design organic polymers using topology diagrams. This strategy enables covalent integration of organic units into ordered topologies and creates a new polymer form, that is, covalent organic frameworks. This is a breakthrough in chemistry because it sets a molecular platform for synthesizing polymers with predesignable primary and high-order structures, which has been a central aim for over a century but unattainable with traditional design principles. This new field has its own features that are distinct from conventional polymers. This Review summarizes the fundamentals as well as major progress by focusing on the chemistry used to design structures, including the principles, synthetic strategies, and control methods. We scrutinize built-in functions that are specific to the structures by revealing various interplays and mechanisms involved in the expression of function. We propose major fundamental issues to be addressed in chemistry as well as future directions from physics, materials, and application perspectives.