Spinal cord and brain atrophy patterns in neuromyelitis optica spectrum disorder and multiple sclerosis.

BACKGROUND: Spinal cord and brain atrophy are common in neuromyelitis optica spectrum disorder (NMOSD) and relapsing-remitting multiple sclerosis (RRMS) but harbor distinct patterns accounting for disability and cognitive impairment. METHODS: This study included 209 NMOSD and 304 RRMS patients and 436 healthy controls. Non-negative matrix factorization was used to parse differences in spinal cord and brain atrophy at subject level into distinct patterns based on structural MRI. The weights of patterns were obtained using a linear regression model and associated with Expanded Disability Status Scale (EDSS) and cognitive scores. Additionally, patients were divided into cognitive impairment (CI) and cognitive preservation (CP) groups. RESULTS: Three patterns were observed in NMOSD: (1) Spinal Cord-Deep Grey Matter (SC-DGM) pattern was associated with high EDSS scores and decline of visuospatial memory function; (2) Frontal-Temporal pattern was associated with decline of language learning function; and (3) Cerebellum-Brainstem pattern had no observed association. Patients with CI had higher weights of SC-DGM pattern than CP group. Three patterns were observed in RRMS: (1) DGM pattern was associated with high EDSS scores, decreased information processing speed, and decreased language learning and visuospatial memory functions; (2) Frontal-Temporal pattern was associated with overall cognitive decline; and (3) Occipital pattern had no observed association. Patients with CI trended to have higher weights of DGM and Frontal-Temporal patterns than CP group. CONCLUSION: This study estimated the heterogeneity of spinal cord and brain atrophy patterns in NMOSD and RRMS patients at individual level, and evaluated the clinical relevance of these patterns, which may contribute to stratifying participants for targeted therapy.

The association between glymphatic system dysfunction and alterations in cerebral function and structure in patients with white matter hyperintensities.

The objective of this study is to explore the relationship between the glymphatic system and alterations in the structure and function of the brain in white matter hyperintensity (WMH) patients. MRI data were collected from 27 WMH patients and 23 healthy controls. We calculated the along perivascular space (ALPS) indices, the anterior corner distance of the lateral ventricle, and the width of the third ventricle for each subject. The DPABISurf tool was used to calculate the cortical thickness and cortical area. In addition, data processing assistant for resting-state fMRI was used to calculate regional homogeneity, degree centrality, amplitude low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF), and voxel-mirrored homotopic connectivity (VMHC). In addition, each WMH patient was evaluated on the Fazekas scale. Finally, the correlation analysis of structural indicators and functional indicators with bilateral ALPS indices was investigated using Spearman correlation analysis. The ALPS indices of WMH patients were lower than those of healthy controls (left: t = -4.949, P < 0.001; right: t = -3.840, P < 0.001). This study found that ALFF, fALFF, regional homogeneity, degree centrality, and VMHC values in some brain regions of WMH patients were alternated (AlphaSim corrected, P < 0.005, cluster size > 26 voxel, rmm value = 5), and the cortical thickness and cortical area of WMH patients showed trend changes (P < 0.01, cluster size > 20 mm2, uncorrected). Interestingly, we found significantly positive correlations between the left ALPS indices and degree centrality values in the superior temporal gyrus (r = 0.494, P = 0.009, P × 5 < 0.05, Bonferroni correction). Our results suggest that glymphatic system impairment is related to the functional centrality of local connections in patients with WMH. This provides a new perspective for understanding the pathological mechanisms of cognitive impairment in the WMH population.

Temporal and topological properties of dynamic networks reflect disability in patients with neuromyelitis optica spectrum disorders.

Approximately 36% of patients with neuromyelitis optica spectrum disorders (NMOSD) suffer from severe visual and motor disability (blindness or light perception or unable to walk) with abnormalities of whole-brain functional networks. However, it remains unclear how whole-brain functional networks and their dynamic properties are related to clinical disability in patients with NMOSD. Our study recruited 30 NMOSD patients (37.70 ± 11.99 years) and 45 healthy controls (HC, 41.84 ± 11.23 years). The independent component analysis, sliding-window approach and graph theory analysis were used to explore the static strength, time-varying and topological properties of large-scale functional networks and their associations with disability in NMOSD. Compared to HC, NMOSD patients showed significant alterations in dynamic networks rather than static networks. Specifically, NMOSD patients showed increased occurrence (fractional occupancy; P < 0.001) and more dwell times of the low-connectivity state (P < 0.001) with fewer transitions (P = 0.028) between states than HC, and higher fractional occupancy, increased dwell times of the low-connectivity state and lower transitions were related to more severe disability. Moreover, NMOSD patients exhibited altered small-worldness, decreased degree centrality and reduced clustering coefficients of hub nodes in dynamic networks, related to clinical disability. NMOSD patients exhibited higher occurrence and more dwell time in low-connectivity states, along with fewer transitions between states and decreased topological organizations, revealing the disrupted communication and coordination among brain networks over time. Our findings could provide new perspective to help us better understand the neuropathological mechanism of the clinical disability in NMOSD.

Male and female are not the same: a multicenter study of static and dynamic functional connectivity in relapse-remitting multiple sclerosis in China.

Background: Sex-related effects have been observed in relapsing-remitting multiple sclerosis (RRMS), but their impact on functional networks remains unclear. Objective: To investigate the sex-related differences in connectivity strength and time variability within large-scale networks in RRMS. Methods: This is a multi-center retrospective study. A total of 208 RRMS patients (135 females; 37.55 ± 11.47 years old) and 228 healthy controls (123 females; 36.94 ± 12.17 years old) were included. All participants underwent clinical and MRI assessments. Independent component analysis was used to extract resting-state networks (RSNs). We assessed the connectivity strength using spatial maps (SMs) and static functional network connectivity (sFNC), evaluated temporal properties and dynamic functional network connectivity (dFNC) patterns of RSNs using dFNC, and investigated their associations with structural damage or clinical variables. Results: For static connectivity, only male RRMS patients displayed decreased SMs in the attention network and reduced sFNC between the sensorimotor network and visual or frontoparietal networks compared with healthy controls [P<0.05, false discovery rate (FDR) corrected]. For dynamic connectivity, three recurring states were identified for all participants: State 1 (sparse connected state; 42%), State 2 (middle-high connected state; 36%), and State 3 (high connected state; 16%). dFNC analyses suggested that altered temporal properties and dFNC patterns only occurred in females: female patients showed a higher fractional time (P<0.001) and more dwell time in State 1 (P<0.001) with higher transitions (P=0.004) compared with healthy females. Receiver operating characteristic curves revealed that the fraction time and mean dwell time of State 1 could significantly distinguish female patients from controls (area under the curve: 0.838-0.896). In addition, female patients with RRMS also mainly showed decreased dFNC in all states, particularly within cognitive networks such as the default mode, frontoparietal, and visual networks compared with healthy females (P < 0.05, FDR corrected). Conclusion: Our results observed alterations in connectivity strength only in male patients and time variability in female patients, suggesting that sex-related effects may play an important role in the functional impairment and reorganization of RRMS.

Altered neural intrinsic oscillations in patients with multiple sclerosis: effects of cortical thickness.

Objective: To investigate the effects of cortical thickness on the identification accuracy of fractional amplitude of low-frequency fluctuation (fALFF) in patients with multiple sclerosis (MS). Methods: Resting-state functional magnetic resonance imaging data were collected from 31 remitting MS, 20 acute MS, and 42 healthy controls (HCs). After preprocessing, we first calculated two-dimensional fALFF (2d-fALFF) maps using the DPABISurf toolkit, and 2d-fALFF per unit thickness was obtained by dividing 2d-fALFF by cortical thickness. Then, between-group comparison, clinical correlation, and classification analyses were performed in 2d-fALFF and 2d-fALFF per unit thickness maps. Finally, we also examined whether the effect of cortical thickness on 2d-fALFF maps was affected by the subfrequency band. Results: In contrast with 2d-fALFF, more changed regions in 2d-fALFF per unit thickness maps were detected in MS patients, such as increased region of the right inferior frontal cortex and faded regions of the right paracentral lobule, middle cingulate cortex, and right medial temporal cortex. There was a significant positive correlation between the disease duration and the 2d-fALFF values in the left early visual cortex in remitting MS patients (r = 0.517, Bonferroni-corrected, p = 0.008 × 4 < 0.05). In contrast with 2d-fALFF, we detected a positive correlation between the 2d-fALFF per unit thickness of the right ventral stream visual cortex and the modified Fatigue Impact Scale (MFIS) scores (r = 0.555, Bonferroni-corrected, p = 0.017 × 4 > 0.05). For detecting MS patients, 2d-fALFF and 2d- fALFF per unit thickness both performed remarkably well in support vector machine (SVM) analysis, especially in the remitting phase (AUC = 86, 83%). Compared with 2d-fALFF, the SVM model of 2d-fALFF per unit thickness had significantly higher classification performance in distinguishing between remitting and acute MS. More changed regions and more clinically relevant 2d-fALFF per unit thickness maps in the subfrequency band were also detected in MS patients. Conclusion: By dividing the functional value by the cortical thickness, the identification accuracy of fALFF in MS patients was detected to be potentially influenced by cortical thickness. Additionally, 2d-fALFF per unit thickness is a potential diagnostic marker that can be utilized to distinguish between acute and remitting MS patients. Notably, we observed similar variations in the subfrequency band.

Unusual 3,4-Oxidative Coupling Polymerization on 1,2,5-Trisubstituted Pyrroles for Novel Porous Organic Polymers.

Porous organic polymers (POPs) have demonstrated promising task-specific applications due to their structure designability and thus functionality. Herein, an unusual 3,4-polymerization on 1,2,5-trisubstituted pyrroles has been developed to give linear polypyrrole-3,4 in high efficiency, with Mn of 20000 and PDI of 1.7. This novel polymerization technique was applied to prepare a series of polypyrrole-based POPs (PY-POP-1-4), which exhibited high BET surface areas (up to 762 m2 g-1) with a meso-micro-supermicro hierarchically porous structure. Furthermore, PY-POPs were doped in the mixed matrix membranes based on the polysulfone matrix to enhance the gas permeability and gas pair selectivity, with H2/N2 selectivity up to 84.6 and CO2/CH4 and CO2/N2 selectivity up to 46.8 and 39.6.

Clinical and cognitive correlates tractography analysis in patients with white matter hyperintensity of vascular origin.

Purpose: White matter hyperintensity lesions (WMHL) in the brain are a consequence of cerebral small vessel disease and microstructural damage. Patients with WMHL have diverse clinical features, and hypertension, advanced age, obesity, and cognitive decline are often observed. However, whether these clinical features are linked to interrupted structural connectivity in the brain requires further investigation. This study therefore explores the white matter pathways associated with WMHL, with the objective of identifying neural correlates for clinical features in patients with WMHL. Methods: Diffusion magnetic resonance imaging (MRI) and several clinical features (MoCA scores, hypertension scores, body mass index (BMI), duration of hypertension, total white matter lesion loads, and education.) highly related to WMHL were obtained in 16 patients with WMHL and 20 health controls. We used diffusion MRI connectometry to explore the relationship between clinical features and specific white matter tracts using DSI software. Results: The results showed that the anterior splenium of the corpus callosum, the inferior longitudinal fasciculus, the anterior corpus callosum and the middle cerebellar peduncle were significantly correlated with hypertension scores (false discovery rate (FDR) = 0.044). The anterior splenium of the corpus callosum, the left thalamoparietal tract, the inferior longitudinal fasciculus, and the left cerebellar were significantly correlated with MoCA scores (FDR = 0.016). The anterior splenium of corpus callosum, inferior fronto-occipital fasciculus, cingulum fasciculus, and fornix/fimbria were significantly correlated with body mass index (FDR = 0.001). Conclusion: Our findings show that hypertension score, MoCA score, and BMI are important clinical features in patients with WMHL, hypertension degree and higher BMI are associated with whiter matter local disconnection in patients with WMHL, and may contribute to understanding the cognitive impairments observed in patients with WMHL.

Recent Progress in Azobenzene-Based Supramolecular Materials and Applications.

Azobenzene-containing small molecules and polymers are functional photoswitchable molecules to form supramolecular nanomaterials for various applications. Recently, supramolecular nanomaterials have received enormous attention in material science because of their simple bottom-up synthesis approach, understandable mechanisms and structural features, and batch-to-batch reproducibility. Azobenzene is a light-responsive functional moiety in the molecular design of small molecules and polymers and is used to switch the photophysical properties of supramolecular nanomaterials. Herein, we review the latest literature on supramolecular nano- and micro-materials formed from azobenzene-containing small molecules and polymers through the combinatorial effect of weak molecular interactions. Different classes including complex coacervates, host-guest systems, co-assembled, and self-assembled supramolecular materials, where azobenzene is an essential moiety in small molecules, and photophysical properties are discussed. Afterward, azobenzene-containing polymers-based supramolecular photoresponsive materials formed through the host-guest approach, polymerization-induced self-assembly, and post-polymerization assembly techniques are highlighted. In addition to this, the applications of photoswitchable supramolecular materials in pH sensing, and CO2 capture are presented. In the end, the conclusion and future perspective of azobenzene-based supramolecular materials for molecular assembly design, and applications are given.

Cerebellar connectome alterations and associated genetic signatures in multiple sclerosis and neuromyelitis optica spectrum disorder.

BACKGROUND: The cerebellum plays key roles in the pathology of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), but the way in which these conditions affect how the cerebellum communicates with the rest of the brain (its connectome) and associated genetic correlates remains largely unknown. METHODS: Combining multimodal MRI data from 208 MS patients, 200 NMOSD patients and 228 healthy controls and brain-wide transcriptional data, this study characterized convergent and divergent alterations in within-cerebellar and cerebello-cerebral morphological and functional connectivity in MS and NMOSD, and further explored the association between the connectivity alterations and gene expression profiles. RESULTS: Despite numerous common alterations in the two conditions, diagnosis-specific increases in cerebellar morphological connectivity were found in MS within the cerebellar secondary motor module, and in NMOSD between cerebellar primary motor module and cerebral motor- and sensory-related areas. Both diseases also exhibited decreased functional connectivity between cerebellar motor modules and cerebral association cortices with MS-specific decreases within cerebellar secondary motor module and NMOSD-specific decreases between cerebellar motor modules and cerebral limbic and default-mode regions. Transcriptional data explained > 37.5% variance of the cerebellar functional alterations in MS with the most correlated genes enriched in signaling and ion transport-related processes and preferentially located in excitatory and inhibitory neurons. For NMOSD, similar results were found but with the most correlated genes also preferentially located in astrocytes and microglia. Finally, we showed that cerebellar connectivity can help distinguish the three groups from each other with morphological connectivity as predominant features for differentiating the patients from controls while functional connectivity for discriminating the two diseases. CONCLUSIONS: We demonstrate convergent and divergent cerebellar connectome alterations and associated transcriptomic signatures between MS and NMOSD, providing insight into shared and unique neurobiological mechanisms underlying these two diseases.

Brain age gap in neuromyelitis optica spectrum disorders and multiple sclerosis.

OBJECTIVE: To evaluate the clinical significance of deep learning-derived brain age prediction in neuromyelitis optica spectrum disorder (NMOSD) relative to relapsing-remitting multiple sclerosis (RRMS). METHODS: This cohort study used data retrospectively collected from 6 tertiary neurological centres in China between 2009 and 2018. In total, 199 patients with NMOSD and 200 patients with RRMS were studied alongside 269 healthy controls. Clinical follow-up was available in 85 patients with NMOSD and 124 patients with RRMS (mean duration NMOSD=5.8±1.9 (1.9-9.9) years, RRMS=5.2±1.7 (1.5-9.2) years). Deep learning was used to learn 'brain age' from MRI scans in the healthy controls and estimate the brain age gap (BAG) in patients. RESULTS: A significantly higher BAG was found in the NMOSD (5.4±8.2 years) and RRMS (13.0±14.7 years) groups compared with healthy controls. A higher baseline disability score and advanced brain volume loss were associated with increased BAG in both patient groups. A longer disease duration was associated with increased BAG in RRMS. BAG significantly predicted Expanded Disability Status Scale worsening in patients with NMOSD and RRMS. CONCLUSIONS: There is a clear BAG in NMOSD, although smaller than in RRMS. The BAG is a clinically relevant MRI marker in NMOSD and RRMS.

PKC signal amplification suppresses non-small cell lung cancer growth by promoting p21 expression and phosphorylation.

Protein kinase C (PKC) activation was previously associated with oncogenic features. However, small molecule inhibitors targeting PKC have so far proved ineffective in a number of clinical trials for cancer treatment. Recent progresses have revealed that most PKC mutations detected in diverse cancers actually lead to loss-of-function, thus suggesting the tumor-suppressive roles of PKC proteins. Unfortunately, the development of chemicals to enhance PKC activity is lagging behind relative to its small molecular inhibitors. Here, we report that a bisindolylmaleimide derivative (3,4-bis(1-(prop-2-ynyl)-1H-indol-3-yl)-1 H-pyrrole-2,5-dione, BD-15) significantly inhibited cell growth in non-small cell lung cancer (NSCLC). Mechanistically, BD-15 treatment resulted in markedly enhanced phosphorylation of PKC substrates and led to cell cycle arrest in G2/M. Further, BD-15 treatment upregulated p21 protein levels and enhanced p21 phosphorylation. BD-15 also promoted caspase3 cleavage and triggered cellular apoptosis. In xenograft mouse models, BD-15 exerted anti-tumor effects to suppress in vivo tumor formation. Collectively, our findings revealed the tumor-suppressive roles of BD-15 through enhancing PKC signaling and thus leading to upregulation of p21 expression and phosphorylation.

Aberrant functional connectivity and temporal variability of the dynamic pain connectome in patients with low back related leg pain.

Neuroimaging studies have suggested a link between the intensity of chronic low back pain intensity and structural and functional brain alterations. However, chronic pain results from the coordination and dynamics among several brain networks that comprise the dynamic pain connectome. Here, we use resting-state functional magnetic resonance imaging and measures of static (sFC) and dynamic functional connectivity (dFC) variability in the typical (0.01-0.1 Hz) and five specific (slow-6 to slow-2) frequency bands to test hypotheses regarding disruption in this variability in low back-related leg pain (LBLP) patients who experience chronic pain and numbness. Twenty-four LBLP patients and 23 healthy controls completed clinical assessments, and partial correlational analyses between altered sFC and dFC variability and clinical measures were conducted. We found a lower within-network sFC in the ascending nociceptive pathway (Asc) and a lower cross-network sFC between nodes of the salience network and the Asc in the typical frequency band. In the slow-5 frequency band, a lower within-network sFC was found in the Asc. Abnormal cross-network sFC was found between nodes of the salience network-Asc (slow-5 and slow-6) and the default mode network-Asc (slow-4 and slow-6). Furthermore, cross-network abnormalities in the typical and certain specific frequency bands were linked to clinical assessments. These findings indicate that frequency-related within- and cross-network communication among the nodes in the dynamic pain connectome is dysfunctional in LBLP patients and that selecting specific frequencies may be potentially useful for detecting LBLP-related brain activity.

Structural and functional hippocampal alterations in Multiple sclerosis and neuromyelitis optica spectrum disorder.

BACKGROUND: Hippocampal involvement may differ between multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). OBJECTIVE: To investigate the morphometric, diffusion and functional alterations in hippocampus in MS and NMOSD and the clinical significance. METHODS: A total of 752 participants including 236 MS, 236 NMOSD and 280 healthy controls (HC) were included in this retrospective multi-center study. The hippocampus and subfield volumes, fractional anisotropy (FA) and mean diffusivity (MD), amplitude of low frequency fluctuation (ALFF) and degree centrality (DC) were analyzed, and their associations with clinical variables were investigated. RESULTS: The hippocampus showed significantly lower volume, FA and greater MD in MS compared to NMOSD and HC (p < 0.05), while no abnormal ALFF or DC was identified in any group. Hippocampal subfields were affected in both diseases, though subiculum, presubiculum and fimbria showed significantly lower volume only in MS (p < 0.05). Significant correlations between diffusion alterations, several subfield volumes and clinical variables were observed in both diseases, especially in MS (R = -0.444 to 0.498, p < 0.05). FA and MD showed fair discriminative power between MS and HC, NMOSD and HC (AUC > 0.7). CONCLUSIONS: Hippocampal atrophy and diffusion abnormalities were identified in MS and NMOSD, partly explaining how clinical disability and cognitive impairment are differentially affected.

14N NMR as a General Tool to Characterize the Nitrogen-Containing Species and Monitor the Nitration Process.

The usefulness of 14N NMR spectroscopy was highly underestimated compared with 15N NMR, which usually required tedious and expensive 15N-labeling manipulations. It is of great significance to make the 14N NMR spectroscopy convenient and useful considering 14N nuclei's high natural abundance of 99.6%. Herein, lots of efforts have been made to generalize routine 14N NMR to characterize nitrogen-containing species by tuning the balance between the solubility and viscosity of the samples. Satisfactory 14N NMR spectra of more than 60 nitrogen-containing compounds have been recorded, and the chemical shifts and the peaks' full width at half-maxima of more than 10 nitrogen-based functionalities have been summarized. Successful monitoring of the ortho-selective nitration of aniline has been demonstrated using the 14N NMR protocol developed in this paper, which will help realize the visualization of nitration processes in the industry.

Modified BuShenYiQi formula alleviates experimental allergic asthma in mice by negative regulation of type 2 innate lymphoid cells and CD4+ type 9 helper T cells and the VIP-VPAC2 signalling pathway.

CONTEXT: Modified BuShenYiQi formula (M-BYF) is derived from BuShenYiQi formula, used for the treatment of allergic asthma. The exact effect and mechanism of M-BYF on the improvement of asthma remain unclear. OBJECTIVE: We investigated the mechanism underlying the therapeutic effect of M-BYF on allergic asthma. MATERIALS AND METHODS: The asthma model was established in female BALB/c mice that were sensitized and challenged with ovalbumin (OVA). Mice in the treated groups were orally treated once a day with M-BYF (7, 14 and 28 g/kg/d) or dexamethasone before OVA challenge. Control and Model group received saline. Pathophysiological abnormalities and percentages of lung type 2 innate lymphoid cells (ILC2s) and Th9 cells were measured. Expression levels of type 2 cytokines and transcription factors required for these cells function and differentiation were analysed. Expression of vasoactive intestinal polypeptide (VIP)-VPAC2 signalling pathway-related proteins, and percentages of VIP expressing (VIP+) cells and VPAC2, CD90 co-expressing (VPAC2+CD90+) cells were detected. RESULTS: M-BYF alleviated airway hyperresponsiveness, inflammation, mucus hypersecretion and collagen deposition in asthmatic mice. M-BYF down-regulated percentages of ILC2s and Th9 cells with lower expression of GATA3, PU.1 and IRF4, reduced IL-5, IL-13, IL-9 and VIP production. The decrease in the expression of VIP-VPAC2 signalling pathway and percentages of VIP+ cells, VPAC2+CD90+ cells were observed after M-BYF treatment. The LD50 value of M-BYF was higher than 90 g/kg. DISCUSSION AND CONCLUSIONS: M-BYF alleviated experimental asthma by negatively regulating ILC2s and Th9 cells and the VIP-VPAC2 signalling pathway. These findings provide the theoretical basis for future research of M-BYF in asthma patient population.

15N Solid-State NMR as Bright Eyes to See the Isomerization of the Azo Bond: Revision of Tris(ß-hydroxyl-azo)-benzene to Tris(ß-keto-hydrazo)-cyclohexane in Porous Organic Polymers.

Porous organic polymers (POPs) have aroused great and wide attention from the materials community, while the identification of their precise structures is still very challenging. The well-defined structures are of great importance in understanding the relationship between the structure and function of the polymer materials, though they are sometimes ignored and do not receive enough attention. In this letter, an efficient 15N labeling technique and 15N solid-state NMR (15N-SSNMR) were combined to obtain strong evidence for the presence of the azo bond and keto-hydrazone structure in the solid state. Thus, the structure of tris(ß-hydroxyl-azo)-benzene in previously proposed hydroxylazobenzene polymers was revised to tris(ß-keto-hydrazo)-cyclohexane in TKH-POPs for the first time. In contrast, similar tautomerization did not occur in the azo coupling polymerization of 1,3,5-triaminobenzene and diazonium salts, i.e., tris(ß-amino-azo)-benzene remained in Azo-POPs. This work will open up a window to develop innovative porous organic polymers more efficiently with the aid of 15N-SSNMR.

Reversible Transformation between Azo and Azonium Bond Other than Photoisomerization of Azo Bond in Main-Chain Polyazobenzenes.

Although side-chain polyazobenzenes have been extensively studied, main-chain polyazobenzenes (abbreviated MCPABs) are rarely reported due to the challenges associated with difficulty in synthetic chemistry and photoisomerization of azo bonds in MCPABs. Thus, it is highly demanded to develop new mechanisms other than photoisomerization of azo bonds in MCPABs to extend their applications. In this work, we created a new series of N-linked MCPABs via fast NaBH4-mediated reductive coupling polymerization on N-substituted bis(4-nitrophenyl)amines. The structure of MCPABs has been characterized by comprehensive solid-state NMR experiments such as CPMAS 13C NMR with long and short contact times, cross-polarization polarization-inversion (CPPI), and cross-polarization nonquaternary suppressed (CPNQS). The azo bonds in MCPABs were found to be promising for acid vapor sensing, being acidified to form azonium ion with significant color change from red to green. And the azonium of MCPABs turned from green to red when exposed to base vapor, thus suitable for base vapor sensing.

Critical Roles of Balanced T Helper 9 Cells and Regulatory T Cells in Allergic Airway Inflammation and Tumor Immunity.

CD4+T helper (Th) cells are important mediators of immune responses in asthma and cancer. When counteracted by different classes of pathogens, naïve CD4+T cells undergo programmed differentiation into distinct types of Th cells. Th cells orchestrate antigen-specific immune responses upon their clonal T-cell receptor (TCR) interaction with the appropriate peptide antigen presented on MHC class II molecules expressed by antigen-presenting cells (APCs). T helper 9 (Th9) cells and regulatory T (Treg) cells and their corresponding cytokines have critical roles in tumor and allergic immunity. In the context of asthma and cancer, the dynamic internal microenvironment, along with chronic inflammatory stimuli, influences development, differentiation, and function of Th9 cells and Treg cells. Furthermore, the dysregulation of the balance between Th9 cells and Treg cells might trigger aberrant immune responses, resulting in development and exacerbation of asthma and cancer. In this review, the development, differentiation, and function of Th9 cells and Treg cells, which are synergistically regulated by various factors including cytokine signals, transcriptional factors (TFs), costimulatory signals, microenvironment cues, metabolic pathways, and different signal pathways, will be discussed. In addition, we focus on the recent progress that has helped to achieve a better understanding of the roles of Th9 cells and Treg cells in allergic airway inflammation and tumor immunity. We also discuss how various factors moderate their responses in asthma and cancer. Finally, we summarize the recent findings regarding potential mechanisms for regulating the balance between Th9 and Treg cells in asthma and cancer. These advances provide opportunities for novel therapeutic strategies that are aimed at reestablishing the balance of these cells in the diseases.

Subtyping relapsing-remitting multiple sclerosis using structural MRI.

BACKGROUND AND PURPOSE: Subtyping relapsing-remitting multiple sclerosis (RRMS) patients may help predict disease progression and triage patients for treatment. We aimed to subtype RRMS patients by structural MRI and investigate their clinical significances. METHODS: 155 relapse-remitting MS (RRMS) and 210 healthy controls (HC) were retrospectively enrolled with structural 3DT1, diffusion tensor imaging (DTI) and resting-state functional MRI. Z scores of cortical and deep gray matter volumes (CGMV and DGMV) and white matter fractional anisotropy (WM-FA) in RRMS patients were calculated based on means and standard deviations of HC. We defined RRMS as "normal" (- 2 < z scores of both GMV and WM-FA), DGM (z scores of DGMV < - 2), and DGM-plus types (z scores of DGMV and [CGMV or WM-FA] < - 2) according to combinations of z scores compared to HC. Expanded disability status scale (EDSS), cognitive and functional MRI measurements, and conversion rate to secondary progressive MS (SPMS) at 5-year follow-up were compared between subtypes. RESULTS: 77 (49.7%) patients were "normal" type, 37 (23.9%) patients were DGM type and 34 (21.9%) patients were DGM-plus type. 7 (4.5%) patients who were not categorized into the above types were excluded. DGM-plus type had the highest EDSS. Both DGM and DGM-plus types had more severe cognitive impairment than "normal" type. Only DGM-plus type showed decreased functional MRI measures compared to HC. A higher conversion ratio to SPMS in DGM-plus type (55%) was identified compared to "normal" type (14%, p < 0.001) and DGM type (20%, p = 0.005). CONCLUSION: Three MRI-subtypes of RRMS were identified with distinct clinical and imaging features and different prognosis.

[Application value of whole exome sequencing in critically ill neonates with inherited diseases].

OBJECTIVE: To study the application value of whole exome sequencing (WES) in critically ill neonates with inherited diseases. METHODS: A total of 66 critically ill neonates with suspected inherited diseases or unclear clinical diagnosis who were admitted to the neonatal intensive care unit were enrolled as subjects. The clinical data of the neonates were collected, and venous blood samples were collected from the neonates and their parents for WES. The clinical manifestations of the neonates were observed to search for related pathogenic gene mutations. RESULTS: Among the 66 critically ill neonates with suspected inherited diseases or unclear clinical diagnosis (34 boys and 32 girls), 14 (21%) were found to have gene mutations by WES. One neonate had no gene mutation detected by WES but was highly suspected of pigment incontinence based on clinical manifestations, and multiplex ligation-dependent probe amplification detected a heterozygous deletion mutation in exons 4-10 of the IKBKG gene. Among the 15 neonates with gene mutations, 10 (67%) had pathogenic gene mutation, 1 (7%) was suspected of pathogenic gene mutation, and 4 (27%) had gene mutations with unknown significance. Among the 15 neonates, 13 underwent chromosome examination, and only 1 neonate was found to have chromosome abnormality. CONCLUSIONS: Chromosome examination cannot be used as a diagnostic method for inherited diseases, and WES detection technology is an important tool to find inherited diseases in critically ill neonates with suspected inherited diseases or unclear clinical diagnosis; however WES technology has some limitation and it is thus necessary to combine with other sequencing methods to achieve an early diagnosis.