Efficacy of Biologics in Patients with Allergic Bronchopulmonary Aspergillosis: A Systematic Review and Meta-Analysis.

BACKGROUND: Treatment of allergic bronchopulmonary aspergillosis (ABPA) is challenging. Biological therapies have been reported as adjunctive treatments for ABPA, primarily in case series or case reports. This study aimed to analyze the efficacy of biologics for managing ABPA both qualitatively and quantitatively. METHODS: All articles on APBA published in October 2023 were searched in PubMed, Web of Science, ClinicalTrials.gov, and Embase databases. The effects of interest were the mean changes from baseline for outcomes, including exacerbation rates, oral corticosteroids usage (OCS), and total immunoglobulin E (IgE) levels. Reported outcomes were quantitatively synthesized by usual or individual patient data (IPD) meta-analyses. PROSPERO registration number: CRD42022373396. RESULTS: A total of 86 studies were included in the systematic review including 346 patients. Sixteen studies on omalizumab were pooled for the usual meta-analysis. Omalizumab therapy significantly reduced exacerbation rates (- 2.29 [95%CI - 3.32, - 1.26]), OCS dosage (- 10.91 mg [95%CI - 18.98, - 2.85]), and total IgE levels (- 273.07 IU/mL [95%CI - 379.30, - 166.84]), meanwhile improving FEV1% predicted (10.09% [95%CI 6.62, 13.55]). Thirty-one studies on dupilumab, mepolizumab, or benralizumab were pooled to perform an IPD meta-analysis, retrospectively. Both dupilumab and mepolizumab significantly reduced exacerbation rates, OCS, and total IgE levels. Benralizumab showed a similar trend, but it was not statistically significant. Tezepelumab showed weak evidence of its effects on ABPA. All five biologics led to milder clinical symptoms (e.g., cough, wheezing) with serious adverse effects that happened once in omalizumab treatment. CONCLUSION: These results indicate the clinical benefit of omalizumab, dupilumab, and mepolizumab in patients with ABPA. Further randomized, controlled studies with a larger sample size and longer follow-up are needed to confirm these findings.

TGF-ß1 promotes SCD1 expression via the PI3K-Akt-mTOR-SREBP1 signaling pathway in lung fibroblasts.

BACKGROUND: Lung fibroblast activation is associated with airway remodeling during asthma progression. Stearoyl-CoA desaturase 1 (SCD1) plays an important role in the response of fibroblasts to growth factors. This study aimed to explore the effects of SCD1 on fibroblast activation induced by transforming growth factor-ß1 (TGF-ß1) and the role of the phosphatidylinositol-3-kinase-AKT serine-threonine protein kinase-mechanistic target of rapamycin (PI3K-Akt-mTOR) pathway on the regulation of SCD1 expression in airway remodeling. METHODS: Female C57BL/6 mice were sensitized and challenged with house dust mites to generate a chronic asthma model. The inhibitor of SCD1 was injected i.g. before each challenge. The airway hyper-responsiveness to methacholine was evaluated, and airway remodeling and airway inflammation were assessed by histology. The effects of SCD1 on fibroblast activation were evaluated in vitro using an SCD1 inhibitor and oleic acid and via the knockdown of SCD1. The involvement of the PI3K-Akt-mTOR-sterol regulatory element-binding protein 1 (SREBP1) pathway in lung fibroblasts was investigated using relevant inhibitors. RESULTS: The expression of SCD1 was increased in fibroblasts exposed to TGF-ß1. The inhibition of SCD1 markedly ameliorated airway remodeling and lung fibroblast activation in peripheral airways. The knockdown or inhibition of SCD1 resulted in significantly reduced extracellular matrix production in TGF-ß1-treated fibroblasts, but this effect was reversed by the addition of exogenous oleic acid. The PI3K-Akt-mTOR-SREBP1 pathway was found to be involved in the regulation of SCD1 expression and lung fibroblast activation. CONCLUSIONS: The data obtained in this study indicate that SCD1 expression contributes to fibroblast activation and airway remodeling and that the inhibition of SCD1 may be a therapeutic strategy for airway remodeling in asthma.

CBX4 Regulates Long-Form Thymic Stromal Lymphopoietin-mediated Airway Inflammation through SUMOylation in House Dust Mite-induced Asthma.

Thymic stromal lymphopoietin presents in two distinct isoforms: short-form (sfTSLP) and long-form (lfTSLP). lfTSLP promotes inflammation, whereas sfTSLP inhibits inflammation, in allergic asthma. However, little is known about the regulation of lfTSLP and sfTSLP during allergic attack in the asthma airway epithelium. Here, we report that small ubiquitin-like modifier (SUMOylation) was enhanced in house dust mite-induced allergic asthma airway epithelium. Inhibition of SUMOylation significantly alleviated airway T-helper cell type 2 inflammation and lfTSLP expression. Mechanistically, chromobox 4 (CBX4), a SUMOylation E3 ligase, enhanced lfTSLP mRNA translation, but not sfTSLP, through the RNA-binding protein muscle excess (MEX)-3B. MEX-3B promoted lfTSLP translation by binding the lfTSLP mRNA through its K homology domains. Furthermore, CBX4 regulated MEX-3B transcription in human bronchial epithelial cells through enhancing SUMOylation concentrations of the transcription factor TFII-I. In conclusion, we demonstrate an important mechanism whereby CBX4 promotes MEX-3B transcription through enhancing TFII-I SUMOylation and MEX-3B enhances the expression of lfTSLP through binding to the lfTSLP mRNA and promoting its translation. Our findings uncover a novel target of CBX4 for therapeutic agents for lfTSLP-mediated asthma.

Orai3 mediates Orai channel remodelling to activate fibroblast in pulmonary fibrosis.

Orai family are a calcium channel of cell membrane extracellular Ca2+ influx which participates in tissue fibrosis. But the roles of Orai3 have less attention on the mechanism of regulating lung fibrosis. In this study, we found that Orai3 expression was increased significantly in BLM-induced lung fibrosis. The knockdown of Orai3 decreased TGF-ß1-induced fibroblast proliferation, ECM production, activation of NFAT1 and Calpain/ERK signal pathway and glycolysis levels. Orai3 interacting with Orai1 was increased in BLM-induced lung fibrosis and TGF-ß1-induced fibroblast, while the Stim1 interacting with Orai1 and SOCE activity was suppressed, leading in a high and stable extracellular Ca2+ influx. Furthermore, the over-expression of Orai3 did not enhance Orai3 interacting with Orai1 under TGF-ß1 free fibroblast. And then, the deeper mechanism of TGF-ß1-induced increased SEPTIN4 promoted Orai3 interacting with Orai1. Our results indicated that Orai3 could be one of the therapy targets for PF in which remodels Orai channel, suppresses SOCE activity and activated fibroblast to alleviate fibrosis progress.

Short isoform thymic stromal lymphopoietin reduces inflammation and aerobic glycolysis of asthmatic airway epithelium by antagonizing long isoform thymic stromal lymphopoietin.

BACKGROUND: Up-regulation of aerobic glycolysis has been reported as a characterization of asthma and facilitates airway inflammation. We has been previously reported that short isoform thymic stromal lymphopoietin (sTSLP) could reduce inflammation in asthmatic airway epithelial cells. Here we wanted to investigate whether the inhibition of sTSLP on asthma is related to aerobic glycolysis. METHODS: Asthmatic model was established in challenging Male BALB/c mice and 16-HBE (human bronchial epithelial) cell line with house dust mite (HDM). Indicators of glycolysis were assessed to measure whether involve in sTSLP regulating airway epithelial cells inflammation in asthmatic model in vivo and in vitro. RESULTS: sTSLP decreased inflammation of asthmatic airway and aerobic glycolysis in mice. HDM or long isoform thymic stromal lymphopoietin (lTSLP) promoted HIF-1α expression and aerobic glycolysis by miR-223 to target and inhibit VHL (von Hippel-Lindau) expression 16-HBE. Inhibition of aerobic glycolysis restrained HDM- and lTSLP-induced inflammatory cytokines production. sTSLP along had almost no potential to alter aerobic glycolysis of 16-HBE. But sTSLP decreased LDHA (lactate dehydrogenase A) and LD (Lactic acid) levels in BALF, and HIF-1α and LDHA protein levels in airway epithelial cells of asthma mice model. lTSLP and sTSLP both induced formation of TSLPR and IL-7R receptor complex, and lTSLP obviously facilitated phosphorylation of JAK1, JAK2 and STAT5, while sTSLP induced a little phosphorylation of JAK1 and STAT5. CONCLUSION: We identified a novel mechanism that lTSLP could promote inflammatory cytokines production by miR-223/VHL/HIF-1α pathway to upregulate aerobic glycolysis in airway epithelial cells in asthma. This pathway is suppressed by sTSLP through occupying binding site of lTSLP in TSLPR and IL-7R receptor complex.

Mechanical property of the helical configuration for a twisted intrinsically straight biopolymer.

We explore the effects of two typical torques on the mechanical property of the helical configuration for an intrinsically straight filament or biopolymer either in three-dimensional space or on a cylinder. One torque is parallel to the direction of a uniaxial applied force, and is coupled to the cross section of the filament. We obtain some algebraic equations for the helical configuration and find that the boundary conditions are crucial. In three-dimensional space, we show that the extension is always a monotonic function of the applied force. On the other hand, for a filament confined on a cylinder, the twisting rigidity and torque coupled to the cross section are irrelevant in forming a helix if the filament is isotropic and under free boundary condition. However, the twisting rigidity and the torque coupled to the cross section become crucial when the Euler angle at two ends of the filament are fixed. Particularly, the extension of a helix can subject to a first-order transition so that in such a condition a biopolymer can act as a switch or sensor in some biological processes. We also present several phase diagrams to provide the conditions to form a helix.

Natural tristability of a confined helical filament with anisotropic bending rigidities.

We find that when c 0 R ∼ 0.5 and τ 0 R < 0.11 < c 0 R , confining a helical filament with anisotropic bending rigidities within a cylindrical tube of radius R can create a natural tristable status which is consisted of two low-pitch helices and one high-pitch helix, where a helical filament is referred to as a filament that has both an intrinsic curvature ( c 0 ) and an intrinsic twist rate ( τ 0 ). The formation of the tristable status also requires that the filament has a significant difference between two bending rigidities and a large twisting rigidity. The relative heights of two low-pitch helices in a tristable status are close to zero, and the smaller the intrinsic twisting angle, the smaller the difference between these two heights. Moreover, at a large intrinsic twisting angle, two low-pitch helices display a large energy difference, and the energy difference increases with decreasing τ 0 . Meanwhile, the relative height of the high-pitch helix is always close to that of a straight line. Finally, at some specific intrinsic parameters, the tristable status can include an isoenergic status with two helices of the same energy but distinct pitches.

Macro- and Micro-Structural Alterations in the Midbrain in Early Psychosis.

Introduction: Early psychosis (EP) is a critical period in the course of psychotic disorders during which the brain is thought to undergo rapid and significant functional and structural changes 1 . Growing evidence suggests that the advent of psychotic disorders is early alterations in the brain's functional connectivity and structure, leading to aberrant neural network organization. The Human Connectome Project (HCP) is a global effort to map the human brain's connectivity in healthy and disease populations; within HCP, there is a specific dataset that focuses on the EP subjects (i.e., those within five years of the initial psychotic episode) (HCP-EP), which is the focus of our study. Given the critically important role of the midbrain function and structure in psychotic disorders (cite), and EP in particular (cite), we specifically focused on the midbrain macro- and micro-structural alterations and their association with clinical outcomes in HCP-EP. Methods: We examined macro- and micro-structural brain alterations in the HCP-EP sample (n=179: EP, n=123, Controls, n=56) as well as their associations with behavioral measures (i.e., symptoms severity) using a stepwise approach, incorporating a multimodal MRI analysis procedure. First, Deformation Based Morphometry (DBM) was carried out on the whole brain 3 Tesla T1w images to examine gross brain anatomy (i.e., seed-based and voxel-based volumes). Second, we extracted Fractional Anisotropy (FA), Axial Diffusivity (AD), and Mean Diffusivity (MD) indices from the Diffusion Tensor Imaging (DTI) data; a midbrain mask was created based on FreeSurfer v.6.0 atlas. Third, we employed Tract-Based Spatial Statistics (TBSS) to determine microstructural alterations in white matter tracts within the midbrain and broader regions. Finally, we conducted correlation analyses to examine associations between the DBM-, DTI- and TBSS-based outcomes and the Positive and Negative Syndrome Scale (PANSS) scores. Results: DBM analysis showed alterations in the hippocampus, midbrain, and caudate/putamen. A DTI voxel-based analysis shows midbrain reductions in FA and AD and increases in MD; meanwhile, the hippocampus shows an increase in FA and a decrease in AD and MD. Several key brain regions also show alterations in DTI indices (e.g., insula, caudate, prefrontal cortex). A seed-based analysis centered around a midbrain region of interest obtained from freesurfer segmentation confirms the voxel-based analysis of DTI indices. TBSS successfully captured structural differences within the midbrain and complementary alterations in other main white matter tracts, such as the corticospinal tract and cingulum, suggesting early altered brain connectivity in EP. Correlations between these quantities in the EP group and behavioral scores (i.e., PANSS and CAINS tests) were explored. It was found that midbrain volume noticeably correlates with the Cognitive score of PA and all DTI metrics. FA correlates with the several dimensions of the PANSS, while AD and MD do not show many associations with PANSS or CAINS. Conclusions: Our findings contribute to understanding the midbrain-focused circuitry involvement in EP and complimentary alteration in EP. Our work provides a path for future investigations to inform specific brain-based biomarkers of EP and their relationships to clinical manifestations of the psychosis course.

Nicotinamide mononucleotide attenuates airway epithelial barrier dysfunction via inhibiting SIRT3 SUMOylation in asthma.

Nicotinamide adenine dinucleotide (NAD+) is an essential element in cellular metabolism that regulates fundamental biological processes. Growing evidence suggests that a decline in NAD+ is a common pathological factor in various diseases and aging. However, its role in airway epithelial barrier function in response to asthma remains underexplored. The current study aims to explore the efficacy of restoring cellular NAD+ concentration through supplementation with the NAD+ precursor, nicotinamide mononucleotide (NMN), in the treatment of allergic asthma and to investigate the role of SIRT3 in mediating the effects of NAD+ precursors. In this research, NMN alleviated airway inflammation and reduced mucus secretion in house dust mite (HDM)-induced asthmatic mice. It also mitigated airway epithelial barrier disruption in HDM-induced asthma in vitro and in vivo. But inhibition of SIRT3 expression abolished the effects of NMN. Mechanistically, HDM induced SIRT3 SUMOylation and proteasomal degradation. Mutation of these two SIRT3 SUMO modification sites enhanced the stability of SIRT3. Additionally, SIRT3 was targeted by SENP1 which acted to de-conjugate SUMO. And down-regulation of SENP1 expression in HDM-induced models was reversed by NMN. Collectively, these findings suggest that NMN attenuates airway epithelial barrier dysfunction via inhibiting SIRT3 SUMOylation in asthma. Blockage of SIRT3 SUMOylation emerges as for the treatment of allergic asthma.

Gut Microbiota and DTI Microstructural Brain Alterations in Rodents Due to Morphine Self-Administration.

The opioid epidemic is an evolving health crisis in need of interventions that target all domains of maladaptive changes due to chronic use and abuse. Opioids are known for their effects on the opioid and dopaminergic systems, in addition to neurocircuitry changes that mediate changes in behavior; however, new research lines are looking at complementary changes in the brain and gut. The gut-brain axis (GBA) is a bidirectional signaling process that permits feedback between the brain and gut and is altered in subjects with opioid use disorders. In this work, we determine longitudinal, non-invasive, and in-vivo complementary changes in the brain and gut in rodents trained to self-administer morphine for two weeks using MRI and 16S rDNA analysis of fecal matter. We assess the changes occurring during both an acute phase (early in the self-administration process, after two days of self-administration) and a chronic phase (late in the self-administration process, after two weeks of self-administration), with all measurements benchmarked against baseline (naïve, non-drug state). Rats were surgically implanted with an intravenous jugular catheter for self-administration of morphine. Rats were allowed to choose between an active lever, which delivers a single infusion of morphine (0.4 mg/kg/infusion), or an inactive lever, which had no consequence upon pressing. Animals were scanned in a 7T MRI scanner three times (baseline, acute, and chronic), and before scanning, fecal matter was collected from each rat. After the last scan session, a subset of animals was euthanized, and brains were preserved for immunohistochemistry analysis. We found early changes in gut microbiota diversity and specific abundance as early as the acute phase that persisted into the chronic phase. In MRI, we identified alterations in diffusivity indices both within subjects and between groups, showing a main effect in the striatum, thalamus, and somatosensory cortex. Finally, immunohistochemistry analyses revealed increased neuroinflammatory markers in the thalamus of rats exposed to morphine. Overall, we demonstrate that morphine self-administration shapes the brain and gut microbiota. In conclusion, gut changes precede the anatomical effects observed in MRI features, with neuroinflammation emerging as a crucial link mediating communication between the gut and the brain. This highlights neuroinflammation as a potential target in addressing the impacts of opioid use.

Greatly Improved the Tunable Amplitude of Ferromagnetism Based on Interface Effect of Flexible Pt/YIG Heterojunctions.

Flexible quantum spin electronic devices based on ferromagnetic insulators have attracted wide attention due to their outstanding advantages of low-power dissipation and noncontact sensing. However, ferromagnetic insulators, such as monocrystalline yttrium iron garnet (Y3Fe5O12, YIG), hve weak stress effects with a small magnetostrictive coefficient (λ110, 10 ppm), making it difficult to achieve a large magnetic tunable amplitude. In this paper, large-scale (with a diameter of 40 mm), flexible Pt/YIG heterojunctions were obtained by double-cavity magnetron sputtering technology, indicating typical soft magnetism and good bending fatigue characteristics. Here, the 3 nm thickness of the Pt layer triggers an obvious magnetic proximity effect, in which the in-plane ferromagnetic resonance field is decreased by 70 Oe compared to flexible Cu/YIG heterojunctions. Meanwhile, it shows a wide tunable amplitude of 110 Oe under the flexible bending stresses, which is induced by the sensitive interface effect of Pt (3 nm)/YIG heterojunctions. The saturation magnetization of Pt/YIG heterojunctions is negatively correlated with Pt thickness rather than the relative stability of Cu/YIG heterojunctions, depending on the magnetic proximity effect. It brings greater application possibilities for flexible stress-sensitive magnetic oxides in spin logic electronic devices.

Construction of Diffeomorphisms with Prescribed Jacobian Determinant and Curl: - that forms a new definition of Averaging Diffeomorphisms.

The Variational Principle (VP) is designed to generate non-folding grids (diffeomorphisms) with prescribed Jacobian determinant (JD) and curl. The solution pool of the original VP is based on an additive formulation and, consequently, is not invariant in the diffeomorphic Lie algebra. The original VP works well when the prescribed pair of JD and curl is calculated from a diffeomorphism, but not necessarily when the prescribed JD and curl are unknown to come from a diffeomorphism. In spite of that, the original VP works effectively in 2D grid generations. To resolve this issue, in this paper, we describe a new version of VP (revised VP), which is based on the composition of transformations and, therefore, is invariant in the Lie algebra. The revised VP seems to have overcome the inaccuracy of the original VP in 3D grid generations. In the following sections, the mathematical derivations are presented. It is shown that the revised VP can calculate the inverse transformation of a known diffeomorphism. Its inverse consistency and transitivity of transformations are also demonstrated numerically. Finally, a new definition of averaging diffeomorphisms based on the revised VP is proposed.

Bistability of a helical filament confined on a cylinder.

The natural configuration of an intrinsically curved and twisted filament is uniquely a helix so that it can be referred to as a helical filament. We find that confining a helical filament on a cylinder can create a bistable state. When c_{0}R=0.5, where c_{0} is the intrinsic curvature of filament and R is the radius of cylinder, the phase diagram for the stability of a helix contains three regimes. Regime I has a small intrinsic twisting rate (ITR) and exhibits a bistable state which consists of two isoenergic helices. In regime II, the filament has a moderate ITR and the bistable state consists of a metastable low-pitch helix and a stable nonhelix. In regime III, the helix is unstable, owing to a large ITR. A similar phenomenon occurs when c_{0}R∼0.5. Monte Carlo simulation confirms these conclusions and indicates further that there are bistable nonhelices in regime III. This bistable system offers a prospective green material since the wide range of parameters and distinctive configurations for bistable states favor its realization and application.

A novel approach to form Normal Distribution of Medical Image Segmentation based on multiple doctors' annotations.

Medical image segmentation annotated by experts provides the labeled data sets for many scientific researches. However, due to the unevenly experienced backgrounds of the experts and limited numbers of patients with certain diseases or illnesses, not only do such labeled data sets have smaller samples but their quality and normality also can range in wide variabilities and be ambiguous. In practice, these segmentations are usually assigned to be the ground truths for the scientific studies, so it may undermine the trustworthiness of the resulting findings. Therefore, it is meaningful to consider how to give a more unified opinion of the annotations among different experts. In this paper, a novel approach to form normal distributions of segmentation is proposed based on multiple doctors' annotations for the same patient. The proposed approach is developed through the following steps: (1) utilize a framework7 of averaging images to construct an averaged annotation based on different given annotations; (2) determine the image registration deformations from the averaged annotation to the given annotations; (3) build a joint multivariate Gaussian distribution over the logorithm of Jacobian determinants and curls of the registration deformations; lastly, (4) simulate a normal distribution of segmentation by the joint Gaussian distribution of registration deformation. This work translates the problem of forming a normal distribution of the image segmentation into a problem of forming joint Gaussian distribution of image registration deformations, which the latter can be reasoned by Jacobian determinant (models local size of pixel cells) and curl (models local rotation of pixel cells) information. In the following sections, a detailed walk-through of the proposed approach is provided along with its analytical mathematics and numerical examples for its effectiveness. A synthetic example of 3 manually defined label image is made to show how to construct a mean label image, and an example of a real cancer image annotated by 3 doctors demonstrates the formation of the normal distribution and the effectiveness of the propose method.

Avasimibe Alleviates Disruption of the Airway Epithelial Barrier by Suppressing the Wnt/ß-Catenin Signaling Pathway.

Avasimibe (Ava) is an acetyl-CoA acetyltransferase 1 (ACAT1) specific inhibitor and an established medicine for atherosclerosis, owing to its excellent and safe anti-inflammation effects in humans. However, its efficacy in asthma has not yet been reported. We first administered varying concentrations of avasimibe to house dust mite (HDM)-induced asthmatic mice; results showed that 20 mg/kg avasimibe most significantly reduced IL-4 and IL-5 production in bronchoalveolar lavage fluid (BALF) and total IgE in serum, and the avasimibe treatment also exhibited lower mucus secretion, decreased goblet and basal cells but increased ciliated cells compared to the HDM group. And the redistribution of adherens junction (AJ) proteins induced by HDM was far more less upon avasimibe administration. However, avasimibe did not reduce the cholesterol ester ratio in lung tissues or intracellular cholesterol ester, which is avasimibe's main effect. Further analysis confirmed that avasimibe impaired epithelial basal cell proliferation independent of regulating cholesterol metabolism and we analyzed datasets using the Gene Expression Omnibus (GEO) database and then found that the KRT5 gene (basal cell marker) expression is correlated with the ß-catenin gene. Moreover, we found that ß-catenin localized in cytomembrane upon avasimibe treatment. Avasimibe also reduced ß-catenin phosphorylation in the cytoplasm and inactivated the Wnt/ß-catenin signaling pathway induced by HDMs, thereby alleviating the airway epithelial barrier disruption. Taken together, these findings indicated that avasimibe has potential as a new therapeutic option for allergic asthma.

Blockade of CBX4-mediated ß-catenin SUMOylation attenuates airway epithelial barrier dysfunction in asthma.

Epithelial barrier dysfunction is involved in the pathogenesis of asthma. Previous studies show that SUMOylation can regulate epithelial junction molecule localization. However, the role of SUMOylation in epithelial barrier dysfunction in asthma remains unclear. This study found that inhibition of SUMOylation attenuates house dust mite (HDM)-induced epithelial barrier dysfunction. The SUMOylation levels of junction molecules were determined by co-immunoprecipitation (CO-IP) and proximity ligation assay (PLA). HDM treatment significantly enhanced SUMOylation levels of ß-catenin, while no effect was seen on ZO-1, Occludin, and E-cadherin SUMOylation levels. Inhibition of ß-catenin SUMOylation through 2-D08 treatment or SUMOylation modification site mutant (K233A) promoted its membrane localization and repressed Wnt/ß-catenin signaling. Further, we identified that CBX4, an E3 ligase, mediated SUMOylation of ß-catenin. Knockdown of CBX4 promoted ß-catenin membrane localization and improved epithelial barrier function. In vivo analysis showed that AAV6-shCBX4-mediated knockdown of CBX4 attenuated HDM-induced allergic airway inflammation and epithelial barrier dysfunction. The findings showed that inhibiting ß-catenin SUMOylation by targeting CBX4 mitigated HDM-induced epithelial barrier dysfunction in asthma.

Bistability induced by a spontaneous twisting rate for a two-dimensional intrinsically curved filament.

We find that a moderate intrinsic twisting rate (ITR) can induce a bistable state for a force-free two-dimensional intrinsically curved filament. There are two different configurations of equal energy in a bistable state so that the filament is clearly different from its three-dimensional counterpart. The smaller the ITR or the larger the intrinsic curvature (IC), the clearer the distinction between two isoenergetic configurations and the longer the filament. In bistable states, the relationship between length and ITR is approximately a hyperbola and relationship between IC and critical ITR is approximately linear. Thermal fluctuation can result in a shift between two isoenergetic configurations, but large bending and twisting rigidities can prevent the shift and maintain the filament in one of these two configurations. Moreover, a filament can have a metastable state and at a finite temperature such a filament has the similar property as that of a filament with bistable state.

Crucial role of the intrinsic twist rate for the size of an intrinsically curved semiflexible biopolymer.

We study the effects of the intrinsic curvature (IC), intrinsic twist rate (ITR), anisotropic bending rigidities, sequence disorder, and temperature (T) on the persistence length (l_{p}) of a two- or three-dimensional semiflexible biopolymer. We develop some general expressions to evaluate exactly these effects. We find that a moderate IC alone reduces l_{p} considerably. Our results indicate that the centerline of the filament keeps as a helix in a rather large range of T when ITR is small. However, a large ITR can counterbalance the effect of IC and the result is insensitive to the twist rigidity. Moreover, a weak randomness in IC and ITR can result in an "overexpanded" state. Meanwhile, when ITR is small, l_{p} is not a monotonic function of T but can have either minimum or maximum at some T, and in the two-dimensional case the maximum is more obvious than that in the three-dimensional case. These results reveal that to obtain a proper size at a finite T for an intrinsically curved semiflexible biopolymer, proper values of bending rigidities and ITR are necessary but a large twist rigidity may be only a by-product. Our findings are instructive in controlling the size of a semiflexible biopolymer in organic synthesis since the mean end-to-end distance and radius of gyration of a long semiflexible biopolymer are proportional to l_{p}.

Sequence-dependent effects on the properties of semiflexible biopolymers.

Using a path integral technique, we show exactly that for a semiflexible biopolymer in constant extension ensemble, no matter how long the polymer and how large the external force, the effects of short-range correlations in the sequence-dependent spontaneous curvatures and torsions can be incorporated into a model with well-defined mean spontaneous curvature and torsion as well as a renormalized persistence length. Moreover, for a long biopolymer with large mean persistence length, the sequence-dependent persistence lengths can be replaced by their mean. However, for a short biopolymer or for a biopolymer with small persistence lengths, inhomogeneity in persistence lengths tends to make physical observables very sensitive to details and therefore less predictable.