Is it a potential pneumonia pathogen in Pseudomonas putida group? First isolation and identification of Pseudomonas plecoglossicida in clinic and a comparison of pathogenicity with Pseudomonasputida.

PURPOSE: Pseudomonas plecoglossicida belongs to the Pseudomonas putida group and is a common aquatic pathogen that induces visceral lesions in fish. However, it has never been previously isolated from human specimen and associated with human infections. In the study, we first investigated the pathogenicity of Pseudomonas plecoglossicida strain "SXY" isolated from a child with infectious pneumonia. METHODS: Using 16S rRNA sequencing, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, and unique biochemical phenotypes, we isolated and identified Pseudomonas plecoglossicida in clinical practice, a highly suspicious pneumonia-related pathogen based on bacteriological examinations and clinical manifestations. Its pathogenicity was assessed and compared with that of Pseudomonas putida clinical strain "ECL" (a recognized pathogen in the Pseudomonas putida group) by a series of in vitro pathogenicity tests (including the growth capacity assay at 37 °C, the lung leukocyte-killing and inflammatory factor release assay, and the whole blood-killing, serum-killing and complement sensitivity assay). RESULTS: All tests demonstrated its ability to cause colonization, infection, and inflammation in the lungs. However, the pathogenicity and risk of bloodstream infection of Pseudomonas plecoglossicida strain "SXY" were limited and weaker than those of Pseudomonas putida strain "ECL". Notably, Pseudomonas plecoglossicida could be incorrectly identified as Pseudomonas putida, based on the biochemical identification of VITEK-2, potentially leading to a high rate of missing infections. CONCLUSIONS: Pseudomonas plecoglossicida is a potential and neglected pneumonia pathogen.

Expert consensus on the diagnosis and therapy of endo-periodontal lesions.

Endo-periodontal lesions (EPLs) involve both the periodontium and pulp tissue and have complicated etiologies and pathogenic mechanisms, including unique anatomical and microbiological characteristics and multiple contributing factors. This etiological complexity leads to difficulties in determining patient prognosis, posing great challenges in clinical practice. Furthermore, EPL-affected teeth require multidisciplinary therapy, including periodontal therapy, endodontic therapy and others, but there is still much debate about the appropriate timing of periodontal therapy and root canal therapy. By compiling the most recent findings on the etiology, pathogenesis, clinical characteristics, diagnosis, therapy, and prognosis of EPL-affected teeth, this consensus sought to support clinicians in making the best possible treatment decisions based on both biological and clinical evidence.

Association between brominated flame retardants (BFRs) and periodontitis: Results from a large population-based study.

BACKGROUND: Brominated flame retardants (BFRs) are widely utilized to mitigate the flammability of various materials. Previous studies have revealed the impact of BFRs exposure on hormonal disruption and bone metabolism which are closely related to periodontitis. However, it remains unknown the potential relationship between BFRs and periodontitis. This study aimed to explore the association between BFRs exposure and periodontitis in US adults. METHODS: The data analyzed in this study were obtained from the National Health and Nutrition Examination Survey (NHANES) 2009-2014. Twelve serum BFRs were quantified using isotope dilution gas chromatography high-resolution mass spectrometry. Univariable and multivariable logistic regression was employed to evaluate the association between serum BFRs and periodontitis. Bayesian kernel machine regression (BKMR) analyses were utilized to assess the association between mixtures of BFRs and periodontitis. RESULTS: A total of 3311 eligible participants were included. Serum BFRs (PBDE-47, PBDE-99, and PBDE-154) were significantly associated with periodontitis, and the odds ratios (ORs) and corresponding 95% confidence intervals(CIs) were 1.15(1.01,1.29), 1.10(1.01,1.20), and 1.12(1.01,1.25), respectively. Notably, these three BFRs were also significantly associated with the severity of periodontitis. Additionally, the BKMR model revealed a significant association between the mixture of all twelve BFRs and periodontitis. CONCLUSIONS: This preliminary study suggests a significant association between specific serum BFRs (PBDE-47, PBDE-99, and PBDE-154) and periodontitis and its severity. Further prospective and experimental studies are warranted to validate our findings.

Basic research for identification and classification of organophosphorus pesticides in water based on ultraviolet-visible spectroscopy information.

In this study, the goal was to develop a method for detecting and classifying organophosphorus pesticides (OPPs) in bodies of water. Sixty-five samples with different concentrations were prepared for each of the organophosphorus pesticides, namely chlorpyrifos, acephate, parathion-methyl, trichlorphon, dichlorvos, profenofos, malathion, dimethoate, fenthion, and phoxim, respectively. Firstly, the spectral data of all the samples was obtained using a UV-visible spectrometer. Secondly, five preprocessing methods, six manifold learning methods, and five machine learning algorithms were utilized to build detection models for identifying OPPs in water bodies. The findings indicate that the accuracy of machine learning models trained on data preprocessed using convolutional smoothing + first-order derivatives (SG + FD) outperforms that of models trained on data preprocessed using other methods. The backpropagation neural network (BPNN) model exhibited the highest accuracy rate at 99.95%, followed by the support vector machine (SVM) and convolutional neural network (CNN) models, both at 99.92%. The extreme learning machine (ELM) and K-nearest neighbors (KNN) models demonstrated accuracy rates of 99.84% and 99.81%, respectively. Following the application of a manifold learning algorithm to the full-wavelength data set for the purpose of dimensionality reduction, the data was then visualized in the first three dimensions. The results demonstrate that the t-distributed domain embedding (t-SNE) algorithm is superior, exhibiting dense clustering of similar clusters and clear classification of dissimilar ones. SG + FD-t-SNE-SVM ranks highest among the feature extraction models in terms of performance. The feature extraction dimension was set to 4, and the average classification accuracy was 99.98%, which slightly improved the prediction performance over the full-wavelength model. As shown in this study, the ultraviolet-visible (UV-visible) spectroscopy system combined with the t-SNE and SVM algorithms can effectively identify and classify OPPs in waterbodies.

The Effects of Irradiation on the Improvement in Oxidation Behavior of MX-ODS Steel in Liquid Pb.

Lead-cooled fast reactors exhibit strong inherent safety performance and good economic features, while material degradation due to corrosion and irradiation is still challenging. Oxide dispersion-strengthened steels are one of the promising candidates for fuel cladding materials. The effects of both irradiation and corrosion on ODS steel need to be further studied. In this work, MX-ODS steel was irradiated by Fe ions at 500 °C up to 46 dpa. Later, the as-received specimen and the irradiated specimen were used to conduct corrosion tests in oxygen-saturated Pb at 550 °C for 1 h. In the as-received specimen, discontinuous oxides penetrated by Pb and Pb in contact with steel matrix were observed, demonstrating unsatisfactory corrosion resistance of the material. However, in the irradiated specimen after corrosion experiment, a protective oxide layer formed and prevented Pb attack. The oxidation behavior differences between the two specimens can be attributed to the defects produced by irradiation and the structural discrepancy in oxides caused by the formation process. A possible mechanism of irradiation on the corrosion is discussed. In the as-received specimen, Fe atoms loss led to voids in the oxides, and lead penetrated the oxides through these voids. In the irradiated specimen, defects left by previous irradiation helped to form a more uniform oxide layer. The adhesive outer magnetite oxide and the Fe ions generated from where grain boundary oxidation developed retarded the presence of voids and made the oxide layer protective.

Machine learning for prediction of acute kidney injury in patients diagnosed with sepsis in critical care.

BACKGROUND AND OBJECTIVE: Acute Kidney Injury (AKI) is a common and severe complication in patients diagnosed with sepsis. It is associated with higher mortality rates, prolonged hospital stays, increased utilization of medical resources, and financial burden on patients' families. This study aimed to establish and validate predictive models using machine learning algorithms to accurately predict the occurrence of AKI in patients diagnosed with sepsis. METHODS: This retrospective study utilized real observational data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. It included patients aged 18 to 90 years diagnosed with sepsis who were admitted to the ICU for the first time and had hospital stays exceeding 48 hours. Predictive models, employing various machine learning algorithms including Light Gradient Boosting Machine (LightGBM), EXtreme Gradient Boosting (XGBoost), Random Forest (RF), Decision Tree (DT), Artificial Neural Network (ANN), Support Vector Machine (SVM), and Logistic Regression (LR), were developed. The dataset was randomly divided into training and test sets at a ratio of 4:1. RESULTS: A total of 10,575 sepsis patients were included in the analysis, of whom 8,575 (81.1%) developed AKI during hospitalization. A selection of 47 variables was utilized for model construction. The models derived from LightGBM, XGBoost, RF, DT, ANN, SVM, and LR achieved AUCs of 0.801, 0.773, 0.772, 0.737, 0.720, 0.765, and 0.776, respectively. Among these models, LightGBM demonstrated the most superior predictive performance. CONCLUSIONS: These machine learning models offer valuable predictive capabilities for identifying AKI in patients diagnosed with sepsis. The LightGBM model, with its superior predictive capability, could aid clinicians in early identification of high-risk patients.

The microbiota-gut-brain axis: A crucial immunomodulatory pathway for Bifidobacterium animalis subsp. lactis' resilience against LPS treatment in neonatal rats.

An imbalanced gut microflora may contribute to immune disorders in neonates due to an immature gut barrier. Bacterial toxins, particularly, can trigger the immune system, potentially resulting in uncontrolled gut and systemic inflammation. Previous research has revealed that Bifidobacterium animalis subsp. lactis (B. lactis) could protect against early-life pathogen infections by enhancing the gut barrier. However, the effects of B. lactis on a compromised immune system remain uncertain. Hence, this study concentrated on the immunomodulatory effects and mechanisms of B. lactis in neonatal rats intraperitoneally injected with lipopolysaccharide (LPS), a bacterial toxin and inflammatory mediator. First, B. lactis significantly alleviated the adverse effects induced by LPS on the growth, development, and body temperature of neonatal rats. Second, B. lactis significantly reduced the immune responses and damage induced by LPS, affecting both systemic and local immune responses in the peripheral blood, gut, and brain. Notably, B. lactis exhibited extra potent neuroprotective and neurorepair effects. Our research found that pre-treatment with B. lactis shaped the diverse gut microecology by altering both microbial populations and metabolic biomolecules, closely linked to immunomodulation. Overall, this study elucidated the multifaceted roles of B. lactis in neonatal hosts against pathogenic infection and immune disorder, revealing the existence of the microbiota-gut-brain axis.

A case report of Pseudomonas citronellolis and Escherichia coli isolated from acute suppurative appendicitis: reveals the potential intestinal colonization and pathogenicity of Pseudomonas citronellolis.

Human infections caused by Pseudomonas citronellolis, an environmental bacterium, are infrequent, with only two cases related to uncommon urinary tract infections and bacteremia reported in recent years. All these cases typically occurred in elderly patients with compromised or decreased immune function. Simultaneously, the epithelial barrier disruption induced by invasive biopsy procedures or gastrointestinal disorders such as gastroenteritis provided a pathway for Pseudomonas citronellolis to infiltrate the organism. In this study, we present the first report of a case where Pseudomonas citronellolis and Escherichia coli were isolated from the inflamed appendix of a patient without underlying conditions. Compared to the Escherichia coli, Pseudomonas citronellolis has never been isolated in patients with appendicitis. We identified the species using MALDI-TOF MS and genetic sequencing. Based on our findings, we highlight the perspective that Pseudomonas citronellolis can colonize the intestines of healthy individuals and may trigger infections like appendicitis.

Sequential autologous CAR-T and allogeneic CAR-T therapy successfully treats central nervous system involvement relapsed/refractory ALL: a case report and literature review.

Background: The central nervous system (CNS) is the most common site of extramedullary invasion in acute lymphoblastic leukemia (ALL), and involvement of the CNS is often associated with relapse, refractory disease, and poor prognosis. Chimeric antigen receptor-T (CAR-T) cell therapy, a promising modality in cancer immunotherapy, has demonstrated significant advantages in the treatment of hematological malignancies. However, due to associated adverse reactions such as nervous system toxicity, the safety and efficacy of CAR-T cell therapy in treating CNSL remains controversial, with limited reports available. Case report: Here, we present the case of a patient with confirmed B-ALL who experienced relapse in both bone marrow (BM) and cerebrospinal fluid (CSF) despite multiple cycles of chemotherapy and intrathecal injections. The infusion of autologous CD19 CAR-T cells resulted in complete remission (CR) in both BM and CSF for 40 days. However, the patient later experienced a relapse in the bone marrow. Subsequently, allogeneic CD19 CAR-T cells derived from her brother were infused, leading to another achievement of CR in BM. Significantly, only grade 1 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) events were detected during the treatment period and showed improvement with symptomatic management. During subsequent follow-up, the patient achieved a disease-free survival of 5 months and was successfully bridged to hematopoietic stem cell transplantation. Conclusion: Our study provides support for the argument that CNS involvement should not be deemed an absolute contraindication to CAR-T cell therapy. With the implementation of suitable management and treatment strategies, CAR-T therapy can proficiently target tumor cells within the CNS. This treatment option may be particularly beneficial for relapsed or refractory patients, as well as those with central nervous system involvement who have shown limited response to conventional therapies. Additionally, CAR-T cell therapy may serve as a valuable bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in these patients.

Cellular-level analyses of SCN5A mutations in left ventricular noncompaction cardiomyopathy suggest electrophysiological mechanisms for ventricular tachycardia.

Left ventricular noncompaction cardiomyopathy (LVNC) is a cardiovascular disease characterized by arrhythmia and heart failure. In this study, LVNC myocardial samples were collected from patients who underwent heart transplantation and were analyzed using exome sequencing. Approximately half of the LVNC patients carried SCN5A variants, which are associated with clinical symptoms of ventricular tachycardia. To investigate the electrophysiological functions of these SCN5A variants and the underlying mechanism by which they increase arrhythmia susceptibility in LVNC patients, functional evaluations were conducted in CHO-K1 cells and human embryonic stem cell-derived cardiomyocytes (hESC-CMs) using patch-clamp or microelectrode array (MEA) techniques. These findings demonstrated that these SCN5A mutants exhibited gain-of-function properties, leading to increased channel activation and enhanced fast inactivation in CHO-K1 cells. Additionally, these mutants enhanced the excitability and contractility of the cardiomyocyte population in hESC-CMs models. All SCN5A variants induced fibrillation-like arrhythmia and increased the heart rate in cardiomyocytes. However, the administration of Lidocaine, an antiarrhythmic drug that acts on sodium ion channels, was able to rescue or alleviate fibrillation-like arrhythmias and secondary beat phenomenon. Based on these findings, it is speculated that SCN5A variants may contribute to susceptibility to arrhythmia in LVNC patients. Furthermore, the construction of cardiomyocyte models with SCN5A variants and their application in drug screening may facilitate the development of precise therapies for arrhythmia in the future.

Association of per- and polyfluoroalkyl substances (PFAS) with periodontitis: the mediating role of sex hormones.

OBJECTIVES: To investigate the association between serum per- and polyfluoroalkyl substances (PFAS) and periodontitis, and further explore the possible mediating role of sex hormones in this association. METHODS: We extracted data from National Health and Nutrition Examination Survey (NHANES) 2009-2014. Univariable and multivariable logistic regression models were performed to investigate the association between serum levels of seven PFASs and periodontitis. Bayesian kernel machine regression (BKMR) was conducted to assess the joint effect of PFASs in mixtures. Mediation analyses were used to explore the potential mediating role of sex hormones. RESULTS: Participants with periodontitis had higher concentrations of serum perfluorooctane sulfonate (PFOS) and perfluorononanoic acid (PFNA) than those without periodontitis (both P < 0.05). In fully adjusted models, high serum concentrations of PFOS and PFNA were positively associated with periodontitis (tertile 3 vs. tertile 1: prevalence ratio (PR) = 1.19 for PFOS, 95% CI: 1.01-1.39; PR = 1.17 for PFNA, 95% CI: 1.02-1.34). The results from the BKMR models consistently showed a positive association between PFAS mixtures and periodontitis. Of note, testosterone and the ratio of testosterone to estradiol significantly mediated the relationship between high level of PFOS and periodontitis, accounting for 16.5% and 31.7% of the total effect, respectively. Sensitivity analyses yielded similar results when using periodontal clinical indices (mean loss of attachment, mean periodontal probing depth, and the number of teeth) as dependent variables. CONCLUSIONS: These findings provide evidence to support a positive association between certain PFASs and periodontitis, which might be partially mediated by sex hormones.

Nel-like Molecule Type 1 Combined with Gold Nanoparticles Modulates Macrophage Polarization, Osteoclastogenesis, and Oral Microbiota in Periodontitis.

The disruption of host-microbe homeostasis and uncontrolled inflammatory response have been considered as vital causes for developing periodontitis, subsequently leading to an imbalance between the bone and immune system and the collapse of bone homeostasis. Consequently, strategies to modulate the immune response and bone metabolization have become a promising approach to prevent and treat periodontitis. In this study, we investigated the cooperative effects of Nel-like molecule type 1 (Nell-1) and gold nanoparticles (AuNPs) on macrophage polarization, osteoclast differentiation, and the corresponding functions in an experimental model of periodontitis in rats. Nell-1-combined AuNPs in in vitro studies were found to reduce the production of inflammatory factors (TNF-α, p < 0.0001; IL-6, p = 0.0012), modulate the ratio of M2/M1 macrophages by inducing macrophage polarization into the M2 phenotype, and inhibit cell fusion, maturation, and activity of osteoclasts. Furthermore, the local application of Nell-1-combined AuNPs in in vivo studies resulted in alleviation of damages to the periodontal and bone tissues, modulation of macrophage polarization and the activity of osteoclasts, and alteration of the periodontal microbiota, in which the relative abundance of the probiotic Bifidobacterium increased (p < 0.05). These findings reveal that Nell-1-combined AuNPs could be a promising drug candidate for the prevention and treatment of periodontitis. However, Nell-1-combined AuNPs did not show organ toxicity or impair the integrity of intestinal epithelium but alter the gut microbiota, leading to the dysbiosis of gut microbiota. The adverse impact of changes in gut microbiota needs to be further investigated. Nonetheless, this study provides a novel perspective and direction for the biological safety assessment of biomaterials in oral clinical applications.

Associations of Urinary Total Arsenic and Arsenic Species and Periodontitis.

AIMS: Arsenic exposure is a significant global public health concern and has been implicated in endocrine disruption and increased oxidative stress, both of which are crucial pathogenic mechanisms of periodontitis. This study aimed to investigate the association of urinary total arsenic and arsenic species with periodontitis and to further explore the potential mediating roles of sex hormones and oxidative stress indicators. METHODS: Data used in this study were derived from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) in the US population. In all, 1063 participants with complete data were included in this study. Weighted logistic regression analyses were used to evaluate the relationship between urinary arsenic and periodontitis. Mediation analyses were used to explore the effects of potential mediators on these associations. RESULTS: High concentrations of urinary dimethylarsinic acid (DMA), monomethylarsonic acid (MMA), 2 types of toxic urinary arsenic (TUA2), and 4 types of toxic urinary arsenic (TUA4) were positively related to periodontitis (P < .05). After adjusting for potential confounders, the positive association remained significant (odds ratio, 1.32; 95% confidence interval, 1.01-1.71). Testosterone may partially mediate the relationship between MMA and periodontitis, with mediating effects of 21.78% and 39.73% of the total effect. No significant mediation effect of oxidative stress indicators was found for this relationship. CONCLUSIONS: This study reports a positive association between urinary MMA and periodontitis, and testosterone may mediate this relationship. Our findings serve as a call for action to avoid the deployment of arsenic-containing therapeutic agents as treatment modalities for oral afflictions.

Association between Mediterranean diet and periodontitis among US adults: The mediating roles of obesity indicators.

OBJECTIVE: This study aimed to assess the association between the Mediterranean diet (MedDiet) and periodontitis in US adults and to further explore the mediating roles of obesity indicators in this association. BACKGROUND DATA: The relationship between MedDiet and periodontitis is controversial. And it is unclear whether obesity indicators are potential mediators of this relationship. METHODS: Using data derived from the National Health and Nutrition Examination Survey (2009-2014). Weighted binary logistic regression and restricted cubic spline were used to assess the association between MedDiet and periodontitis. Weighted ordinal logistic regression was performed to evaluate the relationship between MedDiet and periodontitis severity. The mediating roles of body mass index (BMI) and waist circumference in the relationship between the MedDiet and periodontitis were explored. Association analyses were further performed using mean clinical attachment loss (CAL) or mean periodontal probing depth (PPD) as dependent variables. The false discovery rate method was used to correct the p-values in the regression analyses. RESULTS: A total of 8290 eligible participants (4159 participants with periodontitis and 4131 without periodontitis) were included. A negative association between the MedDiet adherence score and periodontitis was observed in the binary logistic regression model (adjusted odds ratio = 0.94, 95% confidence interval: 0.90-0.97, p = .001). Restricted cubic spline regression revealed a dose-response relationship between the MedDiet adherence score and periodontitis. BMI and waist circumference significantly mediate this association, with mediation proportions of 9.7% (p = .032) and 9.3% (p = .012), respectively. Multivariable ordinal logistic regression showed that the MedDiet adherence score was negatively associated with the severity of periodontitis (all p < .05). Additionally, the MedDiet adherence score was negatively associated with mean PPD or mean CAL (all p < .05). CONCLUSIONS: This study suggests a significant negative association between adherence to the MedDiet and periodontitis and a possible mediating role of obesity indicators in this association. Furthermore, studies are still warranted to confirm our findings.

Proteomics Analysis of Serum Reveals Potential Biomarkers for Heart Failure Patients with Phlegm-Blood Stasis Syndrome.

Heart failure (HF), a complex clinical syndrome, has become a global burden on health and economics around the world. Phlegm-blood stasis syndrome, one of the Traditional Chinese Medicine (TCM) syndrome differentiation, is the core pathogenesis dynamically throughout the occurrence, development, and prognosis of HF. Biomarkers having high sensitivity and specificity are highly demanded to facilitate the accurate differentiation of HF patients with phlegm-blood stasis syndrome. In the present study, serum samples were collected from 20 healthy controls and 40 HF patients (20 with and 20 without phlegm-blood stasis syndrome). We implemented data-independent acquisition mass spectrometry (DIA-MS) for discovery and parallel reaction monitoring (PRM) for validation of biomarkers for heart failure with phlegm-blood stasis syndrome. A total of 84 different proteins were found in the HF with phlegm-blood stasis syndrome (HF-TY) group compared with healthy controls. 37 candidate proteins were selected for the PRM assay, and five validated proteins with high sensitivity and specificity, including insulin-like growth factor-binding protein 4 (IGFBP4), ß-2-microglobulin (B2M), dystroglycan (DAG1), immunoglobulin J chain (JCHAIN), and kallikrein B1 (KLKB1), were considered potential biomarkers for heart failure patients with phlegm-blood stasis syndrome. Newly identified biomarkers might provide insights into the diagnosis and treatment of HF with TCM syndrome differentiation.

Association between polycyclic aromatic hydrocarbons and periodontitis: Results from a large population-based study.

AIM: To explore the association between polycyclic aromatic hydrocarbons (PAHs) (measured using urinary metabolites) and periodontitis using data from the National Health and Nutrition Examination Survey 2009-2014. MATERIALS AND METHODS: Weighted binary logistic regression, Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression were used to evaluate independent and joint associations between the six urinary monohydroxylated metabolites of PAHs (OH-PAHs) and periodontitis. RESULTS: In all, 3413 participants were included in this study. All six urinary OH-PAHs were present at higher levels in the periodontitis group compared with the non-periodontitis group (p < .001). Fully adjusted multivariable logistic regressions showed positive associations between the six urinary OH-PAHs and periodontitis (p < .05). Higher concentrations of OH-PAHs were also positively associated with attachment loss, periodontal pocket depth (PPD) and the number of tooth loss. BKMR and WQS regression yielded similar positive associations between OH-PAH mixtures and periodontitis. CONCLUSIONS: PAHs and their mixture are positively associated with periodontitis, which may provide novel insights into periodontitis prevention from an environmental exposure perspective.

Periodontitis salivary microbiota exacerbates colitis-induced anxiety-like behavior via gut microbiota.

The gut-brain axis is a bidirectional communication system between the gut and central nervous system. Many host-related factors can affect gut microbiota, including oral bacteria, making the brain a vulnerable target via the gut-brain axis. Saliva contains a large number of oral bacteria, and periodontitis, a common oral disease, can change the composition of salivary microbiota. However, the role and mechanism of periodontitis salivary microbiota (PSM) on the gut-brain axis remain unclear. Herein, we investigated the nature and mechanisms of this relationship using the mice with dextran sulfate sodium salt (DSS)-induced anxiety-like behavior. Compared with healthy salivary microbiota, PSM worsened anxiety-like behavior; it significantly reduced the number of normal neurons and activated microglia in DSS mice. Antibiotic treatment eliminated the effect of PSM on anxiety-like behavior, and transplantation of fecal microbiota from PSM-gavaged mice exacerbated anxiety-like behavior. These observations indicated that the anxiety-exacerbating effect of PSM was dependent on the gut microbiota. Moreover, the PSM effect on anxiety-like behavior was not present in non-DSS mice, indicating that DSS treatment was a prerequisite for PSM to exacerbate anxiety. Mechanistically, PSM altered the histidine metabolism in both gut and brain metabolomics. Supplementation of histidine-related metabolites had a similar anxiety-exacerbating effect as that of PSM, suggesting that histidine metabolism may be a critical pathway in this process. Our results demonstrate that PSM can exacerbate colitis-induced anxiety-like behavior by directly affecting the host gut microbiota, emphasizing the importance of oral diseases in the gut-brain axis.

Venetoclax combined with hypomethylating agents and the CAG regimen in relapsed/refractory AML: a single-center clinical trial.

Objective: This study aimed to evaluate the efficacy and safety of venetoclax in combination with hypomethylating agents and CAG (VEN-DCAG) regimens in patients with relapsed/refractory acute myeloid leukemia (R/R AML). Methods: The treatment response was analyzed by retrospective methods in R/R AML patients treated with the VEN-DCAG regimen at our institution. This included, but was not limited to, CR/CRi (complete remission/complete remission with incomplete hematologic recovery) rate, measurable residual disease (MRD) negative rate, and overall survival (OS). Results: 20 patients with R/R AML were recruited, with a median age of 40 years (10-70), 11 of whom were male (55%), and a median follow-up of 10.4 months (0.7-21.8). The overall response rate (ORR) after receiving 1 course of VEN-DCAG was 90% (18/20), with 17 (85%) CR/CRi (10 MRD-CR), 1 (5%) PR, and 2 (10%) NR. Subsequently, 12 patients (7 MRD-CR, 4 MRD+CR, 1 NR) were treated with the VEN-DCAG regimen, and 3 MRD+CR patients turned negative, and 13 patients finally achieved MRD-CR. Among them, 7 patients were in the relapse group, all achieving CR/CRi (6 MRD-CR), and 13 patients in the refractory group, with 10 CR/CRi (7 MRD-CR). The ORR for patients in the relapse and refractory groups was 100% (7/7) and 84.6% (11/13), respectively. Further, all patients experienced adverse events (AEs) of varying degrees of severity, with hematologic AEs primarily consisting of myelosuppression, while non-hematologic AEs were more common in the form of fever, gastrointestinal distress, and infections. 11 patients were followed up with bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT) therapy. At the last follow-up, 11 patients (7 MRD-CR, 4 MRD+CR) who received allo-HSCT, 1 (MRD+CR) died, and 9 patients (6 MRD-CR, 1 PR, 2 NR) who did not receive allo-HSCT, 5 (2 MRD-CR, 1 PR, 2 NR) died as well. Conclusion: The VEN-DCAG regimen may be an effective treatment option for R/R AML patients, with high ORR and MRD negative remission rates in both the relapsed and refractory groups. It is recommend that patients should be bridged to allo-HSCT as soon as possible after induction to CR by the VEN-DCAG regimen, which can lead to a significant long-term survival benefit. Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2300075985.

The associations of coffee consumption, coffee types, and caffeine metabolites with periodontitis: Results from NHANES 2009-2014.

BACKGROUND: Coffee is one of the world's most popular beverages and is the main dietary source of caffeine for most people. The various molecular effects of caffeine suggest that it may enhance bone loss. The purpose of the present study was to investigate the relationship of coffee, coffee types, and caffeine metabolites with periodontitis. METHODS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2009-2014. Total coffee and different types of coffee consumption were acquired through a 24-h dietary recall. Urinary caffeine metabolites were quantified using high-performance liquid chromatography-electrospray ionization-tandem quadrupole mass spectrometry (HPLC-ESI-MS/MS). The association of coffee, coffee types, and caffeine metabolites with periodontitis and its severity were assessed using multivariable logistic regression. RESULTS: A total of 3309 eligible participants were included. After adjusting for potential confounding variables, a positive association was observed between coffee consumption (particularly certain types of coffee) and periodontitis. Notably, a positive correlation was also found between total coffee intake and the severity of periodontitis. Additionally, for urinary caffeine metabolites, there was a significant positive association between 1-methyluric acid (1-MU), 1,3-dimethyluric acid (1,3-DMU), 3,7-dimethyluric acid (3,7-DMU), 1,7-dimethylxanthine (1,7-DMX), or 5-actlyamino-6-amino-3-methyluracil (AAMU) and periodontitis, with adjusted odds ratios and 95% confidence intervals of 1.10 (1.02, 1.19), 1.86 (1.05, 3.29), 0.94 (0.90, 0.98), 1.29 (1.03, 1.62), and 1.15 (1.05, 1.26), respectively. CONCLUSIONS: The present study suggests a positive association of coffee intake (especially certain coffee types) and caffeine metabolites (1-MU, 1,3-DMU, 3,7-DMU, 1,7-DMX, and AAMU) with periodontitis and its severity.