Co-infection dynamics of B. afzelii and TBEV in C3H mice: insights and implications for future research.

Ticks are important vectors of disease, particularly in the context of One Health, where tick-borne diseases (TBDs) are increasingly prevalent worldwide. TBDs often involve co-infections, where multiple pathogens co-exist in a single host. Patients with chronic Lyme disease often have co-infections with other bacteria or parasites. This study aimed to create a co-infection model with Borrelia afzelii and tick-borne encephalitis virus (TBEV) in C3H mice and to evaluate symptoms, mortality, and pathogen level compared to single infections. Successful co-infection of C3H mice with B. afzelii and TBEV was achieved. Outcomes varied, depending on the timing of infection. When TBEV infection followed B. afzelii infection by 9 days, TBEV symptoms worsened and virus levels increased. Conversely, mice infected 21 days apart with TBEV showed milder symptoms and lower mortality. Simultaneous infection resulted in mild symptoms and no deaths. However, our model did not effectively infect ticks with TBEV, possibly due to suboptimal dosing, highlighting the challenges of replicating natural conditions. Understanding the consequences of co-infection is crucial, given the increasing prevalence of TBD. Co-infected individuals may experience exacerbated symptoms, highlighting the need for a comprehensive understanding through refined animal models. This study advances knowledge of TBD and highlights the importance of exploring co-infection dynamics in host-pathogen interactions.

Reticular Ratchets for Directing Electrochemiluminescence.

Electrochemiluminescence (ECL) involves charge transfer between electrochemical redox intermediates to produce an excited state for light emission. Ensuring precise control of charge transfer is essential for decoding ECL fundamentals, yet guidelines on how to achieve this for conventional emitters remain unexplored. Molecular ratchets offer a potential solution, as they enable the directional transfer of energy or chemicals while impeding the reverse movement. Herein, we designed 10 pairs of imine-based covalent organic frameworks as reticular ratchets to delicately manipulate the intrareticular charge transfer for directing ECL transduction from electric and chemical energies. Aligning the donor and acceptor (D-A) directions with the imine dipole effectively facilitates charge migration, whereas reversing the D-A direction impedes it. Notably, the ratchet effect of charge transfer directionality intensified with increasing D-A contrast, resulting in a remarkable 680-fold improvement in the ECL efficiency. Furthermore, dipole-controlled exciton binding energy, electron/hole decay kinetics, and femtosecond transient absorption spectra identified the electron transfer tendency from the N-end toward the C-end of reticular ratchets during ECL transduction. An exponential correlation between the ECL efficiency and the dipole difference was discovered. Our work provides a general approach to manipulate charge transfer and design next-generation electrochemical devices.

Cascaded multicore fiber interferometers for enhanced bending sensing based on the Vernier effect.

In this paper, cascaded modal interferometers constructed by strongly-coupled seven-core fiber (SC-SCF) with different lengths are demonstrated for enhanced bending sensing based on Vernier effect. The free spectral range (FSR) of a single SC-SCF interferometer is determined by the length of SC-SCF. Two SC-SCF interferometers with different FSRs are cascaded, in which, one functions as the sensor while the other functions as the reference. The wavelength shift of the envelope of the output spectrum is much larger than that of a single SC-SCF interferometer due to the Vernier effect. Therefore, enhanced sensing can be achieved. Experimental results show that the bending sensitivity of the proposed sensor is improved from -2.20 nm/m-1 (single SC-SCF interferometer) to 42.32 nm/m-1 (cascaded SC-SCF interferometers). The temperature response of the sensor is also investigated. Our proposed cascaded SC-SCF sensor has advantages of high sensitivity, ease of fabrication, and low cost. It is attractive for high precision bending sensing applications.

Compact-Type Quasi-2D Perovskite Based on Two Conventional 3D Perovskites.

Quasi-2D perovskites are natural quantum well (QW) structures composed of insulating organic layers inserted between conducting [An-1PbnX3n+1]2- slabs. The presence of the bulky organic layer improves the stability but meanwhile sacrifices carrier transport performance. By utilizing two A-site cations of formamidinium (FA+) and cesium (Cs+), we synthesize unique compact-type quasi-2D perovskites CsPbBr3@FABr. Instead of the bulky organic cations, the FA+ cation was employed to work as interlayer "spacer", while the smaller Cs+ cation was chosen to occupy perovskite cages. Transient absorption reveals an energy transfer from small-n-value QWs to large-n-value QWs, enabling a photoluminescence quantum yield (PLQY) of 36.1%. After further promoting the formation of middle-n-value QWs, the homogeneous QW distribution provides a complete energy cascade to access more efficient energy transfer, leading to significant PLQY raise to 70.1%. We break the shackles to report the first case of compact-type quasi-2D perovskites, providing new guidelines for designing high-performance perovskite materials for optoelectronic devices.

Structural differences in the gut microbiome of bats using terrestrial vs. aquatic feeding resources.

Bat gut microbiomes are adapted to the specific diets of their hosts. Despite diet variation has been associated with differences in bat microbiome diversity, the influence of diet on microbial community assembly have not been fully elucidated. In the present study, we used available data on bat gut microbiome to characterize the microbial community assembly of five selected bat species (i.e., Miniopterus schreibersii, Myotis capaccinii, Myotis myotis, Myotis pilosus, and Myotis vivesi), using network analysis. These bat species with contrasting habitat and food preferences (i.e., My. capaccinii and My. pilosus can be piscivorous and/or insectivorous; Mi. schreibersii and My. myotis are exclusively insectivorous; while My. vivesi is a marine predator) offer an invaluable opportunity to test the impact of diet on bat gut microbiome assembly. The results showed that My. myotis showed the most complex network, with the highest number of nodes, while My. vivesi has the least complex structured microbiome, with lowest number of nodes in its network. No common nodes were observed in the networks of the five bat species, with My. myotis possessing the highest number of unique nodes. Only three bat species, My. myotis, My. pilosus and My. vivesi, presented a core microbiome and the distribution of local centrality measures of nodes was different in the five networks. Taxa removal followed by measurement of network connectivity revealed that My. myotis had the most robust network, while the network of My. vivesi presented the lowest tolerance to taxa removal. Prediction of metabolic pathways using PICRUSt2 revealed that Mi. schreibersii had significantly higher functional pathway's richness compared to the other bat species. Most of predicted pathways (82%, total 435) were shared between all bat species, while My. capaccinii, My. myotis and My. vivesi, but no Mi. schreibersii or My. pilosus, showed specific pathways. We concluded that despite similar feeding habits, microbial community assembly can differ between bat species. Other factors beyond diet may play a major role in bat microbial community assembly, with host ecology, sociality and overlap in roosts likely providing additional predictors governing gut microbiome of insectivorous bats.

Rickettsial pathogens drive microbiota assembly in Hyalomma marginatum and Rhipicephalus bursa ticks.

Most tick-borne pathogens (TBPs) are secondarily acquired by ticks during feeding on infected hosts, which imposes 'priority effect' constraints, as arrival order influences the establishment of new species in a microbial community. Here we tested whether once acquired, TBPs contribute to bacterial microbiota functioning by increasing community stability. For this, we used Hyalomma marginatum and Rhipicephalus bursa ticks collected from cattle in different locations of Corsica and combined 16S rRNA amplicon sequencing and co-occurrence network analysis, with high-throughput pathogen detection, and in silico removal of nodes to test for impact of rickettsial pathogens on network properties. Despite its low centrality, Rickettsia showed preferential connections in the networks, notably with a keystone taxon in H. marginatum, suggesting facilitation of Rickettsia colonisation by the keystone taxon. In addition, conserved patterns of community assembly in both tick species were affected by Rickettsia removal, suggesting that privileged connections of Rickettsia in the networks make this taxon a driver of community assembly. However, Rickettsia removal had minor impact on the conserved 'core bacterial microbiota' of H. marginatum and R. bursa. Interestingly, networks of the two tick species with Rickettsia have similar node centrality distribution, a property that is lost after Rickettsia removal, suggesting that this taxon drives specific hierarchical interactions between bacterial microbes in the microbiota. The study indicates that tick-borne Rickettsia play a significant role in the tick bacterial microbiota, despite their low centrality. These bacteria are influential and contribute to the conservation of the 'core bacterial microbiota' while also promoting community stability.

Supermode Bragg grating inscribed in a strongly coupled seven-core fiber and its responses to temperature and curvature.

A Bragg grating is successfully inscribed in a piece of strongly coupled seven-core fiber (SCF). There are two separate Bragg resonance notches observed in the transmission spectrum, corresponding to backward coupling of HE11-like and HE12-like supermodes of the SCF. The mode coupling mechanism of the Bragg grating is theoretically investigated via modeling and analyzing modal properties of the SCF. The theoretical results agree well with the experimental results. Since the SCF is spliced between two standard single mode fibers with central alignments at both ends, the transmission spectrum of the device also contains a set of interference fringe due to modal interference between the supermodes. The device's responses to temperature and curvature are experimentally measured, respectively. The obtained temperature sensitivities and curvature sensitivities of the supermode Bragg grating notches are 9.55 pm/°C and 9.55 pm/°C, -1.8 pm/m-1 and -112.3 pm/m-1, respectively. The obtained temperature sensitivity and curvature sensitivity of one of the interference spectrum dips are 11.8 pm/°C and -3909.8 pm/m-1, respectively. This device is potentially useful for simultaneous measurement of temperature and curvature.

The effects of the prognostic biomarker SAAL1 on cancer growth and its association with the immune microenvironment in lung adenocarcinoma.

BACKGROUND: Inhibition of Serum Amyloid A-like 1 (SAAL1) expression could inhibit cancer progression and improve the prognosis of cancer patients. At present, the correlation between SAAL1 and lung adenocarcinoma (LAC) remains unclear. Therefore, this study surveyed the worth and pathway of SAAL1 in LAC progression and immunity. METHODS: Bioinformatics and immunohistochemistry were used to identify the SAAL1 expression in LAC. The roles of SAAL1 expression in the existence values of LAC patients were explored, and the nomograms were constructed. Clinical values of SAAL1 co-expressed genes were evaluated by COX regression, survival, and Receiver operating characteristic (ROC) analysis. EDU and western blotting methods were used to inquiry the functions and pathways of the SAAL1 in cell growths. The correlation between the SAAL1 level and immune microenvironment was visualized using correlation research. RESULTS: SAAL1 level was elevated in LAC tissues, and was observed in cancer tissues of dead patients. SAAL1 overexpression had something to do with shorter overall survival, progression-free interval, and disease-specific survival in LAC. The area under the curve of SAAL1 was 0.902 in normal tissues and cancer tissues. Inhibition of SAAL1 expression could inhibit cancer cell proliferation, which may be related to the decreased expression of cyclin D1 and Bcl-2 proteins. In LAC, SAAL1 level had something to do with stromal, immune, and estimate scores, and correlated with macrophages, T cells, Th2 cells, CD8 T cells, NK CD56dim cells, DC, eosinophils, NK CD56bright cells, pDC, iDC, cytotoxic cells, Tgd, aDC cells, B cells, Tcm, and TFH levels. SAAL1 overexpression had something to do with existence values and the immunity in LAC. CONCLUSIONS: Inhibition of SAAL1 expression could regulate cancer growth via cyclin D1 and Bcl-2. SAAL1 is a promising prognostic biomarker in LAC patients.

CT for the evaluation of myocardial extracellular volume with MRI as reference: a systematic review and meta-analysis.

OBJECTIVE: Myocardial extracellular volume (ECV) fraction is an important imaging biomarker in clinical decision-making. CT-ECV is a potential alternative to MRI for ECV quantification. We conducted a meta-analysis to comprehensively assess the reliability of CT for ECV quantification with MRI as a reference. METHODS: We systematically searched PubMed, EMBASE, and the Cochrane Library for relevant articles published since the establishment of the database in July 2022. The articles comparing CT-ECV with MRI as a reference were included. Meta-analytic methods were applied to determine the pooled weighted bias, limits of agreement (LOA), and correlation coefficient (r) between CT-ECV and MRI-ECV. RESULTS: Seventeen studies with a total of 459 patients and 2231 myocardial segments were included. The pooled mean difference (MD), LOA, and r for ECV quantification at the per-patient level was (0.07%; 95% LOA: - 0.42 to 0.55%) and 0.89 (95% CI: 0.86-0.91), respectively, while on the per-segment level was (0.44%; 95% LOA: 0.16-0.72%) and 0.84 (95% CI: 0.82-0.85), respectively. The pooled r from studies with the ECViodine method for ECV quantification was significantly higher compared to those with the ECVsub method (0.94 (95% CI: 0.91-0.96) vs. 0.84 (95% CI: 0.80-0.88), respectively, p = 0.03). The pooled r from septal segments was significantly higher than those from non-septal segments (0.88 (95% CI: 0.86-0.90) vs. 0.76 (95% CI: 0.71-0.90), respectively, p = 0.009). CONCLUSION: CT showed a good agreement and excellent correlation with MRI for ECV quantification and is a potentially attractive alternative to MRI. CLINICAL RELEVANCE STATEMENT: The myocardial extracellular volume fraction can be acquired using a CT scan, which is not only a viable alternative to myocardial extracellular volume fraction derived from MRI but is also less time-consuming and costly for patients. KEY POINTS: • Noninvasive CT-ECV is a viable alternative to MRI-ECV for ECV quantification. • CT-ECV using the ECViodine method showed more accurate myocardial ECV quantification than ECVsub. • Septal myocardial segments showed lower measurement variability than non-septal segments for the ECV quantification.

Variation of bacterial community assembly over developmental stages and midgut of Dermanyssus gallinae.

Bacterial microbiota play an important role in the fitness of arthropods, but the bacterial microflora in the parasitic mite Dermanyssus gallinae is only partially explored; there are gaps in our understanding of the microbiota localization and in our knowledge of microbial community assembly. In this work, we have visualized, quantified the abundance, and determined the diversity of bacterial occupancy, not only across developmental stages of D. gallinae, but also in the midgut of micro-dissected female D. gallinae mites. We explored community assembly and the presence of keystone taxa, as well as predicted metabolic functions in the microbiome of the mite. The diversity of the microbiota and the complexity of co-occurrence networks decreased with the progression of the life cycle. However, several bacterial taxa were present in all samples examined, indicating a core symbiotic consortium of bacteria. The relatively higher bacterial abundance in adult females, specifically in their midguts, implicates a function linked to the biology of D. gallinae mites. If such an association proves to be important, the bacterial microflora qualifies itself as an acaricidal or vaccine target against this troublesome pest.

Clinical Value of Artificial Intelligence-Based Computer-Aided Diagnosis System Versus Contrast-Enhanced Ultrasound for Differentiation of Benign From Malignant Thyroid Nodules in Different Backgrounds.

OBJECTIVES: The aim of this study was to compare the value of the AI-SONIC ultrasound-assisted diagnosis system versus contrast-enhanced ultrasound (CEUS) for differential diagnosis of thyroid nodules in diffuse and non-diffuse backgrounds. METHODS: A total of 555 thyroid nodules with pathologically confirmed diagnosis were included in this retrospective study. The diagnostic efficacies of AI-SONIC and CEUS for differentiating benign from malignant nodules in diffuse and non-diffuse backgrounds were evaluated, with pathological diagnosis as the gold standard. RESULTS: The agreement between AI-SONIC diagnosis and pathological diagnosis was moderate in diffuse backgrounds (κ = 0.417) and almost perfect in non-diffuse backgrounds (κ = 0.81). The agreement between CEUS diagnosis and pathological diagnosis was substantial in diffuse backgrounds (κ = 0.684) and moderate in non-diffuse backgrounds (κ = 0.407). In diffuse backgrounds, AI-SONIC had slightly higher sensitivity (95.7 vs 89.4%, P = .375), but CEUS had significantly higher specificity (80.0 vs 40.0%, P = .008). In non-diffuse background, AI-SONIC had significantly higher sensitivity (96.2 vs 73.4%, P < .001), specificity (82.9 vs 71.2%, P = .007), and negative predictive value (90.3 vs 53.3%, P < .001). CONCLUSION: In non-diffuse backgrounds, AI-SONIC is superior to CEUS for differentiating malignant from benign thyroid nodules. In diffuse backgrounds, AI-SONIC could be useful for screening of cases to detect suspicious nodules requiring further examination by CEUS.

Oncolytic adenovirus carrying SPAG9-shRNA enhanced the efficacy of docetaxel for advanced prostate cancer.

Sperm-associated antigen 9 (SPAG9) is closely related to the growth and metastasis of advanced prostate cancer. Docetaxel (DTX) is the gold standard for chemotherapy of prostate cancer, but its side effects decrease the life quality of patients. Therefore, it is urgent to develop combination therapy to increase chemotherapy efficacy for advanced prostate cancer. Oncolytic adenovirus carrying a short hairpin RNA (shRNA) targeting SPAG9 (ZD55-shSPAG9) was applied alone or in combination with docetaxel in prostate cancer cells. Cells were analyzed by cell counting kit-8, Hocehst-33258, transwell and western blot analysis. For in vivo experiments, nude mice were loaded with prostate cancer cells. ZD55-shSPAG9 effectively silenced the expression of SPAG9 in prostate cancer cells in vitro and in vivo. The replication of ZD55-shSPAG9 in prostate cancer cells was not affected by docetaxel, but the combined use of ZD55-shSAPAG9 and docetaxel has a better inhibitory effect on tumor growth and invasion in vitro and in vivo. Our study showed that the combined use of ZD55-shSPAG9 and docetaxel may be a new approach to the treatment of advanced prostate cancer.

Thermostable Keystone Bacteria Maintain the Functional Diversity of the Ixodes scapularis Microbiome Under Heat Stress.

Variations in the composition and diversity of tick microbiome due to high temperatures may influence the hierarchy of community members as a response to environmental change. Modifications in the community structure are hypothesized to drive alterations in the presence and/or abundance of functional pathways in the bacterial metagenome. In this study, this hypothesis was tested by using published 16S rRNA datasets of Ixodes scapularis males incubated at different temperatures (i.e., 4, 20, 30, and 37 °C) in a laboratory setting. Changes in community structure and functional profiles in response to temperature shifts were measured using co-occurrence networks and metagenome inference. Results from laboratory-reared ticks were then compared with those of field-collected ticks. The results from laboratory-reared ticks showed that high temperature altered the structure of the microbial community and decreased the number of keystone taxa. Notably, four taxa were identified as keystone in all the temperatures, and the functional diversity of the tick microbiome was contained in the four thermostable keystone their associated bacterial taxa. Three of the thermostable keystone taxa were also found in free-living ticks collected in Massachusetts. Moreover, the comparison of functional profiles of laboratory-reared and field-collected ticks revealed the existence of an important set of metabolic pathways that were common among the different datasets. Similar to the laboratory-reared ticks, the keystone taxa identified in field-collected ticks alongside their consortia (co-occurring taxa) were sufficient to retain the majority of the metabolic pathways in the functional profile. These results suggest that keystone taxa are essential in the stability and the functional resiliency of the tick microbiome under heat stress.

Electrohydrodynamic printing of submicron-microscale hybrid scaffolds with improved cellular adhesion and proliferation behaviors.

Electrohydrodynamic (EHD) printing has been considered as a mature strategy to mimic the hierarchical microarchitectures in native extracellular matrix (ECM). Most of the EHD-printed scaffolds possess single-dimensional fibrous structures, which cannot mimic the multi-dimensional architectures for enhanced cellular behaviors. Here we developed a two-nozzle EHD printing system to fabricate hybrid scaffolds involving submicron and microscale features. The polyethylene oxide- polycaprolactone (PEO-PCL) submicron fibers were fabricated via solution-based EHD printing with a width of 527 ± 56 nm. The PCL microscale fibers were fabricated via melt-based EHD printing with a width of 11.2 ± 2.3µm. The hybrid scaffolds were fabricated by printing the submicron and microscale fibers in a layer-by-layer manner. The microscale scaffolds were utilized as a control group. Rat myocardial cells (H9C2 cells) were cultured on the two kinds of scaffolds for the culturing period of 1, 3 and 5 d. Biological results indicated that H9C2 cells showed enhanced adhesion and proliferation behaviors on the hybrid scaffold than those on the pure microscale scaffold. This work offers a facile and scalable strategy to fabricate multiscale synthetic scaffolds, which might be further explored to regulate cellular behaviors in the fields of tissue regeneration and biomedical engineering.

Tween-80 improves single/coaxial electrospinning of three-layered bioartificial blood vessel.

Electrospinning is a promising technique for preparing bioartificial blood vessels. Nanofibers prepared by electrospinning can simulate the structure of extracellular matrix to promote cell adhesion and proliferation. However, thorn-like protrusions can appear as defects on electrospun scaffolds and coaxial electrospun nanofibers often have no clear core/shell structure, which can seriously affect the quality of bioartificial blood vessels. To address these problems, Tween 80 is added to the electrospinning solution, which results in a stable Taylor cone, eliminates the thorn-like protrusions on electrospun bioartificial blood vessels, and reduces interfacial effects due to different core/shell solutions during coaxial electrospinning. Simulations, biomechanical tests, and in vivo studies were performed. The results demonstrate the excellent mechanical properties and biocompatibility of the bioartificial blood vessel. This research provides a useful reference for optimizing the electrospinning process for fabricating bioartificial blood vessels.

The influence of mindfulness and moral disengagement on the psychological health and willingness to work of civil servants experiencing compassion fatigue.

Both public administration scholars and practitioners believe that "good governance" relies on the involvement of compassionate officials. However, they overlook the fact that "compassion fatigue" often occurs when officials face the dual pressure arising from superiors' orders and empathy for service receivers. This would inevitably not only affect their individual behaviors, but also influence the effectiveness of their service. A full-scale investigation of animal protection administrators in Taiwan was conducted so as to analyze compassion fatigue that civil servants would encounter and further establish a relationship between various variables and the hypotheses of this study by combining the studies of public administration and psychology. It should be noted that compassion fatigue may affect animal protection administrators' mental health in spite of little influence on their willingness to work hard. However, both "mindfulness" and "moral disengagement" are coping strategies which were developed for helping tackle the dilemma of compassion fatigue. Although applying the strategy of mindfulness can generate more positive impacts on individuals and organizations than that of moral disengagement, animal protection administrators tended to adopt the latter. Accordingly, encouraging animal protection administrators to adopt mindfulness instead of moral disengagement as their coping strategy will be a priority of work for the authorities in the future.

A prospective comparison of four methods for preventing pacemaker pocket infections.

This study aims to evaluate four pacemaker pocket cleaning methods for preventing implantation-related infections. This single-center trial prospectively randomized 910 patients undergoing first-time pacemaker implantation or replacement into four pocket cleaning methods: hemocoagulase (group A, n = 228), gentamicin (group B, n = 228), hemocoagulase plus gentamicin (group C, n = 227), and normal saline (group D, n = 227). Before implanting the pacemaker battery, the pockets were cleaned with gauze presoaked in the respective cleaning solutions. Then, these patients were followed up to monitor the occurrence of infections for 1 month after implantation. Twelve implantation-related infections occurred in 910 patients (1.32%): four patients from group A (1.75%), three patients from group B (1.32%), two patients from group C (0.88%), and three patients from group D (1.32%) (P > .05). Furthermore, two patients developed bloodstream infections (0.22%), and both of these patients were associated with pocket infection (one patient was from group A, while the other patient was from group C, respectively). No cases of infective endocarditis occurred. The differences in the number of infections in these study groups were not statistically significant. The application of hemocoagulase, gentamicin, hemocoagulase plus gentamicin, or normal saline on the presoaked gauze before implantation was equally effective in preventing pocket-associated infections.

Highly sensitive optofluidic refractive index sensor based on a seven-liquid-core Teflon-cladding fiber.

We propose and theoretically demonstrate a highly sensitive optofluidic refractive index (RI) sensor based on a spectral filter formed by a segment of liquid-filled seven-hole Teflon-cladding fiber sandwiched by two standard single mode fibers (SMFs). When liquid flows through the air hole channels of the seven-hole Teflon-cladding fiber, it forms a seven-liquid-core fiber (SLCF) and the lightwaves are well guided by the liquid cores owing to total inner reflection. When the input SMF is aligned to the central core of the SLCF, the light excited in the central core will couple to outer cores periodically along the length of the SCLF. At the detection port, the output SMF is also aligned to the central core of the SLCF. Since the coupling coefficient depends on wavelength, the coupling efficiency is also wavelength dependent, leading to a filter spectrum for a given length of the SLCF. The spectral response of the filter to the change in RI of the liquid cores is numerically simulated based on the coupled-mode theory through finite-element method. The dependence of the RI sensitivity on the diameter and pitch of air holes of the SLCF are studied, respectively. Finally, a very high sensitivity of 25,300 nm/RIU for RI around 1.333 is achieved.

Superparamagnetic iron oxide nanoparticles attenuate lipopolysaccharide-induced inflammatory responses through modulation of toll-like receptor 4 expression.

Superparamagnetic iron oxide nanoparticles (SPIONs) are extensively applied in biomedical fields, such as magnetic resonance imaging and as nanocarriers. However, the biosafety of SPIONs is not completely established, especially their effect on the immune system and inflammatory responses. Toll-like receptor (TLR) signaling is essential for many acute and chronic human inflammatory diseases. Regulation of TLR responses with drugs is helpful for these inflammatory conditions. In this study, we investigated the effects of 10 and 30 nm SPIONs on macrophages in the presence or absence of the TLR4 agonist lipopolysaccharide (LPS). We found that SPIONs inhibited the release of inflammatory cytokines induced by LPS both in murine and human macrophages in a concentration-dependent manner. Meanwhile, SPIONs suppressed inducible nitric oxide synthase expression activated by SPIONs in RAW264.7 macrophages. Additionally, TLR4 mRNA transcription and expression were attenuated with SPIONs treatment, which positively correlated with the release of inflammatory cytokines. In summary, our study demonstrates that SPIONs can suppress inflammatory responses, and the underlying mechanism may be regulated by TLR4 expression. Our present work contributes to clarifying the biosafety of SPIONs and provides a potential approach to alleviate human inflammatory diseases.

The selective Nlrp3 inflammasome inhibitor Mcc950 attenuates lung ischemia-reperfusion injury.

Lung ischemia-reperfusion (IR) occurs in many circumstances and leads to impaired lung function. The NACHT, LRR and PYD domains-containing protein 3 (Nlrp3) inflammasome is reportedly activated during lung IR. Mcc950 is a recently developed Nlrp3 inhibitor. The aim of our study was to test the efficacy of Mcc950 on lung IR injury and to investigate the role of reactive oxygen species (ROS) in Nlrp3 inflammasome activation using a murine lung IR model. The results of the current study confirmed that Nlrp3 was upregulated and activated during lung IR, and inhibiting oxidative stress by the ROS scavenger edaravone attenuated Nlrp3 inflammasome activation. Mcc950 pretreatment significantly alleviated IR-induced lung injury by reducing production of the proinflammatory cytokines Il-1ß and Il-18 and inhibiting neutrophil infiltration and cell apoptosis. Protein coimmunoprecipitation revealed that Mcc950 partially blocked the interaction between Nlrp3 and Nek7 (NimA-related protein kinase 7). Therefore, we conclude that ROS-dependent activation of the Nlrp3 inflammasome contributed to lung IR injury. Mcc950 significantly reduced lung IR injury by blocking Nlrp3 inflammasome activation, and the mechanism was partially attributed to inhibition of the interaction between Nlrp3 and Nek7. Thus, Mcc950 is a promising treatment for the prevention of lung IR injury.