Application of Lactiplantibacillus plantarum hydrogel coating in combination with ice temperature for the preservation of fresh yak meat.

Fresh yak meat is highly nutritious and prone to spoilage, so developing suitable preservation methods is crucial. In this study, hydrogel coatings composed of konjac glucomannan, Lactiplantibacillus plantarum and gallic acid (KGX) were applied to preserve fresh yak meat under ice temperature (-1 °C). After 16 days, KGX group showed lowest total viable count (5.3 ± 0.1 log cfu/g) and total volatile basic nitrogen (13.02 ± 1.40 mg/100 g), which did not exceed the relevant standards of fresh meat. Combined assessments of color, texture, pH, drip loss rate, and thiobarbituric acid reactive substances indicated that KGX coating effectively prolonged yak meat preservation. High-throughput sequencing revealed that KGX coating effectively reduced the abundance of Pseudomonas and Candida. The application of L. plantarum hydrogel coatings in conjunction with ice temperature increased the shelf life of fresh yak meat to 16-20 days, suggesting its potential as a viable preservation method for fresh meat.

The ability of different diffusing enhancers to deliver chlorhexidine into dentinal tubules: An in vitro evaluation.

Background/purpose: Root canal irrigants are difficult to diffuse deep into the dentinal tubules for root canal disinfection. The purpose of this study was to assess the ability of different diffusing enhancers to deliver chlorhexidine (CHX) into dentinal tubules. Materials and methods: The diffusing property of five diffusing enhancers (acetone, DMSO, Triton X-100, JFC-E and azone) into dentinal tubules was firstly assessed using the Rhodamine B. The ability of the diffusing enhancers to deliver CHX into dentinal tubules was then evaluated both qualitatively and quantitatively. A deep dentinal tubule Enterococcus faecalis infection model was further established to test the bactericidal effect of CHX delivered by different diffusing enhancers. Finally, the in vitro cytotoxicity of these diffusing enhancers was tested using the CCK-8 method. Results: Azone, Triton X-100 and JFC-E exhibited the largest maximum diffusing depths at all root canal parts (P < 0.05). Azone group also showed the highest percentage of diffusing depths for all root canal parts, followed by Triton X-100 (P < 0.05). The percentage of dead bacteria in dentinal tubules close to cementum layer was significantly higher in the CHX + azone group than in the other groups (P < 0.05), followed by CHX + Triton X-100 and CHX + JFC-E groups. The concentration of CHX diffusing onto the exterior surface of root was significantly higher in CHX + azone group than in the other groups (P < 0.05). All the diffusing enhancers showed relatively low cytotoxicity. Conclusion: Azone showed the highest diffusing ability with low cytotoxicity and might be employed as a carrier agent for either intracanal irrigants or medications to achieve more thorough root canal disinfection.

Metformin reduced the alkaline resistance of Enterococcus faecalis against calcium hydroxide via Man-PTS EII: in vitro and in vivo studies.

OBJECTIVES: The mannose phosphotransferase system (Man-PTS) plays crucial roles in the adaptive metabolic activity of Enterococcus faecalis (E. faecalis) in adverse environments. The aim of this study was to evaluate the role of Man-PTS in the alkaline resistance of E. faecalis against calcium hydroxide (CH) and the effect of metformin (Met) on the alkaline resistance of E. faecalis to CH. MATERIALS AND METHODS: The regulatory role of Man-PTS EII in the alkaline resistance of E. faecalis was firstly investigated using a wild-type highly alkaline-resistant E. faecalis XS 003, standard ATCC 29212 and Man-PTS EIID gene deficient (△mptD) and overexpressing (+mptD) strains of E. faecalis. RNA sequencing of Met-treated E. faecalis was performed to further validate the effect of Met on Man-PTS. The effect of Met on CH resistance of E. faecalis was verified by evaluating the survival, membrane potential and permeability, intracellular pH and ATP, and the expression of Man-PTS EII and membrane transporter-related genes of E. faecalis. The effect of Met on the ability of CH to remove E. faecalis biofilm on the dentin surface was also tested. The in vivo therapeutic effect of Met plus CH (CHM) was further investigated in a rat apical periodontitis model induced by E. faecalis XS 003. RESULTS: Man-PTS EII significantly promoted the survival ability of E. faecalis in CH and enhanced its resistance to CH. The inhibition of Man-PTS EII by Met resulted in reduced alkaline resistance of E. faecalis in the presence of CH, while also enhancing the antimicrobial properties of CH against E. faecalis biofilm on dentin. Additionally, Met plus CH showed the synergistically promoted intra-canal E. faecalis infection control and healing of periapical lesion in rats. CONCLUSIONS: Met could significantly reduce the alkaline resistance of E. faecalis against CH through the modulation of Man-PTS EII, and improved the antibacterial effect of CH against E. faecalis infection both in vitro and in vivo. CLINICAL RELEVANCE: Met could significantly enhance the ability of CH to control E. faecalis infection through reducing the alkaline resistance of E. faecalis.

CT-based whole lung radiomics nomogram for identification of PRISm from non-COPD subjects.

BACKGROUND: Preserved Ratio Impaired Spirometry (PRISm) is considered to be a precursor of chronic obstructive pulmonary disease. Radiomics nomogram can effectively identify the PRISm subjects from non-COPD subjects, especially when during large-scale CT lung cancer screening. METHODS: Totally 1481 participants (864, 370 and 247 in training, internal validation, and external validation cohorts, respectively) were included. Whole lung on thin-section computed tomography (CT) was segmented with a fully automated segmentation algorithm. PyRadiomics was adopted for extracting radiomics features. Clinical features were also obtained. Moreover, Spearman correlation analysis, minimum redundancy maximum relevance (mRMR) feature ranking and least absolute shrinkage and selection operator (LASSO) classifier were adopted to analyze whether radiomics features could be used to build radiomics signatures. A nomogram that incorporated clinical features and radiomics signature was constructed through multivariable logistic regression. Last, calibration, discrimination and clinical usefulness were analyzed using validation cohorts. RESULTS: The radiomics signature, which included 14 stable features, was related to PRISm of training and validation cohorts (p < 0.001). The radiomics nomogram incorporating independent predicting factors (radiomics signature, age, BMI, and gender) well discriminated PRISm from non-COPD subjects compared with clinical model or radiomics signature alone for training cohort (AUC 0.787 vs. 0.675 vs. 0.778), internal (AUC 0.773 vs. 0.682 vs. 0.767) and external validation cohorts (AUC 0.702 vs. 0.610 vs. 0.699). Decision curve analysis suggested that our constructed radiomics nomogram outperformed clinical model. CONCLUSIONS: The CT-based whole lung radiomics nomogram could identify PRISm to help decision-making in clinic.

Dual-energy CT Radiomics Combined with Quantitative Parameters for Differentiating Lung Adenocarcinoma From Squamous Cell Carcinoma: A Dual-center Study.

RATIONALE AND OBJECTIVES: To evaluate the ability of dual-energy CT(DECT)-based quantitative parameters and radiomics features to differentiate solid lung adenocarcinoma (ADC) from squamous cell carcinoma (SCC). METHODS: This study included 213 patients diagnosed with ADC and SCC who underwent DECT scans at two centers from November 2022 to December 2023. Patients at center 1 were randomly divided into training (n = 114) and internal test set (n = 50) in a 7:3 ratio, with center 2 serving as the external test set (n = 49). Radiologic and clinical data were combined to establish a clinical-radiologic model. Ten types of DECT energy images including conventional images, iodine density (ID), effective atomic number (Zeff), electron density, and virtual mono-energetic images (VMI) were reconstructed in both arterial phases (AP) and venous phases (VP). Quantitative parameters were measured at the uniform enhanced solid portion of the tumor and normalized to the aorta, used to develop a quantification model and calculate the quantitative score (quantscore). Radiologists manually delineated the tumor ROI at the largest level for extracting radiomics features in these 10 energy images. These features were used to establish 10 uni-energy models from which the best-performing features were selected to construct the final radiomics model and calculate a radiomics score (radscore). Then, a combined model was developed using the akaike information criterion(AIC) and compared to the clinical-radiological model to test its diagnostic validity. RESULTS: The independent predictors of the clinical-radiological model included age, gender, and central or peripheral location, and the AUCs for the training set, internal test set, and external test set were 0.808, 0.837, and 0.802. The quantification model incorporated 40 keV CT values, Zeff, normalized Zeff, and the slope of the spectral attenuation curve (λHU) in the AP and normalized ID, Zeff, and λHU in the VP. Uni-energy models based on AP ID maps, AP Zeff maps, and VP VMI 65 keV significantly outperformed AUC= 0.5, and 11 radiomics features were selected from these three models to construct the final radiomics model. The combined model, incorporating age, gender, quantscore, and radscore, significantly outperformed the clinical-radiological model in the training set (AUC=0.952 vs 0.808, P < 0.001), and demonstrated higher performance in both the internal and external test sets, although these differences did not reach statistical significance (AUC=0.870 vs 0.837, for the internal test set [P = 0.542], 0.888 vs 0.802 for the external test sets [P = 0.128]). The evaluation of the combined model demonstrated good discriminative ability and potential for generalization. CONCLUSION: The combined model, integrating quantitative parameters and radiomics features from DECT multi-energy images with clinical-radiological characteristics, can be used as a non-invasive tool to differentiate ADC from SCC.

Ruminal microbial metagenomes and host transcriptomes shed light on individual variability in the growth rate of lambs before weaning: the regulated mechanism and potential long-term effect on the host.

Weaning weight is a reflection of management during the breastfeeding phase and will influence animal performance in subsequent phases, considered important indicators within production systems. The aims of this study were as follows: (i) to investigate variability in the growth rate among individual lambs from ewes rearing single or twin lambs fed with two different diets and (ii) to explore the molecular mechanisms regulating the growth rate and the potential long-term effects on the host. No significant change in lamb average daily gain (ADG) was observed in litter size and diet treatment, and there were large variations among individual lambs (ranging from 0.13 to 0.41 kg/day). Further analysis was conducted on serum amino acids, rumen fermentation characteristics, rumen metagenomics and transcriptome, and hepatic transcriptome of lambs with extremely high (HA; n = 6) and low (LA; n = 6) ADG. We observed significant increases in serum lysine, leucine, alanine, and phenylalanine in the HA group. The metagenome revealed that the HA group presented a higher rumen propionate molar proportion via increasing gene abundance in the succinate pathway for propionate synthesis. For the rumen transcriptome, higher expressed gene sets in the HA group were mainly related to rumen epithelial growth, including cytokine-cytokine receptor interaction, Jak-STAT signaling pathway, and adherens junction. For the liver transcriptome, the upregulated KEGG pathways in the HA group were primarily associated with fatty acid degradation, glyoxylate and dicarboxylate metabolism, cholesterol metabolism, and the immune system. This research suggests that preweaning lambs with high ADG may benefit from rumen development and enhanced liver metabolic and immune function. IMPORTANCE: There is accumulating evidence indicating that the early-life rumen microbiome plays vital roles in rumen development and microbial fermentation, which subsequently affects the growth of young ruminants. The liver is also vital to regulate the metabolism and distribution of nutrients. Our results demonstrate that lambs with high average daily gain (ADG) enhanced microbial volatile fatty acid (VFA) metabolism toward rumen propionate and serum amino acid (AA) production to support host growth. The study highlights that high ADG in the preweaning period is beneficial for the rumen development and liver energy metabolism, leading to better growth later in life. Overall, this study explores the molecular mechanisms regulating the growth rate and the potential long-term effects of increased growth rate on the host metabolism, providing fundamental knowledge about nutrient manipulation in pre-weaning.

Effect of 3D printed teeth and virtual simulation system on the pre-clinical access cavity preparation training of senior dental undergraduates.

BACKGROUND: The objective of the present study was to evaluate the effect of 3D printed teeth and virtual simulation system on the pre-clinical access cavity preparation training of senior dental undergraduates. METHODS: The 3D printed teeth were manufactured based on the micro-CT data of an extracted lower first molar. Ninety-eight senior dental undergraduate students were required to finish the access cavity preparation of lower first molar within 20 min on plastic and 3D printed teeth on the manikin system as well as on a virtual simulation machine respectively with randomly selected sequences. Expert dentists scored the operated teeth. The scores from the virtual simulation system were also recorded. All the scores were analyzed and compared. Following the procedure, two questionnaires were sent to students to further evaluate the feelings and optimal training sequence. RESULTS: No significant differences were found between plastic and 3D printed teeth scores, while virtual simulation achieved a valid/invalid area removal ratio of 96.86% ± 5.08% and 3.97% ± 1.85%, respectively. Most students found plastic teeth training the easiest and favored the three-training combination (36.36%). 71.42% of the students thought the virtual simulation training should be put at the first place of the three trainings. Over 80% of students agreed with incorporating 3D printed teeth and virtual simulation into their routine training courses. In addition, the general advantages and disadvantages of the virtual simulation system and 3D printed teeth training received almost equal recognition by students. CONCLUSIONS: Virtual simulation system training + plastic teeth training + 3D printed teeth training might be the optimal training sequence. Virtual simulation system training could not completely replace the traditional training methods on the manikin system at the moment. With further modifications, 3D printed teeth could be expected to replace the plastic teeth for the pre-clinical access cavity preparation training.

Effects of industrial-scale pickling processes on the dynamic changes in the physicochemical indicators and microbial diversities of Yacai.

The effects of dry-salted and salt-fermented processing on the physicochemical characteristics and microbial communities of Yacai were systematically investigated. The results showed that the contents of total acid, amino acid nitrogen (AAN) and nitrite in the final products of dry-salted Yacai were greater than those in salt-fermented Yacai. Lactic acid was the dominant organic acid in the two types of Yacai. Dry-salted processing is more conducive to forming a high-quality reddish-brown color. During whole pickling process, the microbial diversity of dry-salted Yacai was higher than that of salt-fermented Yacai, particularly in the early and middle stages of fermentation. For dry-salted Yacai, 8 bacteria (Natribacillus, Chromohalobacter, Marinococcus, Lentibacillus, Nesterenkonia, Gracilibacillus, Oceanobacillus and Tetragenococcus) and 1 fungus (Zygosaccharomyces) showed a significant positive correlation with AAN. For salt-fermented Yacai, 8 bacteria (Gracilibacillus, Alkalibacillus, Oceanobacillus, Virgibacillus, Lentibacillus, Salibacterium, Chromohalobacter and Tetragenococcus) and 3 fungi (Zygosaccharomyces, Millerozyma, and Wickerhamomyces) exhibited significant positive correlations with AAN.

Widely targeted metabolomics and flavoromics reveal the effect of Wickerhamomyces anomalus fermentation on the volatile and nonvolatile metabolites of black garlic juice.

Black garlic has a variety of biological activities, but many consumers cannot accept it because of the garlic odor and the bitter taste. In this study, fermentation with yeast Wickerhamomyces anomalus was adopted to improve the flavor of black garlic juice. Although fermentation reduced antioxidant activities, the garlicky odor and bitter taste were weakened. Metabolomic analysis revealed 141 metabolites were significantly differentially regulated. The upregulated metabolites were mainly related to nucleotides, organic acids and their derivatives, while the downregulated metabolites were mainly related to amino acids, lipids and their derivatives. Flavoromics analysis revealed that 137 metabolites were significantly differentially regulated, particularly garlicky and pungent volatiles were significantly downregulated. Correlation analysis indicated that esters are most closely related to nonvolatile metabolites, and lipids degradation was significantly correlated with volatiles. The results indicated that W. anomalus fermentation is an effective strategy to improve the flavor of black garlic juice.

Synthetic macrolides overcoming MLSBK-resistant pathogens.

Conventional macrolide-lincosamide-streptogramin B-ketolide (MLSBK) antibiotics are unable to counter the growing challenge of antibiotic resistance that is conferred by the constitutive methylation of rRNA base A2058 or its G2058 mutation, while the presence of unmodified A2058 is crucial for high selectivity of traditional MLSBK in targeting pathogens over human cells. The absence of effective modes of action reinforces the prevailing belief that constitutively antibiotic-resistant Staphylococcus aureus remains impervious to existing macrolides including telithromycin. Here, we report the design and synthesis of a novel series of macrolides, featuring the strategic fusion of ketolide and quinolone moieties. Our effort led to the discovery of two potent compounds, MCX-219 and MCX-190, demonstrating enhanced antibacterial efficacy against a broad spectrum of formidable pathogens, including A2058-methylated Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, and notably, the clinical Mycoplasma pneumoniae isolates harboring A2058G mutations which are implicated in the recent pneumonia outbreak in China. Mechanistic studies reveal that the modified quinolone moiety of MCX-190 establishes a distinctive secondary binding site within the nascent peptide exit tunnel. Structure-activity relationship analysis underscores the importance of this secondary binding, maintained by a sandwich-like π-π stacking interaction and a water-magnesium bridge, for effective engagement with A2058-methylated ribosomes rather than topoisomerases targeted by quinolone antibiotics. Our findings not only highlight MCX-219 and MCX-190 as promising candidates for next-generation MLSBK antibiotics to combat antibiotic resistance, but also pave the way for the future rational design of the class of MLSBK antibiotics, offering a strategic framework to overcome the challenges posed by escalating antibiotic resistance.

Preoperative prediction of histopathological grading in patients with chondrosarcoma using MRI-based radiomics with semantic features.

BACKGROUND: Distinguishing high-grade from low-grade chondrosarcoma is extremely vital not only for guiding the development of personalized surgical treatment but also for predicting the prognosis of patients. We aimed to establish and validate a magnetic resonance imaging (MRI)-based nomogram for predicting preoperative grading in patients with chondrosarcoma. METHODS: Approximately 114 patients (60 and 54 cases with high-grade and low-grade chondrosarcoma, respectively) were recruited for this retrospective study. All patients were treated via surgery and histopathologically proven, and they were randomly divided into training (n = 80) and validation (n = 34) sets at a ratio of 7:3. Next, radiomics features were extracted from two sequences using the least absolute shrinkage and selection operator (LASSO) algorithms. The rad-scores were calculated and then subjected to logistic regression to develop a radiomics model. A nomogram combining independent predictive semantic features with radiomic by using multivariate logistic regression was established. The performance of each model was assessed by the receiver operating characteristic (ROC) curve analysis and the area under the curve, while clinical efficacy was evaluated via decision curve analysis (DCA). RESULTS: Ultimately, six optimal radiomics signatures were extracted from T1-weighted imaging (T1WI) and T2-weighted imaging with fat suppression (T2WI-FS) sequences to develop the radiomics model. Tumour cartilage abundance, which emerged as an independent predictor, was significantly related to chondrosarcoma grading (p < 0.05). The AUC values of the radiomics model were 0.85 (95% CI, 0.76 to 0.95) in the training sets, and the corresponding AUC values in the validation sets were 0.82 (95% CI, 0.65 to 0.98), which were far superior to the clinical model AUC values of 0.68 (95% CI, 0.58 to 0.79) in the training sets and 0.72 (95% CI, 0.57 to 0.87) in the validation sets. The nomogram demonstrated good performance in the preoperative distinction of chondrosarcoma. The DCA analysis revealed that the nomogram model had a markedly higher clinical usefulness in predicting chondrosarcoma grading preoperatively than either the rad-score or clinical model alone. CONCLUSION: The nomogram based on MRI radiomics combined with optimal independent factors had better performance for the preoperative differentiation between low-grade and high-grade chondrosarcoma and has potential as a noninvasive preoperative tool for personalizing clinical plans.

A clinical-radiomics nomogram based on automated segmentation of chest CT to discriminate PRISm and COPD patients.

Purpose: It is vital to develop noninvasive approaches with high accuracy to discriminate the preserved ratio impaired spirometry (PRISm) group from the chronic obstructive pulmonary disease (COPD) groups. Radiomics has emerged as an image analysis technique. This study aims to develop and confirm the new radiomics-based noninvasive approach to discriminate these two groups. Methods: Totally 1066 subjects from 4 centers were included in this retrospective research, and classified into training, internal validation or external validation sets. The chest computed tomography (CT) images were segmented by the fully automated deep learning segmentation algorithm (Unet231) for radiomics feature extraction. We established the radiomics signature (Rad-score) using the least absolute shrinkage and selection operator algorithm, then conducted ten-fold cross-validation using the training set. Last, we constructed a radiomics signature by incorporating independent risk factors using the multivariate logistic regression model. Model performance was evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analyses (DCA). Results: The Rad-score, including 15 radiomic features in whole-lung region, which was suitable for diffuse lung diseases, was demonstrated to be effective for discriminating between PRISm and COPD. Its diagnostic accuracy was improved through integrating Rad-score with a clinical model, and the area under the ROC (AUC) were 0.82(95 %CI 0.79-0.86), 0.77(95 %CI 0.72-0.83) and 0.841(95 %CI 0.78-0.91) for training, internal validation and external validation sets, respectively. As revealed by analysis, radiomics nomogram showed good fit and superior clinical utility. Conclusions: The present work constructed the new radiomics-based nomogram and verified its reliability for discriminating between PRISm and COPD.

Machine learning-based CT radiomics enhances bladder cancer staging predictions: A comparative study of clinical, radiomics, and combined models.

BACKGROUND: Predicting the accurate preoperative staging of bladder cancer (BLCA), which markedly affects treatment decisions and patient outcomes, using traditional clinical parameters is challenging. Nevertheless, emerging studies in radiomics, especially machine learning-based computed tomography (CT) image-based radiomics, hold promise in improving stage prediction accuracy in various tumors. However, the comparative performance and clinical utility of models for BLCA are under investigation. PURPOSE: We aimed to investigate the application value of machine learning-based CT radiomics in preoperative staging prediction by comparing the performance of clinical, radiomics, and clinical-radiomics combined models. METHODS: A retrospective cohort of 105 patients with initial BLCA was randomized into training (70%) and testing (30%) cohorts. Radiomics features were extracted from CT images using the optimal feature filter, followed by the application of the least absolute shrinkage and selection operator algorithm for optimum feature selection. Furthermore, machine learning algorithms were used to establish a radiomics model within the training cohort. Independent risk factors for muscle-invasive BLCA (MIBC) obtained by multivariate logistic regression (LR) analysis were separately used to construct a clinical model. For a clinical-radiomics fusion model, radiomics features were combined with clinical parameters. Performance was evaluated based on receiver operating characteristic curves, calibration curves, decision curve analysis (DCA), and standard performance metrics. RESULTS: Patients exhibited a significantly higher age (p = 0.029), larger tumor size (p = 0.01), and an increased neutrophil-to-lymphocyte ratio (NLR; p = 0.045) in the MIBC group than in the NMIBC group. LR analysis revealed age (p = 0.026), tumor size (p = 0.007), and NLR (p = 0.019) as significant predictors for constructing the clinical model. In the testing cohort, the radiomics model, which used an Support Vector Machine classifier, achieved the highest area under the curve (AUC) value of 0.857. The clinical-radiomics model outperformed the remaining two models, with AUC values of 0.958 and 0.893 in the training and testing cohorts, respectively. DeLong's test indicated significant differences between the three models. Calibration curves showed good agreement, and DCA confirmed the superior clinical utility of the clinical-radiomics model. CONCLUSIONS: Machine learning-based CT radiomics combined with clinical parameters was a promising approach in staging BLCA accurately, which outperformed the individual models. Integrating radiomics features with clinical information holds the potential to improve personalized treatment planning and patient outcomes in BLCA.

Antibacterial Property and Mechanisms of Au@Ag Core-Shell Nanoparticles with Near-Infrared Absorption Against E. faecalis Infection of Dentin.

Background: Enterococcus faecalis (E. faecalis) is one of the main pathogens responsible for refractory root canal infections in the teeth and shows resistance against various antibacterial managements. Effective control of E. faecalis infection is a prerequisite for successful treatment of refractory apical periodontitis. This study aimed to analyze the antibacterial activity and mechanisms of Au@Ag nanoparticles (NPs) combined with photothermal therapy (PTT) against the original and Ag+-resistant E. faecalis. Methods: Au@AgNPs with optimal shell thicknesses were synthesized and characterized. The antibacterial activity of Au@AgNPs with PTT against the original or Ag+-resistant E. faecalis was evaluated, and the antibiofilm activity was tested on E. faecalis biofilm on the dentin of teeth. The potential antibacterial mechanisms of Au@AgNPs combined with PTT against E. faecalis have also been studied. Moreover, its influence on dentin microhardness and cytotoxicity was assessed. Results: This study revealed that Au@AgNPs combined with PTT showed enhanced antibacterial and antibiofilm effects, no negative effects on dentin microhardness, and low cytotoxicity toward human periodontal ligament cells (hPDLCs). Moreover, Au@AgNPs combined with PTT effectively inhibited the growth of Ag+-resistant E. faecalis. Its antibacterial effects may be exerted through the release of silver ions (Ag+), destruction of the cell membrane, production of reactive oxygen species (ROS) and inhibition of adenosine triphosphate (ATP) production. Hyperthermia generated by Au@AgNPs with PTT reduced membrane fluidity and enhanced Ag+ sensitivity by downregulating fabF expression. The upregulated expression of heat shock genes demonstrated that the Ag+ released from Au@AgNPs compromised the heat adaptation of E. faecalis. Conclusion: PTT significantly enhanced Ag+ sensitivity of the original and Ag+-resistant E. faecalis. Au@AgNPs combined with PTT may have the potential to be developed as a new antibacterial agent to control E. faecalis infections in teeth.

EXAMINING THE IMPACT OF PERMISSIBILITY HYPERCAPNIA ON POSTOPERATIVE DELIRIUM AMONG ELDERLY PATIENTS UNDERGOING THORACOSCOPIC-LAPAROSCOPIC ESOPHAGECTOMY: A SINGLE-CENTER INVESTIGATIVE STUDY.

ABSTRACT: Objective: This study explores how permissive hypercapnia, a key aspect of lung-protective ventilation, impacts postoperative delirium in elderly patients following thoracic surgery. Methods: A single-center trial at The Second Hospital of Anhui Medical University involved 136 elderly patients undergoing thoracoscopic esophageal cancer resection. Randomly assigned to maintain PaCO 2 35-45 mm Hg (group N) or 46-55 mm Hg (group H). Primary outcome: postoperative delirium (POD) incidence 1-3 days post-surgery. Secondary endpoints included monitoring rSO 2 , cardiovascular parameters (MAP, HR), pH, OI, and respiratory parameters (VT, RR, Cdyn, PIP) at specific time points. Perioperative tests assessed CRP/ALB ratio (CAR) and systemic inflammatory index (SII). VAS scores were documented for 3 postoperative days. Results: Postoperatively, group H showed significantly lower POD incidence than group N (7.4% vs. 19.1%, P = 0.043). Group H exhibited higher PaCO 2 and rSO 2 during surgery ( P < 0.05). Patients in group H maintained better cardiovascular stability with higher blood pressure and lower heart rate on T2-4 ( P < 0.05). Respiratory parameters were more stable in group H with lower TV, RR, and PIP, and higher Cdyn during OLV ( P < 0.05). Group H had lower pH and higher OI at T2-4 ( P < 0.05). CRP and CAR levels rose less in group H on the first day and 1 week later ( P < 0.05). Conclusions: Maintaining PaCO 2 at 46-55 mm Hg reduces POD incidence, possibly by enhancing rSO 2 levels and stabilizing intraoperative respiration/circulation.

Mechanisms of Triton X-100 reducing the Ag+-resistance of Enterococcus faecalis.

To investigate the mechanism of Triton X-100 (TX-100) reducing the Ag+-resistance of Enterococcus faecalis (E. faecalis), and evaluate the antibacterial effect of TX-100 + Ag+ against the induced Ag+-resistant E. faecalis (AREf). The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of AgNO3 against E. faecalis with/without TX-100 were determined to verify the enhanced antibacterial activity. Transmission electron microscopy (TEM) was used to observe the morphological changes of E. faecalis after treatment. The intra- and extracellular concentration of Ag+ in treated E. faecalis was evaluated using inductively coupled plasma mass spectrometer (ICP-MS). The changes in cell membrane potential and integrity of treated E. faecalis were also observed using the flow cytometer. Moreover, AREf was induced through continuous exposure to sub-MIC of Ag+ and the antibacterial effect of TX-100 + Ag+ on AREf was further evaluated. The addition of 0.04% TX-100 showed maximal enhanced antibacterial effect of Ag+ against E. faecalis. The TEM and ICP-MS results demonstrated that TX-100 could facilitate Ag+ to enter E. faecalis through changing the membrane structure and integrity. Flow cytometry further showed the effect of TX-100 on membrane potential and permeability of E. faecalis. In addition, the enhanced antibacterial effect of TX-100 + Ag+ was also confirmed on induced AREf. TX-100 can facilitate Ag+ to enter E. faecalis through disrupting the membrane structure and changing the membrane potential and permeability, thus reducing the Ag+-resistance of E. faecalis and enhancing the antibacterial effect against either normal E. faecalis or induced AREf.

Dental pulp regeneration strategies: A review of status quo and recent advances.

Microorganisms, physical factors such as temperature or mechanical injury, and chemical factors such as free monomers from composite resin are the main causes of dental pulp diseases. Current clinical treatment methods for pulp diseases include the root canal therapy, vital pulp therapy and regenerative endodontic therapy. Regenerative endodontic therapy serves the purpose of inducing the regeneration of new functional pulp tissues through autologous revascularization or pulp tissue engineering. This article first discusses the current clinical methods and reviews strategies as well as the research outcomes regarding the pulp regeneration. Then the in vivo models, the prospects and challenges for regenerative endodontic therapy were further discussed.

Targeting programmed cell death in inflammatory bowel disease through natural products: New insights from molecular mechanisms to targeted therapies.

Inflammatory bowel disease (IBD) is an autoimmune disorder primarily characterized by intestinal inflammation and recurrent ulceration, leading to a compromised intestinal barrier and inflammatory infiltration. This disorder's pathogenesis is mainly attributed to extensive damage or death of intestinal epithelial cells, along with abnormal activation or impaired death regulation of immune cells and the release of various inflammatory factors, which contribute to the inflammatory environment in the intestines. Thus, maintaining intestinal homeostasis hinges on balancing the survival and functionality of various cell types. Programmed cell death (PCD) pathways, including apoptosis, pyroptosis, autophagy, ferroptosis, necroptosis, and neutrophil extracellular traps, are integral in the pathogenesis of IBD by mediating the death of intestinal epithelial and immune cells. Natural products derived from plants, fruits, and vegetables have shown potential in regulating PCD, offering preventive and therapeutic avenues for IBD. This article reviews the role of natural products in IBD treatment by focusing on targeting PCD pathways, opening new avenues for clinical IBD management.

Triton X-100 enhanced antibacterial effect of photodynamic therapy against Enterococcus faecalis infection: an in vitro study.

Photodynamic therapy (PDT) is an effective method for bacterial infection control in root canals of teeth with a broad-spectrum antibacterial activity. However, its application in root canal treatment is limited due to its inefficiency under hypoxic conditions and dentin staining. Triton X-100 (TX) shows great potential in enhancing the efficiency of antimicrobial agents through improving bacterial membrane permeability. The present study employed a combination of toluidine blue O (TB)-mediated PDT with TX to target the Enterococcus faecalis (E. faecalis), a bacterium with strong resistance to various antibacterial agents and mostly detected in infected root canals. PDT combined with TX showed enhanced antibacterial efficiency against both planktonic cells and biofilms of E. faecalis. At the same time, TX enhanced the antibacterial effect in dentinal tubules and reduced the incubation time. Mechanism studies revealed that TX improved reactive oxygen species (ROS) production through increasing the proportion of TB monomers. Additionally, increased membrane permeability and wettability were also observed. The findings demonstrated the PDT combined with TX could be used as a highly effective method for the root canal disinfection of teeth.

Triton X-100 counteracts antibiotic resistance of Enterococcus faecalis: An in vitro study.

OBJECTIVES: The high prevalence of antibiotic-resistant bacteria poses a threat to the global public health. The appropriate use of adjuvants to restore the antimicrobial activity of antibiotics against resistant bacteria could be an effective strategy for combating antibiotic resistance. In this study, we investigated the counteraction of Triton X-100 (TX-100) and the mechanisms underlying the antibiotic resistance of Enterococcus faecalis (E. faecalis). METHODS: Standard, wild-type (WT), and induced antibiotic-resistant E. faecalis strains were used in this study. In vitro antibacterial experiments were conducted to evaluate the antimicrobial activities of gentamicin sulfate and ciprofloxacin hydrochloride in the presence and absence of 0.02 % TX-100 against both planktonic and biofilm bacteria. Transcriptomic and untargeted metabolomic analyses were performed to explore the molecular mechanisms of TX-100 as an antibiotic adjuvant. Additionally, membrane permeability, membrane potential, glycolysis-related enzyme activity, intracellular adenosine triphosphate (ATP), and expression levels of virulence genes were assessed. The biocompatibility of different drug combinations was also evaluated. RESULTS: A substantially low TX-100 concentration improved the antimicrobial effects of gentamicin sulfate or ciprofloxacin hydrochloride against antibiotic-resistant E. faecalis. Mechanistic studies demonstrated that TX-100 increased cell membrane permeability and dissipated membrane potential. Moreover, antibiotic resistance and pathogenicity of E. faecalis were attenuated by TX-100 via downregulation of the ABC transporter, phosphotransferase system (PTS), and ATP supply. CONCLUSIONS: TX-100 enhanced the antimicrobial activity of gentamicin sulfate and ciprofloxacin hydrochloride at a low concentration by improving antibiotic susceptibility and attenuating antibiotic resistance and pathogenicity of E. faecalis. CLINICAL SIGNIFICANCE: These findings provide a theoretical basis for developing new root canal disinfectants that can reduce antibiotic resistance.