Signatures of fractional quantum anomalous Hall states in twisted MoTe2.

The interplay between spontaneous symmetry breaking and topology can result in exotic quantum states of matter. A celebrated example is the quantum anomalous Hall (QAH) state, which exhibits an integer quantum Hall effect at zero magnetic field owing to intrinsic ferromagnetism1-3. In the presence of strong electron-electron interactions, fractional QAH (FQAH) states at zero magnetic field can emerge4-8. These states could host fractional excitations, including non-Abelian anyons-crucial building blocks for topological quantum computation9. Here we report experimental signatures of FQAH states in a twisted molybdenum ditelluride (MoTe2) bilayer. Magnetic circular dichroism measurements reveal robust ferromagnetic states at fractionally hole-filled moiré minibands. Using trion photoluminescence as a sensor10, we obtain a Landau fan diagram showing linear shifts in carrier densities corresponding to filling factor v = -2/3 and v = -3/5 ferromagnetic states with applied magnetic field. These shifts match the Streda formula dispersion of FQAH states with fractionally quantized Hall conductance of [Formula: see text] and [Formula: see text], respectively. Moreover, the v = -1 state exhibits a dispersion corresponding to Chern number -1, consistent with the predicted QAH state11-14. In comparison, several non-ferromagnetic states on the electron-doping side do not disperse, that is, they are trivial correlated insulators. The observed topological states can be electrically driven into topologically trivial states. Our findings provide evidence of the long-sought FQAH states, demonstrating MoTe2 moiré superlattices as a platform for exploring fractional excitations.

N6-methyladenosine reader protein YTHDC1 regulates influenza A virus NS segment splicing and replication.

N6-methyladenosine (m6A) modification on viral RNAs has a profound impact on infectivity. m6A is also a highly pervasive modification for influenza viral RNAs. However, its role in virus mRNA splicing is largely unknown. Here, we identify the m6A reader protein YTHDC1 as a host factor that associates with influenza A virus NS1 protein and modulates viral mRNA splicing. YTHDC1 levels are enhanced by IAV infection. We demonstrate that YTHDC1 inhibits NS splicing by binding to an NS 3' splicing site and promotes IAV replication and pathogenicity in vitro and in vivo. Our results provide a mechanistic understanding of IAV-host interactions, a potential therapeutic target for blocking influenza virus infection, and a new avenue for the development of attenuated vaccines.

Fractional Chern Insulator in Twisted Bilayer MoTe_{2}.

A recent experiment has reported the first observation of a zero-field fractional Chern insulator (FCI) phase in twisted bilayer MoTe_{2} moiré superlattices [J. Cai et al., Signatures of fractional quantum anomalous Hall states in twisted MoTe_{2}, Nature (London) 622, 63 (2023).NATUAS0028-083610.1038/s41586-023-06289-w]. The experimental observation is at an unexpected large twist angle 3.7° and calls for a better understanding of the FCI in real materials. In this Letter, we perform large-scale density functional theory calculation for the twisted bilayer MoTe_{2} and find that lattice reconstruction is crucial for the appearance of an isolated flat Chern band. The existence of the FCI state at ν=-2/3 is confirmed by exact diagonalization. We establish phase diagrams with respect to the twist angle and electron interaction, which reveal an optimal twist angle of 3.5° for the observation of FCI. We further demonstrate that an external electric field can destroy the FCI state by changing band geometry and show evidence of the ν=-3/5 FCI state in this system. Our research highlights the importance of accurate single-particle band structure in the quest for strong correlated electronic states and provides insights into engineering fractional Chern insulator in moiré superlattices.

Photodynamic and nitric oxide therapy-based synergistic antimicrobial nanoplatform: an advanced root canal irrigation system for endodontic bacterial infections.

BACKGROUND: The main issues faced during the treatment of apical periodontitis are the management of bacterial infection and the facilitation of the repair of alveolar bone defects to shorten disease duration. Conventional root canal irrigants are limited in their efficacy and are associated with several side effects. This study introduces a synergistic therapy based on nitric oxide (NO) and antimicrobial photodynamic therapy (aPDT) for the treatment of apical periodontitis. RESULTS: This research developed a multifunctional nanoparticle, CGP, utilizing guanidinylated poly (ethylene glycol)-poly (ε-Caprolactone) polymer as a carrier, internally loaded with the photosensitizer chlorin e6. During root canal irrigation, the guanidino groups on the surface of CGP enabled effective biofilm penetration. These groups undergo oxidation by hydrogen peroxide in the aPDT process, triggering the release of NO without hindering the production of singlet oxygen. The generated NO significantly enhanced the antimicrobial capability and biofilm eradication efficacy of aPDT. Furthermore, CGP not only outperforms conventional aPDT in eradicating biofilms but also effectively promotes the repair of alveolar bone defects post-eradication. Importantly, our findings reveal that CGP exhibits significantly higher biosafety compared to sodium hypochlorite, alongside superior therapeutic efficacy in a rat model of apical periodontitis. CONCLUSIONS: This study demonstrates that CGP, an effective root irrigation system based on aPDT and NO, has a promising application in root canal therapy.

A Novel Intumescent MCA-Modified Sodium Silicate/Acrylic Flame-Retardant Coating to Improve the Flame Retardancy of Wood.

The incompatibility between inorganic flame retardants and organic acrylic coatings represents a significant challenge that requires resolution. This work selected environmentally friendly organic aqueous acrylic coatings as the substrate, sodium silicate hydrate as the inorganic flame retardant, and melamine cyanurate (MCA) as the flame-retardant modifier and the flame-retardant co-modifier, with the objective of improving the dispersion and flame-retardant properties of sodium silicate hydrate in the aqueous acrylic coatings. Subsequently, the sodium silicate/MCA/waterborne acrylic acid flame-retardant coating was prepared. The flame-retardant treatment was then applied to poplar veneer in order to create a flame-retardant poplar veneer. The dispersion of the flame-retardant coating was characterized by scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDX), and X-ray diffractometry (XRD). Furthermore, the flame-retardant properties of the flame-retardant poplar veneer were analyzed by thermogravimetry (TG), limiting oxygen index (LOI), and cone calorimeter. The results demonstrated that the MCA-modified sodium silicate flame retardant was well dispersed in aqueous acrylic coatings. The results of the flame-retardant properties of the poplar veneer indicated that the ignition time of the 9% flame retardant-treated poplar veneer was increased by 122.7%, the limiting oxygen index value was increased by 43.0%, and the peak heat release rate (pHRR), the peak total heat release rate (pTHR), and the peak mass loss rate were decreased by 19.9%, 10.8%, and 27.2%, respectively, in comparison to the non-flame retardant-treated poplar veneer. Furthermore, the residual char mass increased by 14.4%, and the residual char exhibited enhanced thickness, density, and regularity. The results demonstrated that MCA was an effective promoter of sodium silicate dispersion in acrylic coatings. Furthermore, the sodium silicate/MCA/waterborne acrylic flame-retardant coating significantly enhance the flame retardancy of wood, and its flame retardant mechanism was consistent with the synergistic silicone-nitrogen expansion flame-retardant mechanism. This work presents a novel approach to enhancing the dispersion of inorganic flame retardants in organic coatings, offering a valuable contribution to the advancement of research and application in the domains of innovative flame retardant coatings and flame retardant wood.

Sodium Silicate/Urea/Melamine Ternary Synergistic Waterborne Acrylic Acid Flame-Retardant Coating and Its Flame-Retardant Mechanism.

Waterborne acrylic coatings, the largest market share of predominant environmentally friendly coatings, face limitations in their extensive application due to their flammability. The flame-retardant properties of the coatings could be significantly enhanced by incorporate inorganic flame retardants. However, inorganic flame retardants tend to aggregate and unevenly disperse in waterborne acrylic coatings, causing a substantial decrease in flame retardancy. In this work, sodium silicate was utilized as a flame retardant, with urea and melamine serving as modifiers and synergistic agents. This combination resulted in the preparation of a sodium silicate/urea/melamine ternary synergistic waterborne acrylic flame-retardant coating. This coating was applied to the surface of poplar veneer to create flame-retardant poplar veneer. Subsequently, various instruments, including a scanning electron microscope (SEM), a limiting oxygen index meter (LOI), a thermogravimetric analyzer (TG), and a cone calorimeter (CONE), were employed to investigate the relevant properties and mechanisms of both the flame-retardant coating and poplar veneer. The results demonstrated that the sodium silicate/urea/melamine ternary synergistic flame retardant did not exhibit aggregation and could be uniformly dispersed in waterborne acrylic coatings. The physical and mechanical properties of the ternary synergistic flame-retardant poplar veneer coating were satisfactory. Melamine and urea, acting as modifiers, not only greatly enhanced the dispersibility of sodium silicate in waterborne acrylic coatings, but also assisted in the formation of a silicon-containing char layer through the generation of nitrogen, achieving ternary synergistic flame retardancy. In conclusion, this work explores a novel method to efficiently and uniformly disperse inorganic flame retardants in organic coatings. It significantly improves the dispersibility and uniformity of inorganic flame retardants in organic polymers, thereby substantially enhancing the flame-retardant performance of coatings. This work provides a theoretical basis for the research and application of new flame-retardant coatings in the field of chemistry and materials.

Personalized radiomics signature to screen for KIT-11 mutation genotypes among patients with gastrointestinal stromal tumors: a retrospective multicenter study.

OBJECTIVES: Gastrointestinal stromal tumors (GISTs) carrying different KIT exon 11 (KIT-11) mutations exhibit varying prognoses and responses to Imatinib. Herein, we aimed to determine whether computed tomography (CT) radiomics can accurately stratify KIT-11 mutation genotypes to benefit Imatinib therapy and GISTs monitoring. METHODS: Overall, 1143 GISTs from 3 independent centers were separated into a training cohort (TC) or validation cohort (VC). In addition, the KIT-11 mutation genotype was classified into 4 categories: no KIT-11 mutation (K11-NM), point mutations or duplications (K11-PM/D), KIT-11 557/558 deletions (K11-557/558D), and KIT-11 deletion without codons 557/558 involvement (K11-D). Subsequently, radiomic signatures (RS) were generated based on the arterial phase of contrast CT, which were then developed as KIT-11 mutation predictors using 1408 quantitative image features and LASSO regression analysis, with further evaluation of its predictive capability. RESULTS: The TC AUCs for K11-NM, K11-PM/D, K11-557/558D, and K11-D ranged from 0.848 (95% CI 0.812-0.884), 0.759 (95% CI 0.722-0.797), 0.956 (95% CI 0.938-0.974), and 0.876 (95% CI 0.844-0.908), whereas the VC AUCs ranged from 0.723 (95% CI 0.660-0.786), 0.688 (95% CI 0.643-0.732), 0.870 (95% CI 0.824-0.918), and 0.830 (95% CI 0.780-0.878). Macro-weighted AUCs for the KIT-11 mutant genotype ranged from 0.838 (95% CI 0.820-0.855) in the TC to 0.758 (95% CI 0.758-0.784) in VC. TC had an overall accuracy of 0.694 (95%CI 0.660-0.729) for RS-based predictions of the KIT-11 mutant genotype, whereas VC had an accuracy of 0.637 (95%CI 0.595-0.679). CONCLUSIONS: CT radiomics signature exhibited good predictive performance in estimating the KIT-11 mutation genotype, especially in prediction of K11-557/558D genotype. RS-based classification of K11-NM, K11-557/558D, and K11-D patients may be an indication for choice of Imatinib therapy.

Proliferating cell nuclear antigen impairs the nuclear import of influenza A virus PB2 and suppresses virus replication.

The genome of Influenza A virus (IAV) transcribes and replicates in the nucleus of cells and the viral ribonucleoprotein (vRNP) complex plays an important role in viral replication. As a major component of the vRNP complex, the polymerase basic protein 2 (PB2) is translocated to the nucleus via its nuclear localization signals mediated by the importins. Herein, it was identified proliferating cell nuclear antigen (PCNA) as an inhibitor of nuclear import of PB2 and subsequent viral replication. Mechanically, PCNA interacted with PB2 and inhibited the nuclear import of PB2. Furthermore, PCNA decreased the binding efficiency of PB2 with importin alpha (importin α) and the K738, K752, and R755 of PB2 were identified as the key sites binding with PCNA and importin α. Furthermore, PCNA was demonstrated to retrain the vRNP assembly and polymerase activity. Taken together, the results demonstrated that PCNA impaired the nuclear import of PB2, vRNP assembly and polymerase activity, which negatively regulated virus replication.

Anti-gp210-positive primary biliary cholangitis: The dilemma of clinical treatment and emerging mechanisms.

Anti-gp210 is the disease-specific anti-nuclear antibody (ANA) of primary biliary cholangitis (PBC). Anti-gp210-positive PBC patients have worse responses to ursodeoxycholic acid (UDCA) as compared with anti-gp210-negative patients. Moreover, anti-gp210-positive patients always present with more severe histopathologic features including lobular inflammation, interfacial hepatitis, and bile duct injury, and have a worse prognosis than their anti-gp210-negative counterparts. Previous studies have identified two antigenic epitopes recognized by anti-gp210. Although the pathogenetic mechanism of anti-gp210 production remains unclear, evidence suggests that the autoimmune response to anti-gp210 production might be due to molecular mimicry induced by bacteria or endogenous peptides. T cells and related cytokines play a critical role in the pathogenesis of PBC, however, the mechanism hasn't been fully understood. Thus, this review focuses on the clinicopathological characteristics of anti-gp210-positive PBC patients, the fundamental research of gp210 antigen, and the possible mechanism of anti-gp210 production to clarify the mechanism of anti-gp210-positive PBC and provide potential molecular targets for disease prevention and treatment in the future.

Preparation of PO43--Intercalated Calcium-Aluminum Hydrotalcites via Coprecipitation Method and Its Flame-Retardant Effect on Bamboo Scrimber.

To improve the flame retardancy of bamboo scrimber, flame-retardant CaAl-PO4-LDHs were synthesized via the coprecipitation method using PO43- as the anion of an intercalated calcium-aluminum hydrotalcite in this work. The fine CaAl-PO4-LDHs were characterized via X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), cold field scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) and thermogravimetry (TG). Different concentrations (1% and 2%) of CaAl-PO4-LDHs were used as flame retardants for the bamboo scrimber, and the flame retardancy of the bamboo scrimber was characterized via cone calorimetry. The results showed that CaAl-PO4-LDHs with excellent structures were successfully synthesized via the coprecipitation method in 6 h and at 120 °C. Compared with the bamboo scrimber without the flame retardant treatment, the peak heat release rate (HRR) of the bamboo scrimber treated with 1% and 2% concentrations of flame-retardant CaAl-PO4-LDHs decreased by 16.62% and 34.46%, the time taken to reach the exothermic peak was delayed by 103 s and 204 s and the Time to Ignition (TTI) was increased by 30% and 40%, respectively. Furthermore, the residual carbon of the bamboo scrimber did not change significantly, increasing by 0.8% and 2.08%, respectively. CO production decreased by 18.87% and 26.42%, respectively, and CO2 production decreased by 11.11% and 14.46%, respectively. The combined results show that the CaAl-PO4-LDHs synthesized in this work significantly improved the flame retardancy of bamboo scrimber. This work exhibited the great potential of the CaAl-PO4-LDHs, which were successfully synthesized via the coprecipitation method and applied as a flame retardant to improve the fire safety of bamboo scrimber.

Antimildew Effect of Three Phenolic Compounds and the Efficacy of Antimildew Sliced Bamboo Veneer.

The development of the bamboo industry has been hindered by environmental issues caused by the application of bamboo preservatives. Chinese herbal phenolic compounds have been shown to possess broad-spectrum, potent antimildew properties, making them promising candidates for the development of new bamboo mildew inhibitors. In this study, we investigated the antimildew properties of three phenolic compounds, eugenol, carvacrol, and paeonol, against common mildews in bamboo materials using the Oxford cup method and the double-dilution method. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to analyze the antimildew mechanism and its effects on mildew cell morphology. Our results showed that carvacrol exhibited the strongest antimildew activity, with minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values of 1.56 mg/mL and 1.76 mg/mL, respectively, followed by eugenol and paeonol. At a concentration of 25 mg/mL, eugenol and carvacrol had an inhibitory rate of over 50% against various mildews. Different concentrations of the three compounds significantly disrupted the morphology and structural integrity of mildew hyphae, with the extent of damage increasing with concentration and treatment duration. In the sliced bamboo mildew prevention experiment, carvacrol at a concentration of 29.25 mg/mL was found to be highly effective against all tested mildews. Our study provides new insights and a theoretical basis for the development of eco-friendly bamboo mildew inhibitors based on plant phenolic compounds.

Screening of Ionic Liquids against Bamboo Mildew and Its Inhibition Mechanism.

Ionic liquids are a class of organic molten salts that consist entirely of cations and anions. They are characterized by their low vapor pressure, low viscosity, low toxicity, high thermal stability, and strong antifungal potential. In this study, the inhibitory performance of ionic liquid cations against Penicillium citrinum, Trichoderma viride, and Aspergillus niger was investigated, along with the mechanism of cell membrane disruption. The Oxford cup method, SEM, and TEM were employed to examine the extent of damage and the specific site of action of ionic liquids on the mycelium and cell structure of these fungi. The results showed that 1-decyl-3-methylimidazole had a strong inhibitory effect on TV; benzyldimethyldodecylammonium chloride had a weak inhibitory effect on PC, TV, AN, and a mixed culture; while dodecylpyridinium chloride exhibited significant inhibitory effects on PC, TV, AN, and Mix, with more prominent effects observed on AN and Mix, exhibiting MIC values of 5.37 mg/mL, 5.05 mg/mL, 5.10 mg/mL, and 5.23 mg/mL, respectively. The mycelium of the mildews showed drying, partial loss, distortion, and uneven thickness. The cell structure showed separation of the plasma wall. The absorbance of the extracellular fluid of PC and TV reached the maximum after 30 min, while that of AN reached the maximum after 60 min. The pH of the extracellular fluid decreased initially and then increased within 60 min, followed by a continuous decrease. These findings provide important insights for the application of ionic liquid antifungal agents in bamboo, medicine, and food.

A predictive nomogram for two-year growth of CT-indeterminate small pulmonary nodules.

OBJECTIVES: Lung cancer is the most common cancer and the leading cause of cancer-related death worldwide. The optimal management of computed tomography (CT)-indeterminate pulmonary nodules is important. To optimize individualized follow-up strategies, we developed a radiomics nomogram for predicting 2-year growth in case of indeterminate small pulmonary nodules. METHODS: A total of 215 histopathology-confirmed small pulmonary nodules (21 benign and 194 malignant) in 205 patients with ultra-high-resolution CT (U-HRCT) were divided into growth and nongrowth nodules and were randomly allocated to the primary (n = 151) or validation (n = 64) group. The least absolute shrinkage and selection operator (LASSO) method was used for radiomics feature selection and radiomics signature determination. Multivariable logistic regression analysis was used to develop a radiomics nomogram that integrated the radiomics signature with significant clinical parameters (sex and nodule type). The area under the curve (AUC) was applied to assess the predictive performance of the radiomics nomogram. The net benefit of the radiomics nomogram was assessed using a clinical decision curve. RESULTS: The radiomics signature and nomogram yielded AUCs of 0.892 (95% confidence interval [CI]: 0.843-0.940) and 0.911 (95% CI: 0.867-0.955), respectively, in the primary group and 0.826 (95% CI: 0.727-0.926) and 0.843 (95% CI: 0.749-0.937), respectively, in the validation group. The clinical usefulness of the nomogram was demonstrated by decision curve analysis. CONCLUSIONS: A radiomics nomogram was developed by integrating the radiomics signature with clinical parameters and was easily used for the individualized prediction of two-year growth in case of CT-indeterminate small pulmonary nodules. KEY POINTS: • A radiomics nomogram was developed for predicting the two-year growth of CT-indeterminate small pulmonary nodules. • The nomogram integrated a CT-based radiomics signature with clinical parameters and was valuable in developing an individualized follow-up strategy for patients with indeterminate small pulmonary nodules.

Colossal mid-infrared bulk photovoltaic effect in a type-I Weyl semimetal.

Broadband, efficient and fast conversion of light to electricity is crucial for sensing and clean energy. The bulk photovoltaic effect (BPVE) is a second-order nonlinear optical effect that intrinsically converts light into electrical current. Here, we demonstrate a large mid-infrared BPVE in microscopic devices of the Weyl semimetal TaAs. This discovery results from combining recent developments in Weyl semimetals, focused-ion beam fabrication and theoretical works suggesting a connection between BPVE and topology. We also present a detailed symmetry analysis that allows us to separate the shift current response from photothermal effects. The magnitude and wavelength range of the assigned shift current may impact optical detectors, clean energy and topology, and demonstrate the utility of Weyl semimetals for practical applications.

Alteration of Colonic Mucosal Permeability during Antibiotic-Induced Dysbiosis.

Although dysbiosis is likely to disturb the mucosal barrier system, the mechanism involved has remained unclear. Here, we investigated alterations of colonic mucosal permeability and tight junction (TJ) molecules in mice with antibiotic-induced dysbiosis. Mice were orally administered vancomycin or polymyxin B for 7 days, and then fecal samples were subjected to microbial 16S rRNA analysis. The colonic mucosal permeability was evaluated by chamber assay. The colonic expression of TJ molecules and cytokines was examined by real-time RT-PCR, Western blotting, and immunohistochemistry. Caco2 cells were stimulated with cytokines and their transepithelial electric resistance (TEER) was measured. Vancomycin-treated mice showed significantly lower gut microbiota diversity than controls, and the same tendency was evident in polymyxin B-treated mice. The colonic mucosal permeability was significantly elevated in both vancomycin- and polymyxin B-treated mice. The expression of claudin 4 in the colonic mucosa was decreased in both vancomycin- and polymyxin B-treated mice. Colonic expression of TNF-α and/or IFN-γ was significantly increased in mice that had been administered antibiotics. TNF-α and IFN-γ stimulation dose-dependently decreased TEER in Caco2 cells. Antibiotic-induced dysbiosis is correlated with the enhancement in colonic tissue permeability, accompanied by a reduction in claudin 4 expression and enhancement in TNF-α and/or IFN-γ expression in mice.

Prognostic impact of neutrophil-to-lymphocyte ratio in cirrhosis: A propensity score matching analysis with a prespecified cut-point.

BACKGROUND & AIMS: An elevated neutrophil-to-lymphocyte ratio (NLR) has received attention as a prognostic surrogate across chronic liver diseases. However, an exact threshold has not been fully elucidated. METHODS: A total number of 589 patients with cirrhosis (LC) were included. The value of NLR was calculated and its optimal cut-off was initially determined by X-tile program. Independent predictors of 90-day mortality were identified with Cox regression model. The Kaplan-Meier method was used to generate survival curves. To reduce influences of selection bias and possible confounders, a 1:2 propensity score matching (PSM) was performed. RESULTS: The X-tile indicated that the difference in survival was most significant for NLR more than 8.9. Serum NLR > 8.9 was an independent indicator in the entire cohort and PSM subset (HR 4.268, 95% CI 2.211-8.238, P < .001; HR 4.209, 95% CI 1.448-12.238, P = .008 respectively). Subgroup analysis showed that NLR > 8.9 was an independent risk factor of 90-day mortality regardless of age, gender, CTP or MELD score. CONCLUSIONS: The value of NLR more than 8.9 is a feasible cut-off across clinical settings among applicable population. The adding of NLR to other conventional predictive systems has the potential to provide incremental value without extra economic cost.

The Link between Type III Reg and STAT3-Associated Cytokines in Inflamed Colonic Tissues.

Reg (regenerating gene) family proteins are known to be overexpressed in gastrointestinal (GI) tissues under conditions of inflammation. However, the pathophysiological significance of Reg family protein overexpression and its regulation is still unclear. In the present study, we investigated the profile of Reg family gene expression in a colitis model and focused on the regulation of Reg IIIß and IIIγ, which are overexpressed in inflamed colonic mucosa. C57BL/6 mice were administered 2% dextran sulfate sodium (DSS) in drinking water for five days, and their colonic tissues were investigated histopathologically at interval for up to 12 weeks. Gene expression of the Reg family and cytokines (IL-6, IL-17, and IL-22) was evaluated by real-time RT-PCR, and Reg IIIß/γ expression was examined by immunohistochemistry. The effects of cytokines on STAT3 phosphorylation and HIP/PAP (type III REG) expression in Caco2 and HCT116 cells were examined by Western blot analysis. Among Reg family genes, Reg IIIß and IIIγ were alternatively overexpressed in the colonic tissues of mice with DSS-induced colitis. The expression of STAT3-associated cytokines (IL-6, IL-17, and IL-22) was also significantly increased in those tissues, being significantly correlated with that of Reg IIIß/γ. STAT3 phosphorylation and HIP/PAP expression were significantly enhanced in Caco2 cells upon stimulation with IL-6, IL-17, and IL-22. In HCT116 cells, those enhancements were also observed by IL-6 and IL-22 stimulations but not IL-17. The link between type III Reg and STAT3-associated cytokines appears to play a pivotal role in the pathophysiology of DSS-induced colitis.

Peptidoglycan Suppresses Phagocytic Activities and Apoptosis of Macrophages in Colonic Mucosa Tissues of Crohn's Disease Patients and In Vitro.

BACKGROUND Rac1 signaling plays a crucial role in controlling macrophage functions in CD. Peptidoglycan triggers several intracellular signaling pathways, including activation of Rac1, to regulate the function of macrophage. Suppressed Rac1 signaling in non-inflamed colonic mucosa of Crohn's disease patients has been shown to correlate with increased innate immunity. MATERIAL AND METHODS We examined the effect of peptidoglycan on Rac1 signaling in macrophages and mucosal tissue samples collected from 10 patients with active Crohn's disease and further investigated the effects of peptidoglycan on apoptosis and phagocytic activities of macrophages in vitro. RESULTS Macrophage infiltration and Rac1 signaling was increased in inflamed mucosal tissues of Crohn's disease patients. Immunoblotting assays revealed that peptidoglycan dose- and time-dependently increased the expression of Rac1-GTP, phosphorylated VAV1, and phosphorylated PAK1in RAW264.7 macrophages, which, however, was attenuated by 6-thioguanine. Peptidoglycan also dose-dependently inhibited phagocytic activities of human peripheral blood monocytic cells (PBMCs), which were partially abated by 6-thioguanine or NSC23766. Flow cytometry showed that peptidoglycan (3 µg/mL) decreased the proportion of apoptotic human PBMCs versus controls. The addition of 6-thioguanine or NSC3766 to peptidoglycan led to a sharper rise in the proportion of apoptotic human PBMCs than 6-thioguanine or NSC3766 alone. CONCLUSIONS Our findings suggest that Rac1 signaling is a common molecular target shared by peptidoglycan and immunosuppressive treatment in intestinal macrophages. Inhibiting Rac1 activation may be crucial for optimizing macrophage immunity for treatment of Crohn's disease.

When Chiral Photons Meet Chiral Fermions: Photoinduced Anomalous Hall Effects in Weyl Semimetals.

The Weyl semimetal is characterized by three-dimensional linear band touching points called Weyl nodes. These nodes come in pairs with opposite chiralities. We show that the coupling of circularly polarized photons with these chiral electrons generates a Hall conductivity without any applied magnetic field in the plane orthogonal to the light propagation. This phenomenon comes about because with all three Pauli matrices exhausted to form the three-dimensional linear dispersion, the Weyl nodes cannot be gapped. Rather, the net influence of chiral photons is to shift the positions of the Weyl nodes. Interestingly, the momentum shift is tightly correlated with the chirality of the node to produce a net anomalous Hall signal. Application of our proposal to the recently discovered TaAs family of Weyl semimetals leads to an order-of-magnitude estimate of the photoinduced Hall conductivity which is within the experimentally accessible range.

Rapid, highly sensitive detection of herpes simplex virus-1 using multiple antigenic peptide-coated superparamagnetic beads.

A sensitive, rapid, and label free magnetic bead aggregation (MBA) assay has been developed that employs superparamagnetic (SPM) beads to capture, purify, and detect model proteins and the herpes simplex virus (HSV). The MBA assay is based on monitoring the aggregation state of a population of SPM beads using light scattering of individual aggregates. A biotin-streptavidin MBA assay had a femtomolar (fM) level sensitivity for analysis times less than 10 minutes, but the response of the assay becomes nonlinear at high analyte concentrations. A MBA assay for the detection of HSV-1 based on a novel peptide probe resulted in the selective detection of the virus at concentrations as low as 200 viral particles (vp) per mL in less than 30 min. We define the parameters that determine the sensitivity and response of the MBA assay, and the mechanism of enhanced sensitivity of the assay for HSV. The speed, relatively low cost, and ease of application of the MBA assay promise to make it useful for the identification of viral load in resource-limited and point-of-care settings where molecular diagnostics cannot be easily implemented.