Unraveling the Dynamic Molecular Motions of a Twin-Cavity Cage with Slow Configurational but Rapid Conformational Interconversions.

Featuring diverse structural motions/changes, dynamic molecular systems hold promise for executing complex tasks. However, their structural complexity presents formidable challenge in elucidating their kinetics, especially when multiple structural motions are intercorrelated. We herein introduce a twin-cavity cage that features interconvertible C3- and C1-configurations, each configuration exhibiting interchangeable P- and M-conformations. This molecule is therefore composed of four interconnected chiral species (P)-C3, (M)-C3, (P)-C1, (M)-C1. We showcase an effective methodology to decouple these sophisticated structural changes into two kinetically distinct pathways. Utilizing time-dependent 1H NMR spectroscopy at various temperatures, which disregards the transition between mirror-image conformations, we first determine the rate constant (kc) for C3- to C1-configuration interconversion; while time-dependent circular dichroism spectroscopy at different temperatures quantifies the observed rate constant (kobs) of ensemble of all structural changes. As kobs >> kc, it allows us to decouple the overall molecular motions into a slow configurational transformation and rapid conformational interconversions, the latter further dissected into two independent conformational interchanges, namely (P)-C3 ⇄ (M)-C3 and (P)-C1 ⇄ (M)-C1. This work therefore sheds light on comprehensive kinetic study of complex molecular dynamics, offering valuable insights for the rational design of smart dynamic materials for applications of sensing, separation, catalysis, molecular machinery, etc.

Identification of MGMT promoter methylation as a specific lipid metabolism biomarker, reveals the feasibility of atorvastatin application in glioblastoma.

BACKGROUND: Glioblastoma is one of the deadliest tumors, and limited improvement in managing glioblastoma has been achieved in the past decades. The unmethylated promoter area of 6-O-Methylguanine-DNA Methyltransferase (MGMT) is a significant biomarker for recognizing a subset of glioblastoma that is resistant to chemotherapy. Here we identified MGMT methylation can also work as a specific biomarker to classify the lipid metabolism patterns between methylated and unmethylated glioblastoma and verify the potential novel therapeutic strategy for unmethylated MGMT glioblastoma. METHODS: Liquid Chromatograph Mass Spectrometer has been applied for non-targeted metabolome and targeted lipidomic profiling to explore the metabolism pattern correlated with MGMT promoter methylation. Transcriptome has been performed to explore the biological differences and the potential mechanism of lipid metabolism in glioblastoma samples. In vivo and ex vivo assays were performed to verify the anti-tumor activity of atorvastatin in the administration of glioblastoma. RESULTS: Multi-omics assay has described a significant difference in lipid metabolism between MGMT methylated and unmethylated glioblastoma. Longer and unsaturated fatty acyls were found enriched in MGMT-UM tumors. Lipid droplets have been revealed remarkably decreased in MGMT unmethylated glioblastoma. In vivo and ex vivo assays revealed that atorvastatin and also together with temozolomide showed significant anti-tumor activity, and atorvastatin alone was able to achieve better survival and living conditions for tumor-hosting mice. CONCLUSIONS: MGMT promoter methylation status might be a well-performed biomarker of lipid metabolism in glioblastoma. The current study can be the basis of further mechanism studies and implementation of clinical trials, and the results provide preclinical evidence of atorvastatin administration in glioblastoma, especially for MGMT unmethylated tumors.

Spontaneous Symmetry Breaking of Achiral Molecules Leading to the Formation of Homochiral Superstructures that Exhibit Mechanoluminescence.

Chirality, with its intrinsic symmetry-breaking feature, is frequently utilized in the creation of acentric crystalline functional materials that exhibit intriguing optoelectronic properties. On the other hand, the development of chiral crystals from achiral molecules offers a solution that bypasses the need for enantiopure motifs, presenting a promising alternative and thereby expanding the possibilities of the self-assembly toolkit. Nevertheless, the rational design of achiral molecules that prefer spontaneous symmetry breaking during crystallization has so far been obscure. In this study, we present a series of six achiral molecules, demonstrating that when these conformationally flexible molecules adopt a cis-conformation and engage in multiple non-covalent interactions along a helical path, they collectively self-assemble into chiral superstructures consisting of single-handed supramolecular columns. When these homochiral supramolecular columns align in parallel, they form polar crystals that exhibit intense luminescence upon grinding or scraping. We therefore demonstrate our molecular design strategy could significantly increase the likelihood of symmetry breaking in achiral molecular synthons during self-assembly, offering a facile access to novel chiral crystalline materials with unique optoelectronic properties.

A donor-acceptor cage for circularly polarized TADF emission.

Herein, we report the first example of chiral donor-acceptor cage DA-2 displaying efficient circularly polarized thermally activated delayed fluorescence (CP-TADF) with |glum| values up to 2.1 × 10-3 and PLQY of 32%. A small ΔEST of 0.051 eV and quasi-parallel (θ = 6°) transition electric and magnetic dipole moments were realized from the through-space charge transfer interaction between the parallelly aligned donor and acceptor in DA-2. This D-A cage configuration has provided a novel design strategy for discovering potential efficient CP-TADF emitters.

Light-Triggered Enhancement of Fluorescence Efficiency in Organic Cages.

The fluorescence efficiency of excited molecules can be enhanced by many external factors. Here, we showcase a surprising phenomenon whereby light is used as a gating source to increase the fluorescence efficiency of organic cages composed of biphenyl subunits. We show that the enhancement of fluorescence is not due to structural changes or ground-state events. Cryo-fluorescence measurements and kinetic studies suggest a restriction of the phenyl-based structures in the excited state, leading to increased fluorescence, which is also supported by time-resolved measurements. Through computational calculations, we propose that the planarization of the biphenyl units within the cages contributes to emission enhancement. This phenomenon offers insights into the design of optoelectronic structures with improved fluorescence properties.

Comparison of thoracolumbar versus non-thoracolumbar osteoporotic vertebral compression fractures in risk factors, vertebral compression degree and pre-hospital back pain.

BACKGROUND: Thoracolumbar spine is at high risk of osteoporotic vertebral compression fractures (OVCF). This study aimed to identify the differences in risk factors, vertebral compression degree and back pain characteristics of thoracolumbar OVCF (TL-OVCF) and non-thoracolumbar OVCF (nTL-OVCF). METHODS: OVCF patients hospitalized in a spine center between June 2016 and October 2020 were retrospectively studied. Demographics, comorbidity, spine trauma, bone mineral density, duration of pre-hospital back pain, extent of vertebral marrow edema, and degree of vertebral compression of patients with nTL-OVCF were summarized and compared to those with TL-OVCF. RESULTS: A total of 944 patients with acute single-segment OVCF were included. There were 708 (75.0%) TL-OVCF located in T11-L2 and 236 (25.0%) nTL-OVCF in lower lumbar (L3-L5) and middle thoracic (T5-T10) spine. The female-male ratio was 4.1 in nTL-OVCF and differed not significantly from TL-OVCF. The middle thoracic OVCF were older and had higher comorbidity of coronary heart disease (21.3%) and cerebral infarction (36.3%) than TL-OVCF (12.1% and 20.6%). In nTL-OVCF the ratio of apparent spine trauma (44.9%) and pre-hospital back pain ≤ 1 week (47.5%) was lower than in TL-OVCF (66.9% and 62.6%). The T-score value of lumbar spine was - 2.99 ± 1.11, - 3.24 ± 1.14, - 3.05 ± 1.40 in < 70, 70-80, > 80 years old TL-OVCF and differed not significantly from nTL-OVCF. The lower lumbar OVCF had more cranial type of vertebral marrow edema (21.8%) and fewer concurrent lumbodorsal fasciitis (30.8%) than TL-OVCF (16.8% and 43.4%). In TL-OVCF the anterior-posterior vertebral height ratio was lower with back pain for > 4 weeks than for ≤ 1, 1-2, and 2-4 weeks. In nTL-OVCF the degree of vertebral compression differed not significantly with pre-hospital back pain for ≤ 1, 1-2, 2-4, and > 4 weeks. CONCLUSIONS: Thoracolumbar spine has 2-folds higher risk of OVCF than non-thoracolumbar spine. Non-thoracolumbar OVCF are not associated with female gender, apparent spine trauma or poor bone mineral density, but tend to maintain the degree of vertebral compression and cause longer duration of pre-hospital back pain.

The inhibition of Aurora A kinase regulates phospholipid remodeling by upregulating LPCAT1 in glioblastoma.

Metabolic reprogramming is a common feature of glioblastoma (GBM) progression and metastasis. Altered lipid metabolism is one of the most prominent metabolic alterations in cancer. Understanding the links between phospholipid remodeling and GBM tumorigenesis may help develop new anticancer strategies and improve treatments to overcome drug resistance. We used metabolomic and transcriptomic analyses to systematically investigate metabolic and molecular changes in low-grade glioma (LGG) and GBM. We then re-established the reprogrammed metabolic flux and membrane lipid composition in GBM based on metabolomic and transcriptomic analyses. By inhibiting Aurora A kinase via RNA interference (RNAi) and inhibitor treatment, we investigated the effect of Aurora A kinase on phospholipid reprogramming LPCAT1 enzyme expression and GBM cell proliferation in vitro and in vivo. We found that GBM displayed aberrant glycerophospholipid and glycerolipid metabolism compared with LGG. Metabolic profiling indicated that fatty acid synthesis and uptake for phospholipid synthesis were significantly increased in GBM compared to LGG. The unsaturated phosphatidylcholine (PC) and phosphatidylethanolamine (PE) levels were significantly decreased in GBM compared to LGG. The expression level of LPCAT1, which is required for the synthesis of saturated PC and PE, was upregulated in GBM, and the expression of LPCAT4, which is required for the synthesis of unsaturated PC and PE, was downregulated in GBM. Notably, the inhibition of Aurora A kinase by shRNA knockdown and treatment with Aurora A kinase inhibitors such as Alisertib, AMG900, or AT9283 upregulated LPCAT1 mRNA and protein expression in vitro. In vivo, the inhibition of Aurora A kinase with Alisertib increased LPCAT1 protein expression. Phospholipid remodeling and a reduction in unsaturated membrane lipid components were found in GBM. Aurora A kinase inhibition increased LPCAT1 expression and suppressed GBM cell proliferation. The combination of Aurora kinase inhibition with LPCAT1 inhibition may exert promising synergistic effects on GBM.

Comparison of acute single versus multiple osteoporotic vertebral compression fractures in radiographic characteristic and bone fragility.

BACKGROUND: Osteoporotic vertebral compression fractures (OVCF) are common in aged population with bone fragility. This study aimed to identify the radiographic and bone fragility characteristic of acute single and multiple OVCF. METHODS: OVCF patients hospitalized in a spine center between June 2016 and October 2020 were retrospectively studied. Demographics, comorbidity, bone mineral density, spine trauma, duration of pre-hospital back pain, anatomical location and distribution pattern of OVCF, extent of vertebral marrow edema, and degree of vertebral compression of patients with multi-segment vertebral fractures (MSVF) were summarized and compared to those with single segment vertebral fractures (SSVF). RESULTS: A total of 1182 patients with 1530 acute fractured vertebrae were included. There were 944 SSVF (79.9%) and 238 MSVF (20.1%) simultaneously involving two (MSVF-2) or three and more vertebra (MSVF-3/m). The Female-Male ratio was 4.4 and differed not significantly between SSVF and MSVF. Females in SSVF were younger than males while MSVF-2 tended to occur in older females. L1, T12, and L2 were the three most frequently fractured vertebra and MSVF involved more vertebra in thoracic and lumbar spine. 31.1% in MSVF-2 and 83.1% in MSVF-3/m had at least two vertebral fractures in adjacent. The fractured thoracolumbar vertebra in MSVF was less compressed than that in SSVF. Apparent spine trauma was reported by 61.4% of SSVF, 44.1% of MSVF-2, and 36.3% of MSVF-3/m, while early hospitalization with pre-hospital back pain ≤ 1 week was 58.9% in SSVF, 45.3% in MSVF-2, and 25.9% in MSVF-3/m. Only females aged 70-80 years old in MSVF-3/m showed lower baseline bone mineral density than in MSVF-2 and SSVF. MSVF were not associated with increased comorbidity of hypertension, diabetes, coronary heart disease, cerebral infarction, and chronic pulmonary disease. CONCLUSIONS: 20% of acute OVCF can involve multiple vertebra without significant spine trauma or lower baseline bone mineral density. Multiple OVCF tend to occur in adjacent vertebra with less thoracolumbar vertebral compression but longer duration of pre-hospital back pain.

Speech Recognition of Accented Mandarin Based on Improved Conformer.

The convolution module in Conformer is capable of providing translationally invariant convolution in time and space. This is often used in Mandarin recognition tasks to address the diversity of speech signals by treating the time-frequency maps of speech signals as images. However, convolutional networks are more effective in local feature modeling, while dialect recognition tasks require the extraction of a long sequence of contextual information features; therefore, the SE-Conformer-TCN is proposed in this paper. By embedding the squeeze-excitation block into the Conformer, the interdependence between the features of channels can be explicitly modeled to enhance the model's ability to select interrelated channels, thus increasing the weight of effective speech spectrogram features and decreasing the weight of ineffective or less effective feature maps. The multi-head self-attention and temporal convolutional network is built in parallel, in which the dilated causal convolutions module can cover the input time series by increasing the expansion factor and convolutional kernel to capture the location information implied between the sequences and enhance the model's access to location information. Experiments on four public datasets demonstrate that the proposed model has a higher performance for the recognition of Mandarin with an accent, and the sentence error rate is reduced by 2.1% compared to the Conformer, with only 4.9% character error rate.

A Pair of Interconverting Cages Formed from Achiral Precursors Spontaneously Resolve into Homochiral Conformers.

Without chiral induction the emergence of homochirality from achiral molecules is rather serendipitous, as the rationale is somewhat ambiguous. We herein provide a plausible solution. From achiral precursors are formed a pair of interconverting cage conformers that exhibit a C3 -axis as the only symmetry element. When their interconversion is impeded with intramolecular H-bonding, each conformer self-sorts into a homochiral crystal, which is driven by a helical network of multivalent intermolecular interactions during the self-assembly of homochiral cage conformers. As no chiral induction is involved throughout, we believe our study could enlighten the rational design for the emergence of homochirality with several criteria: 1) formation of a molecule without inversion center or mirror plane; 2) suppression of the enantiomeric interconversion, and introduction of multivalent interactions along the helical trajectory of screw symmetry within the resulting superstructure.

Wide-Temperature Tunable Phonon Thermal Switch Based on Ferroelectric Domain Walls of Tetragonal KTN Single Crystal.

Ferroelectric domain walls (DWs) of perovskite oxide materials, which can be written and erased by an external electric field, offer the possibility to dynamically manipulate phonon scattering and thermal flux behavior. Different from previous ferroelectric materials, such as BaTiO3, PbTiO3, etc., with an immutable and low Curie temperature. The Curie temperature of perovskite oxide KTa1-xNbxO3 (KTN) crystal can be tuned by altering the Ta/Nb ratio. In this work, the ferroelectric KTa0.6Nb0.4O3 (KTN) single crystal is obtained by the Czochralski method. To understand the role of ferroelectric domains in thermal transport behavior, we perform a nonequilibrium molecular dynamics (NEMD) calculation on monodomain and 90° DWs of KTN at room temperature. The calculated thermal conductivity of monodomain KTN is 9.84 W/(m·k), consistent with experimental results of 8.96 W/(m·k), and distinctly decreased with the number of DWs indicating the outstanding performance of the thermal switch. We further evaluate the thermal boundary resistance (TBR) of KTN DWs. An interfacial thermal resistance value of 2.29 × 10-9 K·m2/W and a large thermal switch ratio of 4.76 was obtained for a single DW of KTN. Our study shows that the ferroelectric KTN can provide great potential for the application of thermal switch at room temperature and over a broad temperature range.

Anti-cancer effect of targeting fibroblast activation protein alpha in glioblastoma through remodeling macrophage phenotype and suppressing tumor progression.

INTRODUCTION: Glioblastoma (GBM) is the most malignant form of glioma and has a poor median survival time. Fibroblast activation protein alpha (FAP) is a dual-specificity serine protease that is strongly associated with the development and progression of human carcinomas. However, relatively little is known about the function of FAP and its potential as a therapeutic target in GBMs. AIMS: In this study, we aimed to explore the role of FAP in GBM through a series of experiments and to evaluate the therapeutic effect of PT100, a small molecule inhibitor of FAP, on GBM. RESULTS: Increased FAP expression was associated with poor survival in glioma. In vitro, FAP knockdown inhibited the process of EMT and caused a decrease in the number of M2 macrophages. In vivo, PT100 was confirmed to suppress the progression of GBMs significantly. CONCLUSIONS: FAP could serve as a biomarker and novel therapeutic target for the treatment of GBM and that PT100 is a promising drug for the treatment of GBM.

Circularly Polarized Laser Emission from Homochiral Superstructures based on Achiral Molecules with Conformal Flexibility.

Without external chiral intervention, it is a challenge to form homochirality from achiral molecules with conformational flexibility. We here report on a rational strategy that uses multivalent noncovalent interactions to clamp the molecular conformations of achiral D-A molecules. These interactions overcome the otherwise dominant dipole-dipole interactions and thus disfavor their symmetric antiparallel stacking. It in turn facilitates parallel packing, leading to spontaneous symmetry breaking during crystallization and thus the formation of homochiral conglomerates. When this emergent homochirality is coupled with optical gain characteristics of the molecules, the homochiral crystals are explored as excellent circularly polarized micro-lasers with low lasing threshold (16.4 µJ cm-2 ) and high dissymmetry factor glum (0.9). This study therefore provides a facile design strategy for supramolecular chiral materials and active laser ones without the necessity of intrinsic chiral element.

Does Simultaneous Fusion of Preexisting Spinal Canal Stenosis Adjacent to Lumbar Degenerative Spondylolisthesis Achieve a Better Clinical Outcome? A Retrospective Study with More than 5-year Follow-Up.

BACKGROUND: In this study, we investigate the effect of simultaneous fusion of preexisting adjacent spinal canal stenosis on the outcome of patients with lumbar spondylolisthesis. METHODS: Patients with lumbar spondylolisthesis who underwent transforaminal lumbar interbody fusion (TLIF) from August 2013 to March 2016 were included. The inclusion criteria were the following: single-level spondylolisthesis (L4 or L5) and mild to moderate spinal stenosis at cranial adjacent segment of the spondylolisthesis segment before operation. According to whether the adjacent stenotic segment was included in the scope of surgery, the patients were divided into two groups: group A, only the spondylolisthesis was treated with single-level TLIF, and the adjacent stenosis was not treated with any surgery; In group B, TLIF were performed in the spondylolisthesis segment and the adjacent stenotic level; no spinal stenosis was found in other levels. The patients were followed up for more than 5 years. The general information before operation, visual analog scale (VAS) scores of low back pain and leg pain, and Oswestry disability index (ODI) scores before operation and at the last follow-up were recorded. RESULTS: A total of 23 patients were included in group A, and 24 patients were included in group B. There was no significant difference between the two groups in gender distribution, age, course of disease, level of slippage, length of stay, degree of spondylolisthesis, stenotic grade of adjacent segment, and intervertebral disk degeneration grade (p> 0.05). The blood loss during surgery in group B was significantly higher than that in group A (p< 0.05). The operation time of group B was longer than that of group A, but the difference was not statistically significant (p = 0.245). There was no significant difference in preoperative VAS and ODI scores between the two groups. At the last follow-up, the VAS scores of low back pain in the two groups were almost the same. However, the VAS scores of leg pain and ODI scores in group B were slightly higher than those in group A at the last follow-up, but the difference was not statistically significant (p> 0.05). If relatives and friends have the similar disease, all the patients of group A and 87.5% of patients in group B would recommend that type of surgery. The satisfaction of group A (100%) was higher than that of group B (79.17%), but the difference was not statistically significant (p = 0.068). CONCLUSIONS: For single-level lumbar spondylolisthesis with mild to moderate spinal stenosis in adjacent segment before operation, decompression and fusion on the level of spondylolisthesis only is a safe, less invasive, and economical surgical option, with good long-term clinical efficacy and high satisfaction rates.

Inhibiting PP2A Upregulates B7-H3 Expression and Potentially Increases the Sensitivity of Malignant Meningiomas to Immunotherapy by Proteomics.

Malignant meningiomas have a high mortality rate and short survival time and currently have no effective treatment. In our study, proteomics analysis was performed to identify highly expressed proteins as therapeutic targets in malignant meningiomas. Cell Counting Kit-8 (CCK-8) assays were performed to verify the effect of LB-100 on the growth of malignant meningiomas. In addition, immunoblotting was used to verify the expression of B7-H3 and phosphorylation of STAT1 (Tyr701) in tissues and cells. Our results show that STAT1 and CD276 (B7-H3) regulated by PP2A were enriched in GO_IMMUNE_EFFECTOR_PROCESS and GO_REGULATION_OF_IMMUNE_SYSTEM_PROCESS. The immunotherapy target protein B7-H3 was confirmed to be upregulated in malignant meningiomas compared with meningothelial (p = 0.0001) and fibroblastic (p = 0.0046) meningiomas. In vitro, the PP2A inhibitor LB-100 suppressed the growth and invasion of malignant meningioma cells. Notably, the PP2A inhibitor LB-100 increased the phosphorylation of STAT1, thereby increasing the expression of the immune checkpoint protein B7-H3 in malignant meningioma cells in vitro. In conclusion, B7-H3 was found to be upregulated in malignant meningiomas. The PP2A inhibitor LB-100 increased the phosphorylation of STAT1 and B7-H3 expression, which could increase the sensitivity of malignant meningiomas to B7-H3 targeted immunotherapy.

Modeling Studies of Gravity Wave Dynamics in Highly Structured Environments: Reflection, Trapping, Instability, Momentum Transport, Secondary Gravity Waves, and Induced Flow Responses.

A compressible numerical model is applied for three-dimensional (3-D) gravity wave (GW) packets undergoing momentum deposition, self-acceleration (SA), breaking, and secondary GW (SGW) generation in the presence of highly-structured environments enabling thermal and/or Doppler ducts, such as a mesospheric inversion layer (MIL), tidal wind (TW), or combination of MIL and TW. Simulations reveal that ducts can strongly modulate GW dynamics. Responses modeled here include reflection, trapping, suppressed transmission, strong local instabilities, reduced SGW generations, higher altitude SGW responses, and induced large-scale flows. Instabilities that arise in ducts experience strong dissipation after they emerge, while trapped smaller-amplitude and smaller-scale GWs can survive in ducts to much later times. Additionally, GW breaking and its associated dynamics enhance the local wind along the GW propagation direction in the ducts, and yield layering in the wind field. However, these dynamics do not yield significant heat transport in the ducts. The failure of GW breaking to induce stratified layers in the temperature field suggests that such heat transport might not be as strong as previously assumed or inferred from observations and theoretical assessments. The present numerical simulations confirm previous finding that MIL generation may not be caused by the breaking of a transient high-frequency GW packet alone.

Heterochiral Diastereomer-Discriminative Diphanes That Form Hierarchical Superstructures with Nonlinear Optical Properties.

In order to study the emergence of homochirality during complex molecular systems, most works mainly concentrated on the resolution of a pair of enantiomers. However, the preference of homochiral over heterochiral isomers has been overlooked, with very limited examples focusing only on noncovalent interactions. We herein report on diastereomeric discrimination of twin-cavity cages (denoted as diphanes) against heterochiral tris-(2-aminopropyl)amine (TRPN) bearing triple stereocenters. This diastereomeric selectivity results from distinct spatial orientation of reactive secondary amines on TRPN. Homochiral TRPNs with all reactive moieties rotating in the same way facilitate the formation of homochiral and achiral meso diphanes with low strain energy, while heterochiral TRPNs with uneven orientation of secondary amines preclude the formation of cage-like entity, since the virtual diphanes exhibit considerably high strain. Moreover, homochiral diphanes self-assemble into an acentric superstructure composed of single-handed helices, which exhibits interesting nonlinear optical behavior. Such a property is a unique occurrence for organic cages, which thus showcases their potential to spawn novel materials with interesting properties and functions.

Visible light-controlled living cationic polymerization of methoxystyrene.

Photo-controlled living polymerization has received great attention in recent years. However, despite the great success therein, the report on photo-controlled living cationic polymerization has been greatly limited. We demonstrate here a novel decolorable, metal-free and visible light-controlled living cationic polymerization system by using tris(2,4-dimethoxyphenyl)methylium tetrafluoroborate as the photocatalyst and phosphate as the chain transfer agent (CTA) for polymerization of 4-methoxystyrene. This polymerization reaction under green LED light irradiation shows clear living characteristics including predictable molar mass, low molar-mass dispersity (D = 1.25), and sequential polymerization capability. In addition, the photocatalytic system exits excellent "on-off" photo switchability and shows the longest "off period" of 36 h up to now for photo-controlled cationic polymerization. Furthermore, the residual photo-catalyst is easily deactivated and decolored with addition of a base after the polymerization. The present study has extended the photo-controlled living cationic polymerization systems with new organic photocatalysts, phosphate CTA and polymerizable monomer as well as the new properties of excellent photostability and in-situ decolored capacity.

Supramolecular Proton Conductors Self-Assembled by Organic Cages.

Proton conduction is vital for living systems to execute various physiological activities. The understanding of its mechanism is also essential for the development of state-of-the-art applications, including fuel-cell technology. We herein present a bottom-up strategy, that is, the self-assembly of Cage-1 and -2 with an identical chemical composition but distinct structural features to provide two different supramolecular conductors that are ideal for the mechanistic study. Cage-1 with a larger cavity size and more H-bonding anchors self-assembled into a crystalline phase with more proton hopping pathways formed by H-bonding networks, where the proton conduction proceeded via the Grotthuss mechanism. Small cavity-sized Cage-2 with less H-bonding anchors formed the crystalline phase with loose channels filled with discrete H-bonding clusters, therefore allowing for the translational diffusion of protons, that is, vehicle mechanism. As a result, the former exhibited a proton conductivity of 1.59 × 10-4 S/cm at 303 K under a relative humidity of 48%, approximately 200-fold higher compared to that of the latter. Ab initio molecular dynamics simulations revealed distinct H-bonding dynamics in Cage-1 and -2, which provided further insights into potential proton diffusion mechanisms. This work therefore provides valuable guidelines for the rational design and search of novel proton-conducting materials.

A Nicotinamide Phosphoribosyltransferase Inhibitor, FK866, Suppresses the Growth of Anaplastic Meningiomas and Inhibits Immune Checkpoint Expression by Regulating STAT1.

Anaplastic meningioma is classified as a World Health Organization (WHO) grade III tumor and shows a strong tendency to recur. Although the incidence of anaplastic meningioma is low, the high rate of recurrence and death still makes treatment a challenge. A proteomics analysis was performed to investigate the differentially expressed proteins between anaplastic meningiomas and fibrous meningiomas by micro-LC-MS/MS. The key metabolic enzyme nicotinamide phosphoribosyltransferase (NAMPT) showed upregulated expression in anaplastic meningiomas. However, targeting NAMPT to treat anaplastic meningiomas has not been reported. In vitro, NAMPT inhibitor -FK866 reduced the viability of anaplastic meningiomas by inducing cell cycle arrest at the G2/M phase. Intriguingly, the NAMPT inhibitor -FK866 decreased the protein expression of immune checkpoints PD-L1 and B7-H3 by down-regulating the STAT1 and p-STAT1 expression in vitro. Furthermore, FK866 suppressed the growth of anaplastic meningiomas in an in vivo xenograft model. The expression of Ki-67 and immune checkpoint proteins (PD-L1 and B7-H3) showed significant differences between the group treated with FK866 and the control group treated with DMSO. In conclusion, the expression of NAMPT, which plays a crucial role in energy metabolism, was upregulated in anaplastic meningiomas. The NAMPT inhibitor -FK866 significantly suppressed the growth of anaplastic meningiomas in vitro and in vivo. More strikingly, FK866 potently inhibited immune checkpoint protein (PD-L1 and B7-H3) expression by regulating STAT1 in vitro and in vivo. Our results demonstrated that NAMPT inhibitors could potentially be an effective treatment method for patients suffering from anaplastic meningiomas.