Loss of Katnal2 leads to ependymal ciliary hyperfunction and autism-related phenotypes in mice.

Autism spectrum disorders (ASD) frequently accompany macrocephaly, which often involves hydrocephalic enlargement of brain ventricles. Katnal2 is a microtubule-regulatory protein strongly linked to ASD, but it remains unclear whether Katnal2 knockout (KO) in mice leads to microtubule- and ASD-related molecular, synaptic, brain, and behavioral phenotypes. We found that Katnal2-KO mice display ASD-like social communication deficits and age-dependent progressive ventricular enlargements. The latter involves increased length and beating frequency of motile cilia on ependymal cells lining ventricles. Katnal2-KO hippocampal neurons surrounded by enlarged lateral ventricles show progressive synaptic deficits that correlate with ASD-like transcriptomic changes involving synaptic gene down-regulation. Importantly, early postnatal Katnal2 re-expression prevents ciliary, ventricular, and behavioral phenotypes in Katnal2-KO adults, suggesting a causal relationship and a potential treatment. Therefore, Katnal2 negatively regulates ependymal ciliary function and its deletion in mice leads to ependymal ciliary hyperfunction and hydrocephalus accompanying ASD-related behavioral, synaptic, and transcriptomic changes.

Early Prediction of Mortality for Septic Patients Visiting Emergency Room Based on Explainable Machine Learning: A Real-World Multicenter Study.

BACKGROUND: Worldwide, sepsis is the leading cause of death in hospitals. If mortality rates in patients with sepsis can be predicted early, medical resources can be allocated efficiently. We constructed machine learning (ML) models to predict the mortality of patients with sepsis in a hospital emergency department. METHODS: This study prospectively collected nationwide data from an ongoing multicenter cohort of patients with sepsis identified in the emergency department. Patients were enrolled from 19 hospitals between September 2019 and December 2020. For acquired data from 3,657 survivors and 1,455 deaths, six ML models (logistic regression, support vector machine, random forest, extreme gradient boosting [XGBoost], light gradient boosting machine, and categorical boosting [CatBoost]) were constructed using fivefold cross-validation to predict mortality. Through these models, 44 clinical variables measured on the day of admission were compared with six sequential organ failure assessment (SOFA) components (PaO2/FIO2 [PF], platelets (PLT), bilirubin, cardiovascular, Glasgow Coma Scale score, and creatinine). The confidence interval (CI) was obtained by performing 10,000 repeated measurements via random sampling of the test dataset. All results were explained and interpreted using Shapley's additive explanations (SHAP). RESULTS: Of the 5,112 participants, CatBoost exhibited the highest area under the curve (AUC) of 0.800 (95% CI, 0.756-0.840) using clinical variables. Using the SOFA components for the same patient, XGBoost exhibited the highest AUC of 0.678 (95% CI, 0.626-0.730). As interpreted by SHAP, albumin, lactate, blood urea nitrogen, and international normalization ratio were determined to significantly affect the results. Additionally, PF and PLTs in the SOFA component significantly influenced the prediction results. CONCLUSION: Newly established ML-based models achieved good prediction of mortality in patients with sepsis. Using several clinical variables acquired at the baseline can provide more accurate results for early predictions than using SOFA components. Additionally, the impact of each variable was identified.

Factors Associated with Smokers Attending More Than One Smoking Cessation Clinic Visit.

Smoking remains a primary cause of cancers, cardiovascular and respiratory diseases and death. Globally, efforts have been made to reduce smoking rates, but the addictive nature of nicotine, a key component of tobacco, makes cessation challenging for smokers. Medical interventions including medical advice and pharmacotherapies are effective methods for smoking cessation. The frequency of medical interventions correlates with success in smoking cessation. This study aims to compare the characteristics of the patients who visited the smoking cessation clinic once with those who visited more than once, in order to identify factors that are associated with repeat clinic visits. A total of 81 patients who have visited the smoking cessation clinic in Kangwon National University Hospital were included. Patients answered the questionnaire at their first visit. If the patient visited only once, the outcome was defined as negative and if the patient visited more than once, the outcome was defined as positive. The proportion of patients who answered "within 5 min" to the Fagerstrom Test for Nicotine Dependence's (FTND) 1st question and answered "yes" to the FTND's 6th question was higher in the negative outcome group. In the logistic regression, patients who had withdrawal symptoms previously were associated with positive outcomes (adjusted OR 3.466, 95% CI 1.088-11.034 and p value = 0.0354). Withdrawal symptoms during previous attempts were positively related to visiting the clinic more than once.

Comparison between radiofrequency ablation and CHIVA procedure in patients with varicose veins.

OBJECTIVE: Conservatrice et Hémodynamique de l'Insuffisance Veineuse en Ambulatoire, the French acronym for CHIVA, is a strategy aimed to convert a venous reflux into a physiological drainage. We compared CHIVA with radiofrequency ablation and determined its possible advantages. METHODS: We retrospectively analyzed the clinical recurrence, ultrasound recurrence, quality of life scores, and complications. They were compared after propensity score matching. RESULTS: 212 limbs of 166 patients were included: 42 limbs underwent radiofrequency ablation and 170 limbs underwent CHIVA. The hospital stay was shorter in the CHIVA group. There was no difference in clinical, ultrasound recurrence, quality of life scores and complications between the two groups. The preoperative saphenous vein diameter was larger in the recurrence cases. CONCLUSIONS: CHIVA showed comparable results to radiofrequency ablation. There was more ultrasound recurrence with larger vein diameters. The CHIVA appears to be a simple and more efficient treatment method when performed on select patients.

Kv7/KCNQ potassium channels in cortical hyperexcitability and juvenile seizure-related death in Ank2-mutant mice.

Autism spectrum disorders (ASD) represent neurodevelopmental disorders characterized by social deficits, repetitive behaviors, and various comorbidities, including epilepsy. ANK2, which encodes a neuronal scaffolding protein, is frequently mutated in ASD, but its in vivo functions and disease-related mechanisms are largely unknown. Here, we report that mice with Ank2 knockout restricted to cortical and hippocampal excitatory neurons (Ank2-cKO mice) show ASD-related behavioral abnormalities and juvenile seizure-related death. Ank2-cKO cortical neurons show abnormally increased excitability and firing rate. These changes accompanied decreases in the total level and function of the Kv7.2/KCNQ2 and Kv7.3/KCNQ3 potassium channels and the density of these channels in the enlengthened axon initial segment. Importantly, the Kv7 agonist, retigabine, rescued neuronal excitability, juvenile seizure-related death, and hyperactivity in Ank2-cKO mice. These results suggest that Ank2 regulates neuronal excitability by regulating the length of and Kv7 density in the AIS and that Kv7 channelopathy is involved in Ank2-related brain dysfunctions.

Learning black- and gray-box chemotactic PDEs/closures from agent based Monte Carlo simulation data.

We propose a machine learning framework for the data-driven discovery of macroscopic chemotactic Partial Differential Equations (PDEs)-and the closures that lead to them- from high-fidelity, individual-based stochastic simulations of Escherichia coli bacterial motility. The fine scale, chemomechanical, hybrid (continuum-Monte Carlo) simulation model embodies the underlying biophysics, and its parameters are informed from experimental observations of individual cells. Using a parsimonious set of collective observables, we learn effective, coarse-grained "Keller-Segel class" chemotactic PDEs using machine learning regressors: (a) (shallow) feedforward neural networks and (b) Gaussian Processes. The learned laws can be black-box (when no prior knowledge about the PDE law structure is assumed) or gray-box when parts of the equation (e.g. the pure diffusion part) is known and "hardwired" in the regression process. More importantly, we discuss data-driven corrections (both additive and functional), to analytically known, approximate closures.

CYFIP2 p.Arg87Cys Causes Neurological Defects and Degradation of CYFIP2.

Here, we report the generation and comprehensive characterization of a knockin mouse model for the hotspot p.Arg87Cys variant of the cytoplasmic FMR1-interacting protein 2 (CYFIP2) gene, which was recently identified in individuals diagnosed with West syndrome, a developmental and epileptic encephalopathy. The Cyfip2+/R87C mice recapitulated many neurological and neurobehavioral phenotypes of the patients, including spasmlike movements, microcephaly, and impaired social communication. Age-progressive cytoarchitectural disorganization and gliosis were also identified in the hippocampus of Cyfip2+/R87C mice. Beyond identifying a decrease in CYFIP2 protein levels in the Cyfip2+/R87C brains, we demonstrated that the p.Arg87Cys variant enhances ubiquitination and proteasomal degradation of CYFIP2. ANN NEUROL 2023;93:155-163.

In-Advance Prediction of Pressure Ulcers via Deep-Learning-Based Robust Missing Value Imputation on Real-Time Intensive Care Variables.

Pressure ulcers (PUs) are a prevalent skin disease affecting patients with impaired mobility and in high-risk groups. These ulcers increase patients' suffering, medical expenses, and burden on medical staff. This study introduces a clinical decision support system and verifies it for predicting real-time PU occurrences within the intensive care unit (ICU) by using MIMIC-IV and in-house ICU data. We develop various machine learning (ML) and deep learning (DL) models for predicting PU occurrences in real time using the MIMIC-IV and validate using the MIMIC-IV and Kangwon National University Hospital (KNUH) dataset. To address the challenge of missing values in time series, we propose a novel recurrent neural network model, GRU-D++. This model outperformed other experimental models by achieving the area under the receiver operating characteristic curve (AUROC) of 0.945 for the on-time prediction and AUROC of 0.912 for 48h in-advance prediction. Furthermore, in the external validation with the KNUH dataset, the fine-tuned GRU-D++ model demonstrated superior performances, achieving an AUROC of 0.898 for on-time prediction and an AUROC of 0.897 for 48h in-advance prediction. The proposed GRU-D++, designed to consider temporal information and missing values, stands out for its predictive accuracy. Our findings suggest that this model can significantly alleviate the workload of medical staff and prevent the worsening of patient conditions by enabling timely interventions for PUs in the ICU.

Suppressed prefrontal neuronal firing variability and impaired social representation in IRSp53-mutant mice.

Social deficit is a major feature of neuropsychiatric disorders, including autism spectrum disorders, schizophrenia, and attention-deficit/hyperactivity disorder, but its neural mechanisms remain unclear. Here, we examined neuronal discharge characteristics in the medial prefrontal cortex (mPFC) of IRSp53/Baiap2-mutant mice, which show social deficits, during social approach. We found a decrease in the proportion of IRSp53-mutant excitatory mPFC neurons encoding social information, but not that encoding non-social information. In addition, the firing activity of IRSp53-mutant neurons was less differential between social and non-social targets. IRSp53-mutant excitatory mPFC neurons displayed an increase in baseline neuronal firing, but decreases in the variability and dynamic range of firing as well as burst firing during social and non-social target approaches compared to wild-type controls. Treatment of memantine, an NMDA receptor antagonist that rescues social deficit in IRSp53-mutant mice, alleviates the reduced burst firing of IRSp53-mutant pyramidal mPFC neurons. These results suggest that suppressed neuronal activity dynamics and burst firing may underlie impaired cortical encoding of social information and social behaviors in IRSp53-mutant mice.

Human pluripotent stem cell-derived macrophages and macrophage-derived exosomes: therapeutic potential in pulmonary fibrosis.

Pulmonary fibrosis (PF) is a fatal chronic disease characterized by accumulation of extracellular matrix and thickening of the alveolar wall, ultimately leading to respiratory failure. PF is thought to be initiated by the dysfunction and aberrant activation of a variety of cell types in the lung. In particular, several studies have demonstrated that macrophages play a pivotal role in the development and progression of PF through secretion of inflammatory cytokines, growth factors, and chemokines, suggesting that they could be an alternative therapeutic source as well as therapeutic target for PF. In this review, we describe the characteristics, functions, and origins of subsets of macrophages involved in PF and summarize current data on the generation and therapeutic application of macrophages derived from pluripotent stem cells for the treatment of fibrotic diseases. Additionally, we discuss the use of macrophage-derived exosomes to repair fibrotic lung tissue.

Glyoxalase 1 as a Therapeutic Target in Cancer and Cancer Stem Cells.

Methylglyoxal (MG) is a dicarbonyl compound formed in cells mainly by the spontaneous degradation of the triose phosphate intermediates of glycolysis. MG is a powerful precursor of advanced glycation end products, which lead to strong dicarbonyl and oxidative stress. Although divergent functions of MG have been observed depending on its concentration, MG is considered to be a potential anti-tumor factor due to its cytotoxic effects within the oncologic domain. MG detoxification is carried out by the glyoxalase system. Glyoxalase 1 (Glo1), the ubiquitous glutathione-dependent enzyme responsible for MG degradation, is considered to be a tumor promoting factor due to it catalyzing the removal of cytotoxic MG. Indeed, various cancer types exhibit increased expression and activity of Glo1 that closely correlate with tumor cell growth and metastasis. Furthermore, mounting evidence suggests that Glo1 contributes to cancer stem cell survival. In this review, we discuss the role of Glo1 in the malignant progression of cancer and its possible use as a promising therapeutic target for tumor therapy. We also summarize therapeutic outcomes of Glo1 inhibitors as prospective treatments for the prevention of cancer.

Prediction and recommendation by machine learning through repetitive internal validation for hepatic veno-occlusive disease/sinusoidal obstruction syndrome and early death after allogeneic hematopoietic cell transplantation.

Using traditional statistical methods, we previously analyzed the risk factors and treatment outcomes of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) after allogeneic hematopoietic cell transplantation. Within the same cohort, we applied machine learning to create prediction and recommendation models. We analyzed 2572 transplants using eXtreme Gradient Boosting (XGBoost) to predict post-transplant VOD/SOS and early death. Using the XGBoost and SHapley Additive exPlanations (SHAP), we found influential factors and devised recommendation models, which were internally verified by repetitive ten-fold cross-validation. SHAP values suggested that gender, busulfan dosage, age, forced expiratory volume, and Disease Risk Index were significant factors for VOD/SOS. The areas under the receiver operating characteristic curves and the areas under the precision-recall curve of the models were 0.740, 0.144 for all VOD/SOS, 0.793, 0.793 for severe to very severe VOD/SOS, and 0.746, 0.304 for early death. According to our single feature recommendation, following the busulfan dosage was the most effective for preventing VOD/SOS. The recommendation method for six adjustable feature sets was also validated, and a subgroup corresponding to five to six features showed significant preventive power for VOD/SOS and early death. Our personalized treatment set recommendation showed reproducibility in repetitive internal validation, but large external cohorts should prospectively validate our model.

Human Pluripotent Stem Cell-Derived Alveolar Epithelial Cells as a Tool to Assess Cytotoxicity of Particulate Matter and Cigarette Smoke Extract.

Human pluripotent stem cells (hPSCs) can give rise to a vast array of differentiated derivatives, which have gained great attention in the field of in vitro toxicity evaluation. We have previously demonstrated that hPSC-derived alveolar epithelial cells (AECs) are phenotypically and functionally similar to primary AECs and could be more biologically relevant alternatives for assessing the potential toxic materials including in fine dust and cigarette smoking. Therefore, in this study, we employed hPSC-AECs to evaluate their responses to exposure of various concentrations of diesel particulate matter (dPM), cigarette smoke extract (CSE) and nicotine for 48 hrs in terms of cell death, inflammation, and oxidative stress. We found that all of these toxic materials significantly upregulated the transcription of pro-inflammatory cytokines such as IL-1α, IL-ß, IL-6, and TNF-α. Furthermore, the exposure of dPM (100 µg/mL) strongly induced upregulation of genes related with cell death, inflammation, and oxidative stress compared with other concentrations of CSE and nicotine. These results suggest that hPSC-AECs could be a robust in vitro platform to evaluate pulmotoxicity of various air pollutants and harmful chemicals.

Fine-Tuning a Robust Metal-Organic Framework toward Enhanced Clean Energy Gas Storage.

The development of adsorbents with molecular precision offers a promising strategy to enhance storage of hydrogen and methane─considered the fuel of the future and a transitional fuel, respectively─and to realize a carbon-neutral energy cycle. Herein we employ a postsynthetic modification strategy on a robust metal-organic framework (MOF), MFU-4l, to boost its storage capacity toward these clean energy gases. MFU-4l-Li displays one of the best volumetric deliverable hydrogen capacities of 50.2 g L-1 under combined temperature and pressure swing conditions (77 K/100 bar → 160 K/5 bar) while maintaining a moderately high gravimetric capacity of 9.4 wt %. Moreover, MFU-4l-Li demonstrates impressive methane storage performance with a 5-100 bar usable capacity of 251 cm3 (STP) cm-3 (0.38 g g-1) and 220 cm3 (STP) cm-3 (0.30 g g-1) at 270 and 296 K, respectively. Notably, these hydrogen and methane storage capacities are significantly improved compared to those of its isoreticular analogue, MFU-4l, and place MFU-4l-Li among the best MOF-based materials for this application.

Early Chronic Memantine Treatment-Induced Transcriptomic Changes in Wild-Type and Shank2-Mutant Mice.

Shank2 is an excitatory postsynaptic scaffolding protein strongly implicated in autism spectrum disorders (ASDs). Shank2-mutant mice with a homozygous deletion of exons 6 and 7 (Shank2-KO mice) show decreased NMDA receptor (NMDAR) function and autistic-like behaviors at juvenile [∼postnatal day (P21)] and adult (>P56) stages that are rescued by NMDAR activation. However, at ∼P14, these mice show the opposite change - increased NMDAR function; moreover, suppression of NMDAR activity with early, chronic memantine treatment during P7-21 prevents NMDAR hypofunction and autistic-like behaviors at later (∼P21 and >P56) stages. To better understand the mechanisms underlying this rescue, we performed RNA-Seq gene-set enrichment analysis of forebrain transcriptomes from wild-type (WT) and Shank2-KO juvenile (P25) mice treated early and chronically (P7-21) with vehicle or memantine. Vehicle-treated Shank2-KO mice showed upregulation of synapse-related genes and downregulation of ribosome- and mitochondria-related genes compared with vehicle-treated WT mice. They also showed a transcriptomic pattern largely opposite that observed in ASD (reverse-ASD pattern), based on ASD-related/risk genes and cell-type-specific genes. In memantine-treated Shank2-KO mice, chromatin-related genes were upregulated; mitochondria, extracellular matrix (ECM), and actin-related genes were downregulated; and the reverse-ASD pattern was weakened compared with that in vehicle-treated Shank2-KO mice. In WT mice, memantine treatment, which does not alter NMDAR function, upregulated synaptic genes and downregulated ECM genes; memantine-treated WT mice also exhibited a reverse-ASD pattern. Therefore, early chronic treatment of Shank2-KO mice with memantine alters expression of chromatin, mitochondria, ECM, actin, and ASD-related genes.

Excitatory synapses and gap junctions cooperate to improve Pv neuronal burst firing and cortical social cognition in Shank2-mutant mice.

NMDA receptor (NMDAR) and GABA neuronal dysfunctions are observed in animal models of autism spectrum disorders, but how these dysfunctions impair social cognition and behavior remains unclear. We report here that NMDARs in cortical parvalbumin (Pv)-positive interneurons cooperate with gap junctions to promote high-frequency (>80 Hz) Pv neuronal burst firing and social cognition. Shank2-/- mice, displaying improved sociability upon NMDAR activation, show impaired cortical social representation and inhibitory neuronal burst firing. Cortical Shank2-/- Pv neurons show decreased NMDAR activity, which suppresses the cooperation between NMDARs and gap junctions (GJs) for normal burst firing. Shank2-/- Pv neurons show compensatory increases in GJ activity that are not sufficient for social rescue. However, optogenetic boosting of Pv neuronal bursts, requiring GJs, rescues cortical social cognition in Shank2-/- mice, similar to the NMDAR-dependent social rescue. Therefore, NMDARs and gap junctions cooperate to promote cortical Pv neuronal bursts and social cognition.

MicroRNAs 21 and 199a-3p Regulate Axon Growth Potential through Modulation of Pten and mTor mRNAs.

Increased mTOR activity has been shown to enhance regeneration of injured axons by increasing neuronal protein synthesis, while PTEN signaling can block mTOR activity to attenuate protein synthesis. MicroRNAs (miRs) have been implicated in regulation of PTEN and mTOR expression, and previous work in spinal cord showed an increase in miR-199a-3p after spinal cord injury (SCI) and increase in miR-21 in SCI animals that had undergone exercise. Pten mRNA is a target for miR-21 and miR-199a-3p is predicted to target mTor mRNA. Here, we show that miR-21 and miR-199a-3p are expressed in adult dorsal root ganglion (DRG) neurons, and we used culture preparations to test functions of the rat miRs in adult DRG and embryonic cortical neurons. miR-21 increases and miR-199a-3p decreases in DRG neurons after in vivo axotomy. In both the adult DRG and embryonic cortical neurons, miR-21 promotes and miR-199a-3p attenuates neurite growth. miR-21 directly bound to Pten mRNA and miR-21 overexpression decreased Pten mRNA levels. Conversely, miR-199a-3p directly bound to mTor mRNA and miR-199a-3p overexpression decreased mTor mRNA levels. Overexpressing miR-21 increased both overall and intra-axonal protein synthesis in cultured DRGs, while miR-199a-3p overexpression decreased this protein synthesis. The axon growth phenotypes seen with miR-21 and miR-199a-3p overexpression were reversed by co-transfecting PTEN and mTOR cDNA expression constructs with the predicted 3' untranslated region (UTR) miR target sequences deleted. Taken together, these studies indicate that injury-induced alterations in miR-21 and miR-199a-3p expression can alter axon growth capacity by changing overall and intra-axonal protein synthesis through regulation of the PTEN/mTOR pathway.

Gene Dosage- and Age-Dependent Differential Transcriptomic Changes in the Prefrontal Cortex of Shank2-Mutant Mice.

Shank2 is an abundant postsynaptic scaffolding protein that is known to regulate excitatory synapse assembly and synaptic transmission and has been implicated in various neurodevelopmental disorders, including autism spectrum disorders (ASD). Previous studies on Shank2-mutant mice provided mechanistic insights into their autistic-like phenotypes, but it remains unclear how transcriptomic patterns are changed in brain regions of the mutant mice in age- and gene dosage-dependent manners. To this end, we performed RNA-Seq analyses of the transcripts from the prefrontal cortex (PFC) of heterozygous and homozygous Shank2-mutant mice lacking exons 6 and 7 at juvenile (week 3) and adult (week 12) stages. Juvenile heterozygous Shank2-mutant mice showed upregulation of glutamate synapse-related genes, downregulation of ribosomal and mitochondrial genes, and transcriptomic changes that are opposite to those observed in ASD (anti-ASD) such as upregulation of ASD_down (downregulated in ASD), GABA neuron-related, and oligodendrocyte-related genes. Juvenile homozygous Shank2 mice showed upregulation of chromatin-related genes and transcriptomic changes that are in line with those occurring in ASD (pro-ASD) such as downregulation of ASD_down, GABA neuron-related, and oligodendrocyte-related genes. Adult heterozygous and homozygous Shank2-mutant mice both exhibited downregulation of ribosomal and mitochondrial genes and pro-ASD transcriptomic changes. Therefore, the gene dosage- and age-dependent effects of Shank2 deletions in mice include differential transcriptomic changes across distinct functional contexts, including synapses, chromatin, ribosomes, mitochondria, GABA neurons, and oligodendrocytes.

Zirconium Metal-Organic Frameworks Integrating Chloride Ions for Ammonia Capture and/or Chemical Separation.

Ammonia capture by porous materials is relevant to protection of humans from chemical threats, while ammonia separation may be relevant to its isolation and use following generation by emerging electrochemical schemes. Our previous work described both reversible and irreversible interactions of ammonia with the metal-organic framework (MOF) material, NU-1000, following thermal treatment at either 120 or 300 °C. In the present work, we have examined NU-1000-Cl, a variant that features a modified node structure-at ambient temperature, Zr6(µ3-O)4(µ3-OH)4(H2O)812+ in place of Zr6(µ3-O)4(µ3-OH)4(OH)4(H2O)48+. Carboxylate termini from each of eight linkers balance the 8+ charge of the parent node, while four chloride ions, attached only by hydrogen bonding, complete the charge balance for the 12+ version. We find that both reversible and irreversible uptake of ammonia are enhanced for NU-1000-Cl, relative to the chloride-free version. Two irreversible interactions were observed via in situ diffuse-reflectance infrared Fourier-transform spectroscopy: coordination of NH3 at open Zr sites generated during thermal pretreatment and formation of NH4+ by proton transfer from node aqua ligands. The irreversibility of the latter appears to be facilitated by the presence chloride ions, as NH4+ formation occurs reversibly with chloride-free NU-1000. At room temperature, chemically reversible (and irreversible) interactions between ammonia and NU-1000-Cl result in separation of NH3 from N2 when gas mixtures are examined with breakthrough instrumentation, as evinced by a much longer breakthrough time (∼9 min) for NH3.

Structural Diversity of Zirconium Metal-Organic Frameworks and Effect on Adsorption of Toxic Chemicals.

While linkers with various conformations pose challenges in the design and prediction of metal-organic framework (MOF) structures, they ultimately provide great opportunities for the discovery of novel structures thereby enriching structural diversity. Tetratopic carboxylate linkers, for example, have been widely used in the formation of Zr-based MOFs due to the ability to target diverse topologies, providing a promising platform to explore their mechanisms of formation. However, it remains a challenge to control the resulting structures when considering the complex assembly of linkers with unpredicted conformations and diverse Zr6 node connectivities. Herein, we systematically explore how solvents and modulators employed during synthesis influence the resulting topologies of Zr-MOFs, choosing H4TCPB-Br2 (1,4-dibromo-2,3,5,6-tetrakis(4-carboxyphenyl)benzene) as a representative tetratopic carboxylate linker. By modulating the reaction conditions, the conformations of the linker and the connectivities of the Zr6 node can be simultaneously tuned, resulting in four types of structures: a new topology (NU-500), she (NU-600), scu (NU-906), and csq (NU-1008). Importantly, we have synthesized the first 5-connected Zr6 node to date with the (4,4,4,5)-connected framework, NU-500. We subsequently performed detailed structural analyses to uncover the relationship between the structures and topologies of these MOFs and demonstrated the crucial role that the flexible linker played to access varied structures by different degrees of linker deformation. Due to a variety of pore structures ranging from micropores to hierarchical micropores and mesopores, the resulting MOFs show drastically different behaviors for the adsorption of n-hexane and dynamic adsorption of 2-chloroethyl ethyl sulfide (CEES) under dry and humid conditions.