Permutation conditional mutual information to quantify TMS-evoked cortical connectivity in disorders of consciousness.

OBJECTIVE: To improve the understanding and diagnostic accuracy of disorders of consciousness (DOC) by quantifying transcranial magnetic stimulation evoked electroencephalography (TMS-EEG) connectivity using Permutation Conditional Mutual Information (PCMI). Approach: PCMI can characterize the functional connectivity between different brain regions. This study employed PCMI to analyze TMS-evoked cortical connectivity (TEC) in 154 DOC patients and 16 normal controls, focusing on optimizing parameter selection for PCMI (Data length, Order length, Time delay). We compared short-range and long-range PCMI values across different consciousness states-unresponsive wakefulness syndrome (UWS), minimally conscious state (MCS), and normal (NOR)-and assessed various feature selection and classification techniques to distinguish these states. Main Results: 1) PCMI can quantify TEC. We found optimal parameters to be Data length: 500ms; Order: 3; Time delay: 6ms. 2) TMS evoked potentials (TEP) for NOR showed a rich response, while MCS patients showed only a few components, and UWS patients had almost no significant components. The values of PCMI connectivity metrics demonstrated its usefulness for measuring cortical connectivity evoked by TMS. From NOR to MCS to UWS, the number and strength of TEC decreased. Quantitative analysis revealed significant differences in the strength and number of TEC in the entire brain, local regions and inter-regions among different consciousness states. 3) A decision tree with feature selection by mutual information performed the best (balanced accuracy: 87.0% and accuracy: 83.5%). This model could accurately identify NOR (100.0%), but had lower identification accuracy for UWS (86.5%) and MCS (74.1%). Significance: The application of PCMI in measuring TMS-evoked connectivity provides a robust metric that enhances our ability to differentiate between various states of consciousness in DOC patients. This approach not only aids in clinical diagnosis but also contributes to the broader understanding of cortical connectivity and consciousness. .

Soy Protein Isolate Gel Subjected to Freezing Treatment: Influence of Methylcellulose and Sodium Hexametaphosphate on Gel Stability, Texture and Structure.

Freezing affects texture and induces the loss of gel quality. This study investigated the effects of methylcellulose (MC) (0.2%, 0.4%, 0.6%) and sodium hexametaphosphate (SHMP) (0.15%, 0.3%) on the gel textural and structural properties of SPI gels before and after freezing, and explores the synergistic enhancement of gel texture and the underlying mechanisms resulting from the simultaneous addition of SHMP and MC to SPI gels. It was revealed that MC improved the strength of SPI gels through its thickening properties, but it could not inhibit the reduction of SPI gels after freezing. The 0.4% MC-SPI gel exhibited the best gel strength (193.2 ± 2.4 g). SHMP inhibited gel reduction during freezing through hydrogen bonding and ionic interactions; it enhanced the freezing stability of SPI gels. The addition of 0.15% SHMP made the water-holding capacity in SPI gels reach the highest score after freezing (58.2 ± 0.32%). The synergistic effect of MC and SHMP could improve the strength and the freezing stability of SPI gels. MC facilitated the release of ionizable groups within SPI, causing negatively charged SHMP groups to aggregate on the SPI and inhibit the freezing aggregation of proteins. These results provide a strong basis for the improvement of cryogenic soy protein gel performance by SHMP and MC.

Highly Effective Nobiletin-MPN in Yeast Microcapsules for Targeted Modulation of Oxidative Stress, NLRP3 Inflammasome Activation, and Immune Responses in Ulcerative Colitis.

Inflammatory bowel disease (IBD) etiology is intricately linked to oxidative stress and inflammasome activation. Natural antioxidant nobiletin (NOB) contains excellent anti-inflammatory properties in alleviating intestinal injury. However, the insufficient water solubility and low bioavailability restrict its oral intervention for IBD. Herein, we constructed a highly efficient NOB-loaded yeast microcapsule (YM, NEFY) exhibiting marked therapeutic efficacy for dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) at a low oral dose of NOB (20 mg/kg). We utilized the metal polyphenol network (MPN) formed by self-assembly of epigallocatechin gallate (EGCG) and FeCl3 as the intermediate carrier to improve the encapsulation efficiency (EE) of NOB by 4.2 times. These microcapsules effectively alleviated the inflammatory reaction and oxidative stress of RAW264.7 macrophages induced by lipopolysaccharide (LPS). In vivo, NEFY with biocompatibility enabled the intestinal enrichment of NOB through controlled gastrointestinal release and macrophage targeting. In addition, NEFY could inhibit NLRP3 inflammasome and balance the macrophage polarization, which favors the complete intestinal mucosal barrier and recovery of colitis. Based on the oral targeted delivery platform of YM, this work proposes a novel strategy for developing and utilizing the natural flavone NOB to intervene in intestinal inflammation-related diseases.

Single session of intermittent theta burst stimulation alters brain activity of patients in vegetative state.

BACKGROUND: Non-invasive brain stimulation is considered as a promising technology for treating patients with disorders of consciousness (DOC). Various approaches and protocols have been proposed; however, few of them have shown potential effects on patients with vegetative state (VS). This study aimed to explore the neuro-modulation effects of intermittent theta burst stimulation (iTBS) on the brains of patients with VS and to provide a pilot investigation into its possible role in treating such patients. METHODS: We conducted a sham-controlled crossover study, a real and a sham session of iTBS were delivered over the left dorsolateral prefrontal cortex of such patients. A measurement of an electroencephalography (EEG) and a behavioral assessment of the Coma Recovery Scale-Revised (CRS-R) were applied to evaluate the modulation effects of iTBS before and after stimulation. RESULTS: No meaningful changes of CRS-R were found. The iTBS altered the spectrum, complexity and functional connectivity of the patients. The real stimulation induced a trend of decreasing of delta power at T1 and T2 in the frontal region, significant increasing of permutation entropy at the T2 in the left frontal region. In addition, brain functional connectivity, particularly inter-hemispheric connectivity, was strengthened between the electrodes of the frontal region. The sham stimulation, however, did not induce any significant changes of the brain activity. CONCLUSIONS: One session of iTBS significantly altered the oscillation power, complexity and functional connectivity of brain activity of VS patients. It may be a valuable tool on modulating the brain activities of patients with VS.

Advancements of the Molecular Directed Design and Structure-Activity Relationship of Ferritin Nanocage.

Ferritin nanocages possess remarkable structural properties and biological functions, making them highly attractive for applications in functional materials and biomedicine. This comprehensive review presents an overview of the molecular characteristics, extraction and identification of ferritin, ferritin receptors, as well as the advancements in the directional design of high-order assemblies of ferritin and the applications based on its unique structural properties. Specifically, this Review focuses on the regulation of ferritin assembly from one to three dimensions, leveraging the symmetry of ferritin and modifications on key interfaces. Furthermore, it discusses targeted delivery of nutrition and drugs through facile loading and functional modification of ferritin. The aim of this Review is to inspire the design of micro/nano functional materials using ferritin and the development of nanodelivery vehicles for nutritional fortification and disease treatment.

Lightweight federated learning for STIs/HIV prediction.

This paper presents a solution that prioritises high privacy protection and improves communication throughput for predicting the risk of sexually transmissible infections/human immunodeficiency virus (STIs/HIV). The approach utilised Federated Learning (FL) to construct a model from multiple clinics and key stakeholders. FL ensured that only models were shared between clinics, minimising the risk of personal information leakage. Additionally, an algorithm was explored on the FL manager side to construct a global model that aligns with the communication status of the system. Our proposed method introduced Random Forest Federated Learning for assessing the risk of STIs/HIV, incorporating a flexible aggregation process that can be adjusted to accommodate the capacious communication system. Experimental results demonstrated the significant potential of a solution for estimating STIs/HIV risk. In comparison with recent studies, our approach yielded superior results in terms of AUC (0.97) and accuracy ( 93 % ). Despite these promising findings, a limitation of the study lies in the experiment for man's data, due to the self-reported nature of the data and sensitive content. which may be subject to participant bias. Future research could check the performance of the proposed framework in partnership with high-risk populations (e.g., men who have sex with men) to provide a more comprehensive understanding of the proposed framework's impact and ultimately aim to improve health outcomes/health service optimisation.

Effect and mechanism of freezing on the quality and structure of soymilk gel induced by different salt ions.

BACKGROUND: The increasing attention toward frozen soy-based foods has sparked interest. Variations exist in the quality and structure of soymilk gels induced by different salt ions, leading to diverse changes post-freezing. This study compared and analyzed the effects of calcium chloride (CC), magnesium chloride (MC) and calcium sulfate (CS) on the quality characteristics and protein structure changes of soymilk gels (CC-S, MC-S and CS-S) before and after freezing, and clarified the mechanisms of freezing on soymilk gel. RESULTS: The formation rate of soymilk gel is influenced by the type of salt ions. In comparison to CS and MC, soymilk gel induced by CC exhibited the fastest formation rate, highest gel hardness, lowest moisture content, and smaller gel pores. However, freezing treatment deteriorated the quality of soymilk gel induced by different salt ions, leading to a decline in textural properties (hardness and chewiness). Among these, the textual state of CC-induced soymilk gel remained optimal, exhibiting the least apparent damage and minimal cooking loss. Freezing treatments prompt a transition of soymilk gel secondary structure from ß-turns to ß-sheets, disrupting the protein's tertiary structure. Furthermore, freezing treatments also fostered the crosslinking between soymilk gel protein, increasing the content of disulfide bonds. CONCLUSION: The quality of frozen soymilk gel is influenced by the rate of gel formation induced by salt ions. After freezing, soymilk gel with faster gelation rates exhibited a greater tendency for the transformation of protein-water interactions into protein-protein interactions. They showed a higher degree of disulfide bond formation, resulting in a more tightly knit and firm frozen gel network structure with denser and more uniformly distributed pores. © 2024 Society of Chemical Industry.

Improvement of physicochemical properties of lycopene by the self-assembly encapsulation of recombinant ferritin GF1 from oyster (Crassostrea gigas).

BACKGROUND: Lycopene (LYC), a carotenoid found in abundance in ripe red fruits, exhibits higher singlet oxygen quenching activity than other carotenoids. However, the stability of LYC is extremely poor due to its high double-bond content. In this paper, a nano-encapsulation strategy based on highly stable marine-derived ferritin GF1 nanocages was used to improve the thermal stability and oxidation resistance of LYC, thereby boosting its functional effectiveness and industrial applicability. RESULTS: The preparation of GF1-LYC nanoparticles benefited from the pH-responsive reversible self-assembly of GF1 to capture LYC molecules into GF1 cavities with a LYC-to-protein ratio of 51 to 1. After the encapsulation of the LYC, the reassembled GF1 nanocages maintained intact morphology and good monodispersity. The GF1-LYC nanoparticles incorporated the characteristic LYC peaks in spectrograms, and their powder form contained the crystalline form of LYC. Molecular docking revealed that LYC bound with the inner triple-axis channel areas of GF1, interacting with VAL139, LYS72, LYS65, TYR69, PHE129, HIS133, HIS62, and TYR134 amino acids through hydrophobic bonds. Fourier transform infrared spectroscopy also demonstrated the bonding of GF1 and LYC. In comparison with free LYC, GF1 reduced the thermal degradation of encapsulated LYC at 37 °C significantly and maintained the 2,2-Diphenyl-1-picrylhydrazyl (DPPH)-scavenging ability of LYC. CONCLUSION: As expected, the water solubility, thermal stability, and antioxidant capacity of encapsulated LYC from GF1-LYC nanoparticles was notably improved in comparison with free LYC, indicating that the shell-like marine ferritin nanoplatform might enhance the stable delivery of LYC and promote its utilization in the field of food nutrition and in other industries. © 2023 Society of Chemical Industry.

Investigation of the effect and mechanism of nanocellulose on soy protein isolate- konjac glucomannan composite hydrogel system.

To enrich the application of nanocomposite hydrogels, we introduced two types of nanocellulose (CNC, cellulose nanocrystals; CNF, cellulose nanofibers) into the soy protein isolate(SPI)- konjac glucomannan (KGM) composite hydrogel system, respectively. The similarities and differences between the two types of nanocellulose as textural improvers of composite gels were successfully explored, and a model was developed to elaborate their interaction mechanisms. Appropriate levels of CNC (1.0 %) and CNF (0.75 %) prolonged SPI denaturation within the system, exposed more buried functional groups, improved molecular interactions, and strengthened the honeycomb structural skeleton formed by KGM. The addition of CNC resulted in greater gel strength (SKC1 2708.53 g vs. Control 810.35 g), while the addition of CNF improved the elasticity (SKF0.75 1940.24 g vs. Control 405.34 g). This was mainly attributed to the reinforcement of the honeycomb-structured, water binding and trapping, and the synergistic effect of covalent (disulfide bonds) and non-covalent interactions (hydrogen bonds, ionic bonds) within the gel network. However, the balance and interactions between proteins and polysaccharides were disrupted in the composite system with excessive CNF addition (≥0.75 %), which broken the stability of the honeycomb-like structure. We expect this study will draw attention on potential applications of CNC and CNF in protein-polysaccharide binary systems and facilitate the creation of novel, superior, mechanically strength-regulated nanofiber composite gels.

Construction of Manganese-Based Oyster (Crassostrea gigas) Ferritin Nanozyme with Catalase-like Enzyme Activity.

MnO2 is a nanozyme that inhibits the decomposition of hydrogen peroxide (H2O2) into a hydroxyl radical (OH•), thus preventing its conversion into reactive oxygen species (ROS). Oyster ferritin (GF1) is a macromolecular protein that provides uniform size and high stability and serves as an excellent template for the biomineralization of nanozyme. This study presents a unique method in which MnO2 is grown in situ in the GF1 cavity, yielding a structurally stable ferritin-based nanozyme (GF1@Mn). GF1@Mn is demonstrated to be stable at 80 °C and pH 4-8, exhibiting a higher affinity with H2O2 than many other catalases (CAT) with a Michaelis constant (Km) of 25.45 mmol/L. In vitro experiments have demonstrated the potential of GF1@Mn to enhance cell survival by reducing nitric oxide (NO) production while mitigating macrophage damage from ROS. The findings are essential to developing ferritin-based nanozymes and hold great potential for applications in functional food development.

Uncovering Brain Network Insights for Prognosis in Disorders of Consciousness: EEG Source Space Analysis and Brain Dynamics.

Accurate prognostic prediction in patients with disorders of consciousness (DOC) is a core clinical concern and a formidable challenge in neuroscience. Resting-state EEG has shown promise in identifying electrophysiological prognostic markers and may be easily deployed at the bedside. However, the lack of brain dynamic modeling and the spatial mixture of signals in scalp EEG have constrained our exploration of biomarkers and comprehension of the mechanisms underlying consciousness recovery. Here, we introduce EEG source space analysis and brain dynamics to investigate the brain networks of patients with DOC (n = 178) with different outcomes (six-month follow-up), followed by graph theory and high-order topological analysis to explore the relationship between network structure and prognosis, and finally assess the importance of features. We show that a positive prognosis is associated with large-scale lower levels of low-frequency hypersynchrony. Moreover, we provide evidence that this pattern is driven not by all brain states but only by specific states. Analyses reveal that the positive prognosis is attributed to the network retaining lower segregation, higher integration, and stronger stability compared to the negative prognosis. Furthermore, our results highlight the importance of brain networks derived from brain dynamics in prognosis. The prognosis models based on clinical and neural features can achieve acceptable and even excellent performance under different outcome definitions (AUC = 0.714-0.893). Overall, our study offers new perspectives for the identification of prognostic biomarkers and provides avenues for profound insights into the mechanisms underlying consciousness improvement or recovery.

A nomogram for predicting the risk of major postoperative complications for patients with meningioma.

PURPOSE: To identify risk factors for major postoperative complications in meningioma patients and to construct and validate a nomogram that identify patients at high risk of these complications. METHODS: The medical records of meningioma patients who underwent surgical resection in our hospital from January 2018 to December 2020 were collected. The patients were divided into a training set (815 cases from the main campus in 2018 and 2019) and a validation set (300 cases from two other campuses in 2020). Major postoperative complications were defined as any new neurological deficits and complications classified as Clavien-Dindo Grading (CDG) II or higher. Univariate and multivariate analyses were conducted using the training set to identify independent risk factors. A nomogram was constructed based on these results. And then validated the nomogram through bootstrap re-sampling in both the training and validation sets. The concordance index (C-index) and the area under the curve (AUC) were used to assess the discriminative ability of the nomogram. The Hosmer-Lemeshow test was performed to evaluate the goodness-of-fit. The optimal cutoff point for the nomogram was calculated using Youden's index. RESULTS: In the training set, 135 cases (16.56%) experienced major postoperative complications. The independent risk factors identified were male sex, recurrent tumors, American Society of Anesthesiologists (ASA) class III-IV, preoperative Karnofsky Performance Scale (KPS) score < 80, preoperative serum albumin < 35 g/L, tumor in the skull base or central sulcus area, subtotal tumor resection (STR), allogeneic blood transfusion, and larger tumor size. A nomogram was constructed based on these risk factors. It demonstrated good predictive performance, with a C-index of 0.919 for the training set and 0.872 for the validation set. The area under the curve (AUC) > 0.7 indicated satisfactory discriminative ability. The Hosmer-Lemeshow test showed no significant deviation from the predicted probabilities. And the cutoff for nomogram total points was about 200 (specificity 0.881 and sensitivity 0.834). CONCLUSIONS: The constructed nomogram demonstrated robust predictive performance for major postoperative complications in meningioma patients. This model can be used by surgeons as a reference in clinical decision-making.

The gap-free genome of mulberry elucidates the architecture and evolution of polycentric chromosomes.

Mulberry is a fundamental component of the global sericulture industry, and its positive impact on our health and the environment cannot be overstated. However, the mulberry reference genomes reported previously remained unassembled or unplaced sequences. Here, we report the assembly and analysis of the telomere-to-telomere gap-free reference genome of the mulberry species, Morus notabilis, which has emerged as an important reference in mulberry gene function research and genetic improvement. The mulberry gap-free reference genome produced here provides an unprecedented opportunity for us to study the structure and function of centromeres. Our results revealed that all mulberry centromeric regions share conserved centromeric satellite repeats with different copies. Strikingly, we found that M. notabilis is a species with polycentric chromosomes and the only reported polycentric chromosome species up to now. We propose a compelling model that explains the formation mechanism of new centromeres and addresses the unsolved scientific question of the chromosome fusion-fission cycle in mulberry species. Our study sheds light on the functional genomics, chromosome evolution, and genetic improvement of mulberry species.

Electrophysiological characteristics of CM-pf in diagnosis and outcome of patients with disorders of consciousness.

BACKGROUND: Deep brain stimulation (DBS) in the centromedian-parafascicular complex (CM-pf) has been reported as a potential therapeutic option for disorders of consciousness (DoC). However, the lack of understanding of its electrophysiological characteristics limits the improvement of therapeutic effect. OBJECTIVE: To investigate the CM-pf electrophysiological characteristics underlying disorders of consciousness (DoC) and its recovery. METHODS: We collected the CM-pf electrophysiological signals from 23 DoC patients who underwent central thalamus DBS (CT-DBS) surgery. Five typical electrophysiological features were extracted, including neuronal firing properties, multiunit activity (MUA) properties, signal stability, spike-MUA synchronization strength (syncMUA), and the background noise level. Their correlations with the consciousness level, the outcome, and the primary clinical factors of DoC were analyzed. RESULTS: 11 out of 23 patients (0/2 chronic coma, 5/13 unresponsive wakefulness syndrome/vegetative state (UWS/VS), 6/8 minimally conscious state minus (MCS-)) exhibited an improvement in the level of consciousness after CT-DBS. In CM-pf, significantly stronger gamma band syncMUA strength and alpha band normalized MUA power were found in MCS- patients. In addition, higher firing rates, stronger high-gamma band MUA power and alpha band normalized power, and more stable theta oscillation were correlated with better outcomes. Besides, we also identified electrophysiological properties that are correlated with clinical factors, including etiologies, age, and duration of DoC. CONCLUSION: We provide comprehensive analyses of the electrophysiological characteristics of CM-pf in DoC patients. Our results support the 'mesocircuit' hypothesis, one proposed mechanism of DoC recovery, and reveal CM-pf electrophysiological features that are crucial for understanding the pathogenesis of DoC, predicting its recovery, and explaining the effect of clinical factors on DoC.

Evaluating the effect of spinal cord stimulation on patient with disorders of consciousness: A TMS-EEG study.

OBJECTIVE: The application of spinal cord stimulation (SCS) in the treatment of disorders of consciousness (DOC) has attracted attention, but its effect on brain activity is still unknown. Transcranial magnetic stimulation combined with EEG (TMS-EEG) can measure cortical activity, which can evaluate the effect of SCS on DOC. METHODS: We record 20 DOC patients' CRS-R values and TMS-EEG data before and after one-session SCS (Pre-SCS and Post-SCS). 20 DOC patients including 10 patients with unresponsive wakefulness syndrome (UWS) and 10 patients with minimally conscious states (MCS). TMS evoked potential (TEP) was used to measure the changes of cortical activity in DOC patients between Pre-SCS and Post-SCS. Firstly, we used the global mean field potential (GMFP) and fast perturbational complexity index (PCIst) to compare the temporal changes of patients' cortical activity. Then, we obtained the frequency feature (natural frequency, NF) based on the TEP time-frequency analysis, and compared the changes of natural frequency between Pre-SCS and Post-SCS. Finally, the study explored the relationship between the patient's baseline CRS-R values and changes of TMS evoked cortical activity in time and frequency domains. RESULTS: After SCS, MCS and UWS groups almost have no changes of CRS-R values (MCS: 9.9 ± 1.52 at Pre-SCS, 10.2 ± 1.48 at Post-SCS; UWS: 5.6 ± 1.26 at Pre-SCS, 5.7 ± 1.34 at Post-SCS). MCS group showed significant increases of GMFP amplitude (around 100 ms and 300 ms) and PCIst values at Post-SCS (p < 0.05). UWS group had no significant changes (p > 0.05). Besides, SCS induced the significant increases of natural frequency for MCS group(p < 0.05), but not for UWS group. At last, the study found that all patient's baseline CRS-R values were significantly correlated with ΔPCIst (r = 0.67, p < 0.005), and ΔNF (r = 0.72, p < 0.001). CONCLUSIONS: SCS can modulate cortical activity of DOC patient, including temporal complexity and natural frequency. The changes of cortical activity caused by SCS are related to patients' consciousness level. TMS-EEG can evaluate the effect of SCS on DOC patients.

Facilitating Pro-survival Mitophagy for Alleviating Parkinson's Disease via Sequence-Targeted Lycopene Nanodots.

The pathogenesis of Parkinson's disease is closely linked to impaired mitochondrial function and abnormal mitophagy. Biocompatible natural antioxidants effectively protect dopaminergic neurons. However, the main challenge in using natural antioxidants for Parkinson's disease therapy is creating a delivery platform to achieve neuron-targeted enrichment. Herein, we synthesized rationally sequence-targeted lycopene nanodots using recombinant human H-ferritin nanocages with lycopene loading into the cavity and lipophilic triphenylphosphonium (TPP) coupling on the outer surface. The nanodots allow for the neural enrichment and mitochondrial regulation of lycopene through blood-brain barrier transcytosis and neuronal mitochondria-targeting capability. These anti-ROS nanodots protect neuronal mitochondrial function and promote PINK1/Parkin-mediated mitophagy in MPTP toxicity-induced neurons in vivo and in vitro, which favors the secretory efflux of pathogenic α-synuclein and the survival of dopaminergic neurons. Moreover, these nanodots restore the Parkinson-like motor symptoms in Parkinson's model mice. This noninvasive sequence-targeted delivery strategy with excellent biocompatibility for pro-survival mitophagy-mediated pathology alleviation makes it a promising approach for treating and preventing Parkinson's disease.

Oyster (Crassostrea gigas) ferritin relieves lead-induced liver oxidative damage via regulating the mitophagy.

Lead can induce oxidative stress and increase lipid peroxidation in biofilms, leading to liver damage and physiological dysfunction. This study aimed to investigate how oyster ferritin (GF1) attenuates lead-induced oxidative damage to the liver in vitro and in vivo. Animal experiments have confirmed that lead exposure can lead to oxidative damage and lipid peroxidation of the liver, and ferritin can regulate the activity of antioxidant enzymes and alleviate pathological changes in the liver. At the same time, oyster ferritin can regulate the expression of oxidative stress-related genes and reduce the expression of inflammasome-related genes. In addition, lead can induce apoptosis and mitophagy, leading to overproduction of reactive oxygen species and cell death, which can be effectively alleviated by oyster ferritin. Overall, this study provides a theoretical foundation for the use of oyster ferritin as a means of mitigating and preventing lead-induced damage.

IL-27 regulates NLRP3 inflammasome activation of MDSCs in experimental Sjögren's syndrome.

Excessive NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation has an important function in the pathogenesis of Sjögren's syndrome (SS). Increased and dysfunctional myeloid-derived suppressor cells (MDSCs) promoted SS. However, NLRP3 inflammasome activation of MDSCs in SS and its regulated components are unclear. Splenic MDSCs were purified by immunomagnetic beads and cultured. Western blot was used to assess NLRP3 inflammasomes. Interleukin-1ß (IL-1ß) and IL-18 were measured using enzyme-linked immunosorbent assay. Here we showed that the NLRP3 inflammasome was activated in non-obese diabetic (NOD) mice with SS-like manifestations. We found that NLRP3 inflammasome activation was augmented in MDSCs of SS mice and NLRP3 inflammasome activation was suppressed in IL-27-deficient NOD mice. Consistent with findings of SS mice in vivo, we observed that NLRP3 inflammasome activation by adenosine triphosphate and lipopolysaccharide was remarkably intensified in MDSCs with IL-27 treatment in vitro. Collectively, our data highlighted that IL-27 regulates NLRP3 inflammasome activation of MDSCs in experimental SS.

Antifouling Surfaces Based on Polyzwitterion Loop Brushes.

Antifouling surfaces have attracted increasing interest in recent years due to their potential application in various fields. In this work, we report a loop polyzwitterionic coating that exhibits excellent resistance to protein adsorption. Triblock and diblock copolymers of 2-[(2-hydroxyethyl)disulfanyl]ethyl methacrylate) (HSEMA) and 2-(dimethylamino)ethyl methacrylate) (DMAEMA) were synthesized by atom-transferred radical polymerization, followed by betainization of the DMAEMA block with 1,3-propane sultone and reduction of the disulfide bond in HSEMA to yield a triblock copolymer comprising a zwitterionic poly(sulfobetaine methacrylate) (PSBMA) midblock and poly(2-sulfanylethyl methacrylate) (PSEMA) terminal blocks as well as its diblock analogue that was of the same composition as the former and half the chain length. Both copolymers adsorbed to the gold substrate via the thiol groups in the terminal PSEMA block(s), creating loop and linear PSBMA brush coatings of comparable thickness, as revealed by X-ray photoelectron spectroscopy and ellipsometry. Adsorption of bovine serum albumin and fibrinogen as model proteins from solution to these surfaces was investigated by a quartz crystal microbalance with dissipation and confocal laser scanning microscopy (CLSM), and platelet and bacterial adhesions were assessed by scanning electron microscopy and CLSM. The results demonstrate that both linear and loop polyzwitterion brushes are excellent in resisting the adsorption of the foulants, and the loop brushes are superior to the linear analogues.