Incorporation of PD-1 blockade into induction chemotherapy improved tumor response in patients with locoregionally advanced nasopharyngeal carcinoma in a retrospective patient cohort.

OBJECTIVE: To investigate the short-term efficacy and safety of induction chemotherapy (IC) combined with anti-PD-1 immunotherapy in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: A total of 217 patients diagnosed with LA-NPC at the First Affiliated Hospital of Nanchang University, including 67 who received IC combined with anti-PD-1 and 150 who received IC, were retrospectively enrolled. Efficacy was evaluated at the end of the IC cycles and one month after radiotherapy based on RECIST v1.1 criteria. Acute toxicities were graded based on the CTCAE v5.0 criteria. Quantitative variables were compared by unpaired t-tests, and categorical variables were evaluated by Fisher Freeman-Halton test or Pearson Chi-square test. RESULTS: At the end of all induction therapy cycles, the objective response rate (ORR) of the IC + anti-PD-1 group was 88.1 % (59/67) as opposed to 70.0 % (105/150) in the IC group. Subgroup analysis showed that patients in both stage Ⅲ and ⅣA achieved a significant improvement in ORR with the inclusion of anti-PD-1 therapy. Patients with T3-4 or N2-3 category appeared to benefit more from anti-PD-1 compared to patients with T1-2 or N0-1 category. However, neither ORR nor the complete response (CR) rate was significantly different between the two treatment groups one month after the end of radiotherapy. In addition, the frequency of Grade 3-4 adverse events were also similar in both groups. CONCLUSIONS: IC combined with anti-PD-1 immunotherapy significantly improved the ORR of LA-NPC patients after induction therapy compared to IC alone.

The role of periodontitis in the development of atherosclerotic cardiovascular disease in participants with the components of metabolic syndrome: a systematic review and meta-analysis.

OBJECTIVES: Prevention of atherosclerotic cardiovascular disease (ASCVD) is important in individuals with metabolic syndrome components (MetS), and periodontitis may play an important role in this process. This study aims to evaluate the association between periodontitis and ASCVD in participants with the components of MetS, including obesity, dysglycemia, hypertension, and dyslipidemia. MATERIALS AND METHODS: This study conducted followed the MOOSE reporting guidelines and the PRISMA 2020 guidelines. EMBASE, MEDLINE, Web of Science, Cochrane Library, PubMed and OpenGrey were searched for observational studies about the linkage of periodontitis to ASCVD in people with MetS components up to April 9, 2023. Cohort, case-control and cross-sectional studies were included after study selection. Quality evaluation was carried out using the original and modified Newcastle-Ottawa Scale as appropriate. Random-effects model was employed for meta-analysis. RESULTS: Nineteen studies were finally included in the quality analysis, and all of them were assessed as moderate to high quality. Meta-analyses among fifteen studies revealed that the participants with periodontitis were more likely to develop ASCVD in those who have dysglycemia (RR = 1.25, 95% CI = 1.13-1.37; p < 0.05), obesity (RR = 1.13, 95% CI = 1.02-1.24; p < 0.05), dyslipidemia (RR = 1.36, 95% CI = 1.13-1.65; p < 0.05), or hypertension (1.20, 95% CI = 1.05-1.36; p < 0.05). CONCLUSIONS: Periodontitis promotes the development of ASCVD in participants with one MetS component (obesity, dysglycemia, hypertension or dyslipidemia). CLINICAL RELEVANCE: In people with MetS components, periodontitis may contribute to the ASCVD incidence.

LIM homeobox 8 reduced apoptosis and promoted periodontal tissue regeneration function of dental pulp stem cells.

Stem cell-mediated tissue regeneration is a promising strategy for repairing tissue defects and functional reconstruction in periodontitis, a common disease that leads to the loss of alveolar bone and teeth. However, stem cell apoptosis, widely observed during tissue regeneration, impairs its efficiency. Therefore, the regulation of stem cell apoptosis is critical for improving regeneration efficiency. The LIM homeobox 8 gene LHX8, belongs to the LIM homeobox family, which was involved in tooth morphogenesis. Here, we found that LHX8 was significantly expressed in dental pulp. LHX8 knockdown significantly increased dental pulp mesenchymal stem cells (DPSCs) apoptosis, as confirmed by RT-PCR, western blotting, flow cytometry, and transmission electron microscopy. Additionally, LHX8 overexpression inhibited apoptosis and enhanced the osteo/odontogenic differentiation potential of hDPSCs in vitro. Furthermore, LHX8-overexpression could enhance the periodontal tissue regeneration efficiency of hDPSCs in mice with periodontitis. In conclusion, the present study indicates that LHX8 inhibits stem cell apoptosis and promotes functional tissue formation in stem cell-based tissue regeneration engineering, suggesting a new therapeutic target to increase the efficacy of periodontal tissue regeneration.

A tantalum-containing zirconium-based metallic glass with superior endosseous implant relevant properties.

Zirconium-based metallic glasses (Zr-MGs) are demonstrated to exhibit high mechanical strength, low elastic modulus and excellent biocompatibility, making them promising materials for endosseous implants. Meanwhile, tantalum (Ta) is also well known for its ideal corrosion resistance and biological effects. However, the metal has an elastic modulus as high as 186 GPa which is not comparable to the natural bone (10-30 GPa), and it also has a relative high cost. Here, to fully exploit the advantages of Ta as endosseous implants, a small amount of Ta (as low as 3 at. %) was successfully added into a Zr-MG to generate an advanced functional endosseous implant, Zr58Cu25Al14Ta3 MG, with superior comprehensive properties. Upon carefully dissecting the atomic structure and surface chemistry, the results show that amorphization of Ta enables the uniform distribution in material surface, leading to a significantly improved chemical stability and extensive material-cell contact regulation. Systematical analyses on the immunological, angiogenesis and osteogenesis capability of the material are carried out utilizing the next-generation sequencing, revealing that Zr58Cu25Al14Ta3 MG can regulate angiogenesis through VEGF signaling pathway and osteogenesis via BMP signaling pathway. Animal experiment further confirms a sound osseointegration of Zr58Cu25Al14Ta3 MG in achieving better bone-implant-contact and inducing faster peri-implant bone formation.

Effect of non-surgical periodontal therapy on hemoglobin A1c in periodontitis patients without diabetes mellitus: A systematic review and meta-analysis.

OBJECTIVES: This systematic review was aimed to evaluate the effect of non-surgical periodontal therapy (NSPT) on hemoglobin A1c (HbA1c) in periodontitis patients without diabetes mellitus (DM). DATA/SOURCES: The present systematic review and meta-analysis were performed through searching the following electronic databases: EMBASE, MEDLINE, Web of Science, Cochrane Library and Open GREY. Interventional studies of periodontitis patients without DM were investigated. HbA1c changes in these patients before and after NSPT were analyzed. Subgroup analysis and sensitivity analysis were employed to identify sources of heterogeneity. STUDY SELECTION: Three reviewers independently selected the eligible studies by screening the titles and abstract. Then, a full-text analysis was performed. The reasons for excluding studies were recorded. Any disagreements were settled by discussion with a fourth reviewer. All the four reviewers extracted and crosschecked the data, and disagreements were resolved by discussion. There are 21 case-series studies (self-controlled studies) and 1 non-randomized interventional studies (NRIs) were included. RESULTS: For periodontitis patients without DM, a total of 469 individuals from 22 studies were enrolled. The pooled analysis demonstrated that it was significantly changed in HbA1c levels at 3-month follow-up (0.16 with 95 % CI 0.04, 0.27; P = 0.008), and 6-month follow-up (0.17 % with 95 % CI 0.08, 0.27; P < 0.001) compared with baseline. Smoking, gender, experience of periodontal therapy and HbA1c value at baseline could be the sources of heterogeneity. CONCLUSIONS: NSPT is potentially beneficial for the management of HbA1c in periodontitis patients with high risks of DM. However, high-quality randomized controlled trials are still necessary to confirm these conclusions. CLINICAL SIGNIFICANCE: The systemic review evaluated the effect of NSPT on HbA1c in periodontitis patients without DM. The analysis may be beneficial to the management and control of the high risks of DM in periodontitis patients.

Application of Slice Culture System for Successional Dental Lamina in Diphyodont Mammals.

Replacement teeth develop from the successional dental lamina (SDL). Understanding how SDL transitions from quiescence to initiation is crucial for preserving dental lamina stem cells in the jawbone microenvironment and for complete tooth regeneration. Miniature pigs are good models for studying human tooth replacement because of their similarities to humans. However, the molecular mechanisms and cellular composition that initiate SDL development remain unclear. One possible reason for this is the limitations of the current methods for culturing SDL in vitro, such as the inability to directly observe tooth morphological changes during culture and low tissue viability. This study aimed to improve the in vitro culture method for SDL. Using a McIlwain Tissue Chopper, we obtained mandibular slices containing deciduous canine and SDL of permanent canine. The slices were approximately 500 µm thick and were cultured on a Transwell membrane supported with metal grids over medium. The SDL developed into the bud stage on the second day and entered the cap stage on the fifth day in vitro. The expression of proliferation markers, cell death markers, and key odontogenetic genes in vitro was similar to that observed in vivo. In conclusion, we successfully applied a slice culture system to the SDL of miniature pigs. This slice culture method allowed us to directly visualize SDL initiation and further elucidate the molecular mechanisms underlying the initiation of permanent tooth development.

Salivary nitrate prevents osteoporosis via regulating bone marrow mesenchymal stem cells proliferation and differentiation.

Background: Nitrate, a key component of saliva, has been shown widely physiological functions in the human body. But its function on bone metabolism remains unclear. The aim of this study was to investigate the function and mechanism of saliva nitrate on osteoporosis and the function of bone marrow mesenchymal stem cells (BMSCs). Methods: Saliva nitrate removal or supplemental interventions were performed for 1 month in ovariectomized (OVX) osteopenia mice. The nitrate levels in saliva and serum were detected. The bone formation and bone microarchitecture in the OVX mouse model were investigated by quantitative Micro--computed tomography imaging, histological staining and serum bone biomarker analysis. The effects of nitrate on the functional homeostasis of BMSCs in OVX mice were explored by Ki67 immunofluorescence staining, Ki67 flow staining, alizarin red staining, qPCR and western blotting. Finally, downstream signaling pathways were screened by proteomics and verified by western blotting. Results: The results showed that nitrate deficiency exacerbated osteoporosis, while nitrate administration prevent osteoporosis in OVX mice. Nitrate increased the expression of PINP, a biomarker of bone formation, in OVX mice. Besides, nitrate enhanced the proliferative capacity and osteogenic function of BMSCs in OVX mice in vitro and in vivo. In addition, nitrate upregulated the expression levels of osteogenesis-related genes ALP, Run2 and OPN of BMSCs. EGFR and mTOR signaling were screened as the key downstream of nitrate, and phosphorylated protein levels of its subfamily members AKT, ERK and S6K were significantly upregulated by nitrate. Conclusion: The present results showed saliva nitrate preventively protects against osteoporosis through enhances the proliferation and osteogenic differentiation potential of BMSCs. The effects of nitrate on bone homeostasis are closely related to the EGFR/AKT/ERK and mTOR/S6K signaling axes. The translational potential of this article: Our study provides experimental evidence for the use of saliva nitrate as an effective candidate for the prevention of osteoporosis and maintenance of bone homeostasis.

ASCOD phenotyping of acute vertebrobasilar artery occlusion treated by mechanical thrombectomy: insight from the PERSIST registry.

OBJECTIVE: Determining the underlying etiology of acute vertebrobasilar artery occlusion (VBAO) is crucial for selecting an appropriate treatment approach. The authors aimed to investigate the distribution of etiology and the association with functional outcomes in patients with acute VBAO who underwent endovascular treatment in which atherosclerosis, small-vessel disease, cardiac pathology, other causes, and dissection (ASCOD) phenotyping was used. METHODS: A retrospective study was conducted at 21 centers in China, involving patients with VBAO who received endovascular treatment within 24 hours of the estimated occlusion time. In the ASCOD phenotyping, each phenotype is graded based on the following categories: 1, likely to be causal; 2, uncertain if causal; and 3, unlikely to be causal. The authors defined a single possible cause as a cause graded 1 in a single domain, and multiple possible causes were graded 1 or 2 regardless of overlap. The primary outcome was unfavorable outcome (modified Rankin Scale [mRS] score of 3-6) at 90 days. The secondary outcomes included shift of mRS score at 90 days, 90-day mortality, successful reperfusion, and National Institutes of Health Stroke Scale score at 24 hours. Multivariable regression analysis was used to assess the association between etiological subtypes and functional outcomes. Multivariate competing-risk regression analysis was performed to analyze the association between etiological subtypes and the risk of recurrent stroke. RESULTS: A total of 577 patients were included in this study. Of these, 521 (90%) had a single possible cause. The most common etiology was A1 (382 cases, 73%), followed by C1 (111 cases, 21%) and O1 (28 cases, 5%-in this study the other causes and dissection subtypes were categorized under the umbrella term of "O" causes). Similar patterns were observed in the multiple possible causes. In the baseline characteristics of the cohort, as rescue therapy, stenting was more frequently used in patients in the A1 group than in the C1 group (53.2% vs 41.7%; p < 0.01). The proportion of atherosclerosis-type etiology increased when the occlusion was located more proximally (p < 0.01). Compared to the A1 group, patients in the C1 group had a lower incidence of unfavorable outcome (OR 0.42, 95% CI 0.24-0.73), which was less likely to shift to a worse mRS score (OR 0.60, 95% CI 0.39-0.91). The O1 subtype was not associated with unfavorable outcome (OR 1.35, 95% CI 0.46-4.01), whereas patients with the O1 subtype were more likely to shift to worse mRS score (OR 2.39, 95% CI 1.09-5.25) and to have a higher 90-day mortality rate (OR 2.60, 95% CI 1.07-6.31). Furthermore, there was no significant association between single etiological subtypes and stroke recurrence within 1 year. CONCLUSIONS: The most common etiology in patients with VBAO was atherosclerosis, followed by cardiac pathology and other. Compared to the A1 subgroup, the C1 subgroup showed better functional outcomes, whereas the O1 subgroup showed worse outcomes. Additionally, there was no statistically significant difference in the recurrence risk.

Single-nucleus transcriptomics uncovers a geroprotective role of YAP in primate gingival aging.

Aging has a profound impact on the gingiva and significantly increases its susceptibility to periodontitis, a worldwide prevalent inflammatory disease. However, a systematic characterization and comprehensive understanding of the regulatory mechanism underlying gingival aging is still lacking. Here, we systematically dissected the phenotypic characteristics of gingiva during aging in primates and constructed the first single-nucleus transcriptomic landscape of gingival aging, by which a panel of cell type-specific signatures were elucidated. Epithelial cells were identified as the most affected cell types by aging in the gingiva. Further analyses pinpointed the crucial role of YAP in epithelial self-renew and homeostasis, which declined during aging in epithelial cells, especially in basal cells. The decline of YAP activity during aging was confirmed in the human gingival tissues, and downregulation of YAP in human primary gingival keratinocytes recapitulated the major phenotypic defects observed in the aged primate gingiva while overexpression of YAP showed rejuvenation effects. Our work provides an in-depth understanding of gingival aging and serves as a rich resource for developing novel strategies to combat aging-associated gingival diseases, with the ultimate goal of advancing periodontal health and promoting healthy aging.

Inhibition of biofouling by in-situ grown zwitterionic hydrogel nanolayer on membrane surface in ultralow-pressurized ultrafiltration process.

Ultralow-pressurized ultrafiltration membrane process with low energy consumption is promising in surface water purification. However, membrane fouling and low selectivity are significant barriers for the wide application of this process. Herein, an ultrathin zwitterionic hydrogel nanolayer was in-situ grown on polysulfone ultrafiltration membrane surface through interfacially-initiated free radical polymerization. The hydrogel-modified membrane possessed improved biological fouling resistance during the dynamic filtration process (bovine serum albumin, Escherichia coli and Staphylococcus aureus), comparing with commercial polysulfone membrane. The enhanced biofouling resistance ability of zwitterionic hydrogel nanolayer was derived from the foulant repulsion of hydration shell and the bactericidal effect of quaternary ammonium, according to the results of foulant-membrane interaction energy analyses and antibacterial performances. In surface water treatment, the zwitterionic hydrogel layer inhibited biofouling and resulted in the formation of a loose and thin biofilm. In addition, the hydrogel-modified membrane possessed 22% improvement in dissolved organic carbon (DOC) removal and 134% increasement in stable water flux, compared to commercial polysulfone membrane. The in-situ grown zwitterionic hydrogel nanolayer on membrane surface offers a prospectively alternative for biofouling control in ultralow-pressurized membrane process.

Preparation of landscape gardening soil using undersized fraction from aged MSW by EDTA or citric acid coupled with humic acid: Effect assessment, properties, and optimization.

Undersized fraction from aged municipal solid waste (UFAMSW), as a kind of soil-like material, has been proved effective in providing a large amount of organic matter and nutrients for soil and plants. The characteristics and effectiveness of heavy metal pollution removal in UFAMSW attracted tremendous research interest from scientists recently. In this study, the heavy metal removal efficiencies and bioavailability of washing on contaminated UFAMSW were evaluated with three washing reagents including ethylene diamine tetra acetic acid (EDTA), citric acid (CA), and humic acid (HA). The effects of chelating agent concentration, pH, and washing time on metal removal were investigated and response surface methodology (RSM) was employed to optimize the washing conditions. The results indicated that the removal efficiencies of Cu, Zn, and Mn could be 53.68%, 52.12%, and 30.63% by EDTA/HA washing and 42.36%, 39.67% and 28.49% by CA/HA washing, respectively. The European Community Bureau of Reference (BCR) sequential extraction was applied to analyze the fraction change of heavy metals in UFAMSW before and after washing, and it was found that chelating agent combined with HA could contribute to the removal of the exchangeable fraction. Physical and chemical properties of UFAMSW were improved to some extent after washing with mixed HA and chelating agent and could achieve the quality standard of landscape gardening soil. Accordingly, the mixture of HA and other chelating agents could be a promising washing process for preparation of landscape gardening soil using UFAMSW.Implications: Our manuscript studies the removal of heavy metals from the contaminated undersized fraction from aged municipal solid waste (UFAMSW). UFAMSW, as a kind of soil-like material, has been proved effective in providing a large amount of organic matter and nutrients for soil and plants however often limited by heavy metal pollution. The UFAMSW used in this experiment was collected after the excavation and screening-sorting of aged refuse from Changshankou Domestic Waste Sanitary Landfill in Wuhan City, Hubei Province, Southern China. This study investigated the effects of EDTA, CA, HA, mixed EDTA/HA, and mixed CA/HA washing on heavy metal removal (Cu, Zn, and Mn), bioavailability of residual heavy metal and properties. The effects of chelating agent concentration, pH, and washing time on metal removal were investigated and then response surface methodology was employed to optimize the washing conditions. The results showed that washing by CA/HA and EDTA/HA, had a higher removal efficiency of heavy metals (Cu, Zn, and Mn) in UFAMSW compared to single HA. Meanwhile, HA has a higher removal for exchangeable fraction of heavy metals, the exchangeable concentration of Cu, Zn, and Mn in CA/HA and EDTA/HA washed UFAMSW were lower compared with UFAMSW washed by single CA and EDTA. Thus, mixing HA with EDTA or CA makes a less risk to environmental and the removal efficiency is acceptable. Additionally, CA/HA and EDTA/HA washing tend to improve soil physicochemical properties and soil fertility. Thus, mixing HA with different washing agent are potential methods for preparation of landscape gardening soil using UFAMSW.

Robust and flexible polyester fiber membrane with under-liquid dual superlyophobicity for efficient on-demand oil-water separation.

Functional materials with under-liquid dual superlyophobicity have generated a great deal of concern from researchers due to their switchable separation ability oil-water mixtures and emulsions. Conceptually, under-liquid dual superlyophobicity is a Cassie state achievable under-liquid through the synergy of an under-liquid double lyophobic surface and the construction of a highly rough surface. However, obtaining an under-liquid dual superlyophobic surface remains difficult due to its thermodynamic contradiction and complex surface composition. Herein, we successfully prepared a functional coating by modifying the mixture of cellulose nanocrystals (CNCs) and nano-TiO2 with perfluorooctanoic acid (PFOA) via a simple method, then obtained a polyester fiber membrane with under-liquid dual superlyophobicity by roll coating method. The surface wettability of the polyester (PET) membrane was altered, transforming it from the original under-water oleophobic/under-oil superhydrophilic state to the under-water superoleophobic/under-oil superhydrophobic state after coated. The resulting membrane was applied to separate oil and water on-demand. The coated PET membrane exhibited high separation efficiency (>99 %) and high separation flux, effectively separating immiscible oil-water systems as well as oil-in-water and water-in-oil emulsions. The coated PET membrane also demonstrated the ability to perform alternate separation of oil-water mixtures through wetting, washing, and rewetting cycles, with repeated processes up to 10 times without significant reduction in separation efficiency. Furthermore, compared with the previous works, our approach offers a simpler and more convenient method for constructing under-liquid dual superlyophobic surface, making it more suitable for continuous corporate production. This study may provide inspiration for the production and application in large-scale of under-liquid dual superlyophobic membranes.

Insights into the poplar cell wall deconstruction following deep eutectic solvent pretreatment for enhanced enzymatic saccharification and lignin valorization.

In this study, a combination of microcosmic and chemical analysis methods was used to investigate deep eutectic solvent (DES) pretreatment effects on cell wall's micromorphology and lignin's dissolution regular, in order to achieve high-performance biorefinery. The atomic force microscope observed that DES pretreatment peeled off non-cellulose components to reduced "anti-degradation barrier", resulting to improve the enzymatic saccharification from 12.36 % to 90.56 %. In addition, DES pretreatment can break the ß-O-4 bond between the lignin units resulting in a decline in molecular weight from 3187 g/mol to 1112 g/mol (0-6 h). However, long pretreatment time resulted regenerated lignin samples repolymerization. Finally, DES has good recoverability which showed saccharification still can reach 51.51 % at 6 h following four recycling rounds and regenerated lignin also had a typical and well-preserved structure. In general, this work offers important information for industrial biorefinery technologies and lignin valorization.

A preventative role of nitrate for hypoxia-induced intestinal injury.

BACKGROUND: Studying effective interventions for hypoxia-induced injury is crucial, particularly in high-altitude areas. Symptoms stemming from intestinal injuries have a significant impact on the health of individuals transitioning from plains to plateau regions. This research explores the effects and mechanisms of nitrate supplementation in preventing hypoxia-induced intestinal injury. METHODS: A hypoxia survival mouse model was established using 7% O2 conditions. The intervention with 4 mM sodium nitrate (NaNO3) in drinking water commenced 7 days prior to hypoxia exposure. Weight monitoring, hematoxylin and eosin (HE) staining, transmission electron microscopy (TEM), and intestinal permeability assays were employed for physiological, histological, and functional analyses. Quantitative PCR (qPCR), Western blot, and immunofluorescence were utilized to analyze the levels of tight junction (TJ) proteins and hypoxia-inducible factor 1α (Hif 1α). RNA sequencing (RNA-seq) identified nitrate's target, and chromatin immunoprecipitation (ChIP) verified the transcriptional impact of Hif 1α on TJ proteins. Villin-cre mice infected with AAV9-FLEX-EGFP-Hif 1α were used for mechanism validation. RESULTS: The results demonstrated that nitrate supplementation significantly alleviated small intestinal epithelial cell necrosis, intestinal permeability, disruption of TJs, and weight loss under hypoxia. Moreover, the nitrate-triggered enhancement of TJs is mediated by Hif 1α nuclear translocation and its subsequent transcriptional function. The effect of nitrate supplementation on TJs was largely attributed to the stimulation of the EGFR/PI3K/AKT/mTOR/Hif 1α signaling pathways. CONCLUSION: Nitrate serves as a novel approach in preventing hypoxia-induced intestinal injury, acting through Hif 1α activation to promote the transcription of TJ proteins. Furthermore, our study provides new and compelling evidence for the protective effects of nitrate in hypoxic conditions, especially at high altitudes.

The spatial transcriptomic landscape of human gingiva in health and periodontitis.

The gingiva is a key oral barrier that protects oral tissues from various stimuli. A loss of gingival tissue homeostasis causes periodontitis, one of the most prevalent inflammatory diseases in humans. The human gingiva exists as a complex cell network comprising specialized structures. To understand the tissue-specific pathophysiology of the gingiva, we applied a recently developed spatial enhanced resolution omics-sequencing (Stereo-seq) technique to obtain a spatial transcriptome (ST) atlas of the gingiva in healthy individuals and periodontitis patients. By utilizing Stereo-seq, we identified the major cell types present in the gingiva, which included epithelial cells, fibroblasts, endothelial cells, and immune cells, as well as subgroups of epithelial cells and immune cells. We further observed that inflammation-related signalling pathways, such as the JAK-STAT and NF-κB signalling pathways, were significantly upregulated in the endothelial cells of the gingiva of periodontitis patients compared with those of healthy individuals. Additionally, we characterized the spatial distribution of periodontitis risk genes in the gingiva and found that the expression of IFI16 was significantly increased in endothelial cells of inflamed gingiva. In conclusion, our Stereo-seq findings may facilitate the development of innovative therapeutic strategies for periodontitis by mapping periodontitis-relevant genes and pathways and effector cells.

Clinical Outcomes of Surgical Crown Reattachment as Treatment for Complicated Crown-Root Fractures: A Retrospective Study.

This retrospective study evaluated the clinical outcomes of surgical crown reattachment in the treatment of complicated crown-root fractures in permanent teeth in 35 patients. Treatments were defined as follows: surgical crown reattachment combined with internal fixation with a fiberreinforced core post, ostectomy, and reattachment of the original crown fragment. Patients were examined to record the periodontal pocket depth (PD), marginal bone loss, tooth migration, and coronal fragment looseness or loss. In most cases, the fracture lines on the palatal aspect were located below the alveolar crest. About 20% to 30% of teeth had periodontal pockets ≥ 3 mm present at least 1 year after surgery. Significant PD differences were observed between the traumatized teeth and adjacent untraumatized teeth at 6 months. The available evidence suggests that surgical crown reattachment is a feasible and effective technique for managing complicated crown-root fractures in permanent teeth.

A multiclass extreme gradient boosting model for evaluation of transcriptomic biomarkers in Alzheimer's disease prediction.

BACKGROUND: Patients with young-onset Alzheimer's disease (AD) (before the age of 50 years old) often lack obvious imaging changes and amyloid protein deposition, which can lead to misdiagnosis with other cognitive impairments. Considering the association between immunological dysfunction and progression of neurodegenerative disease, recent research has focused on identifying blood transcriptomic signatures for precise prediction of AD. METHODS: In this study, we extracted blood biomarkers from large-scale transcriptomics to construct multiclass eXtreme Gradient Boosting models (XGBoost), and evaluated their performance in distinguishing AD from cognitive normal (CN) and mild cognitive impairment (MCI). RESULTS: Independent testing with external dataset revealed that the combination of blood transcriptomic signatures achieved an area under the receiver operating characteristic curve (AUC of ROC) of 0.81 for multiclass classification (sensitivity = 0.81; specificity = 0.63), 0.83 for classification of AD vs. CN (sensitivity = 0.72; specificity = 0.73), and 0.85 for classification of AD vs. MCI (sensitivity = 0.77; specificity = 0.73). These candidate signatures were significantly enriched in 62 chromosome regions, such as Chr.19p12-19p13.3, Chr.1p22.1-1p31.1, and Chr.1q21.2-1p23.1 (adjusted p < 0.05), and significantly overrepresented by 26 transcription factors, including E2F2, FOXO3, and GATA1 (adjusted p < 0.05). Biological analysis of these signatures pointed to systemic dysregulation of immune responses, hematopoiesis, exocytosis, and neuronal support in neurodegenerative disease (adjusted p < 0.05). CONCLUSIONS: Blood transcriptomic biomarkers hold great promise in clinical use for the accurate assessment and prediction of AD.

Molecular mechanisms of cellular metabolic homeostasis in stem cells.

Many tissues and organ systems have intrinsic regeneration capabilities that are largely driven and maintained by tissue-resident stem cell populations. In recent years, growing evidence has demonstrated that cellular metabolic homeostasis plays a central role in mediating stem cell fate, tissue regeneration, and homeostasis. Thus, a thorough understanding of the mechanisms that regulate metabolic homeostasis in stem cells may contribute to our knowledge on how tissue homeostasis is maintained and provide novel insights for disease management. In this review, we summarize the known relationship between the regulation of metabolic homeostasis and molecular pathways in stem cells. We also discuss potential targets of metabolic homeostasis in disease therapy and describe the current limitations and future directions in the development of these novel therapeutic targets.

Deep learning for classifying the stages of periodontitis on dental images: a systematic review and meta-analysis.

BACKGROUND: The development of deep learning (DL) algorithms for use in dentistry is an emerging trend. Periodontitis is one of the most prevalent oral diseases, which has a notable impact on the life quality of patients. Therefore, it is crucial to classify periodontitis accurately and efficiently. This systematic review aimed to identify the application of DL for the classification of periodontitis and assess the accuracy of this approach. METHODS: A literature search up to November 2023 was implemented through EMBASE, PubMed, Web of Science, Scopus, and Google Scholar databases. Inclusion and exclusion criteria were used to screen eligible studies, and the quality of the studies was evaluated by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology with the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool. Random-effects inverse-variance model was used to perform the meta-analysis of a diagnostic test, with which pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR, and diagnostic odds ratio (DOR) were calculated, and a summary receiver operating characteristic (SROC) plot was constructed. RESULTS: Thirteen studies were included in the meta-analysis. After excluding an outlier, the pooled sensitivity, specificity, positive LR, negative LR and DOR were 0.88 (95%CI 0.82-0.92), 0.82 (95%CI 0.72-0.89), 4.9 (95%CI 3.2-7.5), 0.15 (95%CI 0.10-0.22) and 33 (95%CI 19-59), respectively. The area under the SROC was 0.92 (95%CI 0.89-0.94). CONCLUSIONS: The accuracy of DL-based classification of periodontitis is high, and this approach could be employed in the future to reduce the workload of dental professionals and enhance the consistency of classification.

Endo-Periodontal Lesions-An Overlooked Etiology of Odontogenic Sinusitis.

The aim of this study was to analyze the oral etiology of patients with odontogenic sinusitis (ODS) and to compare the differences in demographic data, clinical symptoms, extent of sinus involvement, bone penetration of the maxillary sinus floor (MSF) between different etiologies. A retrospective investigation was conducted on 103 patients with ODS recruited from Beijing TongRen Hospital. All enrolled patients underwent sinus CT, nasal endoscopy, and oral examination. A comparison of the patients' clinical symptoms, the extent of involvement of the sinuses, and bone resorption of the MSF according to odontogenic etiologies was conducted. Follow-up was based on symptoms and clinical examination. The most common odontogenic etiologies were endo-periodontal lesions (EPLs, 49.5%), apical periodontitis (AP, 32.0%), and periodontitis (PE, 8.7%). There were statistically significant differences in age (p = 0.002), sex (p = 0.036), inflammation involving the ethmoid sinus (p = 0.037), and bone penetration of the MSF (p < 0.001) between the AP, EPL, and PE groups. There were no significant differences in sinusitis symptoms (p > 0.005) among patients with different odontogenic etiologies. In conclusion, EPL is a neglected oral etiology with a destructive effect on the bone of the MSF, which deserves more attention in diagnosis and treatment.