Reducing the degree of crosslinking of peptidoglycan in Listeria monocytogenes promoted the secretion of membrane vesicles.

Listeria monocytogenes (LM) is a Gram-positive (G+) bacterium that secretes nanoscale membrane vesicles (MVs). LM MVs comprise various bacterial components and may have potential as an antigen or drug-delivery vehicle; however, the low yield of the LM MVs limits related research. G+-bacterial MVs germinate from the bacterial plasma membrane and must pass through a thick crosslinked peptidoglycan layer for release. Herein, we aimed to increase the release of MVs by reducing the degree of crosslinking of peptidoglycan. We knocked out two genes related to the longitudinal crosslinking of peptidoglycan, dal and dat, and supplemented the knocked-out dal gene through plasmid expression to obtain a stably inherited recombinant strain LMΔdd::pCW633. The structure, particle size, and main protein components of MVs secreted by this recombinant strain were consistent with those secreted from the wild strain, but the yield of MVs was considerably increased (p < 0.05). Furthermore, Listeria ivanovii (LI) was found to secrete MVs that differed in the composition of the main proteins compared with those of LM MVs. The abovementioned method was also feasible for promoting the secretion of MVs from the attenuated LM strain and LI wild-type and attenuated strains. Our study provides a new method to increase the secretion of MVs derived from Listeria that could be extended to other G+ bacteria.

Learning QM/MM potential using equivariant multiscale model.

The machine learning (ML) method emerges as an efficient and precise surrogate model for high-level electronic structure theory. Its application has been limited to closed chemical systems without considering external potentials from the surrounding environment. To address this limitation and incorporate the influence of external potentials, polarization effects, and long-range interactions between a chemical system and its environment, the first two terms of the Taylor expansion of an electrostatic operator have been used as extra input to the existing ML model to represent the electrostatic environments. However, high-order electrostatic interaction is often essential to account for external potentials from the environment. The existing models based only on invariant features cannot capture significant distribution patterns of the external potentials. Here, we propose a novel ML model that includes high-order terms of the Taylor expansion of an electrostatic operator and uses an equivariant model, which can generate a high-order tensor covariant with rotations as a base model. Therefore, we can use the multipole-expansion equation to derive a useful representation by accounting for polarization and intermolecular interaction. Moreover, to deal with long-range interactions, we follow the same strategy adopted to derive long-range interactions between a target system and its environment media. Our model achieves higher prediction accuracy and transferability among various environment media with these modifications.

Rigid ureteroscopic lithotripsy with a pressure-controlling ureteral access sheath for complex steinstrasse.

OBJECTIVE: To evaluate the safety and efficacy of rigid ureteroscopic lithotripsy with a pressure-controlling ureteral access sheath (PC-UAS) for complex steinstrasse. METHODS: Thirty-one consecutive patients (male: 18; female: 13) with steinstrasse were enrolled, six of whom had concurrent kidney stones. The mean cumulative stone size was 2.7 ± 1.3 cm. The patients were treated with rigid ureteroscopic lithotripsy using a PC-UAS. The cavity pressure parameters were set as follows: control value at -15 mmHg to -2 mmHg, warning value at 20 mmHg, and limit value at 30 mmHg. The infusion flow rate was set at 150-200 ml/min. A holmium laser (550 µm) was used to powderize the stone at 2.0-2.5 J/pulse with a frequency of 20-30 pulses/s. Analyses included cavity pressure, operative time, stone-free rates, and complications. RESULTS: Among the 31 patients, 29 were successfully treated with PC-UAS, with nine requiring adjunctive flexible ureteroscopy for stone migration to the kidney. Two procedures were converted to percutaneous nephrolithotomies due to failure of sheath placement. The cavity pressure of all 29 patients was well-maintained below 20 mmHg, with clear vision. The mean operative time was 48.2 ± 17.7 min. No complications, such as ureteral perforation, mucosal avulsion, or hemorrhage, occurred. Two cases of Clavien-Dindo grade I complications occurred. No major complications (Clavien-Dindo grade II-V) occurred. The mean postoperative hospitalization time was 1.7 days. The stone-free rates 1 day and 1 month after surgery were 93.1% and 96.6%, respectively. One patient with residual stones underwent extracorporeal shockwaves. CONCLUSIONS: Rigid ureteroscopic lithotripsy with PC-UAS can effectively control the cavity pressure, shorten the operation time, and improve the efficiency of broken stones, thus reducing the complication rate.

Carbon quantum dots from hemicucur[6]bit and the application for the detection of Pb2.

A macrocyclic compound, hemicucurbit[6]uril (HemiQ[6]), is employed as the carbon source to produce a novel sort of carbon quantum dots (CQDs) with blue fluorescence in aqueous solution. The CQDs are fully identified by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), Nuclear Magnetic Resonance (NMR), zeta potential, ultraviolet/visible (UV-vis) and photoluminescence spectroscopy (PL). The nanomaterial is developed for the analysis of Pb2+ in the light of the Resonance Rayleigh scattering (RRS) changes with the increasing Pb2+ concentration. The proposed probe emerges a high selectivity to Pb2+ and excellent sensitivity in the linear concentration range of 0-6 µM with a detection limit low to 0.42 µM, which is superior to the previous values of Pb2+ sensors, as well as the good anti-interference ability is confirmed by the specifical response to Pb2+ in the presence of other metal cations. Therefore, the proposed analysis of Pb2+ is explored for the application in real samples of tap water and lake water, in satisfied results of acceptable recoveries.

Unraveling transcriptomic signatures and dysregulated pathways in systemic lupus erythematosus across disease states.

OBJECTIVES: This study aims to elucidate the transcriptomic signatures and dysregulated pathways in patients with Systemic Lupus Erythematosus (SLE), with a particular focus on those persisting during disease remission. METHODS: We conducted bulk RNA-sequencing of peripheral blood mononuclear cells (PBMCs) from a well-defined cohort comprising 26 remission patients meeting the Low Lupus Disease Activity State (LLDAS) criteria, 76 patients experiencing disease flares, and 15 healthy controls. To elucidate immune signature changes associated with varying disease states, we performed extensive analyses, including the identification of differentially expressed genes and pathways, as well as the construction of protein-protein interaction networks. RESULTS: Several transcriptomic features recovered during remission compared to the active disease state, including down-regulation of plasma and cell cycle signatures, as well as up-regulation of lymphocytes. However, specific innate immune response signatures, such as the interferon (IFN) signature, and gene modules involved in chromatin structure modification, persisted across different disease states. Drug repurposing analysis revealed certain drug classes that can target these persistent signatures, potentially preventing disease relapse. CONCLUSION: Our comprehensive transcriptomic study revealed gene expression signatures for SLE in both active and remission states. The discovery of gene expression modules persisting in the remission stage may shed light on the underlying mechanisms of vulnerability to relapse in these patients, providing valuable insights for their treatment.

Electronic Spin Alignment within Homologous NiS2/NiSe2 Heterostructures to Promote Sulfur Redox Kinetics in Lithium-Sulfur Batteries.

The catalytic activation of the Li-S reaction is fundamental to maximize the capacity and stability of Li-S batteries (LSBs). Current research on Li-S catalysts mainly focuses on optimizing the energy levels to promote adsorption and catalytic conversion, while frequently overlooking the electronic spin state influence on charge transfer and orbital interactions. Here, hollow NiS2/NiSe2 heterostructures encapsulated in a nitrogen-doped carbon matrix (NiS2/NiSe2@NC) are synthesized and used as a catalytic additive in sulfur cathodes. The NiS2/NiSe2 heterostructure promotes the spin splitting of the 3d orbital, driving the Ni3+ transformation from low to high spin. This high spin configuration raises the electronic energy level and activates the electronic state. This accelerates the charge transfer and optimizes the adsorption energy, lowering the reaction energy barrier of the polysulfides conversion. Benefiting from these characteristics, LSBs based on NiS2/NiSe2@NC/S cathodes exhibit high initial capacity (1458 mAh·g⁻1 at 0.1C), excellent rate capability (572 mAh·g⁻1 at 5C), and stable cycling with an average capacity decay rate of only 0.025% per cycle at 1C during 500 cycles. Even at high sulfur loadings (6.2 mg·cm⁻2), high initial capacities of 1173 mAh·g⁻1 (7.27 mAh·cm⁻2) are measured at 0.1C, and 1058 mAh·g⁻1 is retained after 300 cycles.

Understanding the charge transfer effects of single atoms for boosting the performance of Na-S batteries.

The effective flow of electrons through bulk electrodes is crucial for achieving high-performance batteries, although the poor conductivity of homocyclic sulfur molecules results in high barriers against the passage of electrons through electrode structures. This phenomenon causes incomplete reactions and the formation of metastable products. To enhance the performance of the electrode, it is important to place substitutable electrification units to accelerate the cleavage of sulfur molecules and increase the selectivity of stable products during charging and discharging. Herein, we develop a single-atom-charging strategy to address the electron transport issues in bulk sulfur electrodes. The establishment of the synergistic interaction between the adsorption model and electronic transfer helps us achieve a high level of selectivity towards the desirable short-chain sodium polysulfides during the practical battery test. These finding indicates that the atomic manganese sites have an enhanced ability to capture and donate electrons. Additionally, the charge transfer process facilitates the rearrangement of sodium ions, thereby accelerating the kinetics of the sodium ions through the electrostatic force. These combined effects improve pathway selectivity and conversion to stable products during the redox process, leading to superior electrochemical performance for room temperature sodium-sulfur batteries.

Listeria-vectored cervical cancer vaccine candidate strains reduce MDSCs via the JAK-STAT signaling pathway.

BACKGROUND: Immunosuppressive status is prevalent in cancer patients and increases the complexity of tumor immunotherapy. It has been found that Listeria-vectored tumor vaccines had the potential ability of two-side regulatory effect on the immune response during immunotherapy. RESULTS: The results show that the combined immunotherapy with the LM∆E6E7 and LI∆E6E7, the two cervical cancer vaccine candidate strains constructed by our lab, improves the antitumor immune response and inhibits the suppressive immune response in tumor-bearing mice in vivo, confirming the two-sided regulatory ability of the immune response caused by Listeria-vectored tumor vaccines. The immunotherapy reduces the expression level of myeloid-derived suppressor cells (MDSCs)-inducing factors and then inhibits the phosphorylation level of STAT3 protein, the regulatory factor of MDSCs differentiation, to reduce the MDSCs formation ability. Moreover, vaccines reduce the expression of functional molecules associated with MDSCs may by inhibiting the phosphorylation level of the JAK1-STAT1 and JAK2-STAT3 pathways in tumor tissues to attenuate the immunosuppressive function of MDSCs. CONCLUSIONS: Immunotherapy with Listeria-vectored cervical cancer vaccines significantly reduces the level and function of MDSCs in vivo, which is the key point to the destruction of immunosuppression. The study for the first to elucidate the mechanism of breaking the immunosuppression.

Boron nanosheets as a phosphatase mimicking nanozyme with ultrahigh catalytic activity for prodrug-based cancer therapy.

Boron nanosheets (BNSs) are reported as a new phosphatase mimicking nanozyme. Surprisingly, the catalytic rate of BNSs is up to 17 times those of known phosphatase mimicking nanozymes. By adding polyols and Lewis bases, the catalytic activity of BNSs was attributed to the Lewis acidity of the B centers of the BNSs. Theoretical investigation shows that the B centers are responsible for the catalytic hydrolysis of phosphoesters. Moreover, the biomimetic activity of the BNSs was further explored for enhancing anticancer therapy through nanozyme-catalyzed prodrug conversion.

Association of genetic variation on X chromosome with systemic lupus erythematosus in both Thai and Chinese populations.

OBJECTIVES: X chromosome has been considered as a risk factor for SLE, which is a prototype of autoimmune diseases with a significant sex difference (female:male ratio is around 9:1). Our study aimed at exploring the association of genetic variants in X chromosome and investigating the influence of trisomy X in the development of SLE. METHODS: X chromosome-wide association studies were conducted using data from both Thai (835 patients with SLE and 2995 controls) and Chinese populations (1604 patients with SLE and 3324 controls). Association analyses were performed separately in females and males, followed by a meta-analysis of the sex-specific results. In addition, the dosage of X chromosome in females with SLE were also examined. RESULTS: Our analyses replicated the association of TMEM187-IRAK1-MECP2, TLR7, PRPS2 and GPR173 loci with SLE. We also identified two loci suggestively associated with SLE. In addition, making use of the difference in linkage disequilibrium between Thai and Chinese populations, a synonymous variant in TMEM187 was prioritised as a likely causal variant. This variant located in an active enhancer of immune-related cells, with the risk allele associated with decreased expression level of TMEM187. More importantly, we identified trisomy X (47,XXX) in 5 of 2231 (0.22%) females with SLE. The frequency is significantly higher than that found in the female controls (0.08%; two-sided exact binomial test P=0.002). CONCLUSION: Our study confirmed previous SLE associations in X chromosome, and identified two loci suggestively associated with SLE. More importantly, our study indicated a higher risk of SLE for females with trisomy X.

Electrochemical coupling in subnanometer pores/channels for rechargeable batteries.

Subnanometer pores/channels (SNPCs) play crucial roles in regulating electrochemical redox reactions for rechargeable batteries. The delicately designed and tailored porous structure of SNPCs not only provides ample space for ion storage but also facilitates efficient ion diffusion within the electrodes in batteries, which can greatly improve the electrochemical performance. However, due to current technological limitations, it is challenging to synthesize and control the quality, storage, and transport of nanopores at the subnanometer scale, as well as to understand the relationship between SNPCs and performances. In this review, we systematically classify and summarize materials with SNPCs from a structural perspective, dividing them into one-dimensional (1D) SNPCs, two-dimensional (2D) SNPCs, and three-dimensional (3D) SNPCs. We also unveil the unique physicochemical properties of SNPCs and analyse electrochemical couplings in SNPCs for rechargeable batteries, including cathodes, anodes, electrolytes, and functional materials. Finally, we discuss the challenges that SNPCs may face in electrochemical reactions in batteries and propose future research directions.

Linearly Interlinked Fe-Nx-Fe Single Atoms Catalyze High-Rate Sodium-Sulfur Batteries.

Linearly interlinked single atoms offer unprecedented physiochemical properties, but their synthesis for practical applications still poses significant challenges. Herein, linearly interlinked iron single-atom catalysts that are loaded onto interconnected carbon channels as cathodic sulfur hosts for room-temperature sodium-sulfur batteries are presented. The interlinked iron single-atom exhibits unique metallic iron bonds that facilitate the transfer of electrons to the sulfur cathode, thereby accelerating the reaction kinetics. Additionally, the columnated and interlinked carbon channels ensure rapid Na+ diffusion kinetics to support high-rate battery reactions. By combining the iron atomic chains and the topological carbon channels, the resulting sulfur cathodes demonstrate effective high-rate conversion performance while maintaining excellent stability. Remarkably, even after 5000 cycles at a current density of 10 A g-1, the Na-S battery retains a capacity of 325 mAh g-1. This work can open a new avenue in the design of catalysts and carbon ionic channels, paving the way to achieve sustainable and high-performance energy devices.

Value of annual professional proficiency test results in predicting the theoretical examination score of completion assessment in standardized residency training / 中华医学教育探索杂志

Objective:To investigate the correlation between the annual professional proficiency test results and the theoretical examination score of completion assessment in standardized residency training, as well as the value of the annual professional proficiency test results in predicting whether a resident passes the theoretical examination of completion assessment.Methods:The residents who participated in the annual professional proficiency test of residency training in Affiliated Hospital 2 of Nantong University in 2019-2021 and the completion assessment of residency training in 2020-2022 were selected as subjects, and related data were collected, including sex, education background, personnel type, training specialty, the results of annual professional proficiency test, and the theoretical examination score of completion assessment. According to whether the resident passed the theoretical examination of completion assessment, they were divided into passed group and failed group. SPSS 19.0 was used to perform the chi-square test, the independent samples t-test, and the binary logistic regression analysis; the Pearson correlation coefficient was used for correlation analysis; the sensitivity analysis was represented by ROC curve. Results:Compared with the residents who passed the theoretical examination of completion assessment, the residents who did not pass the examination had a significant reduction in the proportion of the residents from our hospital and a significant increase in the proportion of the residents commissioned by foreign institutions ( χ 2=7.00, P=0.008). The passed group had a significantly higher national percentile of annual professional proficiency test score than the failed group (43.46%±26.61% vs. 23.40%±18.71%, t=6.02, P<0.001). The national percentile of annual professional proficiency test score was positively correlated with the theoretical examination score of completion assessment ( r=0.43, P<0.05). The source of residents commissioned by foreign institutions and the low percentile of annual professional proficiency test score were independent risk factors for failing the theoretical examination of completion assessment ( P=0.020 and P<0.001). The national percentile of annual professional proficiency test score had an area under the ROC curve of 0.73 (95% CI: 0.65-0.80) in predicting the outcome of theoretical examination and had a certain predictive value with a cut-off value of 15.1%. Conclusions:In addition to strengthening homogenization and professional base management for residency training, it is necessary to make full use of the results of annual professional proficiency test in standardized residency training and timely check the professional knowledge of the residents whose a national percentile of <15.1%, so as to effectively improve the pass rate of theoretical examination and the quality of training.

Effects of evodiamine on inflammation and apoptosis of airway epithelial cells in asthma model rats and its mechanism / 中国药房

OBJECTIVE To explore the effects and potential mechanism of evodiamine on inflammatory response and apoptosis of epithelial cells in asthma model rats. METHODS SD rats were separated into control group， model group， evodiamine low-dose group （10 mg/kg）， evodiamine high-dose group （20 mg/kg）， dexamethasone group （positive control， 0.5 mg/kg）， epidermal growth factor （EGF） group [mitogen-activated protein kinase （MAPK） activator， 10 μg]， evodiamine high-dose+EGF group （20 mg/kg evodiamine+10 μg EGF）， with 10 rats in each group. Except for the control group， the other groups were sensitized by 3-point injection of 10% ovalbumin（OVA）-aluminium hydroxide mixture and stimulated by inhalation of 2%OVA nebulized liquid to establish an asthma model. The count of inflammatory cells （macrophages and lymphocytes） in bronchoalveolar lavage fluid （BALF） was detected in each group； pathological changes of lung tissue in rats were observed； the apoptosis of airway epithelial cells， the levels of serum inflammatory factors [tumor necrosis factor-α， interleukin-6 （IL-6） and IL-4]， the expressions of pathway-related proteins p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， signal transduction and transcription activating factor 1 （STAT1）] and apoptosis-related proteins [B cell lymphoma-2 （Bcl-2） and Bcl-2 associated X protein （Bax）] were all detected in lung tissue. RESULTS Compared with the control group， bronchial mucosal edema， thickening of alveolar septa and extensive infiltration of inflammatory cells were observed in the lung tissue of rats in the model group； the number of inflammatory cells， apoptosis rate of airway epithelial cells， the levels of inflammatory factors， p-38 MAPK/p-38 MAPK， and the protein expressions of Bax and STAT1 were increased significantly； the expressions of Bcl-2 protein and Bcl-2/Bax were reduced significantly （P＜0.05）. Compared with the model group， the pathological changes in lung tissues were alleviated to varying degrees in evodiamine low-dose and high-dose groups， and dexamethasone groups， and the above indicators were significantly reversed. However， the change trends of corresponding indicators in the EGF group were opposite to the above （P＜0.05）. EGF could significantly attenuate the effect of high-dose evodiamine on inflammatory response in asthmatic rats （P＜0.05）. CONCLUSIONS Evodiamine can relieve inflammatory reactions and inhibit the apoptosis of airway epithelial cells in asthmatic rats， the mechanism of which may be associated with inhibiting p38 MAPK/STAT1 signaling pathway.

Effects of evodiamine on inflammation and apoptosis of airway epithelial cells in asthma model rats and its mechanism / 中国药房

OBJECTIVE To explore the effects and potential mechanism of evodiamine on inflammatory response and apoptosis of epithelial cells in asthma model rats. METHODS SD rats were separated into control group， model group， evodiamine low-dose group （10 mg/kg）， evodiamine high-dose group （20 mg/kg）， dexamethasone group （positive control， 0.5 mg/kg）， epidermal growth factor （EGF） group [mitogen-activated protein kinase （MAPK） activator， 10 μg]， evodiamine high-dose+EGF group （20 mg/kg evodiamine+10 μg EGF）， with 10 rats in each group. Except for the control group， the other groups were sensitized by 3-point injection of 10% ovalbumin（OVA）-aluminium hydroxide mixture and stimulated by inhalation of 2%OVA nebulized liquid to establish an asthma model. The count of inflammatory cells （macrophages and lymphocytes） in bronchoalveolar lavage fluid （BALF） was detected in each group； pathological changes of lung tissue in rats were observed； the apoptosis of airway epithelial cells， the levels of serum inflammatory factors [tumor necrosis factor-α， interleukin-6 （IL-6） and IL-4]， the expressions of pathway-related proteins p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， signal transduction and transcription activating factor 1 （STAT1）] and apoptosis-related proteins [B cell lymphoma-2 （Bcl-2） and Bcl-2 associated X protein （Bax）] were all detected in lung tissue. RESULTS Compared with the control group， bronchial mucosal edema， thickening of alveolar septa and extensive infiltration of inflammatory cells were observed in the lung tissue of rats in the model group； the number of inflammatory cells， apoptosis rate of airway epithelial cells， the levels of inflammatory factors， p-38 MAPK/p-38 MAPK， and the protein expressions of Bax and STAT1 were increased significantly； the expressions of Bcl-2 protein and Bcl-2/Bax were reduced significantly （P＜0.05）. Compared with the model group， the pathological changes in lung tissues were alleviated to varying degrees in evodiamine low-dose and high-dose groups， and dexamethasone groups， and the above indicators were significantly reversed. However， the change trends of corresponding indicators in the EGF group were opposite to the above （P＜0.05）. EGF could significantly attenuate the effect of high-dose evodiamine on inflammatory response in asthmatic rats （P＜0.05）. CONCLUSIONS Evodiamine can relieve inflammatory reactions and inhibit the apoptosis of airway epithelial cells in asthmatic rats， the mechanism of which may be associated with inhibiting p38 MAPK/STAT1 signaling pathway.

Transcriptomic Features of systemic lupus erythematosus Patients in Flare and Changes during Acute In-Hospital Treatment.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with varying symptoms and multi-organ damage. Relapse-remission cycles often persist for many patients for years with the current treatment. Improved understanding of molecular changes caused by SLE flare and intensive treatment may result in more targeted therapies. METHODS: RNA-sequencing was performed on peripheral blood mononuclear cells (PBMCs) from 65 SLE patients in flare, collected both before (SLE1) and after (SLE2) in-hospital treatment, along with 15 healthy controls (HC). Differentially expressed genes (DEGs) were identified among the three groups. Enriched functions and key molecular signatures of the DEGs were analyzed and scored to elucidate the transcriptomic changes during treatment. RESULTS: Few upregulated genes in SLE1 vs HC were affected by treatment (SLE2 vs SLE1), mostly functional in interferon signalling (IFN), plasmablasts, and neutrophils. IFN and plasmablast signatures were repressed, but the neutrophil signature remained unchanged or enhanced by treatment. The IFN and neutrophil scores together stratified the SLE samples. IFN scores correlated well with leukopenia, while neutrophil scores reflected relative cell compositions but not cell counts. CONCLUSIONS: In-hospital treatment significantly relieved SLE symptoms with expression changes of a small subset of genes. Notably, IFN signature changes matched SLE flare and improvement, while enhanced neutrophil signature upon treatment suggested the involvement of low-density granulocytes (LDG) in disease development.

Biomechanical Analysis of Titanium Dental Implants in the All-on-4 Treatment with Different Implant-Abutment Connections: A Three-Dimensional Finite Element Study.

The type of implant-abutment connection is one of the factors influencing the distribution of occlusal forces. This study aims to investigate the biomechanical performance of the mandibular all-on-4 treatment with different implant-abutment connections. Two connection types with 30° abutments and 18-mm implant fixtures were chosen for the posterior implants of the all-on-4 assembly. For the external hexagon connection (EHC) group, the implants with 4 mm in diameter were used. For the internal hexagon connection (IHC) group, we selected implants with 4.3 mm in diameter. A vertical force of 190 N was applied to the cantilever region. The FEA results indicated that the most stressed region in the two groups was prosthetic screws, followed by multi-unit abutments (MUAs). The lowest values of von Mises stress were both observed on the bone. The peak stress value of the implant screw and implant fixture in the EHC group were 37.75% and 33.03% lower than the IHC group, respectively. For stress distribution patterns, the load force tended to be concentrated at locations where components were interconnected. The EHC and IHC are clinically durable under the tested loading conditions, but the prosthetic screws and MUAs can be the weak point on the posterior implant within the mandibular all-on-four assembly. The peak stress values of implant screw and implant fixture in the EHC groups were lower than the IHC group.

Membrane vesicles derived from Listeria monocytogenes might be a potential antigen delivery vector.

Membrane vesicles (MVs) derived from Listeria monocytogenes (LM) have a natural nanoscale size and contain a variety of bacterial components. We speculated that LM MVs may be a novel delivery vector, but it is necessary to evaluate the safety and immunogenicity of LM MVs in vivo. Here, we isolated LM MVs and tested their safety and immunogenicity both in vitro and in vivo. The results showed that LM MVs stimulated RAW264.7 cells and DC2.4 cells to secrete the inflammatory cytokines IL-1ß, TNF-α, IL-6 and IL-10. Intraperitoneal injection of LM MVs at 80 µg per C57BL/6 mouse did not cause lethal effects or irreversible pathological changes in major organs, indicating that LM MVs were safe. Intraperitoneal immunization of C57BL/6 mice twice with LM MVs mainly induced a high level of LM MV-specific IgG antibodies. In addition, we subcutaneously injected C57BL/6 mice with a mixture of ovalbumin and LM MVs and found that LM MVs exhibited a humoral immune adjuvant effect equal to that of the same amount of alum. The results of this study indicated that LM MVs have good safety and effective immunogenicity and may act as humoral immune adjuvants. Therefore, LM MVs are a potential new choice for antigen and drug delivery vectors.

Ratiometric fluorescent detection of total phosphates in frozen shrimp samples using catalytic active Zr(IV) modified gold nanoclusters.

Phosphate salts are important food additives in a variety of foods. In this study, the Zr(IV) modified gold nanoclusters (Au NCs) were prepared for ratiometric fluorescent sensing of phosphate additives in seafood samples. Compared with bare Au NCs, the synthesized Zr(IV)/Au NCs showed stronger orange fluorescence at 610 nm. On the other hand, the Zr(IV)/Au NCs retained the phosphatase-like activity of Zr(IV) ions and could catalyze the hydrolysis of fluorescent substrate 4-methylumbelliferyl phosphate to produce blue emission at 450 nm. The addition of phosphate salts could effectively inhibit the catalytic activity of Zr(IV)/Au NCs, resulting the fluorescence decrease at 450 nm. However, the fluorescence at 610 nm almost unchanged upon the addition of phosphates. Based on this finding, the ratiometric detection of phosphates using the fluorescence intensity ratio (I450/I610) was demonstrated. The method has been further applied for sensing total phosphates in frozen shrimp samples with satisfactory results.

Bacterial outer membrane vesicle based versatile nanosystem boosts the efferocytosis blockade triggered tumor-specific immunity.

Efferocytosis inhibition is emerging as an attractive strategy for antitumor immune therapy because of the subsequent leak of abundant immunogenic contents. However, the practical efficacy is seriously impeded by the immunosuppressive tumor microenvironments. Here, we construct a versatile nanosystem that can not only inhibit the efferocytosis but also boost the following antitumor immunity. MerTK inhibitor UNC2025 is loaded into the bacterial outer membrane vesicles (OMVs), which are then modified with maleimide (mU@OMVs). The prepared mU@OMVs effectively inhibits the efferocytosis by promoting the uptake while preventing the MerTK phosphorylation of tumor associated macrophages, and then captures the released antigens through forming universal thioether bonds. The obtained in situ vaccine effectively transfers to lymph nodes by virtue of the intrinsic features of OMVs, and then provokes intense immune responses that can efficiently prevent the growth, metastasis and recurrence of tumors in mice, providing a generalizable strategy for cancer immunotherapy.