Characterization of an Emergent Chicken H3N8 Influenza Virus in Southern China: a Potential Threat to Public Health.

Although influenza A viruses of several subtypes have occasionally infected humans, to date only those of the H1, H2, and H3 subtypes have led to pandemics and become established in humans. The detection of two human infections by avian H3N8 viruses in April and May of 2022 raised pandemic concerns. Recent studies have shown the H3N8 viruses were introduced into humans from poultry, although their genesis, prevalence, and transmissibility in mammals have not been fully elucidated. Findings generated from our systematic influenza surveillance showed that this H3N8 influenza virus was first detected in chickens in July 2021 and then disseminated and became established in chickens over wider regions of China. Phylogenetic analyses revealed that the H3 HA and N8 NA were derived from avian viruses prevalent in domestic ducks in the Guangxi-Guangdong region, while all internal genes were from enzootic poultry H9N2 viruses. The novel H3N8 viruses form independent lineages in the glycoprotein gene trees, but their internal genes are mixed with those of H9N2 viruses, indicating continuous gene exchange among these viruses. Experimental infection of ferrets with three chicken H3N8 viruses showed transmission through direct contact and inefficient transmission by airborne exposure. Examination of contemporary human sera detected only very limited antibody cross-reaction to these viruses. The continuing evolution of these viruses in poultry could pose an ongoing pandemic threat. IMPORTANCE A novel H3N8 virus with demonstrated zoonotic potential has emerged and disseminated in chickens in China. It was generated by reassortment between avian H3 and N8 virus(es) and long-term enzootic H9N2 viruses present in southern China. This H3N8 virus has maintained independent H3 and N8 gene lineages but continues to exchange internal genes with other H9N2 viruses to form novel variants. Our experimental studies showed that these H3N8 viruses were transmissible in ferrets, and serological data suggest that the human population lacks effective immunological protection against it. With its wide geographical distribution and continuing evolution in chickens, other spillovers to humans can be expected and might lead to more efficient transmission in humans.

Integrated analysis of miRNA-mRNA expression of newly emerging swine H3N2 influenza virus cross-species infection with tree shrews.

BACKGROUND: Cross-species transmission of zoonotic IAVs to humans is potentially widespread and lethal, posing a great threat to human health, and their cross-species transmission mechanism has attracted much attention. miRNAs have been shown to be involved in the regulation of IAVs infection and immunity, however, few studies have focused on the molecular mechanisms underlying miRNAs and mRNAs expression after IAVs cross-species infection. METHODS: We used tree shrews, a close relative of primates, as a model and used RNA-Seq and bioinformatics tools to analyze the expression profiles of DEMs and DEGs in the nasal turbinate tissue at different time points after the newly emerged swine influenza A virus SW2783 cross-species infection with tree shrews, and miRNA-mRNA interaction maps were constructed and verified by RT-qPCR, miRNA transfection and luciferase reporter assay. RESULTS: 14 DEMs were screened based on functional analysis and interaction map, miR-760-3p, miR-449b-2, miR-30e-3p, and miR-429 were involved in the signal transduction process of replication and proliferation after infection, miR-324-3p, miR-1301-1, miR-103-1, miR-134-5p, miR-29a, miR-31, miR-16b, miR-34a, and miR-125b participate in negative feedback regulation of genes related to the immune function of the body to activate the antiviral immune response, and miR-106b-3p may be related to the cross-species infection potential of SW2783, and the expression level of these miRNAs varies in different days after infection. CONCLUSIONS: The miRNA regulatory networks were constructed and 14 DEMs were identified, some of them can affect the replication and proliferation of viruses by regulating signal transduction, while others can play an antiviral role by regulating the immune response. It indicates that abnormal expression of miRNAs plays a crucial role in the regulation of cross-species IAVs infection, which lays a solid foundation for further exploration of the molecular regulatory mechanism of miRNAs in IAVs cross-species infection and anti-influenza virus targets.

The Future of Molecular Studies through the Lens of Large Language Models.

The rapid advancement of large language models is reshaping research across various fields, offering a novel approach to the complex realm of molecular studies. Our evaluation of GPT-4 and GPT-3.5, focusing on their performance in generating and optimizing molecular structures, highlights GPT-4's strengths in certain aspects of molecular optimization. However, it also revealed challenges in accurately creating complex molecules. Addressing these issues, we propose possible directions for future molecular science research. These suggestions aim to forge new paths for exploring the intricacies of molecular structures, potentially bringing new efficiencies and innovations in the field.

An 800-million-solar-mass black hole in a significantly neutral Universe at a redshift of 7.5.

Quasars are the most luminous non-transient objects known and as a result they enable studies of the Universe at the earliest cosmic epochs. Despite extensive efforts, however, the quasar ULAS J1120 + 0641 at redshift z = 7.09 has remained the only one known at z > 7 for more than half a decade. Here we report observations of the quasar ULAS J134208.10 + 092838.61 (hereafter J1342 + 0928) at redshift z = 7.54. This quasar has a bolometric luminosity of 4 × 1013 times the luminosity of the Sun and a black-hole mass of 8 × 108 solar masses. The existence of this supermassive black hole when the Universe was only 690 million years old-just five per cent of its current age-reinforces models of early black-hole growth that allow black holes with initial masses of more than about 104 solar masses or episodic hyper-Eddington accretion. We see strong evidence of absorption of the spectrum of the quasar redwards of the Lyman α emission line (the Gunn-Peterson damping wing), as would be expected if a significant amount (more than 10 per cent) of the hydrogen in the intergalactic medium surrounding J1342 + 0928 is neutral. We derive such a significant fraction of neutral hydrogen, although the exact fraction depends on the modelling. However, even in our most conservative analysis we find a fraction of more than 0.33 (0.11) at 68 per cent (95 per cent) probability, indicating that we are probing well within the reionization epoch of the Universe.

A study of the spatial distribution characteristics of Chinese surnames.

OBJECTIVES: The spatial distribution of Chinese surnames is diverse and provides rich information about the evolution of human society. This study aims to propose several indices to quantify the spatial distribution characteristics of Chinese common surnames and to explore how these distributions are related to historical evolution. METHODS: This study uses data from China's ID information system covering 1.28 billion people across 362 cities. Based on the location quotient, several new concepts, such as "moderately concentrated cities" and "highly concentrated cities," are defined. Then indices such as range, ununiformity and spatial autocorrelation are proposed and calculated to analyze the spatial characteristics of Chinese common surnames. RESULTS: A significant correlation is observed between the commonness of a surname and its spatial characteristics: the more common the surname, the wider its spatial range, the lower the ununiformity, and the higher the autocorrelation coefficient. These patterns reflect the complex interplay of historical, geographical, and cultural factors influencing surname spatial distribution. CONCLUSIONS: The spatial distribution of Chinese surnames is intricately linked to their historical evolution. Most common surnames, often with deeper historical roots, exhibit wider distributions and lower ununiformity, whereas less common surnames show higher concentrations in specific areas. These quantitative results provide a comprehensive understanding of the evolutionary characteristics of Chinese surnames.

Changes in the alveolar bone morphology among different patterns of incisor inclination during the alignment phase in orthodontic treatment without premolar extraction.

OBJECTIVE: The present study investigated bone remodelling in the upper and lower incisor regions depending on the inclination pattern during the alignment phase of orthodontic treatment (OT). MATERIALS AND METHODS: This prospective clinical study included 71 patients undergoing OT without premolar extraction. Cone beam computed tomography scans were taken before and after the alignment phase and the changes in the inclination, alveolar bone height (ABH) and bone thickness (BT) at levels 2, 3, 4, 6, 8 and 9 mm starting from the cementoenamel junction (CEJ) were determined. RESULTS: Teeth were divided into 'Retroinclination' (lingual crown inclination <0°), 'Proclination-low' (buccal crown inclination between 0° and 5°), or 'Proclination-high' (buccal crown inclination >5°). The alignment phase of OT resulted in ABH loss. The highest ABH loss in the maxilla was observed on the buccal side in the 'Proclination-high' and was 0.71 mm. ABH loss by 1.1 mm was observed in the mandible on the lingual side in the 'Retroinclination' group. The most significant changes in BT by up to 2 mm were observed at levels 6, 8 and 9 mm and these changes exhibited a moderate to strong correlation with the alterations in the inclination of individual incisors. At levels 2, 3 and 4 mm, the highest decrease in BT by up to 0.83 mm was observed on the palatal side of upper incisors in the 'Proclination-high' group. CONCLUSION: The direction and amount of tooth inclination partially determine changes in the bone parameters during the alignment phase.

Accuracy of an autonomous dental implant robotic system in partial edentulism: A pilot clinical study.

OBJECTIVES: Robots are increasingly being used for surgical procedures in various specialties. However, information about the accuracy of robot-assisted dental implant surgery is lacking. This pilot clinical study aimed to investigate the accuracy of an autonomous dental implant robotic (ADIR) system in partially edentulous cases. MATERIAL AND METHODS: The ADIR system was used to place a total of 20 implants in 13 participants. Implant deviation from the planned positions was assessed to determine accuracy. The entry, apex, and angular deviations were described as means ± standard deviation. A two-sample t test was used to compare implant deviation between the flap and flapless groups and between maxillary and mandibular implants (α = .05). RESULTS: The entry, apex, and angular deviations were 0.65 ± 0.32 mm, 0.66 ± 0.34 mm, and 1.52 ± 1.01°, respectively, with no statistically significant difference between the flap and flapless approaches (P > .05). No adverse events were encountered in any of the participants. CONCLUSIONS: DIR accuracy in this clinical series was comparable to that reported for static and dynamic computer-assisted implant surgery. Robotic computer-assisted implant surgery may be useful for dental implant placement, potentially improving the quality and safety of the procedure. CLINICAL RELEVANCE: The findings of this study showed that the ADIR system could be useful for dental implant surgery.

An intelligent process analysis method for rapidly evaluating the quality of Chinese medicine with near-infrared non-contact hyperspectral imaging: A case study of Weifuchun concentrate.

INTRODUCTION: The quality of Chinese medicine preparations can be greatly influenced by the quality of the intermediates such as extracts or concentrates. However, it is highly challenging to evaluate the quality in a rapid and non-contact manner during manufacturing. Here, we introduce an intelligent hyperspectral analysis method integrating a self-built abnormal region removal algorithm with machine learning and demonstrate its utility using the concentrate of Weifuchun (WFC), a traditional Chinese medicine preparation made from Ginseng Radix et Rhizoma Rubra, Rabdosia Amethystoides, and Aurantii Fructus. OBJECTIVE: To rapidly and non-destructively detect quality attributes of the intermediates in the manufacturing processes of Chinese medicine, an intelligent hyperspectral analysis method was developed for simultaneously quantifying the contents of naringin, neohesperidin, rosmarinic acid, and relative density of WFC concentrates. METHODOLOGY: Samples were evenly spread on solid white flat bottom containers, which were batch placed on a horizontal sample stage. Subsequent to the acquisition of near-infrared (NIR) hyperspectral images, abnormal pixels such as large/small bubbles and fine solids were first removed according to the differential pixel values in the binary grayscale map and the Mahalanobis distance metric. Then, partial least squares (PLS) and support vector machine (SVM) algorithms were used to construct hyperspectral quantitative calibration models for quality attributes. The hyperspectral images were reconstructed based on these models to visually evaluate the quality of the concentrates during manufacturing. RESULTS: As a case study, quality attributes of the WFC concentrates including contents of naringin, neohesperidin, rosmarinic acid, and relative density were determined simultaneously, and coefficients of determination of these quantitative correction models were 0.900, 0.891, 0.851, and 0.920, respectively. CONCLUSION: The method proposed in this study favors real-time determination of multiple attributes in viscous samples with industrial application prospects.

CellTalkDB: a manually curated database of ligand-receptor interactions in humans and mice.

Cell-cell communications in multicellular organisms generally involve secreted ligand-receptor (LR) interactions, which is vital for various biological phenomena. Recent advancements in single-cell RNA sequencing (scRNA-seq) have effectively resolved cellular phenotypic heterogeneity and the cell-type composition of complex tissues, facilitating the systematic investigation of cell-cell communications at single-cell resolution. However, assessment of chemical-signal-dependent cell-cell communication through scRNA-seq relies heavily on prior knowledge of LR interaction pairs. We constructed CellTalkDB (http://tcm.zju.edu.cn/celltalkdb), a manually curated comprehensive database of LR interaction pairs in humans and mice comprising 3398 human LR pairs and 2033 mouse LR pairs, through text mining and manual verification of known protein-protein interactions using the STRING database, with literature-supported evidence for each pair. Compared with SingleCellSignalR, the largest LR-pair resource, CellTalkDB includes not only 2033 mouse LR pairs but also 377 additional human LR pairs. In conclusion, the data on human and mouse LR pairs contained in CellTalkDB could help to further the inference and understanding of the LR-interaction-based cell-cell communications, which might provide new insights into the mechanism underlying biological processes.

Sensitive and reliable analysis of endometrial cancer related microRNA using ternary hybridization hairpin probe.

MicroRNA (miRNA), as a kind of small non-coding ribonucleic acid (RNA) that plays a crucial role in regulating transcriptional activities, is a potential biomarker for EC diagnosis. However, reliable detection of miRNA remains a huge challenge, especially for these methods that require multiple probes for signal amplifications, due to the detective deviation caused by variation of probe concentrations. Herein, we present a novel approach for miRNA-205 identification and quantification by employing simply a ternary hairpin probe (TH probe). The ternary hybridization of three sequences results in the construction of the TH probe, which combines high-efficient signal amplification and specific target recognition. A significant number of G-rich sequences have been produced as a result of the enzymes assisted signal amplification process. The G-rich sequences can fold into G-quadruplexes, which can then be detected in a label-free manner by a common fluorescent dye (thioflavin T). Eventually, the approach exhibits a low limit of detection of 278 aM with a wide detection range of 7 orders of magnitude. In summary, the proposed approach possesses a great potential for both clinical diagnosis of EC and fundamental biomedical researches.

Single-cell RNA sequencing reveals enhanced antitumor immunity after combined application of PD-1 inhibitor and Shenmai injection in non-small cell lung cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have altered the clinical management of non-small cell lung cancer (NSCLC). However, the low response rate, severe immune-related adverse events (irAEs), and hyperprogressive disease following ICIs monotherapy require attention. Combination therapy may overcome these limitations and traditional Chinese medicine with immunomodulatory effects provides a promising approach. Shenmai injection (SMI) is a clinically effective adjuvant treatment for cancer with chemotherapy and radiotherapy. Therefore, the combined effects and mechanisms of SMI and programmed death-1 (PD-1) inhibitor against NSCLC was focused on this study. METHODS: A Lewis lung carcinoma mouse model and a lung squamous cell carcinoma humanized mouse model were used to investigate the combined efficacy and safety of SMI and PD-1 inhibitor. The synergistic mechanisms of the combination therapy against NSCLC were explored using single-cell RNA sequencing. Validation experiments were performed using immunofluorescence analysis, in vitro experiment, and bulk transcriptomic datasets. RESULTS: In both models, combination therapy alleviated tumor growth and prolonged survival without increasing irAEs. The GZMAhigh and XCL1high natural killer (NK) cell subclusters with cytotoxic and chemokine signatures increased in the combination therapy, while malignant cells from combination therapy were mainly in the apoptotic state, suggesting that mediating tumor cell apoptosis through NK cells is the main synergistic mechanisms of combination therapy. In vitro experiment confirmed that combination therapy increased secretion of Granzyme A by NK cells. Moreover, we discovered that PD-1 inhibitor and SMI combination blocked inhibitory receptors on NK and T cells and restores their antitumoral activity in NSCLC better than PD-1 inhibitor monotherapy, and immune and stromal cells exhibited a decrease of angiogenic features and attenuated cancer metabolism reprogramming in microenvironment of combination therapy. CONCLUSIONS: This study demonstrated that SMI reprograms tumor immune microenvironment mainly by inducing NK cells infiltration and synergizes with PD-1 inhibitor against NSCLC, suggested that targeting NK cells may be an important strategy for combining with ICIs. Video Abstract.

Application of the adverse outcome pathway concept for investigating developmental neurotoxicity potential of Chinese herbal medicines by using human neural progenitor cells in vitro.

Adverse outcome pathways (AOPs) are organized sequences of key events (KEs) that are triggered by a xenobiotic-induced molecular initiating event (MIE) and summit in an adverse outcome (AO) relevant to human or ecological health. The AOP framework causally connects toxicological mechanistic information with apical endpoints for application in regulatory sciences. AOPs are very useful to link endophenotypic, cellular endpoints in vitro to adverse health effects in vivo. In the field of in vitro developmental neurotoxicity (DNT), such cellular endpoints can be assessed using the human "Neurosphere Assay," which depicts different endophenotypes for a broad variety of neurodevelopmental KEs. Combining this model with large-scale transcriptomics, we evaluated DNT hazards of two selected Chinese herbal medicines (CHMs) Lei Gong Teng (LGT) and Tian Ma (TM), and provided further insight into their modes-of-action (MoA). LGT disrupted hNPC migration eliciting an exceptional migration endophenotype. Time-lapse microscopy and intervention studies indicated that LGT disturbs laminin-dependent cell adhesion. TM impaired oligodendrocyte differentiation in human but not rat NPCs and activated a gene expression network related to oxidative stress. The LGT results supported a previously published AOP on radial glia cell adhesion due to interference with integrin-laminin binding, while the results of TM exposure were incorporated into a novel putative, stressor-based AOP. This study demonstrates that the combination of phenotypic and transcriptomic analyses is a powerful tool to elucidate compounds' MoA and incorporate the results into novel or existing AOPs for a better perception of the DNT hazard in a regulatory context.

Periodontitis-induced oral microbiome alterations provide clues on how periodontitis exacerbates colitis.

AIM: To evaluate whether and how microbiota-derived metabolites associated with periodontitis aggravate colitis in mice. MATERIALS AND METHODS: A mouse model of periodontitis and colitis was constructed. Unbiased transcriptomic analyses of the colon were performed to explore important pathways through which periodontitis exacerbated colitis. Oral and gut bacteria were analysed using 16S rRNA sequencing. Gas chromatography-mass spectrometry was used to observe the alterations of oral and gut metabolites. Isolated intestinal lamina propria lymphocytes were analysed by flow cytometry. Inflammasome pathway was detected using qRT-PCR, Western blotting or ELISA. RESULTS: Periodontitis activated the colonic inflammasome pathway and altered the gut microbial composition and metabolite profiles in mice with colitis. Notably, periodontitis induced increase of the faecal metabolite isoleucine (Ile) which was synthesized by microbiota and plants. Moreover, periodontitis upregulated the Ile levels in saliva, but not in serum, indicating that Ile might be an oral pathobiont-synthesizing metabolite that transited from the oral cavity to the gut. Ile triggered the inflammasome pathway, upregulated the number of inflammatory IL-1ßhigh MHCIIhigh Ly6Chigh monocytes in colonic lamina propria, and exacerbated colitis. Further studies found that the Ile metabolite acetyl-coenzyme A positively regulated NLRP3 inflammasome by KAT5-mediated acetylation of NLRP3. CONCLUSIONS: Our study revealed that alteration in periodontitis-induced microbial metabolites deteriorated colitis in a mouse model and that this was associated with Ile production.

scDeepSort: a pre-trained cell-type annotation method for single-cell transcriptomics using deep learning with a weighted graph neural network.

Advances in single-cell RNA sequencing (scRNA-seq) have furthered the simultaneous classification of thousands of cells in a single assay based on transcriptome profiling. In most analysis protocols, single-cell type annotation relies on marker genes or RNA-seq profiles, resulting in poor extrapolation. Still, the accurate cell-type annotation for single-cell transcriptomic data remains a great challenge. Here, we introduce scDeepSort (https://github.com/ZJUFanLab/scDeepSort), a pre-trained cell-type annotation tool for single-cell transcriptomics that uses a deep learning model with a weighted graph neural network (GNN). Using human and mouse scRNA-seq data resources, we demonstrate the high performance and robustness of scDeepSort in labeling 764 741 cells involving 56 human and 32 mouse tissues. Significantly, scDeepSort outperformed other known methods in annotating 76 external test datasets, reaching an 83.79% accuracy across 265 489 cells in humans and mice. Moreover, we demonstrate the universality of scDeepSort using more challenging datasets and using references from different scRNA-seq technology. Above all, scDeepSort is the first attempt to annotate cell types of scRNA-seq data with a pre-trained GNN model, which can realize the accurate cell-type annotation without additional references, i.e. markers or RNA-seq profiles.

The effect of combination treatment of CO2-laser irradiation and tetracalcium phosphate/dicalcium phosphate anhydrate on dentinal tubules blockage: an in vitro study.

The aim of this study was the evaluation of the in vitro efficacy of a carbon dioxide (CO2) laser, a tetracalcium phosphate/dicalcium phosphate anhydrate (TP/DP) desensitizer and the combination of the desensitizer and additional CO2 laser irradiation as a treatment modality for cervical dentin hypersensitivity. A total of 48 dental specimens, prepared from extracted human premolars and molars, were divided into four groups: a control group, a TP/DP desensitizer paste group, a CO2 laser (10.600-nm wavelength) group, and a paste and laser group. The specimens were coated with nail varnish except in the marked area and were then immersed in 2% methylene blue dye for 1 h. The specimens were then washed, dried, and cut longitudinally. Thereafter, photos of 40 dentin specimens were taken and evaluated. The area of penetration was assessed and reported as percentage of the dentin surface area. Additionally eight dental specimens were examined with the aid of a scanning electron microscope and evaluated. Significant differences in the penetration depth were found for all experimental groups compared to the control group. The lowest penetration area was detected in the paste-laser group (16.5%), followed by the laser (23.7%), the paste (48.5%), and the control group (86.2%). The combined treatment of the CO2 laser and a TP/DP desensitizer was efficient in sealing the dentinal surface and could be a treatment option for cervical dentin hypersensitivity.

A novel approach for gingiva thickness measurements around lower anterior teeth by means of dental magnetic resonance imaging.

OBJECTIVE: This diagnostic accuracy study aims to present the first measurements of gingiva thickness around lower anterior teeth using dental magnetic resonance imaging (MRI) and to compare these measurements with two established methods: (1) gingival phenotype assessment via periodontal probing, and (2) the superimposition of cone-beam computed tomography (CBCT) scans with intraoral scans of teeth and gums. MATERIALS AND METHODS: Ten patients with substantial orthodontic treatment need and anterior mandibular crowding were consecutively included in this clinical case series. After periodontal probing, each patient underwent a CBCT scan, an intraoral scan of the mandible, and an MRI investigation using a novel mandibula 15-channel dental coil. RESULTS: The mean gingiva thickness was 0.72 mm measured on MRI and 0.97 mm measured on CBCT, with a mean difference between the measurement methods of 0.17 ± 0.27 mm (p < 0.001). Measurement agreement between the index tests (MRI and CBCT) and the clinical reference standard (probing) yielded an overall percent agreement of 64.94% and 47.02% for MRI and CBCT, respectively. Teeth with thin phenotypes were associated with lower soft tissue dimensions in both free (MRI: 0.56 mm vs. CBCT: 0.79 mm) and supracrestal gingiva (MRI: 0.75 mm vs. CBCT: 1.03 mm) when compared to those with thick phenotypes. However, only the measurements obtained from MRI scans showed statistically significant differences between the two phenotypes. CONCLUSION: Dental MRI successfully visualizes delicate structures like the gingiva in the anterior mandible and achieves a high correlation with superimposed CBCT scans, with clinically acceptable deviations. CLINICAL RELEVANCE: The present study helps to establish dental MRI as a radiation-free alternative to conventional radiographic methods.

Effects of customized CAD/CAM abutments on cytokine levels in peri-implant crevicular fluid during early implant healing: a pilot study.

OBJECTIVES: This study aimed to assess levels of biomarkers associated with inflammation and tissue destruction in peri-implant crevicular fluid (PICF) of implants provided with customized or standard healing abutments during early implant healing. MATERIALS AND METHODS: Thirty implants were placed in 22 patients with partial posterior edentulism. Subsequently, test group implants (n=15) received one-piece titanium abutments that were fabricated using computer-aided design/computer-aided manufacturing (CAD/CAM). Control group implants (n=15) were provided with standard abutments. PICF collection and standardized periapical radiographs were carried out at suture removal one week later, following crown delivery after 3 months and at 6 months. Expression of C-reactive protein (CRP), interferon-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12A, IL-17A, macrophage inflammatory protein (MIP)-1α, matrix metalloproteinase (MMP)-13, osteopontin, osteoactivin, Receptor Activator of NF-κB (RANK), and TGF-ß were analyzed using a multiplex ELISA kit. RESULTS: Both groups showed a significant decrease in protein expression of CRP, IL-1ß, IL-6, IL-8, MIP-1α, osteopontin, osteoactivin, and TGF-ß, while MMP-13 levels increased during the observation period. A rise in OPG and RANK levels was detected among customized abutments. Expression of CRP was higher, whereas IL-1ß, IL-1α, and MIP-1α were decreased in control compared to test group implants after 6 months. Marginal bone loss did not depend on abutment modality. CONCLUSIONS: Both abutment types showed distinctive temporal expression of inflammatory biomarkers during 6 months following implant placement. TRIAL REGISTRATION: ISRCTN98477184, registration date 18/05/2022 CLINICAL RELEVANCE: Customized healing abutments exert similar effects on inflammation during early implant healing compared to standard healing abutments.

Effects of enamel matrix derivative in nonsurgical periodontal therapy on pro-inflammatory profiles, microbial environment and clinical outcome: a randomized clinical trial.

OBJECTIVES: This study aimed to evaluate the impact of enamel matrix derivative (EMD) application following subgingival instrumentation of residual pockets in periodontitis patients on inflammatory host response, microbiological composition, and clinical outcome. METHODS: In this double-blinded randomized controlled trial, a total of 22 patients with generalized periodontitis stage III or IV presenting with ≥ 6 mm probing pocket depth (PPD) at re-evaluation after initial periodontal therapy were included. Participants were randomly allocated at a 1:1 ratio to subgingival instrumentation with (EMD +) or without (EMD-) non-surgical EMD application into the pocket. PPD, clinical attachment level (CAL), bleeding on probing (BoP), plaque index (PI), as well as a panel of pro-inflammatory cytokines and periodontal pathogen count in the gingival crevicular fluid (GCF) of the respective sites were evaluated at baseline (T0) and six months afterwards (T1). RESULTS: Both treatment groups showed a significant PPD reduction (EMD + 1.33 ± 1.15 mm, p < 0.001; EMD- 1.32 ± 1.01 mm, p < 0.001) as well as CAL gain (EMD + 1.13 ± 1.58 mm, p < 0.001; EMD- 0.47 ± 1.06 mm, p = 0.005) from T0 to T1. While no intergroup differences for PPD reduction were observed, CAL gain was higher in EMD + sites compared to EMD- (p = 0.009). No essential effects on cytokine expression as well as bacterial count were detected. CONCLUSIONS: Application of EMD as an adjunct to subgingival instrumentation of residual pockets yielded benefits regarding CAL gain; however, effects on PPD reduction, inflammatory cytokines, and bacterial count were negligible. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04449393), registration date 26/06/2020. CLINICAL RELEVANCE: Based on the obtained results, additional non-surgical EMD application compared to subgingival instrumentation alone showed no clinically relevant effects on treatment outcome and underlying biological mechanisms.

The effect of occlusal disharmony on a chronic stress-induced animal model of gut microbiota dysbiosis.

BACKGROUND AND OBJECTIVES: Chronic stress (CS) is closely related to intestinal health. Occlusal disharmony (OD) is a risk factor for hypersensitivity to novel stress, and the relationship between OD and the intestinal system with or without other chronic stresses remains unclear. Therefore, the purpose of this study was to investigate whether OD affects the gut microbiota and the intestinal barrier in a CS-exposed animal model. METHODS: OD was induced by making a 0.5-mm-thick incision on the right maxillary molar. CS involved exposure to one stressor per day for 35 days. Sprague-Dawley rats were randomly divided into an untreated control group and OD-, CS- and OD + CS-treated groups. The behavioural tests, serum corticosterone level, gut microbiota composition and tight junction protein expression in colon tissue were measured on the 56th day to elucidate the effect of OD on animals under CS. RESULTS: Significant differences in performance on behavioural tests and serum corticosterone concentrations were observed on day 56 in the OD + CS group compared with the control group. Exposure to occlusal disharmony or chronic stress resulted in a change in the composition of the gut microbiota of rats. Differences in the expression of the tight junction proteins zonula occludens-1 and junctional adhesion molecule-A were observed in colon tissue from the OD + CS group compared with the control group. CONCLUSIONS: We concluded that the significant changes in performance on behavioural tests, serum corticosterone concentrations and microbiota dysbiosis and tight junction protein levels induced by OD with CS may indicate that OD is a potential factor promoting gut microbiota dysbiosis.

Co-treatment of municipal solid waste incineration fly ash (MSWI FA) and municipal sludge: A innovative method to improve sludge dewatering with fly ash dechlorination.

The complexity of municipal sludge dewatering is a bottleneck problem limiting resource utilization. In this paper, adding municipal solid waste incineration fly ash (MSWI FA) to municipal sludge for enhanced dewatering was applied, while the chlorine salt in MSWI FA was simultaneously removed using water in municipal sludge. The effects of different dosages and chemical components of MSWI FA on municipal sludge dewatering, and the removal effect of municipal sludge washing on Cl element were investigated. The results showed that the municipal sludge's specific resistance to filtration after co-treatment was significantly reduced, and more hydrophobic channels were formed in the vacuum suction filtration of the treated municipal sludge, conducive to efficient water removal. The moisture content of municipal sludge was reduced from 96.0% to 48.3%, and the moisture reduction rate increased from 17.7% to 32.1%. The chemical composition of MSWI FA could effectively promote the dewatering of municipal sludge, among which CaO was the best, followed by CaCl2 and NaCl, and KCl was the worst. Simultaneously, the municipal sludge showed a good effect on removing Cl from MSWI FA. The minimum Cl content in the mixture after Co-treatment is 1.5%. These results could provide a new way to dispose of MSWI FA and municipal sludge.