Asymmetric Magnon Frequency Comb.

We theoretically show the asymmetric spin wave transmission in a coupled waveguide-skyrmion structure, where the skyrmion acts as an effective nanocavity allowing the whispering gallery modes for magnons. The asymmetry originates from the chiral spin wave mode localized in the circular skyrmion wall. By inputting two-tone excitations and mixing them in the skyrmion wall, we observe a unidirectional output magnon frequency comb propagating in the waveguide with a record number of teeth (>50). This coupled waveguide-cavity structure turns out to be a universal paradigm for generating asymmetric magnon frequency combs, where the cavity can be generalized to other magnetic structures that support the whispering gallery mode of magnons. Our results advance the understanding of the nonlinear interaction between magnons and magnetic textures and open a new pathway to exploring the asymmetric spin wave transmission and to steering the magnon frequency comb.

Differential expression of circRNAs during osteogenic/odontogenic differentiation of stem cells from apical papilla promoted by blue light-emitting diode.

BACKGROUND: Circular RNA (circRNA) is a key player in regulating the multidirectional differentiation of stem cells. Previous research by our group found that the blue light-emitting diode (LED) had a promoting effect on the osteogenic/odontogenic differentiation of human stem cells from apical papilla (SCAPs). This research aimed to investigate the differential expression of circRNAs during the osteogenic/odontogenic differentiation of SCAPs regulated by blue LED. MATERIALS AND METHODS: SCAPs were divided into the irradiation group (4 J/cm2) and the control group (0 J/cm2), and cultivated in an osteogenic/odontogenic environment. The differentially expressed circRNAs during osteogenic/odontogenic differentiation of SCAPs promoted by blue LED were detected by high-throughput sequencing, and preliminarily verified by qRT-PCR. Functional prediction of these circRNAs was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the circRNA-miRNA-mRNA networks were also constructed. RESULTS: It showed 301 circRNAs were differentially expressed. GO and KEGG analyses suggested that these circRNAs were associated with some signaling pathways related to osteogenic/odontogenic differentiation. And the circRNA-miRNA-mRNA networks were also successfully constructed. CONCLUSION: CircRNAs were involved in the osteogenic/odontogenic differentiation of SCAPs promoted by blue LED. In this biological process, circRNA-miRNA-mRNA networks served an important purpose, and circRNAs regulated this process through certain signaling pathways.

The Effects of Bivalirudin and Ordinary Heparin on the Incidence of Bleeding Events and the Level of Inflammation after Interventional Therapy for Acute Myocardial Infarction.

Objective: To evaluate and compare the efficacy, bleeding events, and inflammation levels of optimized bivalirudin versus ordinary heparin in the context of percutaneous coronary intervention (PCI) for patients with acute myocardial infarction. This approach will underscore the comprehensive scope of the study, addressing multiple dimensions of clinical outcomes. Methods: This study involved 120 acute myocardial infarction patients treated from January 2022 to January 2023, randomly allocated into two groups: the control group received ordinary heparin, and the observation group received bivalirudin. Both groups underwent percutaneous coronary intervention (PCI). The study specifically measured coagulation indexes such as prothrombin time (PT) and activated partial thromboplastin time (aPTT), and inflammatory markers including C-reactive protein (CRP) and interleukin-6 (IL-6). Additionally, the incidence of bleeding events and major adverse cardiovascular events (MACE) within 30 days post-PCI were recorded, with bleeding events categorized according to the Bleeding Academic Research Consortium (BARC) criteria and MACE defined by the occurrence of death, non-fatal myocardial infarction, or stroke. Results: No significant differences were observed in coagulation indexes and pre-operation inflammation levels between the two groups (P > .05). However, at 7 days post-operation, despite both groups showing reduced inflammation-NLR decreased by 25%, hs-CRP by 30%, and IL-10 increased by 20%-the bivalirudin group exhibited notably lower incidence rates of various bleeding events (mucosal 2% vs 6%, gingival 1% vs 4%, puncture site 3% vs 8%, and hematuria 1% vs 5%) within 30 days post-PCI compared to the heparin group. TIMI blood flow grades 3 (indicating normal flow) were achieved in 85% of the bivalirudin group compared to 70% in the heparin group. The incidence of MACE was comparable between groups with both reporting a 5% occurrence rate (P > .05). Conclusion: The study reveals that while both bivalirudin and ordinary heparin effectively prevent MACE post-acute myocardial infarction intervention, bivalirudin significantly reduces postoperative bleeding events and maintains comparable anti-inflammatory effects. This suggests its preferable use in clinical settings, particularly in patient populations at high risk for bleeding. Future research could further explore the specific patient characteristics that optimize bivalirudin's benefits over heparin, enhancing tailored therapeutic approaches. This could potentially include randomized trials focusing on patients with different baseline bleeding risks.

Comparing the effectiveness of caries arrest by micro-operative treatment to operative treatment: A 2-year randomized controlled clinical trial.

OBJECTIVES: To compare the effectiveness of caries arrest by micro-operative treatment (sealing) to operative treatment (flowable resin composite restoration) through a 2-year randomized controlled clinical trial. MATERIALS AND METHODS: A prospective randomized controlled trial was conducted among 7-9-year-old children. At baseline, 630 subjects were screened and 92 children who had at least one carious lesion classified as ICDAS 3 on the pit and fissure of first permanent molar were included. Then they were randomly assigned to the sealant group (73 lesions) and the flowable resin composite group (76 lesions) to receive the corresponding intervention. Lesions status in each group was evaluated every 6 months up to 24 months. Clinical progression of dental caries and materials retention were the outcomes used for group comparisons at p-value < 0.05. RESULTS: After 24 months, three lesions (4.1%) in the sealant group clinically progressed to dentin caries. No lesion in the flowable composite group was observed a progression. The results of Life-table survival analysis show that the cumulative caries arrest rate had no statistically significant difference between the two groups (p = 0.075). However, the cumulative retention rate was 57.5% in the sealant group and 92.1% in the flowable composite group, with significant differences (p < 0.001). The multilevel mixed model showed the sealant had higher risk of retention failure than the flowable composite (OR = 8.66, p < 0.001), while tooth position did not influence material retention (p = 0.083). In addition, the results of Fisher Exact test show that dentin lesions had more retention failure than enamel lesions in the sealant group (p = 0.026). CONCLUSION: Although sealing microcavitated carious lesions of the first permanent molar achieved lower retention rate than resin composite restoration, both sealing and restoration effectively arrested caries progression for two years. CLINICAL RELEVANCE: To preserving dental structure and delaying or eliminating the need for operative procedures, microcavitated carious lesion can be arrested by sealing. TRIAL REGISTRATION: Registered at http://www.chictr.org.cn ; Feb 15th, 2020; No. ChiCTR2000029862.

An experiential service-learning project on oral health examination and education.

BACKGROUND: It has been demonstrated that experiential service-learning is effective in fields including public health and medicine. Preventive Dentistry is a practical course, and Oral Health Examination and Education is a topic that is suitable for teaching with experiential service-learning. This study describes an example of experiential service-learning in Preventive Dentistry named "Oral Health Examination and Education Project" and also evaluates its effectiveness among dental students. METHODS: A total of 108 dental students in their fourth year participated in this project in 2022. The project was composed of six sections: theoretical teaching, field investigation, data collection and analysis, investigation report writing and creating oral health education materials, oral health education and students' evaluation of the project. RESULTS: During this project, students learned how to perform surveys related to oral health, wrote an investigation report, created oral health education materials, and provided oral health education for children. Students were demonstrated an improvement in their academic performance for theoretical knowledge related to Oral Health Examination and Education in comparison with the students in the previous year. Over 90% of students expressed their preference for the learning method of experiential service and believed that it helped them to better understand the course material. They also recommended this teaching method for future classes. CONCLUSIONS: This study indicated that an experiential service-learning approach within this scope was highly beneficial to students because it provided them with the opportunity to understand the practical application of their coursework and obtain valuable experience in the field. This research suggests that oral epidemiology instructors in dental and oral public health programs should pay more attention to incorporate similar experiential projects into their curriculum with the aim of better preparing students for careers in oral public health.

A comparative study of microbial changes in dental plaque before and after single- and multiappointment treatments in patients with severe early childhood caries.

BACKGROUND: The status of dental caries is closely related to changes in the oral microbiome. In this study, we compared the diversity and structure of the dental plaque microbiome in children with severe early childhood caries (S-ECC) before and after general anaesthesia and outpatient treatment. METHODS: Forty children aged 3 to 5 years with S-ECC who had completed whole-mouth dental treatment under general anaesthesia (C1) or in outpatient settings (C2) were selected, 20 in each group. The basic information and oral health status of the children were recorded, and the microbial community structure and diversity of dental plaque before treatment (C1, C2), the day after treatment(C2_0D), 7 days after treatment (C1_7D, C2_7D), 1 month after treatment (C1_1M, C2_1M), and 3 months after treatment (C1_3M, C2_3M) were analysed via 16 S rRNA high-throughput sequencing technology. RESULTS: (1) The alpha diversity test showed that the flora richness in the multiappointment group was significantly greater at posttreatment than at pretreatment (P < 0.05), and the remaining alpha diversity index did not significantly differ between the 2 groups (P > 0.05). The beta diversity analysis revealed that the flora structures of the C1_7D group and the C2_3M group were significantly different from those of the other time points within the respective groups (P < 0.05). (2) The core flora existed in both the pre- and posttreatment groups, and the proportion of their flora abundance could be altered depending on the caries status of the children in both groups. Leptotrichia abundance was significantly (P < 0.05) lower at 7 days posttreatment in both the single- and multiappointment groups. Corynebacterium and Corynebacterium_matruchotii were significantly more abundant in the C1_1M and C1_3M groups than in the C1 and C1_7D groups (P < 0.05). Streptococcus, Haemophilus and Haemophilus_parainfluenzae were significantly more abundant in the C1_7D group than in the other groups (P < 0.05). CONCLUSION: A single session of treatment under general anaesthesia can cause dramatic changes in the microbial community structure and composition within 7 days after treatment, whereas treatment over multiple appointments may cause slow changes in oral flora diversity.

Gut microbiota combined with metabolome dissects long-term nanoplastics exposure-induced disturbed spermatogenesis.

As the concerned emerging pollutants, several lines of evidence have indicated that nanoplastics (NPs) lead to reproductive toxicity. However, the biological mechanism underlying NPs disturbed spermatogenesis remains largely unknown. Therefore, we aimed to reveal the potential mechanism of impaired spermatogenesis caused by long-term NPs exposure from the perspective of integrated metabolome and microbiome analysis. After 12 weeks of gavage of polystyrene nanoplastics (PS-NPs) and animo-modified polystyrene nanoplastics (Amino-NPs), a well-designed two-exposure stages experimental condition. We found that NPs exposure induced apparent abnormal spermatogenesis, which appeared more severe in the Amino-NPs group. Mechanistically, 14 floras associated with glucose and lipid metabolism were significantly altered, as evidenced by 16 S rRNA sequencing. Testicular metabolome revealed that the Top 50 changed metabolites were also enriched in lipid metabolism. Subsequently, the combined gut microbiome and metabolome analysis uncovered the strong correlations between Klebsiella, Blautia, Parabacteroides, and lipid metabolites (e.g., PC, LysoPC and GPCho). We speculate that the dysbiosis of gut microbiota-related disturbed lipid metabolism may be responsible for long-term NPs-induced damaged spermatogenesis, which provides new insights into NPs-induced dysregulated spermatogenesis.

Exploration of the Main Antibiofilm Substance of Lactobacillus plantarum ATCC 14917 and Its Effect against Streptococcus mutans.

Dental plaque, a complex biofilm system established by cariogenic bacteria such as Streptococcus mutans (S. mutans), is the initiator of dental caries. Studies have found that the cell-free supernatant (CFS) of Lactobacilli could inhibit S. mutans biofilm formation. However, the main antibiofilm substance of the Lactobacilli CFS that acts against S. mutans is unclear. The present study found that the CFS of Lactobacillus plantarum (L. plantarum) ATCC 14917 had the strongest antibiofilm effect among the five tested oral Lactobacilli. Further bioassay-guided isolation was performed to identify the main antibiofilm substance. The antibiofilm effect of the end product, named 1-1-4-3, was observed and the structure of it was elucidated by using Q-TOF MS, 2D NMR and HPLC. The results showed that several components in the CFS had an antibiofilm effect; however, the effect of 1-1-4-3 was the strongest, as it could reduce the generation of exopolysaccharides and make the biofilm looser and thinner. After structure elucidation and validation, 1-1-4-3 was identified as a mixture of lactic acid (LA) and valine. Additionally, LA was shown to be the main antibiofilm substance in 1-1-4-3. In summary, this study found that the antibiofilm effect of the L. plantarum CFS against S. mutans was attributable to the comprehensive effect of multiple components, among which LA played a dominant role.

Effect of quorum quenching on biofouling control and microbial community in membrane bioreactors by Brucella sp. ZJ1.

Quorum quenching (QQ) has been demonstrated to be a novel technique for controlling biofouling in membrane bioreactors (MBRs), as it can significantly inhibit biofilm formation by disrupting quorum sensing (QS). The exploration of new QQ bacterial strains and the evaluation of their performance in mitigating membrane fouling in MBR systems is significant. In this study, an efficient QQ strain, Brucella sp. ZJ1 was encapsulated in alginate beads and evaluated for its ability to mitigate biofouling. The findings revealed that MBR with QQ beads extended the operation time by 2-3 times without affecting pollutant degradation. QQ beads maintained approximately 50% QQ activity after more than 50 days operation, indicating a long-lasting and endurable QQ effect. The QQ effect reduced extracellular polymeric substance (EPS) production especially in terms of polysaccharide and protein by more than 40%. QQ beads in the MBR also reduced the cake resistance and the irreversible resistance of membrane biofouling. Metagenomic sequencing suggests that QQ beads suppressed the QS effect and increased the abundance of QQ enzyme genes, ultimately inducing efficient membrane biofouling control.

[Clinical application value of Huanglian Jiedu Pills in improving syndrome of excess heat and fire toxin based on phase â ¡ clinical trial study on plasma ATP, 4-HNE, and ACTH levels].

A randomized, double-blind, placebo-controlled, multi-center phase Ⅱ clinical trial design was used in this study to recruit subjects who were in line with the syndrome of excess heat and fire toxin, and were diagnosed as recurrent oral ulcers, gingivitis, and acute pharyngitis. A total of 240 cases were included and randomly divided into a placebo group and a Huanglian Jiedu Pills group. The clinical efficacy of Huanglian Jiedu Pills in treating the syndrome of excess heat and fire toxin was evaluated by using the traditional Chinese medicine(TCM) syndrome scale. Enzyme-linked immunosorbent assay(ELISA) was used to determine and evaluate the levels of adenosine triphosphate(ATP), 4-hydroxynonenal(4-HNE), and adrenocorticotropic hormone(ACTH) in plasma of the two groups before and after administration and to predict their application value as clinical biomarkers. The results showed that the disappearance rate of main symptoms in the Huanglian Jiedu Pills group was 69.17%, and that in the placebo group was 50.83%. The comparison between the Huanglian Jiedu Pills group and the placebo group showed that 4-HNE before and after administration was statistically significant(P<0.05). The content of 4-HNE in the Huanglian Jiedu Pills group decreased significantly after administration(P<0.05), but that in the placebo group had no statistical significance and showed an upward trend. After administration, the content of ATP in both Huanglian Jiedu Pills group and placebo group decreased significantly(P<0.05), indicating that the energy metabolism disorder was significantly improved after administration of Huanglian Jiedu Pills and the body's self-healing ability also alleviated the increase in ATP level caused by the syndrome of excess heat and fire toxin to a certain extent. ACTH in both Huanglian Jiedu Pills group and placebo group decreased significantly after administration(P<0.05). It is concluded that Huanglian Jiedu Pills has a significant clinical effect, and can significantly improve the abnormal levels of ATP and 4-HNE in plasma caused by the syndrome of excess heat and fire toxin, which are speculated to be the effective clinical biomarkers for Huanglian Jiedu Pills to treat the syndrome of excess heat and fire toxin.

Confronting the Challenge of Cellulose Molecular Weight Measurement: An Accurate, Rapid, and Universal Method with Ionic Liquid as an Additive.

Molecular weight parameters are the key fundamental information of polymer materials, but the accurate characterization of the molecular weight of cellulose is extremely difficult due to its strong hydrogen bonding network. Herein, we demonstrated two new methods to accurately and rapidly measure the molecular weight parameters of cellulose by using 1-butyl-3-methylimidazolium acetate (BmimAc) ionic liquid (IL) as an additive. Cellulose is rapidly dissolved in BmimAc/DMSO (1:1, w/w) at room temperature at first. Then, DMAc is added to dilute the solution, and finally, the molecular weight and molecular weight distribution of cellulose samples are measured by the gel permeation chromatography (GPC) method with BmimAc/DMSO/DMAc (1:1:18, w/w) as the mobile phase. Such a simple method is suitable to all kinds of cellulose samples and exhibits an extremely high analytical efficiency which is 50 times higher than the previous GPC methods. In addition, a viscosity method that is available for industrial application was proposed by using the BmimAc/DMSO/DMAc (1:1:8, w/w) system with low viscosity. The relationship between the intrinsic viscosity of the cellulose/BmimAc/DMSO/DMAc solution and the molecular weight of cellulose is well established and is applicable to cellulose samples of Mw = 4.5 × 104 to 1.8 × 106, which is the widest applicable range among the reported viscosity methods. Overall, two new methods based on the use of BmimAc as an additive have many advantages, such as wide applicable range, simple preparation process, mild dissolution condition, no degradation or aggregation of cellulose, high accuracy, fast detection, and low IL consumption, overcoming the existing problems in the traditional methods. It is expected to be used as a standard procedure to characterize the molecular weight of cellulose in academia and industries.

Tumor microenvironment and redox dual stimuli-responsive polymeric nanoparticles for the effective cisplatin-based cancer chemotherapy.

The serious side effects of cisplatin hindered its clinical application and the nanotechnology might be the potential strategy to address the limitation. However, rapid clearance in the blood circulation and ineffective controlled drug release from nanocarriers hamper the therapeutic efficacy of the nano-delivery system. We constructed a tumor microenvironment and redox dual stimuli-responsive nano-delivery system PEG-c-(BPEI-SS-Pt) by cross-linking the disulfide-containing polymeric conjugate BPEI-SS-Pt with the dialdehyde group-modified PEG2000via Schiff base. After optimized the cross-linking time, 72 h was selected to get the nano-delivery system.1H NMR and drug release assays showed that under the acidic tumor microenvironment (pH 6.5-6.8), the Schiff base can be broken and detached the PEG cross-linked outer shells, displaying the capability to release the drugs with a sequential pH- and redox-responsive manner. Moreover, PEG-c-(BPEI-SS-Pt) showed more effective anti-tumor therapeutic efficacyin vivowith no significant side effects when compared with the drug of cisplatin used in the clinic. This strategy highlights a promising platform with the dual stimuli-responsive profile to achieve better therapeutic efficacy and minor side effects for platinum-based chemotherapy.

T cells participate in bone remodeling during the rapid palatal expansion.

Palatal expansion has been widely used for the treatment of transverse discrepancy or maxillae hypoplasia, but the biological mechanism of bone formation during this procedure is largely unknown. Osteoclasts, which could be regulated by T cells and other components of the immune system, play a crucial role in force-induced bone remodeling. However, whether T cells participate in the palatal expansion process remains to be determined. In this study, we conducted the tooth borne rapid palatal expansion model on the mouse, and detect whether the helper T cells (Th) and regulatory T cells (Treg) could affect osteoclasts and further bone formation. After bonding open spring palatal expanders for 3-day, 5-day, 7-day, and retention for 28-day, micro-computed tomography scanning, histologic, and immunofluorescence staining were conducted to evaluate how osteoclasts were regulated by T cells during the bone remodeling process. We revealed that the increased osteoclast number was downregulated at the end of the early stage of rapid palatal expansion. Type 1 helper T (Th1) cells and Type 17 helper T (Th17) cells increased initially and promoted osteoclastogenesis. Thereafter, the regulatory T (Treg) cells emerged and maintained a relatively high level at the late stage of the experiment to downregulate the osteoclast number by inhibiting Th1 and Th17 cells, which governed the new bone formation. In conclusion, orchestrated T cells are able to regulate osteoclasts at the early stage of rapid palatal expansion and further facilitate bone formation during retention. This study identifies that T cells participate in the palatal expansion procedure by regulating osteoclasts and implies the potential possibility for clinically modulating T cells to improve the palatal expansion efficacy.

MR/NIRF Dual-Mode Imaging of αvß3 Integrin-Overexpressing Tumors Using a Lipopeptide-Based Contrast Agent.

Early diagnosis and noninvasive detection of hepatocellular carcinoma have profound clinical implications for treatment quality and improved prognosis. To obtain high-resolution macroscopic anatomical information and high-sensitivity microscopic optical signals to detect tumors, it is highly desirable to develop dual-mode magnetic resonance imaging (MRI) and near-infrared fluorescent (NIRF) probes. An MR/NIRF dual-mode targeted contrast agent was created by encapsulating cyclic arginine-glycine-aspartate (cRGD) and Cy5.5 in liposomes and characterized by the particle size distribution, cytotoxicity, targeting, and MRI relaxivity. The MR T2 intensity and fluorescence intensity were evaluated in the tumors, livers, and muscles after the injection of cRGD-Liposome-Cy5.5 and Liposome-Cy5.5 at different time points. The average size of cRGD-Liposome-Cy5.5 was 62.33 ± 4.648 nm. The transverse relaxivity (R2) values had a negative correlation with the concentration of molecular probes. The MR signal intensity was enhanced in tumors after the cRGD-Liposome-Cy5.5 injection and not enhanced in liver parenchyma and muscles at the same time. The fluorescence intensity was enhanced in tumors after cRGD-Liposome-Cy5.5 injection in the targeted group. cRGD -Liposome-Cy5.5 as an entirely organic T2-positive dual-mode MR/NIRF targeted contrast agent is therefore able to detect early-stage hepatocellular carcinoma by targeting integrin αvß3, providing advantages for potential clinical utility and ease of clinical transformation.

Measure microbial activity driven oxygen transfer in membrane aerated biofilm reactor from supply side.

This short communication demonstrates for the first time a solely microbial activity driven oxygen influx across a microporous hollow fibre membrane via tracking changes in volume and gas composition of entrapped air supply. A U-shape manometer was used to directly reflect gas influx due to microbial activities. A pressure difference of several hundred pascal was created to draw oxygen while 25 mg-N/L of ammonium was oxidized into nitrite by active biofilm at a hydraulic retention time of 6 h. Calibrated and normalized gas compositions before and after the experiment were processed to unveil the gas exchange and estimate the actual oxygen influx across the membrane. A solely microbial activity driven oxygen influx of 10.7 mg O2/m2/h was observed. Measuring oxygen transfer from supply side provides a more straight-forward perspective on the role of active biofilm in membrane aerated biofilm reactor. The capability of the microbial activity to uptake oxygen on its own could potentially lead to greater energy savings in some MABR applications when strict aeration control is not needed.

In vitro and in vivo evaluation of a sustained-release once-a-day formulation of the novel antihypertensive drug MT-1207.

Hypertension is one of the most common chronic cardiovascular disorders. Sustained-release formulations are developed to maintain drug therapeutic levels throughout the treatment of hypertension, to promote patient compliance and improve patient outcomes. We have developed and tested in in vivo trials a once-a-day tablet formulation for the novel antihypertensive drug MT-1207. The tablets based upon a hydrophilic polymer matrix underwent post-compression parameter and physicochemical characterisations, along with in vitro drug release testing. The most promising formulation containing 31% w/w HPMC K15M gave a 24-hour release of MT-1207 with an almost constant release rate up to 20 hours. Follow in in vivo studies were carried out in Beagle dogs for the optimised sustained-release tablets in comparison to immediate-release tablets. The results showed that a sustained release of MT-1207 from the new formulation was achieved with a drug t1/2 2-2.5 times longer than the immediate-release tablets. Moreover, the AUC0-24h values of both sustained- and immediate-release tablets were identical at the same dose of 30 mg, indicating that the same amount of drug was absorbed in each case. For treatments based upon MT-1207, this development is significant for future commercial exploitation via scale-up and further trials, and for improved patient outcomes.

The enhancing antibiofilm activity of curcumin on Streptococcus mutans strains from severe early childhood caries.

BACKGROUND: Streptococcus mutans (S. mutans) is one of the main cariogenic bacteria for caries. It was found that the clinical strains of S. mutans isolated from caries active population have stronger cariogenic ability than the isolates from caries-free (CF) people. Previous studies have found that curcumin can inhibit biofilm formation of S. mutans UA159. The objective of this study is to explore the antibiofilm effect of curcumin on the clinical isolates of S. mutans from severe early childhood caries(SECC). RESULTS: The isolates from SECC group had more biomass than CF group (t = 4.296, P < 0.001). The acidogenicity and aciduricity of the strains from two groups showed no significant difference. After treatment with curcumin, the viability of biofilm was reduced to 61.865% ± 7.108% in SECC and to 84.059% ± 10.227% in CF group at 24 h (P < 0.05). The net reduction of live bacteria and total bacteria in the SECC group was significantly higher than that of the CF group (live bacteria t = 3.305, P = 0.016; total bacteria t = 2.378, P = 0.045) at 5 min. For 24 h, the net reduction of live bacteria and total bacteria in the SECC group was significantly higher than that of the CF group (live bacteria t = 3.305, P = 0.016; total bacteria t = 2.378, P = 0.045). The reduction of biofilm thickness reduced significantly in 5 min (t = 4.110, P = 0.015) and in 24 h (t = 3.453, P = 0.014). Long-term (24 h) curcumin treatment inhibited the amount of EPS in SECC group from (25.980 ± 1.156) µm3/µm2 to (20.136 ± 1.042) µm3/µm2, the difference was statistically significant (t = 7.510, P < 0.001). The gene of gtfC, gtfD, ftf, gbpB, fruA and srtA in the CF group and the gtfB, gtfC, gtfD, ftf, gbpB, srtA in SECC group were respectively reduced after 5 min curcumin treatment. After 24 h treatment, the gtfB, gtfC, gtfD, ftf, gbpB, fruA and srtA in both two groups were downregulation, all the differences were statistically significant. CONCLUSIONS: Curcumin has antibiofilm activity on clinical strains of S. mutans, especially for those isolated from SECC.

Proteomic and metabolic characterization of membrane vesicles derived from Streptococcus mutans at different pH values.

Bacterial membrane vesicles (MVs) are used as a tool for intercellular communication and seem essential for bacterial survival. However, few data are available on MVs generated by Streptococcus mutans, which is the main aetiological agent of dental caries. The present study presents an integrated proteomics and metabolomics analysis of MVs isolated from S. mutans at initial pH values of 7.5 and 5.5 and explores their function. The results showed that S. mutans releases more MVs with smaller diameters under acidic conditions than under neutral conditions. Proteomic analysis showed 344 common vesicular proteins, including various virulence factors. The expressions of 140 individual proteins and 37 metabolites were altered as a result of culturing S. mutans at different pH values. Co-analyses of proteomic and metabolomics data indicated that ABC transporters underwent significant changes under acid pressure. We concluded that S. mutans produced MVs at different pH values to carry proteins associated with cariogenesis. Moreover, the alterations of S. mutans MVs under acid pressure were associated with ABC transporters. These results increase our knowledge of S. mutans MVs and imply that S. mutans MVs may play a functional role in carious infection. KEY POINTS: • S. mutans MVs contained virulence factor-related proteins, even at low pH values. • Integrated proteomics and metabolomics analysis showed that S. mutans MVs alterations under acidic conditions were associated with ABC transporters.

Determination of the cleavage site of enterovirus 71 VP0 and the effect of this cleavage on viral infectivity and assembly.

Hand, foot, and mouth disease (HFMD) is a major public health concern, especially among infants and young children. The primary pathogen of HFMD is enterovirus 71 (EV71), whose capsid assembly mechanism including capsid protein processing has been widely studied. However, some of its mechanisms remain unclear, such as the VP0 cleavage. This study aimed to identify the cleavage site of the EV71 VP0 capsid protein and to elucidate the effects of EV71 VP0 cleavage on viral infectivity and assembly. A mass spectrometry analysis indicated that the cleavage site of EV71 VP0 is located between residues Lys69 and Ser70. To analyze the importance of either residue to cleavage, we designed single mutations of Lys69, Ser70 and double mutations respectively and implemented these genomes to encapsulation. The results indicated that Ser70 is more important for VP0 cleavage and EV71 infectivity. In addition, exogenous expression of EV71 protease 2A and 3C was used to verify whether they play roles in VP0 cleavage. Analyses also showed that none of them participate in this process. This study provides novel insights into the mechanisms of EV71 capsid maturation, which may be a potential target to improve the productivity and immunogenicity of EV71 vaccines.

Long term impact of surfactants & polymers on the colloidal stability, aggregation and dissolution of silver nanoparticles.

Cetyl trimethyl ammonium bromide (CTAB), Tween 20, polyvinyl pyrrolidone (PVP) and polyethylene glycol (PEG) are among the commonly used surfactants and polymers to stabilize silver nanoparticles (AgNPs). However, their interactions with AgNPs are different. The impact of these surfactants and polymers on the colloidal stability of freshly synthesized uncoated AgNPs was evaluated through a series of long-term experiments and analyzed in terms of their physical and chemical behavior. The cationic surfactant, CTAB was able to produce a mono modal particle size distribution in a prolonged period without affecting the dissolution. In the presence of Tween 20, a non-ionic surfactant, dissolution was promoted in the long run and the particles were preserved with minimal aggregation. In the presence of the polymers, PVP and PEG, the particle structure was not affected even though dissolution was observed. This study presents important insights on the interactions of AgNPs with surfactants and polymers, which could significantly affect the transformations and fate of AgNPs in the aquatic environment.