A Stretchable and Tough Graphene Film Enabled by Mechanical Bond.

The pursuit of fabricating high-performance graphene films has aroused considerable attention due to their potential for practical applications. However, developing both stretchable and tough graphene films remains a formidable challenge. To address this issue, we herein introduce mechanical bond to comprehensively improve the mechanical properties of graphene films, utilizing [2]rotaxane as the bridging unit. Under external force, the [2]rotaxane cross-link undergoes intramolecular motion, releasing hidden chain and increasing the interlayer slip distance between graphene nanosheets. Compared with graphene films without [2]rotaxane cross-linking, the presence of mechanical bond not only boosted the strength of graphene films (247.3 vs 74.8 MPa) but also markedly promoted the tensile strain (23.6 vs 10.2%) and toughness (23.9 vs 4.0 MJ/m3). Notably, the achieved tensile strain sets a record high and the toughness surpasses most reported results, rendering the graphene films suitable for applications as flexible electrodes. Even when the films were stretched within a 20% strain and repeatedly bent vertically, the light-emitting diodes maintained an on-state with little changes in brightness. Additionally, the film electrodes effectively actuated mechanical joints, enabling uninterrupted grasping movements. Therefore, the study holds promise for expanding the application of graphene films and simultaneously inspiring the development of other high-performance two-dimensional films.

Phosphoproteomic Analysis Reveals the Predominating Cellular Processes and the Involved Key Phosphoproteins Essential for the Proliferation of Toxoplasma gondii.

PURPOSE: To explore the essential roles of phosphorylation in mediating the proliferation of T. gondii in its cell lytic life. METHODS: We profiled the phosphoproteome data of T. gondii residing in HFF cells for 2 h and 6 h, representing the early- and late-stages of proliferation (ESP and LSP) within its first generation of division. RESULTS: We identified 70 phosphoproteins, among which 8 phosphoproteins were quantified with the phosphorylation level significantly regulated. While only two of the eight phosphoproteins, GRA7 and TGGT1_242070, were significantly down-regulated at the transcriptional level in the group of LSP vs. ESP. Moreover, GO terms correlated with host membrane component were significantly enriched in the category of cellular component, suggesting phosphoprotein played important roles in acquiring essential substance from host cell via manipulating host membrane. Further GO analysis in the categories of molecular function and biological process and pathway analysis revealed that the cellular processes of glucose and lipid metabolism were regulated by T. gondii phosphoproteins such as PMCAA1, LIPIN, Pyk1 and ALD. Additionally, several phosphoproteins were enriched at the central nodes in the protein-protein interaction network, which may have essential roles in T. gondii proliferation including GAP45, MLC1, fructose-1,6-bisphosphate aldolase, GRAs and so on. CONCLUSION: This study revealed the main cellular processes and key phosphoproteins crucial for the intracellular proliferation of T. gondii, which would provide clues to explore the roles of phosphorylation in regulating the development of tachyzoites and new insight into the mechanism of T. gondii development in vitro.

Association Between Circulating Zinc Levels and Risk Factors of Metabolic Syndrome: Insights from a Bi-directional Mendelian Randomization Analysis and Cross-Sectional Study.

Previous studies on the relationship between zinc and metabolic syndrome (MetS) have yielded inconsistent results. This comprehensive study aimed to elaborately explore the impact of zinc on MetS risk factors. The bi-directional Mendelian randomization (MR) analyses were performed to estimate the causal relationship between zinc and MetS risk factors. Additionally, a retrospective cross-sectional study incorporated 4389 subjects to provide a broader perspective in conjunction with the MR analyses. In the MR analyses, genetically instrumented zinc was positively associated with five of the MetS components in Europeans, including BMI, FBG, HbA1c, TC, and LDL-c (ß (95%CI) = 0.023 (0.019-0.027), 0.019 (0.013-0.025), 0.041 (0.022-0.060), 0.027 (0.013-0.042), and 0.018 (0.010-0.026), respectively). In the cross-sectional study, higher concentration of zinc was strongly associated with increased BMI, LDL-c, and UA (ß (95%CI) = 0.040 (0.010-0.085), 0.026 (0.018-0.035), and 1.529 (0.614-2.445), respectively). Moreover, these unfavorable associations were more obvious in women compared to men, with a borderline significant interaction effect for BMI (P=0.051). Our study showed that higher blood concentration of zinc, an essential trace element, was associated with unfavorable changes of the component metabolic risk factors of MetS, especially with BMI and LDL-c. Notably, these associations seemed to be more pronounced in women rather than in men. Further studies are warranted to elucidate the role of zinc status in the underlying mechanisms of MetS.

Associations of psychological status and ultrasonic characteristics of thyroid nodules in adults during the COVID-19 pandemic.

Background: The morbidity of thyroid cancer has been increasing in the last decades all over the world. In addition to the more sensitive thyroid nodule screening technology, several social and environmental factors might represent credible candidates for this increase. They include psychological stress, lifestyle-associated risk factors, nutritional deficiencies, and environmental pollutants. Foremost, psychological stress had gained high interest as a possible promoter and a modifiable risk factor for thyroid nodules in recent years. The present study was to investigate the clinical characteristics and psychological status of the population during the peak of coronavirus disease 2019 (COVID-19) and assessed the association of psychosocial determinants and the ultrasonic characteristics of thyroid nodules. Methods: In this cross-sectional study, 490 adult subjects who had received at least two doses of COVID-19 vaccine and were not infected with COVID-19, and did not know whether they had thyroid nodules, received thyroid color ultrasound examination and psychological questionnaire survey. Depression, anxiety, and stress were assessed using Depression Anxiety Stress Scales-21 (DASS-21). Sleep quality was rated using the Pittsburgh sleep quality index (PQSI). The characteristics of 243 subjects with thyroid nodules were described and recorded in detail by thyroid color ultrasound, and the correlations between anxiety, depression, sleep quality, clinical indicators, and thyroid nodule ultrasound characteristics were analyzed. Associations between psychological status (mutually adjusted predictors) and ultrasonic characteristics of thyroid nodules (outcome) were modeled using binary logistic regression controlling for sex, age, BMI, TSH, FT3, and FT4. Results: Depression was positively correlated with thyroid hypoechoic nodule (OR = 3.720, 95%CI 1.615-8.570), microcalcification of thyroid nodule (OR = 3.638, 95%CI 1.476-8.966), the aspect ratio of thyroid nodule>1 (OR = 3.860, 95%CI 1.052-14.161), the unclear boundary of thyroid nodule (OR = 4.254, 95%CI 1.359-13.312), and the irregular edge of thyroid nodule (OR = 4.134, 95%CI 1.810-9.439). Anxiety was positively correlated with microcalcification of thyroid nodules (OR = 4.319, 95%CI 1.487-11.409). Stress was positively correlated with thyroid hypoechoic nodules (OR = 4.319, 95%CI 1.487-11.409), microcalcification of thyroid nodules (OR = 2.724, 95%CI 1.038-7.151), and the irregular edge of thyroid nodules (OR = 2.478, 95%CI 1.077-5.705). Conclusion: This study demonstrates that depression, anxiety, and stress were associated with the morbidity of thyroid nodules and thyroid ultrasound characteristics. During COVID-19, people's negative emotions increased significantly compared to before. Negative emotions might be harmful to thyroid health. Therefore, during periods of high stress, strategies to prevent psychological problems should be implemented to improve thyroid health.

Insights into the Correlation of Cross-linking Modes with Mechanical Properties for Dynamic Polymeric Networks.

Simultaneously introducing covalent and supramolecular cross-links into one system to construct dually cross-linked networks, has been proved an effective approach to prepare high-performance materials. However, so far, features and advantages of dually cross-linked networks compared with those possessing individual covalent or supramolecular cross-linking points are rarely investigated. Herein, on the basis of comparison between supramolecular polymer network (SPN), covalent polymer network (CPN) and dually cross-linked polymer network (DPN), we reveal that the dual cross-linking strategy can endow the DPN with integrated advantages of CPN and SPN. Benefiting from the energy dissipative ability along with the dissociation of host-guest complexes, the DPN shows excellent toughness and ductility similar to the SPN. Meanwhile, the elasticity of covalent cross-links in the DPN could rise the structural stability to a level comparable to the CPN, exhibiting quick deformation recovery capacity. Moreover, the DPN has the strongest breaking stress and puncture resistance among the three, proving the unique property advantages of dual cross-linking method. These findings gained from our study further deepen the understanding of dynamic polymeric networks and facilitate the preparation of high-performance elastomeric materials.

Mechanically Interlocked [2]Rotaxane Aerogels with Tunable Morphologies and Mechanical Properties.

Mechanical bonds have been utilized as promising motifs to construct mechanically interlocked aerogels (MIAs) with mechanical adaptivity and multifunctionality. However, fabricating such aerogels with not only precise chemical structures but also dynamic features remains challenging. Herein, we present MIAs carrying dense [2]rotaxane units, which bestow both the stability and flexibility of the aerogel network. Owing to the stable chemical structure of a [2]rotaxane, MIAs possessing a precise and full-scale mechanically interlocked network could be fabricated with the aid of diverse solvents. In addition, the dynamic nature of the [2]rotaxane resulted in morphologies and mechanical performances of the MIAs that can be dramatically modulated under chemical stimuli. We hope that the structure-property relationship in MIAs will facilitate the development of mechanically interlocked materials and provide novel opportunities toward constructing smart materials with multifunctionalities.

Expanded vermiculite supported capric-palmitic acid composites for thermal energy storage.

In this study, the potential application of expanded vermiculite (EVM) as the supporting material and capric-palmitic acid (CA-PA) binary eutectic as the adsorbent mixture to fabricate a form-stable composite CA-PA/EVM by a vacuum impregnation method was investigated. The prepared form-stable composite CA-PA/EVM was then characterized by scanning electronic microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), thermogravimetric analysis (TG), differential scanning calorimetry (DSC) and a thermal cycling test. The maximum loading capacity and melting enthalpy of CA-PA/EVM could reach 51.84% and 67.5 J g-1. Meanwhile, the thermal physical and mechanical properties of the CA-PA/EVM-based thermal energy storage mortars were examined to determine if the composite material based on the newly invented CA-PA/EVM material can be employed for energy conservation and efficiency in the building field. In addition, the law of full-field deformation evolution of CA-PA/EVM-based thermal energy storage mortar under uniaxial compression failure was studied based on digital image correlation (DIC) technology, which provides certain guiding significance for the application of CA-PA/EVM-based thermal energy storage mortars in practical engineering.

Oligo[2]catenane That Is Robust at Both the Microscopic and Macroscopic Scales.

Polycatenanes are extremely attractive topological architectures on account of their high degrees of conformational freedom and multiple motion patterns of the mechanically interlocked macrocycles. However, exploitation of these peculiar structural and dynamic characteristics to develop robust catenane materials is still a challenging goal. Herein, we synthesize an oligo[2]catenane that showcases mechanically robust properties at both the microscopic and macroscopic scales. The key feature of the structural design is controlling the force-bearing points on the metal-coordinated core of the [2]catenane moiety that is able to maximize the energy dissipation of the oligo[2]catenane via dissociation of metal-coordination bonds and then activation of sequential intramolecular motions of circumrotation, translation, and elongation under an external force. As such, at the microscopic level, the single-molecule force spectroscopy measurement exhibits that the force to rupture dynamic bonds in the oligo[2]catenane reaches a record high of 588 ± 233 pN. At the macroscopic level, our oligo[2]catenane manifests itself as the toughest catenane material ever reported (15.2 vs 2.43 MJ/m3). These fundamental findings not only deepen the understanding of the structure-property relationship of poly[2]catenanes with a full set of dynamic features but also provide a guiding principle to fabricate high-performance mechanically interlocked catenane materials.

Highly Strong and Tough Supramolecular Polymer Networks Enabled by Cryptand-Based Host-Guest Recognition.

Supramolecular polymer networks (SPNs) demonstrate great potential in the development of smart materials owing to their attractive dynamic properties. However, as they suffer from the inherent weak bonding of most noncovalent cross-links, it remains a significant challenge to construct SPNs with outstanding mechanical performance. Herein, we exploit the cryptand/paraquat host-guest recognition motifs as cross-links to prepare a class of highly strong and tough SPNs. Unlike those supramolecular cross-links with relatively weak binding abilities, the cryptand-based host-guest interactions have a high association constant and steady complexing structure, which effectively stabilizes the network and resists mechanical deformation under external force. Such favorable structural stability endows our SPNs with greatly enhanced mechanical performance, compared with the control-1 cross-linked by the weakly complexed crown ether/secondary ammonium salt motif (tensile strength: 21.1±0.5 vs 2.8±0.1 MPa; Young's modulus: 102.6±4.8 vs 2.1±0.3 MPa; toughness: 90.4±2.0 vs 10.8±0.6 MJ m-3 ). Moreover, our SPNs also retain abundant dynamic properties including good abilities in energy dissipation, reprocessability, and stimuli-responsiveness. These findings provide novel insights into the preparation of SPNs with enhanced mechanical properties, and promote the development of high-performance intelligent supramolecular materials.

Gender differences in the ideal cutoffs of visceral fat area for predicting MAFLD in China.

BACKGROUND: Since the discovery of metabolic-associated fatty liver disease (MAFLD) in 2020, no report on the connection between the visceral fat area (VFA) and MAFLD has been published in China, and the ideal cutoffs of VFA for predicting MAFLD has not been determined so far. Thus, the purpose of this research was to clarify the relationship between VFA and MAFLD and the ideal cutoffs of VFA to predict MAFLD in the Chinese population. METHODS: Five thousand three hundred forty subjects were included in this research, with 30% randomly selected for the validation set (n = 1602) and 70% for the Training set (n = 3738). The association between VFA and MAFLD was determined by multiple logistic regression. ROC curves were used to evaluate the prediction effect of VFA on MAFLD. RESULTS: Multiple logistic regression analysis revealed that the VFA ORs (95% CIs) were 1.25 (1.20, 1.29) for women and 1.15 (1.12, 1.17) for men. Meanwhile, the VFA quartile OR (95% CI) were 3.07 (1.64, 5.75), 7.22 (3.97, 13.14), 18.91 (10.30, 34.71) for women and 3.07 (1.64, 5.75), 7.22 (3.97, 13.14),18.91 (10.30, 34.71) for men in the Q2, Q3, and Q4 groups compared with Q1. The ROC curve showed the VFA, WC, WHR, and WHtR to predict MAFLD, the AUC value of VFA was the highest and the prediction effect was the best. The ideal cutoffs of VFA to predict MAFLD was 115.55 cm2 for women and 178.35 cm2 for men, and the AUC was 0.788 and 0.795, respectively. Finally, the AUC was 0.773 for women and 0.800 for men in the validation set. CONCLUSION: VFA was an independent predictive factor for MAFLD, and the ideal cutoff of VFA to predict MAFLD was 115.55 cm2 in women and 178.35 cm2 in men.

Amplification of integrated microscopic motions of high-density [2]rotaxanes in mechanically interlocked networks.

Integrating individual microscopic motion to perform tasks in macroscopic sale is common in living organisms. However, developing artificial materials in which molecular-level motions could be amplified to behave macroscopically is still challenging. Herein, we present a class of mechanically interlocked networks (MINs) carrying densely rotaxanated backbones as a model system to understand macroscopic mechanical properties stemmed from the integration and amplification of intramolecular motion of the embedded [2]rotaxane motifs. On the one hand, the motion of mechanical bonds introduces the original dangling chains into the network, and the synergy of numerous such microscopic motions leads to an expansion of entire network, imparting good stretchability and puncture resistance to the MINs. On the other hand, the dissociation of host-guest recognition and subsequent sliding motion represent a peculiar energy dissipation pathway, whose integration and amplification result in the bulk materials with favorable toughness and damping capacity. Thereinto, we develop a continuous stress-relaxation method to elucidate the microscopic motion of [2]rotaxane units, which contributes to the understanding of the relationship between cumulative microscopic motions and amplified macroscopic mechanical performance.

Weldable and closed-loop recyclable monolithic dynamic covalent polymer aerogels.

Owing to their low density, high porosity and unique micro-nanostructures, aerogels are attractive for application in various fields; however, they suffer from shrinkage and/or cracking during preparation, mechanical brittleness, low production efficiency and non-degradation. Herein, we introduce the concept of dynamic covalent polymer chemistry to produce a new class of aerogels-referred to as DCPAs. The resulting lightweight DCPAs have the potential to be prepared on a large scale and feature high porosity (90.7%-91.3%), large degrees of compression (80% strain) and bending (diametral deflection of 30 mm) without any cracks, as well as considerable tensile properties (an elongation with a break at 32.7%). In addition, the DCPAs showcase the emergent characteristics of weldability, repairability, degradability and closed-loop recyclability that are highly desirable for providing versatile material platforms, though hardly achieved by traditional aerogels. Taking advantage of their robust porous structures, we demonstrate the potential of DCPAs for applications in thermal insulation and emulsion separation. These findings reveal that the dynamic covalent bond strategy would be generalized for the production of a new generation of aerogels with customized features for functioning in the field of intelligent and sustainable materials.

The visceral and liver fat are significantly associated with the prevalence of hyperuricemia among middle age and elderly people: A cross-sectional study in Chongqing, China.

Background: The prevalence of hyperuricemia (HUA) has been increasing in recent years. HUA is a crucial risk factor for gout and an independent risk factor for cardiovascular diseases (CVDs). Identifying potentially modifiable factors of HUA is vital for preventing gout and even CVDs. This study aimed to explore the associations of fat distribution with HUA among middle-aged and elderly people in Chongqing, China. Materials and methods: A cross-sectional study was conducted between July 2020 and September 2021. People who underwent quantitative computed tomography (QCT) scans were invited to participate in the study. A total of 3,683 individuals whose clinical characteristics and QCT-based fat distribution measurements included visceral fat area (VFA), subcutaneous fat area (SFA), and liver fat content (LFC) were well-recorded were included. HUA was defined as having a serum uric acid level greater than 420.0 µmol/L. Multivariate logistic regression models were used to evaluate the association between these adipose variables and HUA prevalence. Results: The HUA prevalence was 25.6% (943/3,683), which was 39.6% (817/2,063) in men and 7.8% (126/1,620) in women. In the fully adjusted model (model 4), the comparison of the highest one with the lowest quartiles of adipose variables showed that the multivariable OR (95% confidence intervals) of HUA were 2.08 (1.36-3.16; P for trend = 0.001) for VFA, 0.89 (0.63-1.25; P for trend = 0.651) for SFA, and 1.83 (1.42-2.34; P for trend < 0.0001) for LFC. For VFA, the association was more evident in men than in women. Conclusion: Higher VFA and LFC were significantly associated with the increased prevalence of HUA in middle-aged and elderly Chinese individuals. VFA and LFC may have a predictive effect on HUA. Controlling visceral and liver fat accumulation may be beneficial for middle-aged and older people. HUA can be prevented with specific effective healthy physical activity and balanced diet guidelines.

Identification of novel B-1 transitional progenitors by B-1 lymphocyte fate-mapping transgenic mouse model Bhlhe41 dTomato-Cre.

B-1 lymphocytes exhibit specialized roles in host defense against multiple pathogens. Despite the fact that CD19+CD93+B220lo/- B cells have been identified as B-1 progenitors, the definition for B-1 progenitors remains to be elucidated as CD19+CD93+B220+ B cells are capable to give rise to B-1 cells. Given that transcription factor Bhlhe41 is highly and preferentially expressed in B-1 cells and regulates B-1a cell development, we generated a transgenic mouse model, Bhlhe41dTomato-Cre , for fate mapping and functional analysis of B-1 cells. Bhlhe41dTomato-Cre mice efficiently traced Bhlhe41 expression, which was mainly restricted to B-1 cells in B-cell lineage. We showed an efficient and specific Cre-mediated DNA recombination in adult B-1 cells and neonatal B-1 progenitors rather than B-2 cells by flow cytometric analysis of Bhlhe41 dTomato-Cre/+ Rosa26 EYFP mice. Treatment of Bhlhe41 dTomato-Cre/+ Rosa26 iDTR mice with diphtheria toxin revealed a robust efficacy of B-1 cell depletion. Interestingly, using Bhlhe41 dTomato-Cre mice, we demonstrated that neonatal B-1 progenitors (CD19+CD93+B220lo/-) expressed Bhlhe41 and were identical to well-defined transitional B-1a progenitors (CD19+CD93+B220lo/-CD5+), which only gave rise to peritoneal B-1a cells. Moreover, we identified a novel population of neonatal splenic CD19hidTomato+B220hiCD43loCD5lo B cells, which differentiated to peritoneal B-1a and B-1b cells. Bhlhe41 deficiency impaired the balance between CD19hidTomato+B220lo/-CD5hi and CD19hidTomato+B220hiCD5lo cells. Hence, we identified neonatal CD19hidTomato+B220hiCD43loCD5lo B cells as novel transitional B-1 progenitors. Bhlhe41 dTomato-Cre/+ mouse can be used for fate mapping and functional studies of B-1 cells in host-immune responses.

The hypoxia-driven crosstalk between tumor and tumor-associated macrophages: mechanisms and clinical treatment strategies.

Given that hypoxia is a persistent physiological feature of many different solid tumors and a key driver for cancer malignancy, it is thought to be a major target in cancer treatment recently. Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME), which have a large impact on tumor development and immunotherapy. TAMs massively accumulate within hypoxic tumor regions. TAMs and hypoxia represent a deadly combination because hypoxia has been suggested to induce a pro-tumorigenic macrophage phenotype. Hypoxia not only directly affects macrophage polarization, but it also has an indirect effect by altering the communication between tumor cells and macrophages. For example, hypoxia can influence the expression of chemokines and exosomes, both of which have profound impacts on the recipient cells. Recently, it has been demonstrated that the intricate interaction between cancer cells and TAMs in the hypoxic TME is relevant to poor prognosis and increased tumor malignancy. However, there are no comprehensive literature reviews on the molecular mechanisms underlying the hypoxia-mediated communication between tumor cells and TAMs. Therefore, this review has the aim to collect all recently available data on this topic and provide insights for developing novel therapeutic strategies for reducing the effects of hypoxia.

Supervised mHeath Exercise Improves Health Factors More Than Self-Directed mHealth Exercise: A Clinical Controlled Study.

Wearable physical activity trackers are getting popular for the self-management of weight despite limited evidence of their efficacy. Studies have proven that on-site supervised exercise is superior to unsupervised exercise for many health problems, there is no evidence comparing the effectiveness of remote supervision exercise with self-directed exercise based on mHealth. This study aims to compare the effects of mHealth-based supervised exercise to mHealth-based self-directed exercise on weight control in the overweight and obese population. A nonrandomized controlled clinical study was conducted. Overweight or obese volunteers were given personalized exercise prescriptions based on their HRR (Heart Rate Reserve), all patients were equipped with wearable heartbeat trackers to follow their exercise performance and additional remote supervisions were added to the intervention group. Exercise performances, weight losses, and health examinations were compared between 2 groups after 12 weeks of follow-up. Analysis of covariance (ANCOVA) was used to determine any differences between study groups after intervention. Two groups had the same rate of attrition in 12 weeks of follow-up, but the exercising day, the effective exercising day and the rate of effective exercising day in the supervised group were higher than those in the control group. Weight loss was -2.7 ± 2.8 kg in the intervention group and -2.0 ± 2.9 kg in the control group (P = 0.23). Compared with the control group, participants in the intervention group improved their liver function, kidney function, fasting blood sugar, total cholesterol, and triglyceride. mHealth-based supervised exercise is more effective in health factors improvement than mHealth-based self-directed exercise among overweight and obesity participants.

Toxoplasma gondii rhoptry protein (TgROP18) enhances the expression of pro-inflammatory factor in LPS/IFN-γ-induced murine BV2 microglia cells via NF-κB signal pathway.

Toxoplasma gondii, an opportunistic pathogenic protozoan, exhibits a strong predilection to infect the brain, causing severe neurological diseases, such as toxoplasmic encephalitis (TE), in immunocompromised patients. Microglia, the resident immune cells in the brain, is reported to play important roles in regulating the neuroinflammation mediated by T. gondii infection. Here we demonstrated that the tachyzoites of T. gondii RH strain could significantly upregulate the expression levels of microglial M1 phenotype markers including IL-1ß, IL-6, TNF-α, iNOS and IL18 in activated murine BV2 microglia cells, which were regulated by T. gondii rhoptry protein 18 (TgROP18). Moreover, we found that TgROP18 could enhance the expression of M1 phenotype markers in activated murine BV2 microglia cells via activating NF-κB signal pathway. Additionally, TgROP18 was suggested to interact with the host p65 in activated murine BV2 microglia cells and induce the phosphorylation of p65 at S536. In summary, the present study demonstrated that TgROP18 could promote the activated microglia to polarize to M1 phenotype and enhanced the expression of pro-inflammatory factors via activating NF-κB signal pathway, which could contribute to elucidating the mechanism underlying the neuroinflammation mediated by activated microglia in the brain with T. gondii infection.

Mechanically Interlocked Aerogels with Densely Rotaxanated Backbones.

Mechanically interlocked molecules are considered promising candidates for the construction of self-adaptive materials by virtue of their fascinating structural and dynamic features. However, it is still a great challenge to fabricate such materials with higher complexity and richer functionality. Herein, we propose the concept of mechanically interlocked aerogels (MIAs) in which the three-dimensional (3D) porous frameworks are made of dense mechanically interlocked modules, thereby enabling the integration of mechanical adaptivity and multifunctionality in a single entity. The lightweight MIA monoliths possess a good appearance and hierarchical meso- and submicron-pores. Profiting from the combination of dynamic mechanical bonds and porous skeletons of aerogels, our MIAs are not only mechanically robust (average Young's modulus = 5.80 GPa and specific modulus = 130.5 kN·m/kg) but also showcase favorable mechanical adaptivity and responsiveness under external stimuli. Taking advantage of the above integrative merits, we demonstrate the multifunctionality of our MIAs in terms of iodine uptake, thermal insulation, and selective adsorption of organic dyes. Our work opens the door to designing intelligent aerogels with delicate topological chemical structures while facilitating the development of mechanically interlocked materials.

An efficient and cost-effective method for the purification of human basophils.

Human basophils are terminally differentiated granulocytes that are least abundant in the peripheral blood but play important roles in allergic diseases. Studies on human basophils are limited by the high cost on the isolation of human basophils by magnetic-activated cell sorting (MACS) for negative depletion of non-basophils, followed by CD123-based positive selection of basophils. Moreover, such CD123-based purification of basophils may be limited by blocking of the binding of IL-3/anti-CD123 to the surface CD123. Here we identified SSClow CD4- CD127- HLA-DR- CRTH2high as unique markers for the identification of human basophils through stringent flow cytometric analysis of leukocytes from buffy coat. We established an efficient and cost-effective method for isolating human basophils from buffy coat based on positive magnetic selection of CRTH2+ cells followed by flow cytometric sorting of SSClow CD4- CD127- HLA-DR- CRTH2high cells. Approximately 1 to 1.5 million basophils were isolated from one buffy coat with a purity of >97%. Basophils purified by this method were viable and efficiently responded to key regulators of basophils including IL-3 and anti-IgE. This method can be used for purifying human basophils for subsequent functional studies.

Bioadhesive poly(methyl vinyl ether-co-maleic anhydride)-TPGS copolymer modified PLGA/lipid hybrid nanoparticles for improving intestinal absorption of cabazitaxel.

A bioadhesive nanocarrier, PTNP, was constructed by utilizing a novel poly(methyl vinyl ether-co-maleic anhydride)- D-α-Tocopheryl polyethylene glycol succinate (PVMMA-TPGS) copolymer in the PLGA/lipid hybrid nanoparticles (PLGA NPs) for improving oral delivery of cabazitaxel (CTX). The PVMMA-TPGS was synthesized by the ring-opening polymerization of the anhydride groups with the hydroxyl groups, combining the bioadhesive property of PVMMA with P-glycoprotein (P-gp) inhibitory effect of TPGS. The CTX-loaded PTNPs (CTX-PTNPs) were prepared by an emulsification-solvent evaporation method and performed a spherical appearance with a uniform particle size of 192.2 nm. The CTX-PTNPs were surface negatively charged, and exhibited good drug loading (10.2%) and encapsulation efficiency (92.1%). A sustained drug release and high stability in simulated gastrointestinal environment were confirmed in in vitro studies. The in vitro mucin adhesion and in vivo intestinal retention experiments indicated that the PTNPs had a stronger bioadhesive effect and a notably longer intestinal retention than the control PLGA NPs, due to the interaction of PVMMA on the PTNP surface with the intestinal mucosa. Moreover, an enhanced intestinal permeability of the PTNPs was also verified in in vivo and ex vivo intestinal permeation studies, which was probably attributed to the extended retention of PTNPs in intestinal mucosa and the P-gp inhibitory effect of TPGS. As respected, in in vivo pharmacokinetic study, the Tmax and oral bioavailability of CTX were dramatically improved to 1.08 h and 28.84% by the PTNPs, respectively, obviously superior to the CTX solution and the PLGA NPs, further demonstrating the high-efficiency in oral delivery of CTX. Hence, this bioadhesive carrier is proposed to be a potential and promising strategy for increasing oral absorption of small molecule insoluble drugs.