Advancing the Boundaries of Immunotherapy in Lung Adenocarcinoma with Idiopathic Pulmonary Fibrosis by a Biomimetic Proteinoid Enabling Selective Endocytosis.

The coexistence of lung adenocarcinoma (LUAD) with idiopathic pulmonary fibrosis (IPF), which has been extensively documented as a prominent risk factor for checkpoint inhibitor-related pneumonitis (CIP) in patients undergoing immunotherapy, has long been considered a restricted domain for the use of immune checkpoint inhibitors (ICIs). To overcome it, an approach was employed herein to specifically target PD-L1 within the cellular interior, surpassing the conventional focus solely on the cytomembrane, thereby facilitating the development of ICIs capable of distinguishing between LUAD cells and noncancerous cells based on their distinctive endocytic propensities. By exploiting the aurophilicity-driven self-assembly of a PD-L1 binding peptide (PDBP) and subsequently encapsulating it within erythrocyte membranes (EM), the resulting biomimetic ICIs protein EMS-PDBP exhibited extraordinary selectivity in internalizing LUAD cells, effectively targeting PD-L1 within cancer cells while hindering its membrane translocation. The EMS-PDBP treatment not only reactivated the antitumor immune response in the LUAD orthotopic allograft mouse model but also demonstrated a favorable safety profile by effectively eliminating any immune-related adverse events (irAEs). Most significantly, EMS-PDBP successfully and safely restored the antitumor immune response in a mouse model of LUAD with coexistent IPF, thus shattering the confines of ICIs immunotherapy. The reported EMS-PDBP collectively offers a potential strategy for immune reactivation to overcome the limitations of immunotherapy in LUAD coexisting with IPF.

Rewiring chaperone-mediated autophagy in cancer by a prion-like chemical inducer of proximity to counteract adaptive immune resistance.

Chaperone-mediated autophagy (CMA), a proteolytic system contributing to the degradation of intracellular proteins in lysosomes, is upregulated in tumors for pro-tumorigenic and pro-survival purposes. In this study, bioinformatics analysis revealed the co-occurrence of upregulated CMA and PD-L1 accumulation in metastatic melanoma with adaptive immune resistance (AIR) to anti-PD1 treatment, suggesting the potential therapeutic effects of rewiring CMA for PD-L1 degradation. Furthermore, this co-occurrence is attributed to IFN-γ-mediated compensatory up-regulation of PD-L1 and CMA, accompanied by enhanced macropinocytosis. Drawing inspiration from the cellular uptake of prions via macropinocytosis, a prion-like chemical inducer of proximity called SAP was engineered using self-assembly of the designed chiral peptide PHA. By exploiting sensitized macropinocytosis, SAP clandestinely infiltrates tumor cells and subsequently disintegrates into PHA, which reprograms CMA by inducing PD-L1 close to HSPA8. SAP degrades PD-L1 in a CMA-dependent manner and effectively restores the anti-tumor immune response in both allografting and Hu-PDX melanoma mouse models with AIR while upholding a high safety profile. Collectively, the reported SAP not only presents an immune reactivation strategy with clinical translational potential for overcoming AIR in cutaneous melanomas but serves as a reproducible example of precision-medicine-guided drug development that fully leverages specific cellular indications in pathological states.

Addressing data scarcity in optical matrix multiplier modeling using transfer learning.

We present and experimentally evaluate the use of transfer learning to address experimental data scarcity when training neural network (NN) models for Mach-Zehnder interferometer mesh-based optical matrix multipliers. Our approach involves pretraining the model using synthetic data generated from a less accurate analytical model and fine-tuning it with experimental data. Our investigation demonstrates that this method yields significant reductions in modeling errors compared to using an analytical model or a standalone NN model when training data is limited. Utilizing regularization techniques and ensemble averaging, we achieve <1 dB root-mean-square error on the 3×3 matrix weights implemented by a photonic chip while using only 25% of the available data.

Tumor necrosis factor-like cytokine 1A plays a role in inflammatory bowel disease pathogenesis.

The binding of tumor necrosis factor-like cytokine 1A (TL1A) to death receptor 3 (DR3) plays an important role in the interaction between dendritic cells (DCs) and T cells and contributes to intestinal inflammation development. However, the mechanism by which DCs expressing TL1A mediate helper T (Th) cell differentiation in the intestinal lamina propria (LP) during the pathogenesis of inflammatory bowel disease remains unclear. In this study, we found that TL1A/DR3 promoted Th1 and Th17 cell differentiation in T-T and DC-T cell interaction-dependent manners. TL1A-deficient CD4+ T cells failed to polarize into Th1/Th17 cells and did not cause colonic inflammation in a T cell transfer colitis model. Notably, TL1A was located in the cytoplasm and nuclei of DCs, positively regulated the DC-specific ICAM-grabbing nonintegrin/RAF1/nuclear factor κB signaling pathway, enhanced the antigen uptake ability of DCs, and promoted TLR4-mediated DC activation, inducing naive CD4+ T cell differentiation into Th1 and Th17 cells. Our work reveals that TL1A plays a regulatory role in inflammatory bowel disease pathogenesis.

Prevalence, clinical characteristics, and 3-dimensional radiographic analysis of supernumerary teeth in Guangzhou, China: a retrospective study.

OBJECTIVE: The aim was to investigate the prevalence and clinical and 3-dimensional (3D) radiographic characteristics of supernumerary teeth (ST) in a paediatric dental population. The factors associated with ST eruption potential were analysed, and the optimal extraction time for nonerupted ST was discussed. METHODS: A retrospective study was performed in a 13,336-participant baseline population aged 3-12 years for whom panoramic radiographs had been obtained in the hospital from 2019 to 2021. The medical records and radiographic data were reviewed to identify patients with ST. Both the demographic variables and ST characteristics were recorded and analysed . RESULTS: In total, 890 patients with 1,180 ST were screened from the 13,336 baseline population. The ratio of males (679) to females (211) was approximately 3.2:1. Generally, ST occurred singularly and were frequently found in the maxilla (98.1%). A total of 40.8% of ST were erupted, and the 6-year-old age group presented the highest eruption rate (57.8%). The eruption rate of ST was highly negatively correlated with age. A total of 598 patients additionally underwent cone- beam computed tomography (CBCT). According to the CBCT images, the majority of ST were conical, normally oriented, palatally situated, nonerupted and symptomatic. The most common ST-associated complication was failed eruption of adjacent teeth. In addition, symptomatic ST were more common in the 7- to 8- and 9- to 10-year-old age groups. The eruption rate of ST was 25.3% among the patients who had undergone CBCT. A normal orientation and the labial position were significant protective factors for ST eruption, with odds ratios (ORs) of 0.004 (0.000-0.046) and 0.086 (0.007-1.002), respectively. Age and the palatal position were significant risk factors, with ORs of 1.193 (1.065-1.337) and 2.352 (1.377-4.02), respectively. CONCLUSIONS: This study provides a detailed analysis of ST characteristics in 3-12 year old children. Age as well as the position and orientation of ST were reliable predictors of the ST eruption. An age of 6 years old may be the optimal time for extraction of nonerupted ST to maximize the utilization of eruption potential and reduce the incidence of ST-associated complications.

The First Phytochemical Investigation of Artemisia divaricate: Sesquiterpenes and Their Anti-Inflammatory Activity.

Artemisia divaricate belongs to the Artemisia genus of the family of Compositae, a sort of perennial herb endemic in most regions of China. For the first time, a phytochemical investigation was carried out on the whole plant of Artemisia divaricate, resulting in the identification of 39 sesquiterpenes, with 9 of them being new (1-9). The structures of the new compounds were fully established using extensive analysis of MS and 1D and 2D NMR spectroscopic data and density functional theory (DFT) NMR calculations. Their structures involve germacrane, eudesmane, and bisabolane types. All the new isolates were evaluated for their anti-inflammatory activities in lipopolysaccharide (LPS)-stimulated murine macrophages of RAW 264.7 cells. Compounds 2 and 8 showed a significant inhibition effect on NO production, with IC50 values of 5.35 ± 0.75 and 7.68 ± 0.54 µM, respectively.

Effectiveness of online caries management platform in children's caries prevention: A randomized controlled trial.

Purpose: To construct an online caries management platform and evaluate its efficacy in children's caries prevention based on caries risk. Methods: The study participants were second-grade pupils. The caries risk assessment tool (CAT) was used to grade caries risk for all participants, who were randomly divided into the experimental (114 pupils) and control (111 pupils) groups. The experimental group used the Internet for caries management, while the control group was managed by traditional lecturing in classroom. The caries status of each surface of the first permanent molars was recorded. The basic information and oral health knowledge, attitude, and behaviors of participants were collected by questionnaire. One year later, outcome data were collected. Pearson's chi-squared test was used to analyze the caries risk assessment items and oral health behaviors. The Mann-Whitney U-test was used to analyze the decayed-missing-filled surfaces (DMFS) index, plaque index, and scores of oral health knowledge and attitude. P < 0.05 was considered statistically significant. This study was available on the website of Chinese Clinical Trials Register (No: MR-44-22-012947). Results: After 1 year, the oral health knowledge score was improved by 20.58% (P < 0.001) in the experimental group and 6.02% in the control group. The plaque index was improved by 49.60% (P < 0.001) in the experimental group and 21.01% in the control group. The DMFS index increased in both groups but there were no significant differences (P = 0.608). The experimental group had a better improvement effect in caries risk assessment items than the control group, including "whether the frequency of eating sugary snacks or drinks between meals is more than 3 times/day" (P = 0.033) and the use of fluoridated toothpaste (P = 0.020). The experimental group was better than the control group in reported oral health behaviors, including frequency of eating sweets before sleep (P = 0.032), brushing time (P = 0.001), and the filled rate (proportion of FS in DMFS) of first permanent molars (P = 0.003). Conclusions: The online caries management platform showed more advantages than traditional lecturing in improving oral health knowledge and behaviors (oral hygiene practice, sugar consumption behavior, and medical treatment behavior). This platform provides a reliable implementation path for the occurrence and continuous improvement of oral health-related behaviors.

Methionine enkephalin inhibits colorectal cancer by remodeling the immune status of the tumor microenvironment.

There is evidence that methionine enkephalin (MENK), an opioid peptide, promotes anti-tumor immune responses. In this study, the effect of MENK on colorectal cancer (CRC) and its mechanisms of action were examined in vivo. The intraperitoneal administration of 20 mg/kg MENK effectively inhibited MC38 subcutaneous colorectal tumor growth in mice. MENK inhibited tumor progression by increasing the immunogenicity and recognition of MC38 cells. MENK down-regulated the oncogene Kras and anti-apoptotic Bclxl and Bcl2, suppressed Il1b, Il6, iNOS, and Arg1 (encoding inflammatory cytokines), and increased Il17a and Il10 levels. MENK promoted a tumor suppressive state by decreasing the immune checkpoints Pd-1, Pd-l1, Lag3, Flgl1, and 2b4 in CRC. MENK also altered the immune status of the tumor immune microenvironment (TIME). It increased the infiltration of M1-type macrophages, CD8+T cells, and CD4+T cells and decreased the proportions of G-MDSCs, M-MDSCs, and M2-type macrophages. MENK accelerated CD4+TEM and CD8+TEM cell activation in the TIME and up-regulated IFN-γ, TNF-α, and IL-17A in CD4+T cells and Granzyme B in CD8+T cells. In addition, analyses of PD-1 and PD-L1 expression indicated that MENK promoted the anti-tumor immune response mediated by effector T cells. Finally, OGFr was up-regulated at the protein and mRNA levels by MENK, and the inhibitory effects of MENK on tumor growth were blocked by NTX, a specific blocker of OGFr. These finding indicate that MENK remodels the TIME in CRC to inhibit tumor progression by binding to OGFr. MENK is a potential therapeutic agent for CRC, especially for improving the efficacy of immunotherapy.

Metasurface for highly-efficient on-chip classical and quantum all-optical modulation.

Metasurface made of artificially two-dimensional structured subwavelength-scaled nanostructures gives rise to unprecedented efficient way to realize on-chip all-optical modulation, in both classical regime and quantum regime.

CD30L is involved in the regulation of the inflammatory response through inducing homing and differentiation of monocytes via CCL2/CCR2 axis and NF-κB pathway in mice with colitis.

The pathogenesis of inflammatory bowel diseases (IBD) is complex, and dysregulated immune responses play a pivotal role in its occurrence and development. Our previous studies indicated that CD30L may participate in monocyte-mediated inflammation in patients with UC through the activation of circulating monocytes. However, it remains unclear how CD30L participates in monocyte-mediated inflammation in IBD by activation of circulating monocytes. In this study, we observed an increase in the expression of CD30L and chemokine receptor type 2 (CCR2) on circulating monocytes and pro-inflammatory monocytes in the colon lamina propria in mice with dextran sulfate sodium salt (DSS)-induced colitis. Moreover, there was a positive correlation between the expression levels of CCR2 and CD30L (r = 0.8817, p = 0.0480) in monocytes. In Cd30l-/- mice with DSS-induced colitis, the percentage and absolute number of circulating monocytes and pro-inflammatory monocytes decreased with the downregulation of CCR2. Stimulation via CD30L by immobilized anti-CD30L mAb suppressed the expression of pNF-κB p65, pIκBα, p65 and CCR2 and up-regulated the expression of IκBα in the sorted pro-inflammatory monocytes in Cd30l-/- mice with DSS-induced colitis. The mRNA levels of Ccr2 in the sorted pro-inflammatory monocytes were significantly down-regulated with the presence of immobilized RM153 and inhibitors of NF-κB (BAY 11-7082) in WT mice with DSS-induced colitis. Our results suggested that CD30L could promote the inflammatory response by inducing the homing and differentiation of monocytes via the chemokine ligand 2 (CCL2)/CCR2 axis and NF-κB signaling pathway in mice with colitis. These findings provide a novel target for monocyte-based immunotherapy against IBD.

Clinical Efficacy of Laparoscopic Billroth II Subtotal Gastrectomy Plus Lienal Polypeptide Injection for Gastric Cancer.

Objective: To evaluate the clinical efficacy of laparoscopic Billroth II subtotal gastrectomy plus lienal polypeptide injection for gastric cancer. Methods: Between May 2018 and January 2021, 110 patients with gastric cancer treated in Jingzhou First People's Hospital were recruited and assigned via the random number table method to either an observation group or a control group, with 55 patients in each group. All patients received laparoscopic Billroth II subtotal gastrectomy, and the observation group additionally received lienal polypeptide injection. Outcome measures include surgical indexes, clinical efficacy, and adverse events. Results: The patients in the observation group had significantly less intraoperative hemorrhage volume, smaller surgical wounds, shorter time lapse before passing gas and hospital stay, and longer operation time than those in the control group (P < 0.001). The observation group showed significantly higher efficacy than the control group (P=0.001). The observation group had a significantly lower incidence of toxic side effects and adverse events than the control group (P < 0.05). After treatment, the CD3+ and CD4+ levels were significantly elevated and the CD8+ level was decreased, with higher CD3+ and CD4+ levels and lower CD8+ levels in the observation group than in the control group (P < 0.05). Conclusion: In the treatment of patients with gastric cancer, laparoscopic Billroth II subtotal gastrectomy plus lienal polypeptide injection features promising efficacy, improves the immune function of patients, effectively reduces the occurrence of toxic side effects and adverse reactions, with less trauma and rapid recovery, which shows good potential for use in clinical application.

Erratum: A general-purpose Nanohybrid fabricated by Polymeric Au(I)-peptide precursor to wake the function of Peptide Therapeutics: Erratum.

[This corrects the article DOI: 10.7150/thno.47243.].

Immune-related gene signature predicts clinical outcomes and immunotherapy response in acute myeloid leukemia.

BACKGROUND: The immune response in the bone marrow microenvironment has implications for progression and prognosis in acute myeloid leukemia (AML). However, few immune-related biomarkers for AML prognosis and immunotherapy response have been identified. We aimed to establish a predictive gene signature and to explore the determinants of prognosis in AML. METHODS: Immune-related genes with clinical significance were screened by a weighted gene co-expression network analysis. Seven immune-related genes were used to establish a gene signature by a multivariate Cox regression analysis. Based on the signature, low- and high-risk groups were compared with respect to the immune microenvironment, immune checkpoints, pathway activities, and mutation frequencies. The tumor immune dysfunction and exclusion (TIDE) method was used to predict the response to immune checkpoint blockade (ICB) therapy. The Connectivity Map database was used to explore small-molecule drugs expected to treat high-risk populations. RESULTS: A seven-gene prognostic signature was used to classify patients into high- and low-risk groups. Prognosis was poorer for patients in the former than in the latter. The high-risk group displayed higher levels of immune checkpoint molecules (LAG3, PD-1, CTLA4, PD-L2, and PD-L1), immune cell infiltration (dendritic cells, T helper 1, and gamma delta T), and somatic mutations (NPM1 and RUNX1). Moreover, hematopoietic stem cell/leukemia stem cell pathways were enriched in the high-risk phenotype. Compared with that in the low-risk group, the lower TIDE score for the high-risk group implied that this group is more likely to benefit from ICB therapy. Finally, some drugs (FLT3 inhibitors and BCL inhibitors) targeting the expression profiles associated with the high-risk group were generated using Connectivity Map. CONCLUSION: The newly developed immune-related gene signature is an effective biomarker for predicting prognosis in AML and provides a basis, from an immunological perspective, for the development of comprehensive therapeutic strategies.

Enhanced Chemodynamic Therapy and Chemotherapy via Delivery of a Dual Threat ArtePt and Iodo-Click Reaction Mediated Glutathione Consumption.

Cisplatin has been used as standard regimen for hepatocellular carcinoma (HCC), but its therapeutic efficacy is greatly limited by the drug resistance. Cisplatin alone cannot achieve an ideal therapeutic outcome. Herein, a dual threat hybrid artemisinin platinum (ArtePt) is synthesized to combine chemodynamic therapy (CDT) with chemotherapy. On the one hand, artesunate can react with intracellular ferrous ion to generate reactive oxygen species (ROS) via Fenton reaction for CDT. On the other hand, cisplatin can target DNA for chemotherapy. However, GSH in cancer cells can effectively consume free radicals and detoxify cisplatin simultaneously, which compromised the efficacy of CDT and chemotherapy. Hence, an amphiphilic polymer with an iodine atom in the side chain is designed and encapsulated ArtePt to form NP(ArtePt). This iodine containing polymer NP(ArtePt) can effectively deplete intracellular GSH via an Iodo-Click reaction, thereby enhancing the effect of CDT as well as chemotherapy. Thereafter, a patient-derived xenograft model of hepatic carcinoma (PDXHCC ) is established to evaluate the therapeutic effect of NP(ArtePt), and a significant antitumor effect is achieved with NP(ArtePt). Overall, this study provides an effective strategy to combine CDT with chemotherapy to enhance the efficacy of cisplatin via Iodo-Click reaction, opening a new avenue for the cancer treatment.

Aucuboside Inhibits the Generation of Th17 Cells in Mice Colitis.

Aucuboside is an iridoid glycoside extracted from traditional Chinese medicine such as Rehmannia glutinosa, possessing a wide range of biological activities, including antioxidant, anti-aging, anti-inflammatory, and anti-fibrotic effects. The effects of aucuboside on inflammatory bowel disease (IBD) have not been studied. Therefore, the effects of aucuboside on the generation of Foxp3+ regulatory T (Treg) cells and IL-17-producing T helper (Th17) cells in colitis were studied. A mouse colitis model was established by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) to mimic human IBD. The generation of Treg and Th17 cells was evaluated by flow cytometry. Aucuboside significantly alleviated colitis symptoms, including weight loss, high disease activity index, and inflammatory responses. The generation of Th17 cells in colitis was significantly inhibited by aucuboside and accompanied by the suppression of IL-17 expression. In Raw264.7 cells, the LPS-induced increase in IL-17 expression was also suppressed by aucuboside, which was significantly blocked by the RORγt inhibitor sr2211. In addition, the decrease in the proportion of Treg cells was also partially reversed by aucuboside, which may reflect the aucuboside-induced inhibition of Th17 cells. This previously unrecognized immunoregulatory function of aucuboside may have clinical applications in IBD.

Sulfur-doped carbon nanotubes with hierarchical micro/mesopores for high performance pseudocapacitive supercapacitors.

Increasing the specific surface area and the amount of doping heteroatoms is an effective means to improve the electrochemical properties of carbon nanotubes (CNTs). The usual activation method makes it difficult for the retention of the heteroatoms while enlarging the specific surface area, and it can be found from literatures that specific surface area and S-content of carbon-based electrode materials are mutually exclusive. Here, CNTs with high specific surface area and sulfur content are constructed by simple activation of sulfonated polymer nanotubes with KHCO3, and the excellent electrochemical performance can be explained by the following points: first, KHCO3can be decomposed into K2CO3, CO2and H2O during the activation process. The synergistic action of physical activation (CO2and H2O) and chemical activation (K2CO3) equips the electrode material with high specific surface area of 1840 m2g-1and hierarchical micro/mesopores, which is beneficial to its double-layer capacitance. Second, compared with reported porous CNTs prepared by chemical activation (KOH) or physical activation (CO2or H2O), the mild activator KHCO3makes the sulfur content at a high level of 4.6 at%, which is very advantageous for high pseudocapacitance performance.

A nano-predator of pathological MDMX construct by clearable supramolecular gold(I)-thiol-peptide complexes achieves safe and potent anti-tumor activity.

As alternatives to small-molecular proteolysis-targeting chimeras (PROTAC), peptide-based molecular glues (MG) are a broad range of dual-functional ligands that simultaneously bind with targetable proteins and E3 ligases by mimicking proteinprotein interaction (PPI) partners. Methods: Herein, we design a peptide-derived MG to target a tumor-driving protein, MDMX, for degradation, and nanoengineered it into a supramolecular gold(I)-thiol-peptide complex (Nano-MP) to implement the proteolysis recalcitrance, cellular internalization, and glutathione-triggered release. To optimize the tumor targeting, a pH-responsive macromolecule termed polyacryl sulfydryl imidazole (PSI) was synthesized to coat Nano-MP. Results: As expected, Nano-MP@PSI induced the MDMX degradation by ubiquitination and subsequently restored the anti-cancer function of p53 and p73. Nano-MP@PSI revealed potent anti-cancer activities in an orthotopic xenograft mouse model of retinoblastoma by intraocular injection and a patient-derived xenograft model of malignant pancreatic cancer by systemic injection, while maintaining a favorable safety profile and showing a highly favorable clearable profile of excretion from the living body. Conclusion: Collectively, this work not only provided a clinically viable paradigm for the treatment of a wide variety of tumors by multiple administration types, but, more importantly, it bridged the chasm between peptides and PROTACs, and likely reinvigorated the development of peptide-derived proteolysis-targeting chimeras for a great variety of diseases.

Factors Affecting Future Caries Occurrence Among Preschoolers in Northern Guangdong: A Longitudinal Study.

PURPOSE: This study aimed to investigate the new development of caries among preschoolers in northern Guangdong and to assess caries-related factors to distinguish groups with different caries risk levels. METHODS: Baseline data were recorded for participants from September to November 2019, and participants were reexamined from September to November 2020. A longitudinal observation of 11,973 preschoolers was conducted. The simplified debris index (DI-S) and decayed-missing-filled tooth (dmft) index values were obtained for each participant. RESULTS: Factors associated with whether caries would occur in the future and one-year increase in dmft (Δdmft) included baseline dmft, baseline DI-S, and baseline age. The risk ratio (RR) of caries occurrence and the number of teeth with new-onset caries were 4.482 (95% confidence interval, 4.056-4.957) and 2.945 (2.742-3.165) in the participants with baseline dmft ≥3, which were higher than those with baseline dmft =1 or 2. In the baseline caries-free group, whether caries would occur in the future was related to the baseline DI-S (95% confidence interval, 0.022-0.062). The caries incidence of maxillary central incisors (27.9%) was the highest among teeth of preschoolers without caries at baseline, whereas the caries incidence of mandibular first deciduous molars (42.7%) was the highest among teeth of preschoolers with caries at baseline. CONCLUSION: Baseline dmft is a good predictor of future caries. Children with baseline caries-free status, baseline dmft >0, and baseline dmft ≥3 should be treated with preventive interventions of different intensities and frequencies. The occurrence of future caries in baseline caries-free participants is related to oral hygiene status. Measures to prevent caries on smooth surfaces, such as topical fluoridation, should be applied to all preschoolers. Preschoolers with caries at baseline may be given priority for pit and fissure sealing.

The impact of caries status on supragingival plaque and salivary microbiome in children with mixed dentition: a cross-sectional survey.

BACKGROUND: Supragingival plaque and saliva are commonly used for microbiome analysis. Many epidemiological studies have identified deciduous teeth caries as a risk factor for caries development in first permanent molar (FPM); nevertheless, to the best of our knowledge, there are no reports on the effects of deciduous teeth caries on the microbiome of healthy FPM. Additionally, it remains unclear whether saliva can be used instead of supragingival plaque for caries microbial studies. Therefore, we aimed to elucidate this issue, and to characterize and compare the oral microbiome of healthy FPMs in children with different caries statuses and that from children with and without caries in a similar microhabitat, by PacBio sequencing. Currently, few studies have investigated the oral microbiome of children using this technique. METHODS: Thirty children (aged 7-9 years) with mixed dentition were enrolled; 15 had dental caries, and 15 did not. Supragingival plaques of deciduous molars and maxillary FPMs, and non-stimulating saliva samples were collected. DNA was extracted and the v1-v9 regions of 16S rRNA were amplified. Subsequently, PacBio sequencing and bioinformatic analyses were performed for microbiome identification. RESULTS: The microbial alpha diversity of the saliva samples was lower than that of the supragingival plaque (p < 0.05); however, no differences were detected between deciduous teeth and FPMs (p > 0.05). In addition, the alpha and beta diversity of children with and without caries was also similar (p > 0.05). Nonmetric multidimensional scaling and Adonis analyses indicated that the microbial structure of salivary and supragingival plaque samples differ (p < 0.05). Further analysis of deciduous teeth plaque showed that Streptococcus mutans, Propionibacterium acidifaciens, and Veillonella dispar were more abundant in children with caries than in those without (p < 0.05); while in FPMs plaque, Selenomonas noxia was more abundant in healthy children (p < 0.05). No differences in microorganisms abundance were found in the saliva subgroups (p > 0.05). CONCLUSION: We have determined that supragingival plaque was the best candidate for studying carious microbiome. Furthermore, S. mutans, V. dispar, and P. acidifaciens were highly associated with deciduous teeth caries. S. noxia may be associated with the abiding health of FPM; however, this requires additional studies.

Fabrication of ordered mesoporous POMs/SiO2-NH2 nanofibers for production of DFF from 5-HMF for cellulose wastewater resource recovery.

5-hydroxymethylfurfural (5-HMF) is a biomass cellulose platform product that can be transformed into the valuable resource 2,5-diformylfuran (DFF). Polyoxometalates (POMs) have important applications in resource recovery technologies and cellulose wastewater treatment. Ordered mesoporous H5PMo10V2O40/SiO2-NH2 (wt%) nanofibers (HPMoV/meso-SiO2-NH2 (wt%)) were synthesized by the combining in-situ fabrication and electrospinning techniques, using H5PMo10V2O40 (HPMoV) and organic-silica as precursors. Aiming the recovery and transformation of 5-HMF, aerobic oxidation of 5-HMF was explored using these nanofibers as catalysts, while the best yield of DFF (90.0%) was obtained upon HPMoV/meso-SiO2-NH2 (23%) nanofibers after 8 h at 120 °C using oxygen (1.0 MPa). The selectivity to DFF was improved by changing the hydrophilicity of the HPMoV@SiO2 nanofibers to hydrophobicity by modifying SiO2 nanofibers with -NH2R compared to mesoporous SiO2 nanofibers, which allowed the formed DFF to be isolated. In the recycling test, HPMoV@SiO2-NH2 showed good performance, and no leaching of active sites from SiO2-NH2 due to the interactions between them occurred after 10 cycles. The production of DFF from the real cellulosic wastewater was obtained with 118% yield based on 5-HMF conversion by HPMoV/meso-SiO2-NH2 (23) and oxygen, which was contributed to the one-pot conversion of sugar, furan and 5-HMF in the wastewater.