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.

Cellular toxicity and pharmacokinetic study of butachlor by ultra-performance liquid chromatography-tandem mass spectrometry based on tandem mass spectrometry cubed technique.

Butachlor is an aromatic amide compound that plays a role as a herbicide, a xenobiotic, and an environmental contaminant. The aim of this work was to develop a highly selective and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method based on the tandem mass spectrometry cubed technique to determine butachlor in a biological matrix. Butachlor and internal standard acetochlor were separated on a Waters Acquity ultra-performance liquid chromatography BEH C18 column (2.1 × 50 mm, 1.7 µm) with gradient elution using 0.1% formic acid aqueous solution (A) and acetonitrile (B) as mobile phases. The transitions selected for tandem mass spectrometry cubed quantitative analysis in positive ion mode were: for butachlor, mass-to-charge ratio 312.2→238.1→162.1; for acetochlor, mass-to-charge ratio 270.1→224.0→148.1. The total running time for each sample was 5.5 min. The ultra-performance liquid chromatography-tandem mass spectrometry cubed method showed a linear relationship (R2 ≥ 0.995) in the concentration range of 0.5-100 ng/ml. The intra and interday accuracies are within the range of -10.6%-4.3% and precisions are between 4.48% and 13.14%. The novelty of the method is the use of tandem mass spectrometry cubed scanning mode, which improves selectivity and sensitivity. The results indicated that butachlor was cellular toxic. The safety of butachlor should be considered when it is used as a herbicide.

Impact of off-hour admission on the MACEs of patients with acute myocardial infarction.

BACKGROUND: In China, on more than 100 weekends or holidays, only on-duty cardiologists are available during admissions. This study aimed to analyze the impact of admission time on major adverse cardiovascular events (MACEs) in patients with acute myocardial infarction (AMI). METHODS: This prospective observational study enrolled patients with AMI between October 2018 and July 2019. The patients were assorted into off-hour (admitted on weekends or national holidays) and on-hour groups. The outcome was MACEs at admission and 1 year after discharge. RESULTS: A total of 485 patients with AMI were enrolled in this study. The occurrence of MACEs was significantly higher in the off-hour group compared with the on-hour group (P < .05). Multivariate regression analysis showed that age (HR = 1.047, 95% CI: 1.021-1.073), blood glucose level (HR = 1.029, 95% CI: 1.009-1.050), multivessel disease (HR = 1.904, 95% CI: 1.074-3.375), and off-hour hospital admission (HR = 1.849, 95% CI: 1.125-3.039) were all independent risk factors for in-hospital MACEs, while percutaneous coronary intervention (HR = 0.210, 95% CI: 0.147-0.300) and on-hour admission (HR = 0.723, 95% CI: 0.532-0.984) were protective factors for MACEs 1 year after discharge. CONCLUSION: The "off-hour effect" still existed in patients with AMI, and the risk of MACEs in the hospital and 1 year after discharge was higher for off-hour admission.

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.

Module-Patterned Polymerization towards Crystalline 2D sp2 -Carbon Covalent Organic Framework Semiconductors.

Despite rapid progress over the past decade, most polycondensation systems even upon a small structural variation of the building units eventually result in amorphous polymers other than the desired crystalline covalent organic frameworks. This synthetic dilemma is a central and challenging issue of the field. Here we report a novel approach based on module-patterned polymerization to enable efficient and designed synthesis of crystalline porous polymeric frameworks. This strategy features a wide applicability to allow the use of various knots of different structures, enables polycondensation with diverse linkers, and develops a diversity of novel crystalline 2D polymers and frameworks, as demonstrated by using the C=C bond-formation polycondensation reaction. The new sp2 -carbon frameworks are highly emissive and enable up-conversion luminescence, offer low band gap semiconductors with tunable band structures, and achieve ultrahigh charge mobilities close to theoretically predicted maxima.

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.

Editing Light Emission with Stable Crystalline Covalent Organic Frameworks via Wall Surface Perturbation.

The ordered π skeletons of covalent organic frameworks make them viable light-emitting materials but their limited tunability has precluded further implementation. Here we report the synthesis of hydrazone-linked frameworks which are stable in water, acid, and base, and demonstrate their utility as a platform for light emission. The polygonal backbone is designed to be luminescent and partially π conjugated while the pore wall is docked with single atom or unit to induce resonance, hyperconjugation, and tautomerization effects. These effects can be transmitted to the backbone, so that the framework can emit three primary colors of light. The wall can be perturbated with multiple surface sites, rendering the material able to edit diverse emission colors in a predesignable and digital way. The systems show high activity, stability, tunability, and sensibility: a set of features attractive for light-emitting and sensing applications.

Application of spectral CT in the diagnosis of contrast encephalopathy following carotid artery stenting: a case report.

BACKGROUND: Contrast encephalopathy is a rare complication of carotid artery stenting (CAS). Contrast encephalopathy is a diagnosis of exclusion that often needs to be distinguished from high perfusion syndrome, cerebral haemorrhage, subarachnoid haemorrhage (SAH), cerebral infarction and so on. CASE PRESENTATION: In this study, we report on a 70-year-old man who was admitted to the hospital with transient ischaemic attacks presenting paroxysmal weakness of limbs in the previous 2 years. He had severe stenosis of the left internal carotid artery diagnosed by digital subtraction angiography (DSA) and underwent CAS. Two hours after the operation, the patient developed paralysis of the right upper limb, unclear speech, fever and restlessness. Emergency skull computed tomography (CT) showed swelling and a linear high-density area in the left cerebral hemisphere. To clarify the components of this high-density area in the traditional CT, the patient had spectral CT, which made the diagnosis of the leakage of contrast clear. After 1 week of supportive treatment, the patient improved. CONCLUSIONS: Spectral CT can easily distinguish the components of high-density areas on traditional CT, which is haemorrhage, calcification or iodine contrast leakage. Therefore, spectral CT is worth consideration for the differential diagnosis of complications of vascular intervention.

Pituitary Apoplexy Leading to Cerebral Infarction: A Systematic Review.

BACKGROUND: Cerebral infarction caused by pituitary apoplexy (PA) is rare. To characterize the clinical features of cerebral infarction caused by PA, we performed a systematic review. SUMMARY: The clinical symptoms are mainly sudden headache, hemiplegia, visual impairment, disturbance of consciousness, and ophthalmalgia in patients with cerebral infarction caused by PA. Treatment for this type of infarction is different from treatment for general acute cerebral infarction. Compared to patients who underwent emergency surgery and conservative treatment, patients treated with delayed surgery showed a better prognosis and a lower mortality rate. Compared to patients who underwent craniotomy or conservative treatment, patients who underwent transsphenoidal surgery (TSS) not only improved well but also showed a lower mortality rate. Key Messages: PA rarely causes cerebral infarction, which is a critical condition with a poor prognosis and is more common in men. Delayed surgery and TSS appear to confer a better prognosis in patients with this condition.

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.

A Stable and Conductive Metallophthalocyanine Framework for Electrocatalytic Carbon Dioxide Reduction in Water.

Transformation of carbon dioxide to high value-added chemicals becomes a significant challenge for clean energy studies. Here a stable and conductive covalent organic framework was developed for electrocatalytic carbon dioxide reduction to carbon monoxide in aqueous solution. The cobalt(II) phthalocyanine catalysts are topologically connected via robust phenazine linkage into a two-dimensional tetragonal framework that is stable under boiling water, acid, or base conditions. The 2D lattice enables full π conjugation along x and y directions as well as π conduction along the z axis across the π columns. With these structural features, the electrocatalytic framework exhibits a faradaic efficiency of 96 %, an exceptional turnover number up to 320 000, and a long-term turnover frequency of 11 412 hour-1 , which is a 32-fold improvement over molecular catalyst. The combination of catalytic activity, selectivity, efficiency, and durability is desirable for clean energy production.

Topology-Templated Synthesis of Crystalline Porous Covalent Organic Frameworks.

A strategy is presented for the synthesis of crystalline porous covalent organic frameworks via topology-templated polymerization. The template is based on imine-linked frameworks and their (001) facets seed the C=C bond formation reaction to constitute 2D sp2 carbon-conjugated frameworks. This strategy is applicable to templates with different topologies, enables designed synthesis of frameworks that cannot be prepared via direct polymerization, and creates a series of sp2 carbon frameworks with tetragonal, hexagonal, and kagome topologies. The sp2 carbon frameworks are highly luminescent even in the solid state and exhibit topology-dependent π transmission and exciton migration; these key fundamental π functions are unique to sp2 carbon-conjugated frameworks and cannot be accessible by imine-linked frameworks, amorphous analogues, and 1D conjugated polymers. These results demonstrate an unprecedented strategy for structural and functional designs of covalent organic frameworks.

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.

The Effect of Winter Temperature on Patients with Ischemic Stroke.

BACKGROUND The incidence of ischemic stroke increases in winter. This study aimed to explore the effect of winter temperatures on the risk factors, etiology, coagulation, and degree of neurological impairment in patients with ischemic stroke using temperature and rainfall data from the Guangzhou Meteorological Bureau during the winter months of December, January, and February. MATERIAL AND METHODS We divided 112 patients with ischemic stroke into low-temperature and non-low-temperature groups. The low-temperature group experienced an average daily winter temperature of <13°C for five consecutive days within the 14 days before hospital admission and an average temperature of <13°C on admission. The non-low-temperature group experienced an average daily temperature of >13°C in the 14 days before hospital admission and an average daily temperature of >13°C on admission. Neurological deficits were scored and monitored using the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) for disability in stroke. Blood pressure and coagulation indices of prothrombin time (PT) and thromboplastin time (TT) were recorded. RESULTS Compared with the non-low-temperature group, the low-temperature group showed a significantly increased proportion of patients with hypertension and large artery atherosclerotic stroke, more prolonged PT, and higher NIHSS scores. However, TT was reduced in the low-temperature group (P<0.05). CONCLUSIONS When the average winter temperature was <13°C, the risk factors, etiology, coagulation factors, and degree of neurological impairment of patients with ischemic stroke were significantly different from patients with ischemic stroke during warmer temperature.

High-Precision Size Recognition and Separation in Synthetic 1D Nanochannels.

Covalent organic frameworks (COFs) allow elaborate manufacture of ordered one-dimensional channels in the crystal. We defined a superlattice of COFs by engineering channels with a persistent triangular shape and discrete pore size. We observed a size-recognition regime that is different from the characteristic adsorption of COFs, whereby pore windows and walls were cooperative so that triangular apertures sorted molecules of one-atom difference and notch nanogrooves confined them into single-file molecular chains. The recognition and confinement were accurately described by sensitive spectroscopy and femtosecond dynamic simulations. The resulting COFs enabled instantaneous separation of mixtures at ambient temperature and pressure. This study offers an approach to merge precise recognition, selective transport, and instant separation in synthetic 1D channels.

Ion Conduction in Polyelectrolyte Covalent Organic Frameworks.

Covalent organic frameworks (COFs) with ordered one-dimensional channels could offer a predesigned pathway for ion motion. However, implanting salts into bare channels of COFs gives rise to a limited ion conductivity. Here, we report the first example of polyelectrolyte COFs by integrating flexible oligo(ethylene oxide) chains onto the pore walls. Upon complexation with lithium ions, the oligo(ethylene oxide) chains form a polyelectrolyte interface in the nanochannels and offer a pathway for lithium ion transport. As a result, the ion conductivity was enhanced by more than 3 orders of magnitude compared to that of ions across the bare nanochannels. The polyelectrolyte COFs promoted ion motion via a vehicle mechanism and exhibited enhanced cycle and thermal stabilities. These results suggest that the strategy for engineering a polyelectrolyte interface in the 1D nanochannels of COFs could open a new way to solid-state ion conductors.

Light-Emitting Covalent Organic Frameworks: Fluorescence Improving via Pinpoint Surgery and Selective Switch-On Sensing of Anions.

Covalent organic frameworks (COFs) offer ordered π structures that are useful for developing light-emitting materials. However, most COFs are weak in luminescence. Here we report the conversion of less emissive COFs into light-emitting materials via a pinpoint surgery on the pore walls. Deprotonation of the N-H bond to form an anionic nitrogen species in the hydrazone linkage can eliminate the nitrogen-related fluorescence quenching pathway. The resulting COF enhances the fluorescence in a linear proportion to the progress of deprotonation, achieving a 3.8-fold improved emission. This pinpoint N-H cleavage on the pore walls can be driven only by the fluoride anion while other halogen anions, including chloride, bromide, and iodide, remain inactive, enabling the selective fluorescence switch-on sensing of the fluoride anion at a ppb level.

N-WASp is required for Schwann cell cytoskeletal dynamics, normal myelin gene expression and peripheral nerve myelination.

Schwann cells elaborate myelin sheaths around axons by spirally wrapping and compacting their plasma membranes. Although actin remodeling plays a crucial role in this process, the effectors that modulate the Schwann cell cytoskeleton are poorly defined. Here, we show that the actin cytoskeletal regulator, neural Wiskott-Aldrich syndrome protein (N-WASp), is upregulated in myelinating Schwann cells coincident with myelin elaboration. When N-WASp is conditionally deleted in Schwann cells at the onset of myelination, the cells continue to ensheath axons but fail to extend processes circumferentially to elaborate myelin. Myelin-related gene expression is also severely reduced in the N-WASp-deficient cells and in vitro process and lamellipodia formation are disrupted. Although affected mice demonstrate obvious motor deficits these do not appear to progress, the mutant animals achieving normal body weights and living to advanced age. Our observations demonstrate that N-WASp plays an essential role in Schwann cell maturation and myelin formation.

Phosphorylation of AQP4 by LRRK2 R1441G impairs glymphatic clearance of IFNγ and aggravates dopaminergic neurodegeneration.

Aquaporin-4 (AQP4) is essential for normal functioning of the brain's glymphatic system. Impaired glymphatic function is associated with neuroinflammation. Recent clinical evidence suggests the involvement of glymphatic dysfunction in LRRK2-associated Parkinson's disease (PD); however, the precise mechanism remains unclear. The pro-inflammatory cytokine interferon (IFN) γ interacts with LRRK2 to induce neuroinflammation. Therefore, we examined the AQP4-dependent glymphatic system's role in IFNγ-mediated neuroinflammation in LRRK2-associated PD. We found that LRRK2 interacts with and phosphorylates AQP4 in vitro and in vivo. AQP4 phosphorylation by LRRK2 R1441G induced AQP4 depolarization and disrupted glymphatic IFNγ clearance. Exogeneous IFNγ significantly increased astrocyte expression of IFNγ receptor, amplified AQP4 depolarization, and exacerbated neuroinflammation in R1441G transgenic mice. Conversely, inhibiting LRRK2 restored AQP4 polarity, improved glymphatic function, and reduced IFNγ-mediated neuroinflammation and dopaminergic neurodegeneration. Our findings establish a link between LRRK2-mediated AQP4 phosphorylation and IFNγ-mediated neuroinflammation in LRRK2-associated PD, guiding the development of LRRK2 targeting therapy.

MSC-Derived Extracellular Vesicles Alleviate NLRP3/GSDMD-Mediated Neuroinflammation in Mouse Model of Sporadic Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease, with sporadic form being the predominant type. Neuroinflammation plays a critical role in accelerating pathogenic processes in AD. Mesenchymal stem cell (MSC)-derived small extracellular vesicles (MSC-sEVs) regulate inflammatory responses and show great promise for treating AD. Induced pluripotent stem cell (iPSC)-derived MSCs are similar to MSCs and exhibit low immunogenicity and heterogeneity, making them promising cell sources for clinical applications. This study examined the anti-inflammatory effects of MSC-sEVs in a streptozotocin-induced sporadic mouse model of AD (sAD). The intracisternal administration of iPSC-MSC-sEVs alleviated NLRP3/GSDMD-mediated neuroinflammation, decreased amyloid deposition and neuronal apoptosis, and mitigated cognitive dysfunction. Furthermore, it explored the role of miR-223-3p in the iPSC-MSC-sEVs-mediated anti-inflammatory effects in vitro. miR-223-3p directly targeted NLRP3, whereas inhibiting miR-223-3p almost completely reversed the suppression of NLRP3 by MSC-sEVs, suggesting that miR-223-3p may, at least partially, account for MSC-sEVs-mediated anti-inflammation. Results obtained suggest that intracisternal administration of iPSC-MSC-sEVs can reduce cognitive impairment by inhibiting NLRP3/GSDMD neuroinflammation in a sAD mouse model. Therefore, the present study provides a proof-of-principle for applying iPSC-MSC-sEVs to target neuroinflammation in sAD.