Molecular Planarization of Raman Probes to Avoid Background Interference for High-Precision Intraoperative Imaging of Tumor Micrometastases and Lymph Nodes.

The intraoperative imaging applications of a large number of Raman probes are hampered by the overlap of their signals with the background Raman signals generated by biological tissues. Here, we describe a molecular planarization strategy for adjusting the Raman shift of these Raman probes to avoid interference. Using this strategy, we modify the backbone of thiophene polymer-poly(3-hexylthiophene) (P3HT), and obtain the adjacent thiophene units planarized polycyclopenta[2,1-b;3,4-b']dithiophene (PCPDT). Compared with P3HT whose signal is disturbed by the Raman signal of lipids in tissues, PCPDT exhibits a 60 cm-1 blueshift in its characteristic signal. Therefore, the PCPDT probe successfully avoids the signal of lipids, and achieves intraoperative imaging of lymph nodes and tumor micrometastasis as small as 0.30 × 0.36 mm. In summary, our study presents a concise molecular planarization strategy for regulating the signal shift of Raman probes, and brings a tunable thiophene polymer probe for high-precision intraoperative Raman imaging.

A large-cohort study of 2971 cases of epulis: focusing on risk factors associated with recurrence.

BACKGROUND: To analyze the clinicopathological features of different histological subtypes of epulis, and evaluate the risk factors associated with recurrence. MATERIALS AND METHODS: A retrospective study including 2971 patients was performed. The patients' sex, age, location, size, histological subtypes, recurrence information, oral hygiene habits, periodontitis symptoms and smoking history were retrieved from the patient medical records and follow-up information. RESULTS: Among the 2971 cases, focal fibrous hyperplasia (FFH) was the most common lesion (60.92%), followed by peripheral ossifying fibroma (POF) (29.32%), pyogenic granuloma (PG) (8.08%) and peripheral giant cell granuloma (PGCG) (1.68%). The peak incidence of epulis was in the third and fourth decade of life, with a mean age of 45.55 years. Female predominance was found in all types of lesions with a female to male ratio of 1.71:1. PG had the highest recurrence rate (17.18%), followed by POF (12.98%), FFH (9.55%) and PGCG (8.82%). Histological subtypes were significantly correlated with the recurrence of epulis (P = 0.013). Regular supportive periodontal therapy (P = 0.050) had a negative correlation with recurrence, whereas symptoms of periodontitis (P < 0.001) had a positive correlation with the recurrence of epulis. CONCLUSIONS: Controlling the periodontal inflammation and regular supportive periodontal therapy might help reduce the recurrence of epulis.

Molecular Regulation of Polymeric Raman Probes for Ultrasensitive Microtumor Diagnosis and Noninvasive Microvessle Imaging.

Raman imaging is a powerful tool for the diagnosis of cancers and visualization of various biological processes. Polymers possessing excellent biocompatibility are promising probes for Raman imaging. However, few polymers are reported to serve as Raman probes for in vivo imaging, mainly due to the intrinsic weak Raman signal intensity and fluorescence interference of these polymers. Herein, a poly(indacenodithiophene-benzothiadiazole) (IDT-BT) polymer is presented, which emits unprecedentedly strong Raman signals under the near-infrared wavelength (785 nm) excitation, thus functioning as a Raman probe for ultrasensitive in vivo Raman imaging. Further mechanistic studies unveil that the unique Raman feature of the IDT-BT polymer relies on molecularly regulating its absorbance edge adjacent to the desired excitation wavelength, thus avoiding fluorescence interference and simultaneously emitting strong Raman scattering under preresonant excitation. Taking advantage of this discipline, the IDT-BT polymeric probe successfully realizes intraoperative Raman imaging of micrometastasis as small as 0.3 mm × 0.3 mm, comparable to the most sensitive Raman probes currently reported. Impressively, the IDT-BT enables noninvasive microvascular imaging, which is not achieved using other Raman probes. This work opens a new avenue toward the development of polymeric Raman probes for in vivo Raman imaging.

Effects of the enhanced public health intervention during the COVID-19 epidemic on respiratory and gastrointestinal infectious diseases in China.

The public health interventions to mitigate coronavirus disease 2019 (COVID-19) could also potentially reduce the global activity of influenza. However, this strategy's impact on other common infectious diseases is unknown. We collected data of 10 respiratory infectious (RI) diseases, influenza-like illnesses (ILIs), and seven gastrointestinal infectious (GI) diseases during 2015-2020 in China and applied two proportional tests to check the differences in the yearly incidence and mortality, and case-fatality rates (CFRs) over the years 2015-2020. The results showed that the overall RI activity decreased by 7.47%, from 181.64 in 2015-2019 to 168.08 per 100 000 in 2020 (p < 0.001); however, the incidence of influenza was seen to have a 16.08% escalation (p < 0.001). In contrast, the average weekly ILI percentage and positive influenza virus rate decreased by 6.25% and 61.94%, respectively, in 2020 compared to the previous 5 years (all p < 0.001). The overall incidence of GI decreased by 45.28%, from 253.73 in 2015-2019 to 138.84 in 2020 per 100 000 (p < 0.001), and with the greatest decline seen in hand, foot, and mouth disease (HFMD) (64.66%; p < 0.001). The mortality and CFRs from RI increased by 128.49% and 146.95%, respectively, in 2020, compared to 2015-2019 (p < 0.001). However, the mortality rates and CFRs of seven GI decreased by 70.56% and 46.12%, respectively (p < 0.001). In conclusion, China's COVID-19 elimination/containment strategy is very effective in reducing the incidence rates of RI and GI, and ILI activity, as well as the mortality and CFRs of GI diseases.

Golgi membrane protein GP73 modified-liposome mediates the antitumor effect of survivin promoter-driven HSVtk in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide, and there is currently no effective therapeutic strategy in clinical practice. Gene therapy has great potential for decreasing tumor-induced mortality but has been clinically limited because of the lack of tumor-specific targets and insufficient gene transfer. The study of targeted transport of therapeutic genes in HCC treatment seems to be very important. In this study, we evaluated a gene therapy approach targeting HCC using the herpes simplex virus thymidine kinase/ganciclovir (HSVtk/GCV) suicide gene system in HCC cell lines and in an in vivo human HCC xenograft mouse model. GP73-modified liposomes targeted gene delivery to the tumor tissue, and the survivin promoter drove HSVtk expression in the HCC cells. Our results showed that the survivin promoter was specifically activated in tumor cells and HSVtk was expressed selectively in tumor cells. Combined with GCV treatment, HSVtk expression resulted in suppression of HCC cell proliferation via enhancing apoptosis. Moreover, tail vein injection of GP73-HSVtk significantly suppressed the growth of xenograft tumors through an apoptosis-dependent pathway and extended the survival of tumor-bearing mice without damaging the mice liver functions. Taken together, this study demonstrates an effective cancer-specific gene therapy strategy using the herpes simplex virus thymidine kinase/ganciclovir (HSVtk/GCV) suicide gene system for HCC that can be further developed for future clinical trials.

Preparation of Amphiphilic Poly(ethylene glycol)- b-poly(γ-butyrolactone) Diblock Copolymer via Ring Opening Polymerization Catalyzed by a Cyclic Trimeric Phosphazene Base or Alkali Alkoxide.

Biobased poly(γ-butyrolactone) (PγBL) as a fully biodegradable and bioabsorbable biomaterial has shown superior properties compared to those of other aliphatic polyesters. It is of great importance to prepare amphiphilic block copolymer containing PγBL block to make ordered nano-objects for biomedical applications such as drug delivery systems. However, such an amphiphilic copolymer containing PγBL segment was never successfully prepared mostly due to the synthetic challenges of ring-opening polymerization (ROP) of nonstrained γ-butyrolactone (γBL) monomer. Here, we reported the first preparation of amphiphilic poly(ethylene glycol)- b-poly(γ-butyrolactone) (PEG- b-PγBL) diblock copolymer by using PEG as a macroinitiator. We applied two types of bases to initiate the ROP of γBL. An organic cyclic trimeric phosphazene base (CTPB) was first applied to activate the terminal hydroxyl group of PEG as macroinitiator for ROP of γBL. On the other hand, sodium hydride was used to activate the hydroxyl group of PEG to form sodium alkoxide as an initiating system for ROP of γBL. Both catalytic/initiating system showed moderate control on ROP of γBL and successfully produced PEG- b-PγBL diblock copolymers with varied molecular weights and relatively narrow molecular weight distributions. The effects of catalytic systems, activation temperatures, and monomer concentrations on γBL conversion and molecular weight of PEG- b-PγBL were carefully explored. The thermal properties and phase behaviors of obtained PEG- b-PγBL were also investigated.

miR-675 promotes odontogenic differentiation of human dental pulp cells by epigenetic regulation of DLX3.

In a previous study, we showed that microRNA-675 (miR-675) was significantly down-regulated in patients with tricho-dento-osseous (TDO) syndrome. One of the main features of TDO syndrome is dentin hypoplasia. Thus, we hypothesize that miR-675 plays a role in dentin development. In this study, we determined the role of miR-675 in the odontogenic differentiation of human dental pulp cells (hDPCs). Stable overexpression and knockdown of miR-675 in hDPCs were performed using recombinant lentiviruses containing U6 promoter-driven miR-675 and short hairpin-miR675 expression cassettes, respectively. Alkaline phosphatase (ALP) assay, Alizarin red staining assay, quantitative polymerase chain reaction (qPCR), Western blot analysis, and immunofluorescent staining revealed the promotive effects of miR-675 on the odontogenic differentiation of hDPCs. Further, we found that miR-675 facilitates the odontogenic differentiation process of hDPCs by epigenetic regulation of distal-less homeobox (DLX3). Thus, for the first time, we determined that miR-675 regulates the odontogenic differentiation of hDPCs by inhibiting the DNA methyltransferase 3 beta (DNMT3B)-mediated methylation of DLX3. Our findings uncover an unanticipated regulatory role for miR-675 in the odontogenic differentiation of hDPCs by epigenetic changes in DLX3 and provide novel insight into dentin hypoplasia feature in TDO patients.

[Association of interleukin-10 gene polymorphism with enterovirus 71 infection in children].

OBJECTIVE: To study the association of interleukin-10 (IL-10) -1082A/G, -819C/T, and -592C/A polymorphisms with IL-10 level and the severity of enterovirus 71 (EV71) infection in children. METHODS: A total of 137 children with hand-foot-mouth disease due to EV71 infection were enrolled as EV71 infection group, which was further divided into mild group with 91 children and severe group with 46 children, and 122 healthy children who underwent physical examination were enrolled as healthy control group. Related clinical data were collected. ELISA was used to measure the serum level of IL-10, and polymerase chain reaction-restriction fragment length polymorphism was used to analyze IL-10 -1082A/G, -819C/T and -592C/A polymorphisms. RESULTS: Compared with the healthy control group, the children with EV71 infection had significantly higher frequency of -1082 AA genotype and A allele (P<0.05). Among the children with EV71 infection, the severe group had significantly higher frequency of -1082 AA genotype and A allele than the mild group (P<0.05), while there was no significant difference in the distribution of IL-10 -819C/T and IL-10 -592C/A polymorphisms between the two groups (P>0.05). The severe group had a significantly higher serum level of IL-10 than the mild group and the healthy control group. IL-10 -1082 AA genotype, -819 TT genotype, and -592 AA genotype were associated with the low expression of IL-10 (P<0.05). As for haplotype, the EV71 infection group had a significantly lower frequency of GCC haplotype than the healthy control group (P<0.05). In the severe group, the children with ATA haplotype had a significantly lower IL-10 level than those with other haplotypes, and the children with GCC haplotype had a significantly higher IL-10 level than those with other haplotypes (P<0.05). There was no significant difference in IL-10 level between children with different haplotypes in the mild group and the healthy control group (P>0.05). CONCLUSIONS: IL-10 gene polymorphisms are associated with IL-10 expression and the severity of EV71 infection in children.

Peritoneal lavage with povidone-iodine solution in colorectal cancer-induced rats.

BACKGROUND: Although peritoneal lavage with povidone-iodine (PVPI) is frequently performed after surgery on the gastrointestinal tract, the effects of PVPI on the intestinal epithelial barrier are unknown. The purpose of this study was to investigate the effects of abdominal irrigation with PVPI on the intestinal epithelial barrier in a colorectal cancer (CRC)-induced rat model. MATERIALS AND METHODS: The CRC model was induced in rats with azoxymethane and dextran sodium sulfate. Next, a total of 24 male CRC-induced rats were randomly divided into three groups (n = 8): (1) a sham-operated group, (2) an NS group (peritoneal lavage 0.9% NaCl), and (3) a PVPI group (peritoneal lavage with 0.45%-0.55% PVPI). The mean arterial pressure was continuously monitored throughout the experiment. The levels of plasma endotoxin and D-lactate, blood gases, and protein concentration were measured. The ultrastructural changes of the epithelial tight junctions were observed by transmission electron microscopy. RESULTS: The mean arterial pressure after peritoneal lavage was lower in the PVPI group than that in the NS group. The protein concentration and levels of endotoxin and D-lactate were higher in the PVPI group than they were in the PVPI group. In addition, PVPI treatment resulted in a markedly severe metabolic acidosis and intestinal mucosal injury compared with NS rats. CONCLUSIONS: Peritoneal lavage with PVPI dramatically compromises the integrity of the intestinal mucosa barrier and causes endotoxin shock in CRC rats. It is unsafe for clinical applications to include peritoneal lavage with PVPI in colorectal operations.

Phosphazene Bases as Organocatalysts for Ring-Opening Polymerization of Cyclic Esters.

Over the past several years, organocatalyzed polymerization reactions have attracted considerable attention, and these efforts have led to major advances. A large number of organic compounds have been proven active for the polymerization of a large variety of monomers. In particular, phosphazene bases (PBs) are a family of extremely strong, non-nucleophilic, and uncharged auxiliary bases, and have shown their remarkable potential as organocatalysts for the ring-opening polymerization (ROP) of cyclic monomers. By deprotonation of weak acids or in combination with lithium cation, PBs significantly enhance the nucleophilicity of the initiator/chain-end, thus allowing fast and usually controlled anionic polymerization. In this feature article, the recent advances in phosphazene-catalyzed ROP of cyclic esters are summarized. This review is divided into three sections, including general features, design and synthesis, and catalytic applications. It aims to provide a critical analysis of PB-mediated ROP systems and a useful guide for the further design of organocatalysts applied to polymer synthesis. An outlook is given at the end.

New Copper(II) Coordination Compounds Assembled from Multifunctional Pyridine-Carboxylate Blocks: Synthesis, Structures, and Catalytic Activity in Cycloalkane Oxidation.

Two new copper(II) coordination compounds, namely a 1D coordination polymer [Cu(µ-cpna)(phen)(H2O)]n (1) and a discrete tetracopper(II) derivative [Cu(phen)2(H2O)]2[Cu2(µ-Hdppa)2(Hdppa)2] (2), were hydrothermally synthesized from copper(II) chloride as a metal source, 5-(4-carboxyphenoxy)nicotinic acid (H2cpna) or 5-(3,4-dicarboxylphenyl)picolinic acid (H3dppa) as a principal building block, and 1,10-phenanthroline (phen) as a crystallization mediator. Compounds 1 and 2 were isolated as air-stable microcrystalline solids and fully characterized by elemental and thermogravimetric analyses, IR spectroscopy, powder and single-crystal X-ray diffraction. In the solid state, the structure of 1 discloses the linear interdigitated 1D coordination polymer chains with the 2C1 topology. The crystal structure of an ionic derivative 2 shows that the mono- and dicopper(II) units are extended into the intricate 1D hydrogen-bonded chains with the SP 1-periodic net (4,4)(0,2) topology. Thermal stability and catalytic properties of 1 and 2 were also investigated. In fact, both Cu derivatives act as efficient homogeneous catalysts (catalyst precursors) for the mild oxidation of cycloalkanes by hydrogen peroxide to give the corresponding alcohols and ketones; the substrate scope and the effects of type and amount of acid promoter as well as bond-, regio-, and stereo-selectivity features were investigated.

DLX3 promotes bone marrow mesenchymal stem cell proliferation through H19/miR-675 axis.

The underlying molecular mechanism of the increased bone mass phenotype in Tricho-dento-osseous (TDO) syndrome remains largely unknown. Our previous study has shown that the TDO point mutation c.533A>G, Q178R in DLX3 could increase bone density in a TDO patient and transgenic mice partially through delaying senescence in bone marrow mesenchymal stem cells (BMSCs). In the present study, we provided a new complementary explanation for TDO syndrome: the DLX3 (Q178R) mutation increased BMSCs proliferation through H19/miR-675 axis. We found that BMSCs derived from the TDO patient (TDO-BMSCs) had stronger proliferation ability than controls by clonogenic and CCK-8 assays. Next, experiments of overexpression and knockdown of wild-type DLX3 via lentiviruses in normal BMSCs confirmed the results by showing its negative role in cell proliferation. Through validated high-throughput data, we found that the DLX3 mutation reduced the expression of H19 and its coexpression product miR-675 in BMSCs. Function and rescue assays suggested that DLX3, long noncoding RNA H19, and miR-675 are negative factors in modulation of BMSCs proliferation as well as NOMO1 expression. The original higher proliferation rate and the expression of NOMO1 in TDO-BMSCs were suppressed after H19 restoration. Collectively, it indicates that DLX3 regulates BMSCs proliferation through H19/miR-675 axis. Moreover, the increased expression of NOMO1 and decreased H19/miR-675 expression in DLX3 (Q178R) transgenic mice, accompanying with accrual bone mass and density detected by micro-CT, further confirmed our hypothesis. In summary, we, for the first time, demonstrate that DLX3 mutation interferes with bone formation partially through H19/miR-675/NOMO1 axis in TDO syndrome.

Morphological analyses and a novel de novo DLX3 mutation associated with tricho-dento-osseous syndrome in a Chinese family.

Tricho-dento-osseous (TDO) syndrome, an autosomal-dominant disorder, affects the morphological appearance of the tooth enamel, hair, and bone. Previous studies have confirmed that mutations in the DLX3 gene are responsible for TDO. In this study, we describe a Chinese patient with the typical traits of TDO - kinky hair, enamel hypoplasia, skull and jaw bones thickening, and sclerosis. Unfortunately, as a result of excessive attrition, we were unable to assess taurodontism. Examination of the tooth ground section showed a thin layer of enamel with no rods on the patient's tooth and abnormalities in Tomes' granular layer and the dentinal tubules. Scanning electron microscopy and energy-dispersive X-ray spectroscopy of the tooth enamel showed significant differences between the patient and the control individuals. A hair sample from the patient observed under a laser-scanning microscope showed longitudinal grooves in the hair shaft. Dual-energy X-ray absorptiometry measurement showed that the bone mineral density values of the patient's bones was much higher than normal. Finally, genetic analysis revealed a novel de novo missense mutation c.533A>G (p.Q178R) in the conserved homeodomain of the DLX3 gene. This DLX3 mutation is the sixth causative mutation for TDO to be identified so far.

Periodontitis promotes the progression of diabetes mellitus by enhancing autophagy.

Objective: This study aims to identify the periodontitis factor that activates excessive autophagy in pancreatic ß cells, resulting in organic lesions of pancreatic islet tissues and diminished insulin secretion, thereby accelerating the progression of diabetes mellitus (DM). Methods: Sprague-Dawley (SD) rats were induced with periodontitis (PD), type 2 diabetes mellitus (T2DM), or the combination of T2DM and PD (DP) through a high-sugar/high-fat diet and ligation of the tooth neck with silk thread. Alveolar bone resorption was assessed using Micro-CT, blood glucose levels were measured with a blood glucose meter, pancreatic tissue pathology was examined through HE staining, and the expression of autophagy-related proteins Beclin1 and LC3II/LC3I was analyzed using Western blotting. Results: Micro-CT results revealed more pronounced alveolar bone resorption and root bifurcation exposure in the PD and DP groups compared to the control group, with the DP group exhibiting the most severe condition. HE staining demonstrated the formation of periodontal pockets, severe alveolar bone destruction, and abnormal pancreatic islet tissue morphology in the PD and DP groups. The serum levels of IL-6, TNF-α, and IL-1ß increased sequentially in the control, DM, PD, and DP groups (P < 0.05). Relative expressions of GCK and GLUT-2 mRNA decreased in the PD group compared to the control group (P > 0.05), while the mRNA expressions in the DP and DM groups increased (P < 0.05), with the DP group exhibiting higher levels than the DM group (P < 0.05). Western blot results indicated increased expression levels of autophagy proteins Beclin1 and LC3II/LC3I in the DM and DP groups compared to the control group (P < 0.05), with the DP group exhibiting higher levels than the DM group (P < 0.05). Conclusion: The findings demonstrate that periodontal inflammatory factors may promote the enhancement of pancreatic cell autophagy in diabetic rats.

Enhancing proton transport in polyvinylidenedifluoride membranes and reducing biofouling for improved hydrogen production in microbial electrolysis cells.

Hydrophilic porous membranes, exemplified by polyvinylidene fluoride (PVDF) membranes, have demonstrated significant potential for replacing ion exchange membranes in microbial electrolysis cells (MECs). Membrane fouling remains a major challenge in MECs, impeding proton transport and consequently limiting hydrogen production. This study aims to investigate a synergistic antifouling strategy for PVDF membrane through the incorporation of a coating composed of polydopamine (PDA), polyethyleneimine (PEI), and silver nanoparticles (AgNPs). The PDA-PEI-Ag@PVDF membrane not only effectively mitigates fouling through steric and electrostatic repulsion forces, but also amplifies ion transport by facilitating water diffusion and electromigration. The PDA-PEI-Ag@PVDF membrane exhibited a reduced membrane resistance of 1.01 mΩ m2 and PDA-PEI-Ag modifying PVDF membrane was found to be effective in enhancing the proton transportation of PVDF membrane. Therefore, the enhanced hydrogen production rate of 2.65 ± 0.02 m3/m3/d was achieved in PDA-PEI-Ag@PVDF-MECs.

Association of interleukin 10 and interferon gamma gene polymorphisms with enterovirus 71 encephalitis in patients with hand, foot and mouth disease.

Enterovirus 71 (EV71) is one of the common causative agents of hand, foot and mouth disease (HFMD), and is associated with several outbreaks with neurological complications including encephalitis. This study investigated the polymorphisms of interferon gamma (IFN-γ)+874 T/A and interleukin 10 (IL-10)-1082 G/A in 65 Chinese patients with EV71 encephalitis and 113 Chinese HFMD patients without complications. The polymorphisms of IFN-γ+874 T/A and IL-10-1082 G/A were determined by polymerase chain reaction (PCR)-amplification refractory mutation system (ARMS) and PCR-sequence-specific primer (SSP) analysis, respectively. The IFN-γ + 874 A allele was observed with significantly greater frequency in patients with EV71 encephalitis (76.2%) compared with HFMD patients without complications (61.1%, p < 0.01). Similarly, the IL-10 - 1082 A allele was observed with significantly greater frequency in patients with EV71 encephalitis (86.2%) compared with HFMD patients without complications (77.0%, p < 0.05). IFN-γ + 874 A and IL-10 - 1082 A alleles are associated with susceptibility to EV71 encephalitis in Chinese patients.

On the inverse temperature transition and development of an entropic elastomeric force of the elastin mimetic peptide [LGGVG](3, 7).

We report on a molecular dynamics simulation based study of the thermal and mechanical properties of the elastin mimetic peptide [LGGVG](n) (n = 3, 7). Our findings indicate that this peptide undergoes an inverse temperature transition as the temperature is raised from ~20 °C to 42 °C. The thermal behavior is similar to what has been observed in other well studied short mimetic peptides of elastin. Both [LGGVG](n) (n = 3, 7) peptides exhibit an increase in the number of side chain contacts and peptide-peptide hydrogen bonds when the temperature is raised from ~20 °C to 42 °C. These observations are accompanied by a decrease in the number of proximal water molecules and number of peptide-water hydrogen bonds. This work also reports on a comparison of the thermal and mechanical properties of [LGGVG](3) and [VPGVG](3) and quantifies the interaction with surrounding waters of hydration under mechanically strained conditions. It is demonstrated, via a quasi-harmonic approach, that both model peptides exhibit a reduction in the population of low-frequency modes and an increase in population of high-frequency modes upon elongation. The shift in population of frequency modes causes the peptide entropy to decrease upon elongation and is responsible for the development of an entropic force that gives rise to elasticity. These observations are in disagreement with a previously published notion that model elastin peptides, such as [VPGVG](18), increase in entropy upon elongation.

Multiple roles of Runt-related transcription factor-2 in tooth eruption: bone formation and resorption.

OBJECTIVE: The aim was to provide a comprehensive review of the current knowledge of the multiple roles of Runt-related transcription factor-2 (RUNX2) in regulating tooth eruption, focusing on the molecular mechanisms regarding tooth eruption mediated by RUNX2. DESIGN: Relevant literatures in PubMed, Medline, and Scopus database were searched, and a narrative review was performed. The multiple roles of RUNX2 in regulating tooth eruption was reviewed and discussed. RESULTS: Aberrant RUNX2 expression leads to disturbed or failed tooth eruption. Tooth eruption involves both the process of bone formation and bone resorption. RUNX2 promotes osteogenesis around the radicular portion of the dental follicle that provides the biological force for tooth eruption through inducing the expression of osteogenesis-related genes in dental follicle cells/osteoblasts. On the other hand, through indirect and direct pathways, RUNX2 regulates osteoclastogenesis and the formation of the eruption pathway. CONCLUSION: RUNX2 exerts a pivotal and complex influence in regulating tooth eruption. This review provides a better understanding of the function of RUNX2 in tooth eruption, which is beneficial to illuminate the precise molecular mechanism of osteogenesis and bone resorption, aiding the development of effective therapy for the failure of tooth eruption.

Biocompatible Nanotube-Strontium/polydopamine-arginine-glycine-aspartic acid coating on Ti6Al4V enhances osteogenic properties for biomedical applications.

Titanium (Ti) alloys, particularly Ti6 Al4 V, are the most commonly used biomedical implant material. Ti alloys are biologically inert, so there have been continuous efforts to improve their osteogenic properties and clinical performance. Since TiO2 nanotubes (NT) appear to be excellent drug platforms, and strontium reportedly enhances osteogenesis, we constructed a TiO2 nanotube coating on the surface of Ti6 Al4 V and immersed it in Sr (OH)2 solution in order to incorporate Sr into TiO2 nanotubes (NT-Sr). The results of field emission scanning electron microscope and X-ray diffraction analysis verified the fabrication of NT-Sr. We next added polydopamine (PDA) and cyclo- (arginine-glycine-aspartic acid-phenylalanine-cysteine) [c(RGDfC)] peptides to further promote biocompatibility of the implant. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy confirmed the existence of PDA and c(RGDfC). Mesenchymal stem cells (MSCs) were planted on Ti, NT, NT-Sr, NT-Sr/PDA, and NT-Sr/PDA-RGD surfaces. The adhesion and differentiation of MSCs on different surfaces were evaluated. The mRNA expression of alkaline phosphatase, runt-related transcription factor 2 (Runx2) and type I collagen (Col I) of different groups were also tested. Finally, we observed that the NT-Sr/PDA-RGD group showed significantly better performance than other groups in terms of the differentiation and osteogenesis-related gene expression of MSCs. Thus, the NT-Sr/PDA-RGD complex may be an important modification strategy for Ti, as it shows excellent osteogenic potential.

Streptococcus mutans-associated bacteria in dental plaque of severe early childhood caries.

BACKGROUND: Streptococcus mutans (S. mutans) is a potential pathogenic bacteria of dental caries. However, the level of S. mutans is low in some children with severe early childhood caries (SECC). AIM: To evaluate the effect of S. mutans level on dental microbiome and cariogenesis. METHODS: The oral microbiota was compared between caries-free group (CF) and SECC group.16S rRNA gene sequencing was used for S. mutans level bacterial community analysis. The candidate bacteria that were closely related with S. mutans abundance were identified and confirmed by absolute quantitative real-time PCR in clinical dental plaque samples from CF and SECC groups. RESULTS: Through in-depth analysis of dental plaque microorganism, Leptotrichia, Selenomonas and Prevotella_7 were found in the S. mutans-low group (p < 0.05) and Porphyromonas, Selenomonas_3 were found in the S. mutans-high group (p < 0.05). Through quantitative real-time PCR, Leptotrichia, Selenomonas and Prevotella_7 were identified as the potential biomarkers of SECC when S. mutans was at a low level. CONCLUSION: Leptotrichia, Selenomonas and Prevotella_7 are identified as potential biomarkers in SECC with a low abundance or without S. mutans. Our study may shed light on the understanding of caries occurrence in SECC with low abundance of S. mutans. ABBREVIATIONS: S. mutans, Streptococcus mutans; CF, caries-free; SECC, severe early childhood caries; ECC, early childhood caries; rRNA, ribosome RNA; qPCR, Quantitative real-time PCR; OTUs, operational taxonomic units; ANOVA, analysis of variance; LDA, Linear discriminant analysis; LEfSe, Linear discriminant analysis effect size; COG, Groups of proteins; NMDS, Non-MetricMulti-Dimensional Scaling; IL-1ß, interleukin -1ß; IL-6, interleukin-6; IL-8, interleukin-8; IL-10, interleukin-10.