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Background: Esophageal diseases (ED) are a kind of common diseases of upper digestive tract. Previous studies have proved that metabolic disorders are closely related to the occurrence and development of ED. However, there is a lack of evidence for causal relationships between metabolites and ED, as well as between metabolite ratios representing enzyme activities and ED. Herein, we explored the causality of genetically determined metabolites (GDMs) on ED through Mendelian Randomization (MR) study., Methods: Two-sample Mendelian randomization analysis was used to assess the causal effects of genetically determined metabolites and metabolite ratios on ED. A genome-wide association analysis (GWAS) encompassing 850 individual metabolites along with 309 metabolite ratios served as the exposures. Meanwhile, the outcomes were defined by 10 types of ED phenotypes, including Congenital Malformations of Esophagus (CME), Esophageal Varices (EV), Esophageal Obstructions (EO), Esophageal Ulcers (EU), Esophageal Perforations (EP), Gastroesophageal Reflux Disease (GERD), Esophagitis, Barrett's Esophagus (BE), Benign Esophageal Tumors (BETs), and Malignant Esophageal Neoplasms (MENs). The standard inverse variance weighted (IVW) method was applied to estimate the causal relationship between exposure and outcome. Sensitivity analyses were carried out using multiple methods, including MR-Egger, Weighted Median, MR-PRESSO, Cochran's Q test, and leave-one-out analysis. P < 0.05 was conventionally considered statistically significant. After applying the Bonferroni correction for multiple testing, a threshold of P < 4.3E-05 (0.05/1159) was regarded as indicative of a statistically significant causal relationship. Furthermore, metabolic pathway analysis was performed using the web-based MetaboAnalyst 6.0 software., Results: The findings revealed that initially, a total of 869 candidate causal association pairs ( P ivw < 0.05) were identified, involving 442 metabolites, 145 metabolite ratios and 10 types of ED. However, upon applying the Bonferroni correction for multiple testing, only 36 pairs remained significant, involving 28 metabolites (predominantly lipids and amino acids), 5 metabolite ratios and 6 types of ED. Sensitivity analyses and reverse MR were performed for these 36 causal association pairs, where the results showed that the pair of EV and 1-(1-enyl-palmitoyl)-2-linoleoyl-GPE (p-16:0/18:2) did not withstand the sensitivity tests, and Hexadecenedioate (C16:1-DC) was found to have a reverse causality with GERD. The final 34 robust causal pairs included 26 metabolites, 5 metabolite ratios and 5 types of ED. The involved 26 metabolites predominantly consisted of methylated nucleotides, glycine derivatives, sex hormones, phospholipids, bile acids, fatty acid dicarboxylic acid derivatives, and N-acetylated amino acids. Furthermore, through metabolic pathway analysis, we uncovered 8 significant pathways that played pivotal roles in five types of ED conditions., Conclusions: This study integrated genomics with metabolomics to assess causal relationships between ED and both metabolites and metabolite ratios, uncovering several key metabolic features in ED pathogenesis. These findings have potential as novel biomarkers for ED and provide insights into the disease's etiology and progression. However, further clinical and experimental validations are necessary., (© 2024. The Author(s).)

Background: Overall Survival (OS) and Progression-Free Interval (PFI) as survival times have been collected in The Cancer Genome Atlas (TCGA). It is of biomedical interest to consider their dependence in pathway detection and survival prediction. We intend to develop novel methods for integrating PFI as condition based on parametric survival models for identifying pathways associated with OS and predicting OS., Results: Based on the framework of conditional probability, we developed a family of frailty-based parametric-models for this purpose, with exponential or Weibull distribution as baseline. We also considered two classes of existing methods with PFI as a covariate. We evaluated the performance of three approaches by analyzing RNA-seq expression data from TCGA for lung squamous cell carcinoma and lung adenocarcinoma (LUNG), brain lower grade glioma and glioblastoma multiforme (GBMLGG), as well as skin cutaneous melanoma (SKCM). Our focus was on fourteen general cancer-related pathways. The 10-fold cross-validation was employed for the evaluation of predictive accuracy. For LUNG, p53 signaling and cell cycle pathways were detected by all approaches. Furthermore, three approaches with the consideration of PFI demonstrated significantly better predictive performance compared to the approaches without the consideration of PFI. For GBMLGG, ten pathways (e.g., Wnt signaling, JAK-STAT signaling, ECM-receptor interaction, etc.) were detected by all approaches. Furthermore, three approaches with the consideration of PFI demonstrated better predictive performance compared to the approaches without the consideration of PFI. For SKCM, p53 signaling pathway was detected only by our Weibull-baseline-based model. And three approaches with the consideration of PFI demonstrated significantly better predictive performance compared to the approaches without the consideration of PFI., Conclusions: Based on our study, it is necessary to incorporate PFI into the survival analysis of OS. Furthermore, PFI is a survival-type time, and improved results can be achieved by our conditional-probability-based approach., (© 2024. The Author(s).)

Objectives: To reveal the force profiles recorded by haptic autonomous robotic force feedback during the transcrestal sinus floor elevation (TSFE) process, providing a reference for the surgery strategy during TSFE., Materials and Methods: A total of 42 maxillary sinus models with different angles of the sinus floor (30°, 40°, 50°, 60°, 70°, 80°, and 90°, compared to vertical plane) were 3D printed. Implant site preparation was performed using a robotic system, and the total force (Ft) and axial force along the drill (Fz) during the surgery were recorded by the haptic robotic arm. The actual initial breakthrough point (drill contacting sinus floor) and complete breakthrough point (drill penetrating the sinus floor) were defined visually (the actual IBP and the actual CBP). The theoretical initial breakthrough point (the theoretical IBP) and the theoretical complete breakthrough point (the theoretical CBP) defined by the robot-guided system and the CBCT were determined by real-time force feedback and imaging distance measurement, respectively. The distance from the bottom of the resin model to the actual IBP and the actual CBP was defined as Di and Dt, respectively., Results: The difference in Fz began to increase significantly at 70°, while the difference in Ft became significant at 60°. When the angle was greater than 70°, there was no significant difference in the discrepancy between the actual and theoretical perforation points. Compared to judging the breakthrough point by CBCT, real-time force feedback TSFE under robotic surgery achieved more accurate initial breakthrough point detection., Conclusions: The smaller the angle, the larger the breakthrough force for the drill. The real-time force feedback of haptic robotic system during TSFE could provide reliable reference for dentists. More clinical studies are needed to further validate the application of robotic surgery assisted TSFE., (© 2024 Wiley Periodicals LLC.)

Ovarian cancer (OC) is one of the most common malignancies and a leading cause of death among women worldwide. The ubiquitin pathway plays an important role in OC development. Using the single nucleotide polymorphism data obtained using the prevalence and dominance strategies, four ubiquitin marker genes were identified according to their expression levels: BARD1, BRCA2, FANCA, and BRCA1. Based on these four genes, a consensus clustering of OC expression data was performed. The significant differences in the survival analysis, ESTIMATE, and CIBERSORT results among the clusters indicated the pivotal role of these four genes in OC development. Of the ubiquitin-representative genes in each cluster, two ubiquitin genes, TOP2A and MYLIP , were identified in the survival risk model after univariate survival, Least Absolute Shrinkage and Selection Operator regression, and multivariate survival analyses. The reliability and robustness of both the training and validation data were confirmed by comparing the significant survival difference between high- and low-risk patients. We further explored the association between our risk model and clinical outcomes as well as predicted potentially interacting drugs. The co-expression network showed clear interactions among the four marker genes and two model genes and between high- and low-risk differentially expressed genes. Significantly enriched genes were found in pathways associated with ion channels, channel activity, and neuroactive ligand-receptor interactions. Therefore, suggesting the involvement of ubiquitin genes in the survival and development of OC through neurohumoral regulation. Our results will provide valuable reference or supplementary information for studies investigating OC diagnosis and therapies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objectives: To assess the accuracy and effectiveness among operators with different levels of experience in a robot-assisted immediate implant surgery., Materials and Methods: The study included four participants who had received dental training at the same institution but have varying levels of clinical experience in implant dentistry, denoted as undergraduate student (UG), dental resident (DR), specialist with no robot experience (IS) and specialist with robot experience (RS). Following comprehensive theoretical training in robot-assisted implant operation, each operator participated in five robotic-assisted implant procedures at 21 sites, resulting in the implant surgery of a total of 20 implants. Subsequently, the accuracy of the implants was assessed by analyzing the preoperative planning and the postoperative CBCT scans, and the time required for each procedure was also recorded., Results: Angular deviation in UG, DR, IS and RS group was 0.82 ± 0.27°, 0.55 ± 0.27°, 0.83 ± 0.27°, and 0.56 ± 0.36°, respectively. The total deviation of the implant platform point was 0.28 ± 0.10 mm, 0.26 ± 0.16 mm, 0.34 ± 0.08 mm and 0.31 ± 0.06 mm, respectively. The total deviation of the apical point was 0.30 ± 0.08 mm, 0.25 ± 0.18 mm, 0.31 ± 0.09 mm, and 0.31 ± 0.05 mm, respectively. The time spent was 10.37 ± 0.57 min, 10.56 ± 1.77 min, 9.93 ± 0.78 min, and 11.76 ± 0.78 min for each operator. As the number of operations increased, the operation time decreased, but there was no significant difference in implant accuracy between the different groups., Conclusions: Within the scope of this study, robot-assisted implant surgery demonstrated high accuracy, with no significant differences in performance between operators with varying levels of clinical experience or implant robot-user experience. Furthermore, the learning curve for robotic implant surgery is steep and consistent., Clinical Relevance: Robot-assisted implant surgery demonstrates consistent high accuracy across operators of varying clinical and robotic experience levels, highlighting its potential to standardize procedures and enhance predictability in clinical outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The prediction of sepsis, especially early diagnosis, has received a significant attention in biomedical research. In order to improve current medical scoring system and overcome the limitations of class imbalance and sample size of local EHR (electronic health records), we propose a novel knowledge-transfer-based approach, which combines a medical scoring system and an ordinal logistic regression model., Materials and Methods: Medical scoring systems (i.e. NEWS, SIRS and QSOFA) are generally robust and useful for sepsis diagnosis. With local EHR, machine-learning-based methods have been widely used for building prediction models/methods, but they are often impacted by class imbalance and sample size. Knowledge distillation and knowledge transfer have recently been proposed as a combination approach for improving the prediction performance and model generalization. In this study, we developed a novel knowledge-transfer-based method for combining a medical scoring system (after a proposed score transformation) and an ordinal logistic regression model. We mathematically confirmed that it was equivalent to a specific form of the weighted regression. Furthermore, we theoretically explored its effectiveness in the scenario of class imbalance., Results: For the local dataset and the MIMIC-IV dataset, the VUS (the volume under the multi-dimensional ROC surface, a generalization measure of AUC-ROC for ordinal categories) of the knowledge-transfer-based model (ORNEWS) based on the NEWS scoring system were 0.384 and 0.339, respectively, while the VUS of the traditional ordinal regression model (OR) were 0.352 and 0.322, respectively. Consistent analysis results were also observed for the knowledge-transfer-based models based on the SIRS/QSOFA scoring systems in the ordinal scenarios. Additionally, the predicted probabilities and the binary classification ROC curves of the knowledge-transfer-based models indicated that this approach enhanced the predicted probabilities for the minority classes while reducing the predicted probabilities for the majority classes, which improved AUCs/VUSs on imbalanced data., Discussion: Knowledge transfer, which combines a medical scoring system and a machine-learning-based model, improves the prediction performance for early diagnosis of sepsis, especially in the scenarios of class imbalance and limited sample size., Competing Interests: Declaration of competing interest None, (Copyright © 2024. Published by Elsevier Ltd.)

Horizontal platelet-rich fibrin (H-PRF) contains a variety of bioactive growth factors and cytokines that play a key role in the process of tissue healing and regeneration. The blood collection tubes used to produce Solid-PRF (plasmatrix (PM) tubes) have previously been shown to have a great impact on the morphology, strength and composition of the final H-PRF clot. Therefore, modification to PM tubes is an important step toward the future optimization of PRF. To this end, we innovatively modified the inner wall surface of the PM tubes with plasma and adjusted the gas environment inside the PM tubes to prepare super-hydrophilic anaerobic plasmatrix tubes (SHAP tubes). It was made anaerobic for the preparation of H-PRF with the aim of improving mechanical strength and bioactivity. The findings demonstrated that an anaerobic environment stimulated platelet activation within the PRF tubes. After compression, the prepared H-PRF membrane formed a fibrous cross-linked network with high fracture strength, ideal degradation characteristics, in addition to a significant increase in size. Thereafter, the H-PRF membranes prepared by the SHAP tubes significantly promoted collagen synthesis of gingival fibroblast and the mineralization of osteoblasts while maintaining excellent biocompatibility, and advantageous antibacterial properties. In conclusion, the newly modified PRF tubes had better platelet activation properties leading to better mechanical strength, a longer degradation period, and better regenerative properties in oral cell types including gingival fibroblast and alveolar osteoblasts. It also improves the success rate of H-PRF preparation in patients with coagulation dysfunction and expands the clinical application scenario.

Background: Disseminated tumor cells (DTCs) are thought to be the initiators of tumor recurrence and metastasis. However, based on the current imaging examination methods, early detection of DTCs is extremely difficult due to their small number and dormant state., Methods: We used the SE-iFISH approach to detect bone marrow DTCs (mDTCs) in patients with breast or prostate cancer, and compared it with various imaging examination methods to explore its role in predicting metastasis and prognosis., Results: Fifteen patients were enrolled in this study. Among them, 11 patients showed imaging-confirmed bone metastases in different sites of the body, of which seven patients had iliac mDTCs and signs of iliac bone metastases on imaging. For the remaining four patients, imaging confirmed that the bone metastatic foci were far from the ilium, but in one patient, mDTCs were detected in the ilium. Interestedly, iliac mDTCs were also detected in two out of four patients who had no sign of bone metastases on imaging. Furthermore, the epithelial marker, CK18, was ubiquitously expressed in mDTCs, but its expression was very low in peripheral circulating tumor cells (pCTCs). The Kaplan-Meier plot suggested that CK18+ mDTCs ≥ 5 was related to poor overall survival (OS) compared with that of CK18+ mDTCs < 5 in breast cancer patients (median OS: 22.1 vs. 46.9 months; log-rank, p = 0.035)., Conclusions: SE-iFISH examination for mDTCs is more sensitive than the conventional methods used for detecting bone metastases. mDTC detection facilitated the early finding of tumor cells in the bone marrow and ≥5 CK18+ mDTCs was associated with a poor prognosis in breast cancer patients.

Objective: 5-aminolevulinic acid (5-ALA) is a precursor of the photosensitizer Protoporphyrin IX (PpIX) and photodynamic therapy (PDT) with 5-ALA has been used in clinical practice. However, tumor cellular hypoxia severely affects the efficiency of photodynamic therapy. In this study, photodynamic therapy was combined with tirapazamine to investigate the effects of the combined intervention and the related mechanisms it may involve., Methods: Colony formation assays were used to demonstrate cell proliferation. Transwell assays were performed to observe the effect on cell invasion and metastasis after the corresponding intervention. DCFH-DA probe was used to detect the reactive oxygen species content. Flow cytometry was used to detect the effects of the interventions on apoptosis and cell cycle. The relevant pathways that may be involved are explored by examining the expression levels of the relevant proteins and genes., Results: Colony formation assays indicated that the combined intervention inhibited cell proliferation. Transwell assays demonstrated that PDT combined with TPZ effectively inhibited tumor cell invasion and metastasis. In addition, fluorescence intensity generated by DCFH-DA oxidation was detected indicating that the combined intervention increased the formation of reactive oxygen species. Flow cytometry clearly showed that the combination of PDT and TPZ further increased apoptosis and cell cycle arrest. The results of western blotting and qRT-PCR experiments confirmed that the combination therapy inhibited HIF-1α/VEGF axis and the PI3K/Akt/mTOR pathway activation., Conclusion: 5-ALA-PDT combined with TPZ can inhibit cell proliferation, increase apoptosis, and inhibit the PI3K/Akt/mTOR pathway, thus inhibiting tumor growth and metastasis and improving anti-cancer effects., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The effects of traction forces at different angles on impacted central incisors(ICI)with varying inverted angles (IA) may be different. The objective of this study was to analyze the biomechanical effects of different force directions (FD) on developmentally inverted ICI with multi-angle variations and to offer insights and guidance for the treatment of inverted ICI., Methods: Three-dimensional finite element method was employed to simulate clinical scenarios of inverted ICI traction. As such, 0.2 N of force (direction: antero-superior angles of 90°, 100°, 110°, 120°, and 130° relative to the long axis of the inverted ICI crown) was applied to the inverted ICI with inverse angles (IA) of 40°, 30°, 20°, 10° and 0°. Inverted ICI apical displacement and Von Mises stress on periodontal ligament (PDL) and alveolar bone were compared., Results: IA and FD showed minimal influence on the stress distribution in the PDL, as higher stresses were concentrated in the apical region. The higher stresses in the alveolar bone are focused on the cervical and apical regions of the tooth. In particular, IA exerts a more significant impact on stress distribution in the alveolar bone than FD. The influence of IA on the apical displacement of inverted ICI is larger than that of FD., Conclusions: To promote the health of the root and periodontal tissues, it is recommended to use an angle of 100°-110° relative to the long axis of the ICI crown when dealing with a large IA (> 20°) developmentally inverted ICI. Conversely, an angle of 110°-120° can be used., (© 2024. The Author(s).)

Purpose: To compare corneal biomechanical properties and intraocular pressure (IOP) measurements in patients who underwent Descemet's stripping with endothelial keratoplasty (DSEK) with those of the follow healthy eyes., Methods: In this retrospective comparative study, a total of 35 eyes of 35 patients who underwent DSEK by a single surgeon from 2015.02 to 2019.12 were enrolled along with their fellow healthy eyes. Corneal biomechanical parameters were assessed at least 3 months post-DSEK using Corneal Visualization Scheimpflug Technology (CST). IOP was measured by CST, Goldmann applanation tonometry (GAT), and MacKay-Marg tonometer., Results: Central corneal thickness (CCT) and stiffness parameter at first applanation (SP-A1) were significantly increased after DSEK when compared to the fellow eyes. In DSEK eyes, biomechanically-corrected intraocular pressure (bIOP) and MacKay-Marg IOP correlated significantly with GAT IOP measurements, with bIOP showed the lowest IOP values. All the IOP values did not correlate with CCT. However, GAT-IOP and MacKay-Marg IOP showed a positive correlation with SP-A1., Conclusion: The corneal stiffness increased after DSEK. Central corneal thickness may have less influence than corneal biomechanics on IOP measurements in eyes after DSEK. Biomechanically-corrected IOP obtained by CST seemed to be lower than other tonometry techniques in DSEK eyes, perhaps because of correction for corneal stiffness, CCT and age., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Wu, Tian, Li, Hong, Wang and Xu.)

Purpose: To evaluate whether depth of focus after the implantation of extended depth of focus (EDoF) intraocular lenses (IOLs) correlates with pupillary size., Methods: This retrospective case series study evaluated eyes undergoing cataract surgery with implantation of EDoF IOLs. At least one month postoperatively, the depth of focus (DoF) was measured to determine the correlation with pupillary size, age, anterior chamber depth (ACD), axial length (AXL), and corneal spherical aberrations (SA)., Results: The study evaluated 64 eyes of 49 patients. The mean depth of focus was 2.67 diopters (D). The mean preoperative photopic pupil size was 3.36 mm. A significant negative association was found between preoperative photopic pupil size and depth of focus (r = 0.30, Pearson's correlation coefficient) and between preoperative mesopic pupil size and depth of focus (r = 0.274, Pearson's correlation coefficient)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This study assesses the influence of hyperkalemia on both disease severity and the risk of mortality among patients admitted to the emergency room., Methods: This retrospective observational study utilized data from the Chinese Emergency Triage Assessment and Treatment database (CETAT, version 2.0), which was designed to evaluate and optimize management strategies for emergency room (ER) patients. Patients were systematically categorized based on serum potassium levels. Relationships between serum potassium levels, risk of mortality, and the severity of illness were then analyzed using multifactorial logistic regression and through Receiver Operating Characteristic (ROC) analysis. The effectiveness of various treatments at lowering potassium levels was also investigated., Results: 12,799 emergency patients were enrolled, of whom 20.1% (n = 2,577) were hypokalemic and 2.98% (n = 381) were hyperkalemic. Among hyperkalemic patients, the leading reasons for visiting the ER were altered consciousness 23.88% (n = 91), cardiovascular symptoms 22.31% (n = 85), and gastrointestinal symptoms 20.47% (n = 78). Comparative analysis with patients exhibiting normal potassium levels revealed hyperkalemia as an independent factor associated with mortality in the ER. Mortality risk appears to positively correlate with increasing potassium levels, reaching peaks when blood potassium levels ranged between 6.5 and 7.0. Hyperkalemia emerged as a strong predictor of death in the ER, with an Area Under the Curve (AUC) of 0.89. The most frequently prescribed treatment for hyperkalemia patients was diuretics (57.32%, n = 188), followed by intravenous sodium bicarbonate (50.91%, n = 167), IV calcium (37.2%, n = 122), insulin combined with high glucose (27.74%, n = 91), and Continuous Renal Replacement Therapy (CRRT) for 19.82% (n = 65). Among these, CRRT appeared to be the most efficacious at reducing potassium levels. Diuretics appeared relatively ineffective, while high-glucose insulin, sodium bicarbonate, and calcium preparations having no significant effect on the rate of potassium decline., Conclusion: Hyperkalemia is common in emergency situations, especially among patients with altered consciousness. There is a strong positive correlation between the severity of hyperkalemia and mortality risk. CRRT appears to be the most effective potassium reducting strategy, while the use of diuretics should be approached with caution., (© 2024. The Author(s).)

ABSTRACT Designed to meet the specific needs of the printing industry exhaust gas emissions, this paper proposes a method for the degradation of gaseous acetic acid ester organics that is environmentally friendly, safe, and simple to use: micro-nano cavitation technology. In the process of using micro-nano cavitation technology to degrade acetic acid ester organics, the products in the degradation process were analyzed by gas chromatography-mass (GC-MS) spectrometry, and the degradation pathways of acetic acid ester organics were identified. Under high temperatures and high pressure caused by cavitation collapse, the C-C bond and C-O bond on the main chain of organic matter are cleaved to form low molecular products. Low-molecular intermediate products are continuously produced as the reaction advances, and these intermediate products are further oxidized and decomposed into carbon dioxide and water. Besides, the factors that influence the degradation rate of acetic acid ester organics were investigated. Based on the experimental data, acetic acid esters can degrade with the greatest efficiency when their initial concentration is 200 ± 50 mg/m 3 and their treatment time is 20∼30 min. Moreover, the experiment was optimized using the response surface method. The results suggested that for an initial concentration of 155.544 mg/m 3 and a reaction time of 21.961 min, the best degradation rate was 0.251 min -1 . Micro-nano cavitation technology is a novel and promising technology for the degradation of volatile organic compounds, with a wide range of practical applications.

Objective: This study aims to develop a compound biomaterial to achieve effective soft tissue regeneration., Methodology: Compound hyaluronic acid (CHA) and liquid horizontal-platelet-rich fibrin (H-PRF) were mixed at a ratio of 1:1 to form a CHA-PRF gel. Human gingival fibroblasts (HGFs) were used in this study. The effect of CHA, H-PRF, and the CHA-PRF gel on cell viability was evaluated by CCK-8 assays. Then, the effect of CHA, H-PRF, and the CHA-PRF gel on collagen formation and deposition was evaluated by qRT‒PCR and immunofluorescence analysis. Finally, qRT‒PCR, immunofluorescence analysis, Transwell assays, and scratch wound-healing assays were performed to determine how CHA, H-PRF, and the CHA-PRF gel affect the migration of HGFs., Results: The combination of CHA and H-PRF shortened the coagulation time of liquid H-PRF. Compared to the pure CHA and H-PRF group, the CHA-PRF group exhibited the highest cell proliferation at all time points, as shown by the CCK-8 assay. Col1a and FAK were expressed at the highest levels in the CHA-PRF group, as shown by qRT‒PCR. CHA and PRF could stimulate collagen formation and HGF migration, as observed by fluorescence microscopy analysis of COL1 and F-actin and Transwell and scratch healing assays., Conclusion: The CHA-PRF group exhibited greater potential to promote soft tissue regeneration by inducing cell proliferation, collagen synthesis, and migration in HGFs than the pure CHA or H-PRF group. CHA-PRF can serve as a great candidate for use alone or in combination with autografts in periodontal or peri-implant soft tissue regeneration.

Periodontitis, a chronic oral disease instigated by bacteria, severely compromises human oral health. The prevailing clinical treatment for periodontitis involves mechanical scraping in conjunction with antibiotics. Phototherapy is employed to rapidly remove the bacteria and achieve periodontitis treatment, effectively circumventing the adverse effects associated with traditional therapies. Constructing 2D/2D van der Waals (VDW) heterojunctions is a key strategy for obtaining excellent photocatalytic activity. Herein, a 2D/2D violet phosphorus (VP)/Ti 3 C 2 VDW heterojunction is designed using an interfacial engineering strategy. By constructing an electron transport "bridge" (P-Ti bond) at the heterogeneous interface as an effective transfer channel for photogenerated carriers, a compact monolithic structure between the VP and Ti 3 C 2 phases is formed, and the spatial barrier for electron transfer at the interface is eliminated. Meanwhile, the strong directional built-in electric field induced by the intensive electron-coupling effect at the heterogeneous interface served as an internal driving force, which greatly accelerates the exciton dissociation and charge transfer in the photocatalytic process. These excited photogenerated electrons and holes are trapped by O 2 and H 2 O on the surfaces of Ti 3 C 2 and VP, respectively, and are subsequently catalytically converted to antibacterial reactive oxygen species (ROS). The VP/Ti 3 C 2 VDW heterojunction eradicated 97.5% and 98.48% of Staphylococcus aureus and Escherichia coli , respectively, by photocatalytic and photothermal effects under visible light for 10 min. The VP/Ti 3 C 2 nanoperiodontal dressing ointment effectively attenuated inflammatory response, reduced alveolar bone resorption, and promoted periodontal soft and hard tissue repair. Its periodontitis therapeutic effect outperforms the clinically used Periocline.

Background: Patients with obstructive sleep apnea hypopnea syndrome (OSAHS) combined with resistant hypertension (RH) have a high risk of developing primary aldosteronism (PA). This study investigated the aldosterone-renin ratio (ARR), plasma aldosterone concentration (PAC), and plasma renin activity (PRA) to determine the optimal cutoff values for PA diagnosis in patients with OSAHS combined with RH., Methods: Patients diagnosed with moderate and severe OSAHS combined with RH were recruited from the inpatient clinic of the Department of Endocrinology at Ji'an Central Hospital between October 2020 and April 2023. The included patients were divided into PA and no-PA groups. Diagnostic accuracy measures were calculated for each group, and receiver operating characteristic (ROC) curves were generated., Results: A total of 241 patients were included, of which 103 had positive ARR screening results in the diagnostic accuracy analysis and 66 were diagnosed with PA. PAC and ARR showed moderate predictive capacity for PA, with area under the curve (AUC) values of 0.66 [95% confidence interval (CI): 0.55-0.77] and 0.72 (95% CI: 0.63-0.82), respectively, while PRA exhibited a limited predictive capacity (AUC = 0.51, 95% CI: 0.40-0.63). Using 45 as the optimal cutoff value for ARR, the sensitivity was 86% and the specificity was 52%. The optimal cutoff value for PAC was 17, with a sensitivity of 78% and a specificity of 55%. Notably, in patients with severe OSAHS, ARR at screening demonstrated significant predictive value for PA, with an AUC of 0.84 (95% CI: 0.72-0.96), a sensitivity of 85%, and a specificity of 76%. Conversely, in patients with moderate OSAHS, only ARR demonstrated significant predictive value for PA diagnosis, while PAC did not demonstrate notable diagnostic value., Conclusion: ARR and PAC are initial screening tools for PA, facilitating early detection, particularly in low-resource settings. In patients with OSAHS and RH, the ARR and PAC thresholds for PA diagnosis may require more stringent adjustment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Yan, Zou, Li, Zeng, He, Guo, Wang, Zheng, Fu, Wang, Peng, Zhou, Luo, Luo, Li, Liu, Hu and Shen.)

Ethnopharmacological Relevance: Aconitum carmichaelii is widely used in traditional Chinese medicine clinics as a bulk medicinal material. It has been used in China for more than two thousand years. Nevertheless, the stems and leaves of this plant are usually discarded as non-medicinal parts, even though they have a large biomass and exhibit therapeutic properties. Thus, it is crucial to investigate metabolites of different parts of Aconitum carmichaelii and explore the relationship between metabolites and toxicity to unleash the utilization potential of the stems and leaves., Aim of the Study: Using plant metabolomics, we aim to correlate different metabolites in various parts of Aconitum carmichaelii with toxicity, thereby screening for toxicity markers. This endeavor seeks to offer valuable insights for the development of Aconitum carmichaelii stem and leaf-based applications., Materials and Methods: UHPLC-Q-Orbitrap MS/MS-based plant metabolomics was employed to analyze metabolites of the different parts of Aconitum carmichaelii. The cardiotoxicity and hepatotoxicity of the extracts from different parts of Aconitum carmichaelii were also investigated using zebrafish as animal model. Toxicity markers were subsequently identified by correlating toxicity with metabolites., Results: A total of 113 alkaloids were identified from the extracts of various parts of Aconitum carmichaelii, with 64 different metabolites in stems and leaves compared to daughter root (Fuzi), and 21 different metabolites in stems and leaves compared to mother root (Wutou). The content of aporphine alkaloids in the stems and leaves of Aconitum carmichaelii is higher than that in the medicinal parts, while the content of the diester-diterpenoid alkaloids is lower. Additionally, the medicinal parts of Aconitum carmichaelii exhibited cardiotoxicity and hepatotoxicity, while the stems and leaves have no obvious toxicity. Finally, through correlation analysis and animal experimental verification, mesaconitine, deoxyaconitine, and hypaconitine were used as toxicity markers., Conclusion: Given the low toxicity of the stems and leaves and the potential efficacy of aporphine alkaloids, the stems and leaves of Aconitum carmichaelii hold promise as a valuable medicinal resource warranting further development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Gut microbes supporting body growth are known but the mechanisms are less well documented. Using the microbial tryptophan metabolite indole, known to regulate prokaryotic cell division and metabolic stress conditions, we mono-colonized germ-free (GF) mice with indole-producing wild-type Escherichia coli ( E. coli ) or tryptophanase-encoding tnaA knockout mutant indole-non-producing E. coli . Indole mutant E. coli mice showed multiorgan growth retardation and lower levels of glycogen, cholesterol, triglycerides, and glucose, resulting in an energy deficiency despite increased food intake. Detailed analysis revealed a malfunctioning intestine, enlarged cecum, and reduced numbers of enterochromaffin cells, correlating with a metabolic phenotype consisting of impaired gut motility, diminished digestion, and lower energy harvest. Furthermore, indole mutant mice displayed reduction in serum levels of tricarboxylic acid (TCA) cycle intermediates and lipids. In stark contrast, a massive increase in serum melatonin was observed-frequently associated with accelerated oxidative stress and mitochondrial dysfunction. This observational report discloses functional roles of microbe-derived indoles regulating multiple organ functions and extends our previous report of indole-linked regulation of adult neurogenesis. Since indoles decline by age, these results imply a correlation with age-linked organ decline and levels of indoles. Interestingly, increased levels of indole-3-acetic acid, a known indole metabolite, have been shown to correlate with younger biological age, further supporting a link between biological age and levels of microbe-derived indole metabolites. The results presented in this resource paper will be useful for the future design of food intervention studies to reduce accelerated age-linked organ decline.

Introduction: Variable partners and breakpoints have been reported in patients with ROS1-rearranged NSCLC. Here, we investigated the association of fusion partners and breakpoints with crizotinib efficacy in NSCLCs with common ROS1 fusions., Methods: DNA and RNA next-generation sequencing (NGS) and immunohistochemistry were performed to characterize ROS1 fusions., Results: Using DNA NGS, we identified ROS1 fusions in 210 cases, comprising 171 common (CD74/EZR/TPM3/SDC4/SLC34A2-ROS1) and 39 uncommon (variants identified in <5%) ROS1 fusion cases. DNA NGS detected variable ROS1 genomic breakpoints in common ROS1 fusions, whereas RNA NGS found ROS1 breakpoints mainly occurring in exons 32, 34 and 35, resulting in long (exon 32) and short (exon 34 or 35) ROS1 fusions. ROS1 immunohistochemistry revealed that membranous and cytoplasmic staining was predominant in long ROS1 fusions, whereas cytoplasmic staining was predominant in short ROS1 fusions (p = 0.006). For patients who received first-line crizotinib, median progression-free survival (mPFS) was lower in patients with long ROS1 fusions than those with short ROS1 fusions (8.0 versus 24.0 mo, p = 0.006). Moreover, mPFS for patients with and without TP53 mutations was 8.0 and 19.0 months, respectively (p = 0.159); mPFS for patients with and without BIM deletion polymorphism was 5.0 and 22.0 months, respectively (p = 0.003). When analyzing together with fusion partners, patients with long CD74/SLC34A2-ROS1 fusions were found to have shorter PFS than those with other ROS1, regardless of the presence or absence of TP53 mutations (p < 0.001 and p = 0.002, respectively)., Conclusions: Long CD74/SLC34A2-ROS1 fusions, which retain transmembrane regions in ROS1 and fusion partners, are associated with poor response to crizotinib independent of TP53 mutations., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

The demands of intensified aquaculture production and escalating disease prevalence underscore the need for efficacious probiotic strategies to enhance fish health. This study focused on isolating and characterising potential probiotics from the gut microbiota of the emerging aquaculture species jade perch (Scortum barcoo). Eighty-seven lactic acid bacteria and 149 other bacteria were isolated from the digestive tract of five adult jade perch. The screening revealed that 24 Enterococcus hirae isolates inhibited the freshwater pathogens Aeromonas sobria and Streptococcus iniae. Co-incubating E. hirae with the host gut suspensions demonstrated a two- to five-fold increase in the size of growth inhibition zones compared to the results when using gut suspensions from tilapia (a non-host), indicating host-specificity. Genome analysis of the lead isolate, E. hirae R44, predicted the presence of antimicrobial compounds like enterolysin A, class II lanthipeptide, and terpenes, which underlay its antibacterial attributes. Isolate R44 exhibited desirable probiotic characteristics, including survival at pH values within the range of 3 to 12, bile tolerance, antioxidant activity, ampicillin sensitivity, and absence of transferable antimicrobial resistance genes and virulence factors commonly associated with hospital Enterococcus strains (IS16, hylEfm, and esp). This study offers a foundation for sourcing host-adapted probiotics from underexplored aquaculture species. Characterisation of novel probiotics like E. hirae R44 can expedite the development of disease mitigation strategies to support aquaculture intensification., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Osteomyelitis is primarily caused by bacterial infections, and treatment requires precise sequential therapy, including antibacterial therapy in the early stages and bone defect reconstruction in later stages. We aimed to synthesize core-shell-structured zinc oxide/silver sulfide heterogeneous nanoparticles (ZnO/Ag 2 S NPs) using wet chemical methods. Using density functional theory and ultraviolet photoelectron spectroscopy, we showed that the optimized band structure endowed ZnO/Ag 2 S NPs with photodynamic properties under near-infrared (NIR) irradiation. Moreover, ZnO/Ag 2 S NPs exhibited a distinguished and stable photothermal performance within the same wavelength range. With single-wavelength irradiation, ZnO/Ag 2 S NPs achieved a bifunctional antibacterial effect during the acute stage of osteomyelitis. Antibacterial action was confirmed through colony-forming unit (CFU) counting assays, scanning electronic microscopy (SEM) observations, live-dead staining, growth curves, and quantitative real-time polymerase chain reaction (qPCR) assays. The Ag 2 S coating on the NPs realized the sustained release of zinc ions, thereby controlling the zinc ion concentration. Alkaline phosphatase (ALP) staining, alizarin red S (ARS) staining, and qPCR assays confirmed that the ZnO/Ag 2 S NPs exhibited good osteogenic effects in vitro . These effects were verified in an in vivo mouse femur model during chronic stages using micro-computed tomography (micro-CT) and histological analysis. This study provides a novel biocompatible core-shell nanomaterial for the two-phase treatment of osteomyelitis, contributing to versatile nanotherapies for infections and inflammation.

Objectives: To compare the accuracy of immediate implant placement of cylindrical implants (CI) and tapered implants (TI) of different lengths using a robotic dental implant system., Materials and Methods: CI and TI of three lengths (8, 10, and 12 mm) each were digitally planned and placed in a three-dimensional printed extraction socket model under robotic guidance. There were six groups with three samples in each group, resulting in a total of 18 samples. Implant angular deviation, platform point deviation (total, lateral, depth), and implant apical point deviation (total, lateral, depth) were recorded and compared between the different groups., Results: The angular deviations for CI 8 mm, CI 10 mm, CI 12 mm, TI 8 mm, TI 10 mm, and TI 12 mm were 1.32° ± 0.19°, 1.03° ± 0.56°, 1.31° ± 0.38°, 1.27° ± 0.64°, 1.10° ± 0.43° and 1.05° ± 0.45°, respectively. The total deviations of platform and apical points for CI 8 mm, CI 10 mm, CI 12 mm, TI 8 mm, TI 10 mm, and TI 12 mm were 0.79 ± 0.18 mm, 0.77 ± 0.33 mm; 0.64 ± 0.21 mm, 0.55 ± 0.17 mm; 0.64 ± 0.37 mm, 0.65 ± 0.34 mm; 0.68 ± 0.26 mm, 0.71 ± 0.20 mm; 0.70 ± 0.12 mm, 0.66 ± 0.23 mm; and 0.71 ± 0.15 mm, 0.77 ± 0.29 mm, respectively, and had no significant differences., Conclusions: Within the limitation of this study, acceptable accuracy can be achieved for both TI and CI using robotic systems. Our study demonstrated that the implant shape and length did not affect the accuracy of immediate implant placement under robotic guidance in vitro. However, further trials are required to confirm their efficacy in clinical practice., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Curcumin (CUR), a natural compound extracted from turmeric, has shown potential as a photosensitizer in photodynamic therapy (PDT). The aim of this work was to enhance the efficacy of CUR by modifying it using titanium dioxide (TiO 2 ) nanoparticles and a cationic polymer called Sofast to create a nanocomposite TiO 2 -CUR-Sofast (TCS). Compared to unmodified CUR, TCS exhibited a broadening toward longer wavelength in the absorption wavelength within the 400-550 nm range, leading to improved CUR absorption. Cellular uptake efficiency of TCS was also enhanced, and it demonstrated nearly 4.7-fold higher reactive oxygen species (ROS) generation than CUR. Furthermore, TCS displayed the ability to attach to the cell membrane and enter cells within a 30-min incubation period. Upon irradiation, TCS exhibited remarkable cytotoxicity, resulting in a significant reduction in the viability of various cancer cells. Autofluorescence lifetime imaging of intracellular reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD) enzymes indicated that cancer cells treated with TCS and irradiation undergo a metabolic pathway shift from oxidative phosphorylation to glycolysis. These findings highlight the potential of TCS as an effective PDT agent for cancer treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

One-dimensional molecular crystal waveguide (MCW) can transmit self-generated electrochemiluminescence (ECL), but heavy optical loss occurs because of the small difference in the refractive index between the crystal and its surroundings. Herein, we report a micropipette electrode-supported MCW (MPE/MCW) for precisely controlling the far-field transmission of ECL in air with a low optical loss. ECL is generated from one terminal of the MCW positioned inside the MPE, which is transmitted along the MCW to the other terminal in air. In comparison with conventional waveguides on solid substrates or in solutions, the MPE/MCW is propitious to the total internal reflection of light at the MCW/air interface, thus confining the ECL efficiently in MCW and improving the waveguide performance with an extremely low-loss coefficient of 4.49 × 10 -3 dB μm -1 . Moreover, by regulation of the gas atmosphere, active and passive waveguides can be resolved simultaneously inside MPE and in air. This MPE/MCW offers a unique advantage of spatially controlling and separating ECL signal readout from its generation, thus holding great promise in biosensing without or with less electrical/chemical disturbance.

Gold nanocages (AuNCs) have been invented and developed over two decades as biomaterial in clinical medicine with great application potential. AuNCs have a characteristic structure of porous walls with hollow interior and a compact size. This makes it possible for them to transport biomolecules or drugs with the advantages of their photothermal effects that could help further destroy germs or tumors while also regulating the release of drugs inside. Furthermore, their bioactivity and application can be broadened by using cell-membrane display technology. AuNCs have shown tremendous potential in antibacterial activity, inflammation modulation, and tissue regeneration, which is required in periodontitis and peri-implantitis treatment. Thus, this article provides an overview of AuNCs synthesis, characteristics, surface modifications, and clinical applications, aiming to serve as a reference for the design and fabrication of AuNCs-based smart materials for periodontal or peri-implant application., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

RNA editing plays an extensive role in the initiation and progression of cancer. However, the overall profile and molecular functions of RNA editing in different ovarian cancer subtypes have not been fully characterized and elucidated. Here, we conducted a study on RNA editing in four cohorts of ovarian cancer subtypes through large-scale parallel reporting and bioinformatics analysis. Our findings revealed that RNA editing patterns exhibit subtype-specific characteristics within cancer subtypes. The expression pattern of ADAR and the number of differential editing sites varied under different conditions. CCOC and EOC exhibited significant editing deficiency, whereas HGSC and MOC displayed significant editing excess. The sites within the turquoise module of the coedited network also revealed their correlation with ovarian cancer. In addition, we identified an average of over 40,000 cis -edQTLs in the four subtypes. Finally, we explored the association between RNA editing and drug response, uncovering several potentially effective editing-drug pairs (EDP) and suggesting the conceivable utility of RNA editing sites as therapeutic targets for cancer treatment. Overall, our comprehensive study has identified and characterized RNA editing events in various subtypes of ovarian cancer, providing a new perspective for ovarian cancer research and facilitating the development of medical interventions and treatments., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

This study investigated the effects of the timing of caffeine (3 mg/kg body mass) ingestion on three-point shooting accuracy and other performance parameters during a basketball exercise simulation test (BEST). Eighteen college basketball players (mean ± SD: age = 24.4 ± 1.5 years, height = 181.7 ± 9.5 cm, body mass = 80.9 ± 13.2 kg) underwent one familiarization trial and three main conditions in a randomized order: (a) placebo (maltodextrin) and placebo, (b) caffeine and placebo, and (c) placebo and caffeine. Participants ingested either the placebo or caffeine pill 75 and 15 min before performing four quarters of the BEST and a three-point shooting protocol. During each quarter, participants completed 16 rounds of the BEST and ten three-point shots. Vertical jump height, 6 m sprint timing, BEST completion timing, three-point shooting accuracy, heart rate, rate of perceived exertion, blood glucose, blood lactate, and psychological measures pertaining to performance were measured. The BEST completion timing differed among conditions (placebo and placebo = 26.4 ± 2.0 s, caffeine and placebo = 25.8 ± 2.0 s, placebo and caffeine = 25.9 ± 2.1 s; p = .031) but not three-point shooting accuracy (placebo and placebo = 12.33 ± 4.10; caffeine and placebo = 12.61 ± 2.81; placebo and caffeine = 11.67 ± 3.77; p = .648), vertical jump height, or sprint times. Manipulating ingestion timing of caffeine did not improve three-point shooting accuracy, vertical jump height, or 6 m sprint timings, but caffeine can improve performance times during simulated basketball exercise irrespective of ingestion timing.

Objective: This study aims to investigate the relationship between serum vitamin D, total IgE levels and chronic spontaneous urticaria (CSU)., Methods: We collected data from 101 patients with chronic spontaneous urticaria (experimental group) and 115 healthy normal subjects (control group) in the same period of physical examination., Results: The results showed that the number of deficient and absolute deficient 25-hydroxyvitamin D in the experimental group was significantly lower than in the control group ( P < 0.05). Pearson correlation analysis showed that the activity score of CSU patients was negatively correlated with serum vitamin D ( r = -0.2278, P = 0.0220) and positively correlated with IgE ( r = 0.2078, P = 0.0380). It was observed that serum vitamin D in CSU patients was negatively correlated with their activity ( r = -0.2278, P = 0.0220) and positively correlated with age ( r = 0.2675, P = 0.0069). The Point-biserial correlation analysis revealed that gender was positively correlated with serum vitamin D (Pearson correlation coefficient = 0.286, P = 0.004) and UAS score (Pearson correlation coefficient = 0.273, P = 0.006). Ordinal logistic regression analysis showed that only serum vitamin D was correlated to activity scores ( P = 0.008). In addition to activity scores, age ( P = 0.005) and gender ( P = 0.04) were correlated to serum vitamin D., Conclusion: The activity score of CSU patients was negatively correlated with serum vitamin D and positively correlated with IgE. Serum vitamin D in CSU patients was negatively correlated with activity score and disease duration and positively correlated with age and gender., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Dermatology.)

Central carbon and energy metabolism are the most concerned metabolic pathways in 13 C-Metabolic flux analysis ( 13 C-MFA). However, some α-keto acids, ribonucleoside triphosphate (NTPs) and deoxyribonucleoside triphosphate (dNTPs) involved in central carbon and energy metabolism pathways were unstable or reactive, leading to inaccurate metabolic flux analysis. To achieve accurate 13 C-MFA of central carbon and energy metabolism, we proposed a dual strategy for the detection of 101 metabolites in glucose metabolism pathways. N-Methylphenylethylamine (MPEA) was utilized for derivatization of 4 carboxyl (α-keto acids) and 8 phosphate metabolites (NTPs and dNTPs). After derivatization, the MPEA derivatives were investigated to be stable for 4 weeks under 4 °C and detected with high intensity in ∼10 4  cells. On the other hand, we analyzed an additional 89 metabolites in central carbon and energy metabolic pathways were directly analyzed by liquid chromatography tandem mass spectrometry (LC-MRM-MS). The limit of detection (LODs) of our method were as low as 0.05 ng/mL and the linear range was at least two orders of magnitude with determination coefficient (R 2 ) > 0.9701. The relative standard divisions (RSDs) of intra- and inter-day of 95% metabolites were below 20%. In addition, the isotope list of 82 detected metabolites in central carbon and energy metabolism were generated according to isotopologues and isotopomers for each metabolite resulting from 13 C incorporation. Accurate assessment of mass isotopomer distributions (MIDs) of intracellular 13 C-labeled metabolites was achieved in [U- 13 C]-glucose cultured HepG2 cells by our dual strategy. Finally, we performed MID analysis of 101 metabolites in central carbon and energy metabolism. Overall, this dual method is reproducible and robust for application on 13 C-MFA and has a great potential for studying clinical isotope labeled samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The extra copy of the methyl-CpG-binding protein 2 (MeCp2) gene causes MeCP2 duplication syndrome (MDS), a neurodevelopmental disorder characterized by intellectual disability and autistic phenotypes. However, the disturbed microbiome and metabolic profiling underlying the autistic-like behavioral deficits of MDS are rarely investigated. Here we aimed to understand the contributions of microbiome disruption and associated metabolic alterations, especially the disturbed neurotransmitters in MDS employing a transgenic mouse model with MeCP2 overexpression. We analyzed metabolic profiles of plasma, urine, and cecum content and microbiome profiles by both 16 s RNA and shotgun metagenomics sequence technology. We found the decreased levels of Firmicutes and increased levels of Bacteroides in the single MeCP2 gene mutation autism-like mouse model, demonstrating the importance of the host genome in a selection of microbiome, leading to the heterogeneity characteristics of microbiome in MDS. Furthermore, the changed levels of several neurotransmitters (such as dopamine, taurine, and glutamate) implied the excitatory-inhibitory imbalance caused by the single gene mutation. Concurrently, a range of microbial metabolisms of aromatic amino acids (such as tryptophan and phenylalanine) were identified in different biological matrices obtained from MeCP2 transgenic mice. Our investigation revealed the importance of genetic variation in accounting for the differences in microbiomes and confirmed the bidirectional regulatory axis of microbiota-gut-brain in studying the role of microbiome on MDS, which could be useful in deeply understanding the microbiome-based treatment in this autistic-like disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Recently, liquid platelet-rich fibrin (PRF), a rich source of concentrated platelets and growth factors, has emerged as a promising agent for stimulating tissue regeneration. However, its specific efficacy in chondrocyte proliferation and cartilage regeneration remains underexplored. To address this question, we investigated liquid PRF obtained through horizontal centrifugation and compared its effects with hyaluronic acid (HA), a high molecular weight glucosamine supplement widely used in clinical practice to safeguard against chondral damage. Materials and Methods: Liquid PRF, produced using horizontal centrifugation (liquid H-PRF) at 500 g for 8 min, served as our experimental agent. We conducted cell viability and proliferation assays using PRF-conditioned medium. We assessed the chondrocyte phenotype of ATDC5 cells through toluidine blue and alcian blue staining, real-time polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescence staining. Furthermore, we examined the expression of genes involved in inflammation through RT-PCR and Western blot analysis. Results: Liquid H-PRF exerted notable effects on chondrocytes, influencing proliferation, inflammatory responses, and chondrogenic differentiation. The H-PRF group displayed significantly higher expression of chondrogenic markers, including Col2a1, compared to HA-treated cells, whereas aggrecan expression was significantly higher in the HA group. PRF also demonstrated the ability to reduce inflammatory levels in chondrogenic ATDC5 cells, and this effect was further enhanced when PRF from the buffy coat zone was added. In comparison, chondrocytes cultured in the HA group produced significantly fewer inflammatory factors than those in the PRF group, as confirmed qualitatively by Western blot analysis. Conclusion: Liquid H-PRF emerged as a potent stimulator for chondrogenesis and a regulator of the inflammatory response, achieving levels similar to HA. Moreover, liquid H-PRF exhibited strong potential for enhancing the production of cartilage extracellular matrix and promoting chondrogenic regeneration with notably increased Col2a1 levels. Future research should encompass animal studies and human trials to further evaluate the comparative effectiveness of liquid PRF versus HA, potentially as an alternative or complementary strategy for future clinical applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Xia, Zeng, Qiu, Wei, Cheng, Wang, Zhang, Ke, Miron and He.)

Backgroud: Regardless of application scenarios, proper mechanical characteristics and degradation properties are prerequisites for horizontal platelet rich fibrin (H-PRF) to manifest its ability. Among the methods used to modify PRF, thermal manipulation is promising as it is easy to handle without adding extra additives. Yet there is no consensus on optimal temperature treatment. This study aimed to investigate the effects of heating on the biological and mechanical characteristics of H-PRF and explore the optimum heating temperature for H-PRF thermal treatment., Methods: We employed a series of temperature gradients, room temperature, 50℃, 75℃, 90℃, 105℃. The microstructure and the mechanical properties were recorded by Scanning Electron Microscope (SEM) and tensile strength tests respectively. The degradation rate of H-PRF membranes was examined by digestion assay with plasmin and trypsin. The viability of cells within H-PRF membranes and the proliferation of osteoblasts cultured with extracts from different H-PRF groups was evaluated using CCK-8 assays., Results: Compared with the nonheated group, overheated manipulation beyond 90℃ can significantly prolong the degradation properties for up to 3 to 4 weeks and enhance the mass stress of H-PRF membranes. A high-temperature treatment of 105℃ accompanied by the cell activity beneath H-PRF reduced more than half, and thus, the biological effect on human osteoblasts (hFOBs) also reduced dramatically., Conclusions: High thermal manipulation can prolong the degradation properties and enhance the mechanical properties of PRF membranes accompanied by the loss of biological effect., (© 2023. The Author(s).)

Amino compounds are widely present in complex mixtures in chemistry, biology, medicine, food, and environmental sciences involving drug impurities and metabolisms of proteins, biogenic amines, neurotransmitters, and pyrimidine in biological systems. Nuclear magnetic resonance (NMR) spectroscopy is an excellent tool for simultaneously identifying and quantifying these in-mixture compounds but has a limit-of-detection (LOD) over several micromolarities (>5 μM). To break such a sensitivity barrier, we developed a sensitive and rapid method by combining the probe-induced sensitivity enhancement and nonuniform-sampling-based 1 H- 13 C HSQC 2D-NMR (PRISE-NUS-HSQC). We introduced two 13 CH 3 tags for each analyte to respectively increase the 1 H and 13 C abundances for up to 6 and 200 fold. This enabled high-resolution detection of 0.4-0.8 μM analytes in mixtures in 5 mm tubes with a 5 min acquisition on 600 MHz spectrometers. The method is much more sensitive and faster than traditional 1 H- 13 C HSQC methods (∼50 μM, >10 h). Using sulfanilic acid as a single reference, furthermore, we established a database covering chemical shifts and relative-response factors for >100 compounds, enabling reliable identification and quantification. The method showed good quantitation linearity, accuracy, precision, and applicability in multiple biological matrices, offering a rapid and sensitive approach for quantitative analysis of large cohorts of chemical, medicinal, metabolomic, food, and other mixtures.

Cervical cancer, the second most common female malignant tumor, seriously threatens women's health and lives. Despite the availability of the HPV vaccine, effective treatment options for cervical cancer are still lacking. New research perspectives now clarify that RNA editing dysregulation and changes in circRNA expression are jointly involved in disease pathogenesis, so molecular changes associated with circRNA and RNA editing may provide clues for the development of new therapeutic strategies for cervical cancer. In this study, we designed a series of pipelines to identify and analyze dysregulated RNA editing events in circRNAs. Our findings indicate a decrease in A-to-I RNA editing levels in cervical cancer compared to normal tissues, and editing may influence the back-splicing process of circRNAs through structural modifications of Alu elements. Moreover, our research reveals that RNA editing could modulate circRNA biogenesis by influencing RNA binding protein (RBP) binding on a transcriptome-wide scale, as well as influence the expression and coding potential of circRNAs. Importantly, we identified three RNA editing sites that could serve as potential biomarkers. In summary, our study presents a comprehensive landscape of RNA editing perturbations in circRNAs, providing new insights into the complex relationship between RNA editing and circRNA dysregulation in cervical cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Cardiometabolic diseases are associated with low-grade inflammation early in life and persists into old age. The long latency period presents opportunities for early detection, lifestyle modification and intervention. However, the performance of conventional biomarker assays to detect low-grade inflammation has been variable, particularly for early-stage cardiometabolic disorder including prediabetes and subclinical atherosclerotic vascular inflammation. During the last decade, the application of nuclear magnetic resonance (NMR) spectroscopy for metabolic profiling of biofluids in translational and epidemiological research has advanced to a stage approaching clinical application. Proton ( 1 H)-NMR profiling induces no destructible physical changes to specimens, and generates quantitative signals from deconvoluted spectra that are highly repeatable and reproducible. Apart from quantitative analysis of amino acids, lipids/lipoproteins, metabolic intermediates and small proteins, 1 H-NMR technology is unique in being able to detect composite signals of acute-phase and low-grade inflammation indicated by glycosylated acetyls (GlycA) and N-acetylneuraminic acid (sialic acid) moieties (GlycB). Different from conventional immunoassays that target epitopes and are susceptible to conformational variation in protein structure and binding, GlycA and GlycB signals are stable over time, and maybe complementary as well as superior to high-sensitivity C-reactive protein and other inflammatory cytokines. Here we review the physicochemical principles behind 1 H-NMR profiling of GlycA and GlycB, and the available evidence supporting their potential clinical application for the prediction of incident (pre)diabetes, cardiovascular disease, and adverse outcomes., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Neovascular age-related macular degeneration (AMD) is responsible for the majority of severe vision loss cases and is mainly caused by choroidal neovascularization (CNV). This condition persists or recurs in a subset of patients and regresses after 5 or more years of anti-vascular endothelial growth factor (VEGF) treatment. The precise mechanisms of CNV continue to be elucidated. According to our previous studies, macrophages play a critical role in CNV. Herein, we aimed to determine the morphological changes in macrophages in CNV to help us understand the dynamic changes., Methods: Mice were subjected to laser injury to induce CNV, and lesion expansion and macrophage transformation were examined by immunofluorescence and confocal analysis. Several strategies were used to verify the dynamic changes in macrophages. Immunofluorescence and confocal assays were performed on choroidal flat mounts to evaluate the morphology and phenotype of macrophages in different CNV phases, and the results were further verified by western blotting and RT-PCR., Results: The location of infiltrated macrophages changed after laser injury in the CNV mouse model, and macrophage morphology also dynamically changed. Branching macrophages gradually shifted to become round with the progression of CNV, which was certified to be an M2 phenotypic shift., Conclusions: Dynamic changes in macrophage morphology were observed during CNV formation, and the round-shaped M2 phenotype could promote neovascularization. In general, the changes in morphology we observed in this study can help us to understand the critical role of macrophages in CNV progression and exploit a potential treatment option for CNV indicated by a shift in macrophage polarity., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Long non-coding RNAs (LncRNAs) are non-protein coding transcripts more than 200 nucleotides in length. Deep sequencing technologies have unveiled lncRNAs can harbor translatable short open reading frames (sORFs). Yet the regulatory mechanisms governing lncRNA translation events remain poorly understood. Here, we exhaustively detected the sequence, functional element, and structure features relevant to lncRNA translation in human. Extensive identification and analysis reveal that translatable lncRNAs contain richer protein-coding related sequence features, cap-dependent and cap-independent translation initiation mechanisms, and more stable secondary structures, as compared to untranslatable lncRNAs. These findings strongly support lncRNAs serve as a repository for the production of new small peptides. Based on the feature fusion affecting translation and the extreme gradient boosting (XGBoost) algorithm, we developed the first computational tool that dedicated for predicting translatable lncRNAs, named TransLncPred. Benchmark experimental results show that our method outperforms several state-of-the-art RNA coding potential prediction tools on the same training and testing datasets. The 100-time 10-fold cross-validation tests also demonstrate that regulatory element-derived features, especially N7-methylguanosine (m7G) and internal ribosome entry site (IRES), contribute to the improvement in predictive performance., Competing Interests: Declaration of competing interest None Declared., (Copyright © 2023. Published by Elsevier Ltd.)

Background: The effects of horizontal platelet-rich fibrin (H-PRF) bone block on the healing and immune response during sinus augmentation have not been fully investigated histologically at early time points., Methods: Eighteenth male New Zealand white rabbits underwent bilateral sinus augmentation and were divided into two groups: deproteinized bovine bone mineral (DBBM) alone and H-PRF + DBBM (H-PRF bone block) group. Maxilla samples were collected at 3, 7 and 14 days post sinus augmentation procedures and analyzed using histological staining for the number of inflammatory cells, new blood vessels and evidence for early osteoclast bone turnover/remodeling. Furthermore, the effects of H-PRF bone blocks on the migration of osteoblasts and THP-1 macrophages were evaluated using a Transwell assay in vitro., Results: A higher number of immune cells were found in the H-PRF bone block group at 3 and 7 days post-surgery when compared to the DBBM alone group,most notably in the regions close to the mucosal lining and bone plates. Furthermore, a significantly greater number of new blood vessel formations and early signs of osteoclast development were found in the H-PRF bone block group at 14 days. The in vitro transwell assay further confirmed that culture medium from H-PRF bone block markedly promote the migration of osteoblasts and THP-1 macrophages., Conclusions: The findings from this study have shown that H-PRF bone block is capable of increasing early immune cell infiltration leading to the acceleration of neovascularization and speeding the process of bone metabolism in vivo following maxillary sinus grafting with DBBM., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Ulcerative colitis (UC), belonging to inflammatory bowel disease (IBD), is a chronic and relapsing inflammatory disorder of the gastrointestinal tract, which has not been completely cured in patients so far. Valeriana jatamansi is a Chinese medicine used clinically to treat "diarrhea," which is closely related to UC. This study was to elucidate the therapeutic effects of V. jatamansi extract (VJE) on dextran sodium sulfate (DSS)-induced UC in mice and its underlying mechanism. In this work, VJE effectively ameliorates the symptoms and histopathological scores and reduces the production of inflammatory factors in UC mice. The colon untargeted metabolomics analysis and 16S rDNA sequencing showed remarkable differences in colon metabolite profiles and intestinal microbiome composition between the control and DSS groups, and VJE intervention can reduce these differences. Thirty-two biomarkers were found and modulated the primary pathways including pyrimidine metabolism, arginine biosynthesis, and glutathione metabolism. Meanwhile, twelve significant taxa of gut microbiota were found. Moreover, there is a close relationship between endogenous metabolites and intestinal flora. These findings suggested that VJE ameliorates UC by inhibiting inflammatory factors, recovering intestinal maladjustment, and regulating the interaction between intestinal microbiota and host metabolites. Therefore, the intervention of V. jatamansi is a potential therapeutic treatment for UC.

Purpose: To explore clinical indicators to predict perceived pain during second-eye phacoemulsification surgery in patients with bilateral cataracts., Setting: Shanghai General Hospital, China., Design: A case‒control study and a prospective cohort study., Methods: Patients with age-related cataract who underwent first-eye or second-eye uneventful phacoemulsification surgery were enrolled. Before surgery, ocular examination results, including vessel area density (VAD) and vessel skeleton density (VSD), obtained by optical coherence tomography angiography examination of the iris were performed. Patients completed a visual analog scale pain survey 3 times postoperatively: 1 hour, 3 hours, and 24 hours postoperatively., Results: 70 patients were enrolled in the case‒control study, and the pain scores of the second-eye surgery group under local anesthesia were significantly greater than those of the first-eye surgery group ( P = .0005). Preoperative iris VAD in the second-eye group affected perioperative pain scores ( P = .0047). The optimal cutoff value of VAD was 0.2167 with a specificity of 76% and a sensitivity of 62%. In the prospective cohort study, 124 patients were included in the second-eye group. Preoperative iris VAD ( P = .0361) and the time interval ( P = .0221) were independent factors for second-eye surgery pain. Combined with preoperative iris VAD and surgical interval, the negative predictive value and positive predictive value were 0.95 and 0.29 for predicting moderate pain or above, the sensitivity and specificity were 0.97 and 0.23, respectively., Conclusions: The combination of iris VAD and the time interval between both eye surgeries can be an effective method to predict the timing of the second-eye cataract surgery and to avoid intraoperative pain., (Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Exposome is the future of next-generation environmental health to establish the association between environmental exposure and diseases. However, due to low concentrations of exposure chemicals, exposome has been hampered by lacking an effective analytical platform to characterize its composition. In this study, by combining the benefit of chemical isotope labeling and pseudo-multiple reaction monitoring (CIL-pseudo-MRM), we have developed one highly sensitive and high-throughput platform (CIL-ExPMRM) by isotope labeling urinary exposure biomarkers. Dansyl chloride (DnsCl), N -methylphenylethylamine (MPEA), and their isotope-labeled forms were used to derivatize polar hydroxyl and carboxyl compounds, respectively. We have programmed a series of scripts to optimize MRM transition parameters, curate the MRM database (>70,000 compounds), predict accurate retention time (RT), and automize dynamic MRMs. This was followed by an automated MRM peak assignment, peak alignment, and statistical analysis. A computational pipeline was eventually incorporated into a user-friendly website interface, named CIL-ExPMRM (http://www.exposomemrm.com/). The performance of this platform has been validated with a relatively low false positive rate (10.7%) across instrumental platforms. CIL-ExPMRM has systematically overcome key bottlenecks of exposome studies to some extent and outperforms previous methods due to its independence of MS/MS availability, accurate RT prediction, and collision energy optimization, as well as the ultrasensitivity and automated robust intensity-based quantification. Overall, CIL-ExPMRM has great potential to advance the exposomic studies based on urinary biomarkers.

Objectives: The aim of the present study was to compare the barrier function during bacterial invasion and wound healing properties of 3 commonly used membranes including horizontal platelet-rich fibrin (H-PRF) against two commercially available resorbable collagen membranes., Materials and Methods: H-PRF membranes were prepared by collecting venous blood from 3 healthy volunteers using a 700 g for 8-min centrifugation protocol followed by compression into membranes. To evaluate their barrier function, 3 groups (H-PRF membrane, collagen membrane A (Bio-Gide, Geistlich), collagen membrane B (Megreen, Shanxi Ruisheng Biotechnology Co) were placed between an inner chamber and outer chamber and inoculated with S. aureus. At 2 h, 24 h, and 48 h post-inoculation, cultures from the inner and outer chambers were assessed for bacterial CFUs. Then, scanning electron microscope (SEM) was utilized to visualized the morphological destruction by bacteria of the inner and outer surfaces of the membranes. To assess the wound healing properties of each membrane, leachates from each group were applied to human gingival fibroblasts (HGF) and a scratch assay was performed at 24 h and 48 h., Results: S. aureus showed a minimal bacterial attachment or invasion rate through either collagen membranes at 2 h post-inoculation, yet over time demonstrated rapid degradation, especially on the rougher surface. While PRF demonstrated higher number of CFUs after 2 h, no significant penetration/degradation of the H-PRF membranes was observed at 24 h and 48 h in the H-PRF group. Both collagen membranes demonstrated significant morphological changes 48 h post-bacterial innoculation, while minimal obvious morphological changes were observed in the H-PRF group. The wound healing assay also demonstrated significantly better wound closure rates in the H-PRF group., Conclusion: H-PRF membranes exhibited better barrier function towards S. aureus over 2 days of innoculation and better wound healing ability when compared to two commercially available collagen membranes., Clinical Relevance: This study provides further evidence for the application of H-PRF membranes during guided bone regeneration by minimizing bacterial invasion. Furthermore, H-PRF membranes have significantly better ability to promote wound healing., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The F-box protein 43 (FBXO43), also referred to as endogenous meiotic inhibitor 2 (EMI2), has been linked to the advancement of various types of cancer, such as hepatocellular carcinoma, breast cancer, cholangiocarcinoma, and gastric cancer. Nevertheless, the precise function of FBXO43 in colorectal cancer (CRC) remains unclear. This study employed data from The Cancer Genome Atlas (TCGA) and clinical specimens to analyze the expression, prognostic value, and chemotherapeutic advantages of FBXO43 in CRC., Methods: Level 3 RNA sequencing data pertaining to 631 cases of colon and rectal adenocarcinomas (COAD-READ) were downloaded from TCGA. The data were utilized to analyze the expression, prognosis, and related signal pathways of FBXO43. The expression of FBXO43 in clinical samples was subsequently confirmed through the use of real-time quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Lastly, a tissue microarray (TMA) consisting of 120 cases of CRC and corresponding normal tissues was established to investigate the relationship between FBXO43 and survival outcomes., Results: Results from both the TCGA analysis and clinical samples indicated that FBXO43 was significantly upregulated in CRC tissues in comparison to normal tissues. Moreover, high level of FBXO43 was found to be relevant to malignant clinical features, such as differentiation, lymph node metastasis, and pathological stage, as well as unfavorable prognosis in CRC patients. Subgroup analysis further demonstrated that FBXO43 could be an effective parameter for stratifying low-risk CRC patients. Notably, survival analysis showed that patients with high level of FBXO43 had worse overall survival (OS) and disease-free survival (DFS) following adjuvant chemotherapy, and FBXO43 was distinctly upregulated in chemotherapy-resistant patients' primary CRC tissues., Conclusions: FBXO43 was upregulated and associated with poor prognosis of CRC; patients with high expression of FBXO43 may not be benefit from adjuvant chemotherapy., Competing Interests: No potential conflicts of interest were disclosed., (Copyright 2023, Liu et al.)

Developing highly sensitive multiplex immunoassays is urgently needed to guide medical research and improve clinical diagnosis. Here, we report the proximity electrochemiluminescence (ECL) generation enabled by gold microbeads (GMBs) for improving the detection sensitivity and multiplexing capacity of ECL immunoassays (ECLIAs). As demonstrated by microscopy and finite element simulation, GMBs can function as spherical ultramicroelectrodes for triggering ECL reactions in solutions. Employing GMBs as solid carriers in the bead-based ECLIA, the electrochemical oxidation of a coreactant can occur at both the GMB surface and the substrate electrode, allowing the coreactant radicals to diffuse only a short distance of ∼100 nm to react with ECL luminophores that are labeled on the GMB surface. The ECL generation via this proximity low oxidation potential (LOP) route results in a 21.7-fold increase in the turnover frequency of ECL generation compared with the non-conductive microbeads that rely exclusively on the conventional LOP route. Moreover, the proximity ECL generation is not restricted by the diffusion distance of short-lived coreactant radicals, which enables the simultaneous determination of multiple acute myocardial infarction biomarkers using size-encoded GMB-based multiplex ECLIAs. This work brings new insight into the understanding of ECL mechanisms and may advance the practical use of multiplex ECLIAs.

Missing values (MVs) can adversely impact data analysis and machine-learning model development. We propose a novel mixed-model method for missing value imputation (MVI). This method, ProJect (short for Protein inJection), is a powerful and meaningful improvement over existing MVI methods such as Bayesian principal component analysis (PCA), probabilistic PCA, local least squares and quantile regression imputation of left-censored data. We rigorously tested ProJect on various high-throughput data types, including genomics and mass spectrometry (MS)-based proteomics. Specifically, we utilized renal cancer (RC) data acquired using DIA-SWATH, ovarian cancer (OC) data acquired using DIA-MS, bladder (BladderBatch) and glioblastoma (GBM) microarray gene expression dataset. Our results demonstrate that ProJect consistently performs better than other referenced MVI methods. It achieves the lowest normalized root mean square error (on average, scoring 45.92% less error in RC&#95;C, 27.37% in RC&#95;full, 29.22% in OC, 23.65% in BladderBatch and 20.20% in GBM relative to the closest competing method) and the Procrustes sum of squared error (Procrustes SS) (exhibits 79.71% less error in RC&#95;C, 38.36% in RC full, 18.13% in OC, 74.74% in BladderBatch and 30.79% in GBM compared to the next best method). ProJect also leads with the highest correlation coefficient among all types of MV combinations (0.64% higher in RC&#95;C, 0.24% in RC full, 0.55% in OC, 0.39% in BladderBatch and 0.27% in GBM versus the second-best performing method). ProJect's key strength is its ability to handle different types of MVs commonly found in real-world data. Unlike most MVI methods that are designed to handle only one type of MV, ProJect employs a decision-making algorithm that first determines if an MV is missing at random or missing not at random. It then employs targeted imputation strategies for each MV type, resulting in more accurate and reliable imputation outcomes. An R implementation of ProJect is available at https://github.com/miaomiao6606/ProJect., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Direct-infusion tandem mass spectrometry (DI-MS/MS) is an excellent tool for large cohort high-throughput quantitative metabolomics, MS imaging and single cell studies but incapable of discriminating isomers/isobars with similar MS spectral features. With experimental and density-functional theory (DFT) approaches, here, we comprehensively investigated the fragmentation pathways and characteristics of differential ion-mobility spectrometry (DMS) for three citrate isomers (citrate, isocitrate, glucaro-1,4-lactone) and an isobar (quinate) co-existing in biological sample such as urine. Results showed that all these compounds gave better MS spectra in negative-ion mode than positive-ion one and had numerous fragment ions under collision-induced dissociation (CID) with sequential losses of H 2 O and CO 2 . All observed fragment ions were assignable by combining experimental with DFT calculation results. A DI-DMS-MS/MS method was then developed to simultaneously quantify these four isomers/isobars with m/z 191-87 (CoV, -5.5 V), 191-73 (CoV, -3.5 V), 191-85 (CoV, -29.5 V) and m/z 191-93 (CoV, -41.5 V) for citrate, isocitrate, glucaro-1,4-lactone and quinate, respectively. The low limit-of-quantification was below 5.5 nM whilst accuracy was above 94% for all above compounds. The urinary concentrations of them in human and C57BL/6 mouse samples were further quantified showing clear inter-individual and inter-species level differences with significantly higher levels of isocitrate, glucaro-1,4-lactone and quinate in human urine samples than mouse ones. This provides an approach to understand the detailed fragmentation pathways for organic isomers/isobars and a high-throughput MS strategy to quantify them in complex mixtures for metabolomics, lipidomics, foodomics and exposomics especially when chromatographic separations are not useable., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)