Integrated genomic analysis of antibiotic resistance and virulence determinants in invasive strains of Streptococcus pneumoniae.

Introduction: Streptococcus pneumoniae is an important human pathogen that may cause severe invasive pneumococcal diseases (IPDs) in young children and the elderly. A comprehensive comparative whole-genome analysis of invasive and non-invasive serotype strains offers great insights that are applicable to vaccine development and disease control. Methods: In this study, 58 invasive (strains isolated from sterile sites) and 71 non-invasive (serotypes that have not been identified as invasive in our study) pneumococcal isolates were identified among the 756 pneumococcal isolates obtained from seven hospitals in Zhejiang, China (2010-2022). Serotyping, antimicrobial resistance tests, and genomic analyses were conducted to characterize these strains. Results and discussion: The three most invasive serotypes were 23F, 14, and 6B. The invasive pneumococcal isolates' respective resistance rates against penicillin, ceftriaxone, tetracycline, and erythromycin were 34.5%, 15.5%, 98.3%, and 94.7%. Whole-genome sequencing indicated that the predominant invasive clonal complexes were CC271, CC876, and CC81. The high rate of penicillin non-susceptible Streptococcus pneumoniae (PNSP) is related to the clonal distribution of resistance-conferring penicillin-binding proteins (PBP). Interestingly, we found a negative correlation between invasiveness and resistance in the invasive pneumococcal serotype strains, which might be due to the proclivity of certain serotypes to retain their ß-lactam resistance. Moreover, the mutually exclusive nature of zmpC and rrgC+srtBCD suggests their intricate and potentially redundant roles in promoting the development of IPD. These findings reveal significant implications for pneumococcal vaccine development in China, potentially informing treatment strategies and measures to mitigate disease transmission.

Characterizing the impact of species/strain-specific Lactiplantibacillus plantarum with community assembly and metabolic regulation in pickled Suancai.

To investigate the colonization and impact of the specific Lactiplantibacillus plantarum strains, four isolated strains were applied in pickled Suancai which is a traditional pickled mustard (Brassica juncea). Results showed that strain-8 with the highest lactic acid bacteria (LAB) counts and acetic acid (p < 0.05). There were 11.42 % ∼ 32.35 % differential volatile compounds detected, although nitriles, esters, and acids were predominant. L. plantarum disturbed the microbial community, in which the microbial composition of strain-11 was most similar to the naturally fermented sample. Amino acids, carbohydrate metabolism, and metabolism of cofactors and vitamins were the main functional classes because of the similar dominant microbes (Lactiplantibacillus and Levilactobacillus). The functional units were separated based on NMDS analysis, in which bacterial chemotaxis, amino acid-related units, biotin metabolism, fatty acid biosynthesis, and citrate cycle were significantly different calculated by metagenomeSeq and Benjamin-Hochberg methods (p < 0.05). The contents of most flavor compounds were consistent with their corresponding enzymes. In particular, glucosinolates metabolites were different and significantly related to the myrosinase and metabolic preference of LAB. Therefore, this study revealed the impact mechanism of the specific L. plantarum strains and provided a perspective for developing microbial resources to improve the flavor diversity of fermented vegetables.

Limited protection of pneumococcal vaccines against emergent Streptococcus pneumoniae serotype 14/ST876 strains.

PURPOSE: Streptococcus pneumoniae (Spn) is a major cause of child death. We investigated the epidemiology of S. pneumoniae in a pediatric fever clinic and explored the genomics basis of the limited vaccine response of serotype 14 strains worldwide. METHODS: Febrile disease and pneumonia were diagnosed following criteria from the WHO at the end of 2019 at a tertiary children's hospital. Spn was isolated by culture from nasopharyngeal (NP) swabs. The density was determined by lytA-base qPCR. Isolates were serotyped by Quellung and underwent antimicrobial susceptibility testing. Whole-genome sequencing was employed for molecular serotyping, MLST, antibiotic gene determination, SNP calling, recombination prediction, and phylogenetic analysis. RESULTS: The presence of pneumococcus in the nasopharynx (87.5%, 7/8, p = 0.0227) and a high carriage (100%, 7/7, p = 0.0123) were significantly associated with pneumonia development. Living with siblings (73.7%, 14/19, p = 0.0125) and non-vaccination (56.0%, 28/50, p = 0.0377) contributed significantly to the Spn carriage. Serotype 14 was the most prevalent strain (16.67%, 5/30). The genome analysis of 1497 serotype 14 strains indicated S14/ST876 strains were only prevalent in China, presented limited vaccine responses with higher recombination activities within its cps locus, and unique variation patterns in the genes wzg and lrp. CONCLUSION: With the lifting of the one-child policy, it will be crucial for families with multiple children to get PCV vaccinations in China. Due to the highly variant cps locus and distinctive variation patterns in capsule shedding and binding proteins genes, the prevalent S14/ST876 strains have shown poor response to current vaccines. It is necessary to continue monitoring the molecular epidemiology of this vaccine escape clone.

Unveiling the Structural Self-Reconstruction and Identifying the Reactive Center of a V, Fe Co-Doped Cobalt Precatalyst toward Enhanced Overall Water Splitting by Operando Raman Spectroscopy.

The development of efficient and stable bifunctional electrocatalysts based on non-noble metals for water electrolysis is both urgent and challenging. However, unresolved issues remain regarding the challenge of identifying the active phase and gaining a comprehensive understanding of its surface reconstruction and functionality throughout the reaction process. In this study, we have combined doping and heterostructure construction by a one-step electrodeposition and a subsequent activation treatment to synthesize Fe, V co-doped Co3O4/Co(OH)2 and Co/Co(OH)2 heterointerfaces (referred to as A-Co60Fe1.1V). These heterointerfaces, composed of Co/Co(OH)2 and Co3O4/Co(OH)2, are proposed to facilitate charge transfer process during catalysis. X-ray photoelectron spectroscopy (XPS) analysis demonstrates that the introduction of V and Fe dopants increases the valence state of Co centers in Co3O4 and Co(OH)2. Further operando Raman spectroscopy reveals that Co(OH)2 and Co3O4 with the high-valence Co centers remain stable during the hydrogen evolution reaction (HER) process. These high-valence Co centers are believed to promote the crucial water dissociation step and therefore enhance the overall HER catalysis. On the other hand, during the oxygen evolution reaction (OER), Fe, V co-doping leads to an earlier formation of the active CoOOH species, while Fe doping can further help stabilize the more reactive ß-CoOOH species instead of the less reactive γ-CoOOH. As a result, the A-Co60Fe1.1V catalyst exhibits significantly improved catalytic activity for both HER and OER that it requires low overpotentials of 51 and 250 mV, respectively, to attain a current density of 10 mA cm-2. Moreover, when utilized as both the cathode and anode in alkaline water electrolysis, the A-Co60Fe1.1V catalyst can operate at a mere 1.54 V voltage while maintaining 10 mA cm-2, surpassing the majority of non-noble metal catalysts. Remarkably, it also exhibits stability for at least 40 h at ∼100 mA cm-2.

In vivo real-time assessment of developmental defects in enamel of anti-Act1 mice using optical coherence tomography.

The purpose of this study was to explore the feasibility of using optical coherence tomography (OCT) for real-time and quantitative monitoring of enamel development in gene-edited enamel defect mice. NF-κB activator 1, known as Act1, is associated with many inflammatory diseases. The antisense oligonucleotide of Act1 was inserted after the CD68 gene promoter, which would cover the start region of the Act1 gene and inhibit its transcription. Anti-Act1 mice, gene-edited mice, were successfully constructed and demonstrated amelogenesis imperfecta by scanning electron microscope (SEM) and energy dispersive X-ray (EDX) spectroscopy. Wild-type (WT) mice were used as the control group in this study. WT mice and anti-Act1 mice at 3 weeks old were examined by OCT every week and killed at eight weeks old. Their mandibular bones were dissected and examined by OCT, micro-computed tomography (micro-CT), and SEM. OCT images showed that the outer layer of enamel of anti-Act1 mice was obviously thinner than that of WT mice but no difference in total thickness. When assessing enamel thickness, there was a significant normal linear correlation between these methods. OCT could scan the imperfect developed enamel noninvasively and quickly, providing images of the enamel layers of mouse incisors.

Phosphoproteomic insight into the changes in structural proteins of muscle architecture associated with texture softening of grass carp (Ctenopharyngodon idella) fillets during chilling storage.

Texture is an important sensory attribute of fish affected by modifications of structural proteins in muscle architecture. To investigate the changes in protein phosphorylation during texture softening of fish, the proteins of grass carp muscle after chilling storage of 0 day and 6 days were compared by phosphoproteomics, and their association with texture was analyzed. Totally 1026 unique phosphopeptides on 656 phosphoproteins were identified as differential. They were mainly classified as intracellular myofibril and cytoskeleton, and extracellular matrix, of which the molecular function and biological process were binding into supramolecular assembly and myofilament contraction. The concomitant dephosphorylation of kinases and assembly regulators indicated dephosphorylation and disassembly tendency of sarcomeric architecture. Correlation analysis defined the relation between texture and dephosphorylation of myosin light chain, actin, collagen and cytoskeleton. This study revealed that protein phosphorylation may affect the texture of fish muscle through regulating sarcomeric assembly of structural proteins in muscle architecture.

Densifying Crystalline-Amorphous Ni3S2/NiOOH Interfacial Sites To Boost Electrocatalytic O2 Production.

The development of an efficient and low-cost electrocatalyst for oxygen evolution reaction (OER) is the key to improving the overall efficiency of water electrolysis. Here, we report the design of a three-dimensional (3-D) heterostructured Ni9S8/Ni3S2 precatalyst composed of unstable Ni9S8 and inert Ni3S2 components, which undergoes in situ electrochemical activation to generate an amorphous-NiOOH/Ni3S2 heterostructured catalyst. In situ Raman spectroscopy combined with ex situ characterizations, such as X-ray diffraction, X-ray photoelectron spectroscopy, and transmission electron microscopy, reveals that during the activation, Ni9S8 loses the sulfur element to form nickel oxides and eventually transforms to amorphous NiOOH at O2-evolving potentials, while the Ni3S2 component is rather inert that its majority in the bulk remains, thus forming a 3-D congee-like NiOOH/Ni3S2 heterostructure with the Ni3S2 crystalline particles randomly dispersed among amorphous NiOOH species. Unlike the sparse heterostructure that consists of a layer of NiOOH on top of Ni3S2, our unique congee-like NiOOH/Ni3S2 heterostructure provides plentiful reactive amorphous-crystalline interfacial sites. Moreover, the partial electron transfer between the NiOOH and remaining Ni3S2, benefiting from their dense interfacial sites, contributes to a higher valence state of the Ni3+ active centers in NiOOH, hence optimizing the adsorption of OER intermediates. Density functional theory calculations further disclose that the electronic structure regulation not only optimizes the Gibbs free energy of intermediate adsorption but also tunes the OH* absorption behavior to be exothermic, elucidating the spontaneous occurrence of OH* absorption and hence improves the OER. Therefore, a low overpotential of only 197 mV at an O2-evolving current density of 10 mA/cm2, a small Tafel slope of 38.8 mV/dec, and good stability are achieved on the amorphous-NiOOH/crystalline-Ni3S2 heterostructured catalyst.

[Corrigendum] Comparison of the biological characteristics of human mesenchymal stem cells derived from exfoliated deciduous teeth, bone marrow, gingival tissue, and umbilical cord.

Subsequently to the publication of this paper, an interested reader drew to the authors' attention that, in Fig. 3 on p. 4973, the data panels shown for the "Osteogenesis" row of data for the GMSC and BMSC experiments appeared to be overlapping, such the data may have been derived from the same original source. After having examined their original data, the authors have realized that the data panel selected for the GMSC "Osteogenesis" experiment was inadvertently chosen incorrectly. The corrected version of Fig. 3 is shown below. Note that this error did not significantly affect the results or the conclusions reported in this paper, and all the authors agree to this Corrigendum. The authors are grateful to the editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused.[Molecular Medicine Reports 18: 4969­4977, 2018; DOI: 10.3892/mmr.2018.9501].

Bioactive components and the molecular mechanism of Shengxian Decoction against lung adenocarcinoma based on network pharmacology and molecular docking.

OBJECTIVE: The aim of this study was to identify the active components of Shengxian Decoction (SXT) and to elucidate the multi-component, multi-target, and multi-pathway regulatory mechanisms underlying the efficacy of SXT in treating lung adenocarcinoma (LUAD). METHODS: The effects of SXT extract on proliferation, migration, and invasion capabilities of human LUAD cells were determined through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), wound healing, and Transwell assays. High-Performance Liquid Chromatography (HPLC) was employed to pinpoint the primary active constituents of SXT. The SXT-active component-target-pathway network and protein-protein interaction (PPI) network were constructed based on network pharmacology. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using DAVID. The clinical significance of key targets was assessed using several external databases, and molecular docking confirmed the binding affinities between key targets and SXT active components. RESULTS: SXT significantly inhibited the proliferation, migration and invasion of human LUAD cells. HPLC identified and quantified seven active SXT components. Network pharmacology yielded 197 targets, 128 signaling pathways, and 448 GO terms. The PPI network and external validation underscored 13 key targets significantly associated with the influence of SXT on LUAD progression. Molecular docking demonstrated strong interactions between SXT active components and key targets. CONCLUSION: SXT treats LUAD through a multifaceted approach involving various components, targets, and pathways. This research offers novel insights into the constituents and molecular mechanisms of SXT in LUAD therapy.

Unraveling the contribution of pre-salting duration to microbial succession and changes of volatile and non-volatile organic compounds in Suancai (a Chinese traditional fermented vegetable) during fermentation.

Pre-salting is an important pre-treatment during production of Suancai as it provides flavor precursor and microbial community for subsequent fermentation. To investigate the effect of pre-salting duration on fermentation of Suancai, the physicochemical properties, microbial composition, non-volatile and volatile organic compounds profiles of Suancai pre-salted for 1 month (1 M) and 7 months (7 M) were analyzed during fermentation for 30 days. Results showed that 7 M led to higher salt content, faster depletion of reducing sugars, and more titratable acidity. Additionally, more lactic acid and acetic acid, and less umami amino acid (Glu) and GABA were observed in 7 M. Longer pre-salting duration (7 M) promoted formation of mild-flavor volatile compounds, and significantly reduced isothiocyanates with pungent off-flavor. Moreover, 7 M promoted abundance of genera Chromohalobacter, Vibrio and Pichia, while reducing abundance of Lactobacillus, Debaryomyces and Kazachstania throughout fermentation. These results implicated that longer pre-salting duration facilitated more acidic, milder flavor and less pungent off-odor in Suancai. This study provided a perspective for pre-salting as a control point for improving quality of fermented vegetable.

Expert consensus on early childhood caries management.

Early childhood caries (ECC) is a significant chronic disease of childhood and a rising public health burden worldwide. ECC may cause a higher risk of new caries lesions in both primary and permanent dentition, affecting lifelong oral health. The occurrence of ECC has been closely related to the core microbiome change in the oral cavity, which may be influenced by diet habits, oral health management, fluoride use, and dental manipulations. So, it is essential to improve parental oral health and awareness of health care, to establish a dental home at the early stage of childhood, and make an individualized caries management plan. Dental interventions according to the minimally invasive concept should be carried out to treat dental caries. This expert consensus mainly discusses the etiology of ECC, caries-risk assessment of children, prevention and treatment plan of ECC, aiming to achieve lifelong oral health.

Vascularized pulp regeneration via injecting simvastatin functionalized GelMA cryogel microspheres loaded with stem cells from human exfoliated deciduous teeth.

Dental pulp necrosis are serious pathologic entities that causes tooth nutrition deficiency and abnormal root development, while regeneration of functional pulp tissue is of paramount importance to regain tooth vitality. However, existing clinical treatments, which focus on replacing the necrotic pulp tissue with inactive filling materials, fail to restore pulp vitality and functions, thus resulting in a devitalized and weakened tooth. Currently, dental pulp regeneration via stem cell-based therapy for pulpless teeth has raised enormous attention to restore the functional pulp. Here, a novel design of injectable simvastatin (SIM) functionalized gelatin methacrylate (GelMA) cryogel microspheres (SMS) loaded with stem cells from human exfoliated deciduous teeth (SHEDs) was established to refine SHEDs biological behaviors and promote in vivo vascularized pulp-like tissue regeneration. In this system, SIM encapsulated poly (lactide-co-glycolide) (PLGA) nanoparticles were incorporated into GelMA cryogel microspheres via cryogelation and O1/W/O2 emulsion method. SMS with sustained release of SIM promoted SHEDs adhesion, proliferation and exhibited cell protection properties during the injection process. Furthermore, SMS enhanced SHEDs odontogenic differentiation and angiogenic potential, and SHEDs loaded SMS (SHEDs/SMS) are beneficial for human umbilical vein endothelial cells (HUVECs) migration and angiogenesis, demonstrating their potential for use in promoting vascularized tissue regeneration. SHEDs/SMS complexes were injected into cleaned human tooth root segments for subcutaneous implantation in nude mice. Our results demonstrated that SHEDs/SMS could induce vessel-rich pulp-like tissue regeneration in vivo and that such an injectable nano-in-micro multistage system for the controlled delivery of bioactive reagents would be suitable for clinical application in endodontic regenerative dentistry.

Effect of pneumococcal conjugate vaccine availability on Streptococcus pneumoniae infections and genetic recombination in Zhejiang, China from 2009 to 2019.

Pneumococcal pneumonia is one of the main reasons for child death worldwide. Pneumococcal conjugate vaccines (PCVs) are considered the most effective strategy for pneumococcal disease (PD) prevention, but how a pause in PCV vaccination affects the prevalence of PD or the genetic evolution of Streptococcus pneumoniae genetic evolution is unknown. Based on the unique PCV introduction timeline (vaccine unavailable during April 2015-April 2017) in China, we aimed to evaluate the effect of interrupted PCV availability on PD and pneumococcal genome variation. Pneumococcal isolates (n = 386) were collected retrospectively from eight sites in Zhejiang, China from 2009 to 2019 in which 184 pathogenic (isolates from sterile and infection sites) strains were identified. An interrupted time series analysis was conducted to estimate changes in PD and the recombination frequency of whole genome-sequenced strains was estimated via SNP calling. We found that both PD and pneumococcal genome variation were affected by interrupted PCV availability. The proportion (∼70%) of vaccine-type pneumococcal LRTI (VT-LRTI) in all LRTI cases decreased to ∼30% in the later PCV7 period and rebounded to ∼70% in children once PCV7 became unavailable in April 2015 (p = 0.0007). The major clone CC271 strains showed slowed (p = 0.0293) recombination frequency (decreased from 2.82 ± 1.16-0.72 ± 0.21) upon PCV removal. Our study illustrated for the first time that VT-LRTI fluctuated upon interrupted vaccine availability in China and causing a decreased of recombination frequency of vaccine types. Promoting a nationwide continuous vaccination programme and strengthening S. pneumoniae molecular epidemiology surveillance are essential for PD prevention.

Global genome and comparative transcriptomic analysis reveal the inulin consumption strategy of Lactiplantibacillus plantarum QS7T.

Sichuan pickle is a natural combination of probiotics and dietary fibers, in which a strain Lactiplantibacillus plantarum QS7T was found to be capable of efficiently metabolizing inulin. However, the underlying molecular mechanism of inulin consumption by the strain QS7T is unclear. Therefore, this study firstly investigated the metabolic characteristics of inulin in the strain QS7T, and the results showed it could grow very well on the medium containing inulin as a carbon source (maximum OD600 nm, 1.891 ± 0.028) and degrade both short-chain oligofructose and long-chain fructan components through thin layer chromatography analysis. Genomic sequencing and analysis revealed a high percentage of functional genes associated with carbohydrate transport and metabolism, particularly glycoside hydrolase (GH) genes responsible for hydrolysing carbohydrates, within the genome of the strain QS7T. Furthermore, comparative transcriptomic analysis of L. plantarum QS7T in response to inulin or glucose indicated that functional genes associated with inulin consumption including several genes encoding PTS sugar transporters and two predicted GH32 family genes encoding beta-fructofuranosidase and beta-fructosidase were significantly up-regulated by inulin compared to the gene expression on glucose. In conclusion, we obtained a mechanistic understanding of interplay between probiotic L. plantarum QS7T derived from Sichuan pickle and natural dietary fiber, inulin; totally two operons including a sacPTS1 operon responsible for metabolizing short-chain oligofructose primarily in the cytoplasm and a fos operon responsible for extracellularly degrading all moderate and long-chain fructan components linked to inulin consumption by L. plantarum QS7T.

Spontaneous Dissolution of Oxometalates Boosting the Surface Reconstruction of CoMOx (M = Mo, V) to Achieve Efficient Overall Water Splitting in Alkaline Media.

Bimetallic materials have been regarded as promising catalysts for efficient alkaline water splitting. However, the spontaneous reconstruction of the surface structures of the catalysts before catalysis has long been overlooked. Here, we present that in situ dissolution of MoO42- in CoMoO4 boosts spontaneous surface reconstruction in an alkaline medium. Our results reveal that CoMoO4 microrod arrays function as precatalysts that undergo spontaneous surface reconstruction under alkaline conditions, forming a layer of Co3O4/CoMoO4 and CoOOH/CoMoO4 heterostructures. X-ray photoelectron spectroscopy (XPS) combined with in situ Raman spectroscopy reveals that in such activated CoMoO4 (A-CoMoO4), the partial electron transfer from Co to Mo sites helps induce a higher valence state of Co centers and the heterostructure of Co3O4/CoMoO4 may promote the generation of CoOOH, which is very likely the precursor to the active Co4+ species for oxygen evolution reaction (OER) catalysis. During the hydrogen evolution reaction (HER), Co3O4 generated after surface reconstruction can promote the dissociation of water, which is considered the rate-determining step of the alkaline HER. Hence, A-CoMoO4 exhibits superior bifunctional electrocatalytic activities that the overpotentials at a working current density of 10 mA cm-2 for the HER and OER are only 13 and 264 mV, respectively. Inspired by the remarkable bifunctionality, the electrolytic cell employing A-CoMoO4 as both anode and cathode shows an appealing potential of 1.51 V to deliver 10 mA cm-2 for overall water splitting. Similarly, CoVOx also shows the spontaneous surface reconstruction behavior in the alkaline medium, which we propose can be extended to a series of oxometalate catalysts.

TGF-ß2 and TGF-ß1 differentially regulate the odontogenic and osteogenic differentiation of mesenchymal stem cells.

OBJECTIVE: To explore the effects of transforming growth factor-ß2 (TGF-ß2) and TGF-ß1 on the odontogenic and osteogenic differentiation of mesenchymal stem cells (MSCs). DESIGN: We used lentiviral transduction to knock down TGF-ß1 or TGF-ß2 in stem cells from dental apical papilla (SCAPs), and to generate bone marrow mesenchymal stem cells (BMSCs) with overexpression of TGF-ß1 or TGF-ß2. We investigated the odontogenic and osteogenic differentiation abilities of these transductants in vitro and in vivo. RESULTS: In vitro, TGF-ß2 knockdown in SCAPs reduced the expression of odontoblast-related markers DSPP and DMP-1, and increased the expression of osteoblast-related markers OCN and RUNX-2. Conversely, TGF-ß1 knockdown had the opposite effects. TGF-ß2 overexpression promoted expression of odontoblast-related markers in BMSCs at early differentiation, but inhibited the expression of odontoblast-related markers at later stages. TGF-ß2 overexpression attenuated expression of osteogenic-related markers in BMSCs, while TGF-ß1 overexpression enhanced odontoblast-related and osteoblast-related markers. SCAP or BMSC transductants were transplanted underneath kidneys in vivo. Masson staining showed that knockdown of TGF-ß1, but not TGF-ß2 promoted the expression of type I collagen in SCAPs. Immunohistochemical staining showed that TGF-ß2 knockdown inhibited DSPP expression in SCAPs, but TGF-ß1 knockdown had no obvious effect on DSPP expression. In vivo, TGF-ß1 overexpression and TGF-ß2 overexpression had no effect on the expression of type I collagen and DSPP in BMSCs. CONCLUSIONS: TGF-ß2 promotes odontogenic differentiation of SCAPs and attenuates osteogenic differentiation of SCAPs and BMSCs. TGF-ß1 promotes osteogenic differentiation of BMSCs and plays a complex role in regulating odontogenic differentiation of MSCs.

Hsa-miRNA-143-3p regulates the odontogenic differentiation of human stem cells from the apical papilla by targeting NFIC.

AIM: To evaluate the effects of hsa-miRNA-143-3p on the cytodifferentiation of human stem cells from the apical papilla (hSCAPs) and the post-transcriptional regulation of Nuclear factor I-C (NFIC). METHODOLOGY: miRNA expression profiles in human immature permanent teeth and during hSCAP differentiation were examined. hSCAPs were treated with miR-143-3p overexpression or silencing viruses, and the proliferation and odontogenic and osteogenic differentiation of these stem cells, and the involvement of the NFIC pathway, were investigated. Luciferase reporter and NFIC mutant plasmids were used to confirm NFIC mRNA as a direct target of miR-143-3p. NFIC expression analysis in the miR-143-3p overexpressing hSCAPs was used to investigate whether miR-143-3p functioned by targeting NFIC. Student's t-test and chi-square tests were used for statistical analysis. RESULTS: miR-143-3p expression was screened by microarray profiling and was found to be significantly reduced during hSCAP differentiation (p < .05). Overexpression of miR-143-3p inhibited the mineralization of hSCAPs significantly (p < .05) and downregulated the levels of odontogenic differentiation markers (NFIC [p < .05], DSP [p < .01] and KLF4 [p < .01]), whereas silencing of miR-143-3p had the opposite effect. The luciferase reporter gene detection and bioinformatic approaches identified NFIC mRNA as a potential target of miR-143-3p. NFIC overexpression reversed the inhibitory effect of miR-143-3p on the odontogenic differentiation of hSCAPs. CONCLUSIONS: miR-143-3p maintained the stemness of hSCAPs and modulated their differentiation negatively by directly targeting NFIC. Thus, inhibition of this miRNA represents a potential strategy to promote the regeneration of damaged tooth roots.

Combined Photothermotherapy and Chemotherapy of Oral Squamous Cell Carcinoma Guided by Multifunctional Nanomaterials Enhanced Photoacoustic Tomography.

BACKGROUND: Squamous cell carcinoma of the head and neck is the sixth most common cancer worldwide, with 40% occurring in the oral cavity. Although the level of early diagnosis and treatment of OSCC has improved significantly, the five-year survival rate of advanced patients remains unsatisfactory. However, the main challenges before us are how to get an early and accurate diagnosis and how to formulate effective treatment. Nanoparticle-based chemo-photothermal therapy has proven to be a promising non-invasive approach to treating oral squamous cell carcinoma treatment. METHODS: In this study, we tried to design and synthesize multifunctional hyaluronic acid (HA) modified gold nanorods/mesoporous silica-based nanoparticles loaded with doxorubicin hydrochloride (DOX) for photoacoustic imaging (PAI) guided cooperative chemo-photothermal therapy. RESULTS: The resultant nanocomposite shows favorable biocompatibility, relatively low cytotoxicity, ideal drug loading capability and strong PAI signals. In addition, they showed an excellent photothermal conversion efficiency of 49.02% for photothermal therapy (PTT). Moreover, in vivo and in vitro experiments have shown that synergistic chemo-photothermal therapy has better therapeutic effects than chemotherapy alone or PTT (P < 0.05). After being injected into the CAL-27 tumor-bearing mice, the DOX-AuNRs@mSiO2-HA nanoparticles could accumulate rapidly at the tumor sites and achieve complete ablation of tumors when combined with near-infrared laser irradiation, without obvious side effects on normal tissues. CONCLUSION: Our research provides a solid demonstration of the potential of DOX-AuNRs@mSiO2-HA as a multifunctional platform in PAI-guided photothermal chemotherapy for oral squamous cell carcinoma.

Comparative evaluation of package types in alleviating textural softening and package-swelling of Paocai during storage: Insight into microbial invasion, cell wall pectinolysis and alteration in sugar and organic acid profiles.

The present study aimed to investigate the effect of initial vacuum package (VP), air package (AP) and salt-solution package (NP) on texture softening and package-swelling of Paocai by comparing the changes in physicochemical properties, pectinolysis, microstructure, microbial profile, as well as sugar and organic acid profiles during storage. Results showed that, when compared with AP and NP, with suppressive microbial invasion and less total pectinase activity, VP could retain more soluble pectin and induce more compact microstructure of Paocai, leading to higher hardness of Paocai during storage. As for package-swelling, VP mitigated gas-production in package by changing the microbial composition and metabolic patterns of sugar and organic acid in Paocai, especially targeted regulating the abundance of genus Kazachstania. This study provided a perspective for appropriate packaging technology to control the pectinase activity as well as cell-invading and gas-producing microorganisms for manufacturing fermented vegetable with better texture and non-package-swelling.