ProJect: a powerful mixed-model missing value imputation method.

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_C, 27.37% in RC_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_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_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.

A novel approach to the analysis of Overall Survival (OS) as response with Progression-Free Interval (PFI) as condition based on the RNA-seq expression data in The Cancer Genome Atlas (TCGA).

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.

Controllable and Low-Loss Electrochemiluminescence Waveguide Supported by a Micropipette Electrode.

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.

Mass spectrometry-based metabolomics: a guide for annotation, quantification and best reporting practices.

Mass spectrometry-based metabolomics approaches can enable detection and quantification of many thousands of metabolite features simultaneously. However, compound identification and reliable quantification are greatly complicated owing to the chemical complexity and dynamic range of the metabolome. Simultaneous quantification of many metabolites within complex mixtures can additionally be complicated by ion suppression, fragmentation and the presence of isomers. Here we present guidelines covering sample preparation, replication and randomization, quantification, recovery and recombination, ion suppression and peak misidentification, as a means to enable high-quality reporting of liquid chromatography- and gas chromatography-mass spectrometry-based metabolomics-derived data.

Causal effects of genetically determined metabolites and metabolite ratios on esophageal diseases: a two-sample Mendelian randomization study.

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.

Development of a super-hydrophilic anaerobic tube for the optimization of platelet-rich fibrin.

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.

Why was the study done?   Direct anaerobic environment effects on fibrin formation have been insufficiently studied.The effect of hydrophilic change caused by nitrogen plasma treatment on H-PRF coagulation has not been fully studied.Optimal preparation of H-PRF in patients with poor coagulation function was needed in clinical application.What is new?  The coagulation of H-PRF correlated with the level of dissolved oxygen concentrations. Anaerobic environment significantly accelerates fibrin formation and platelet activation.Nitrogen plasma treatment can remarkably enhance the hydrophilicity of the inner surface of glass blood collecting tubes, thereby promoting the activation of platelets and the formation of fibrin network.The H-PRF prepared in the tubes with anaerobic environment and hydrophilic surface showed high fracture strength, promoted collagen synthesis of gingival fibroblast and the mineralization of osteoblasts.What is the impact?  The work is aimed at developing super-hydrophilic anaerobic plasmatrix tubes (SHAP tubes) for studying gas environment and hydrophilicity participation in fibrin formation in H-PRF preparation and investigating the influence of platelet activation in the anaerobic environment.This study provides a successful trial to convert the physiological process into biotechnological application. The SHAP tubes proposed within this article was an effective versatile H-PRF preparation device, which provided a promising alternative for tissue engineering.

Effect of implant shape and length on the accuracy of robot-assisted immediate implant surgery: An in vitro study.

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.

Correlation between pupillary size and depth of focus after the implantation of extended depth of focus intraocular lenses.

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).

Influence of dental implant clinical experience on the accuracy of robot-assisted immediate implant placement: an in vitro study.

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.

Timing of Caffeine Ingestion Does Not Improve Three-Point Shooting Accuracy in College Basketball Players.

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.

The impact of hyperkalemia on ICU admission and mortality: a retrospective study of Chinese emergency department data.

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.

Effect of force direction and impaction angulation during dilaceration impacted central incisor traction: a finite element analysis.

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.

Therapeutic Effects of Valeriana jatamansi on Ulcerative Colitis: Insights into Mechanisms of Action through Metabolomics and Microbiome Analysis.

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.

Natural variation of Alfin-like family affects seed size and drought tolerance in rice.

The Alfin-like (AL) family is a group of small plant-specific transcriptional factors involved in abiotic stresses in dicotyledon. In an early study, we found an AL gene in rice that was associated with grain yield under drought stress. However, little information is known about the AL family in rice. In this study, AL genes in the rice genome were identified, and the OsAL proteins were found to locate in the nucleus and have no transcriptional self-activation activity. The expression of the OsALs was regulated by different environmental stimulations and plant hormones. Association and domestication analysis revealed that natural variation of most OsALs was significantly associated with yield traits, drought resistance and divergence in grain size in indica and japonica rice varieties. Hap1 of OsAL7.1 and Hap7 of OsAL11 were favorable haplotypes of seed weight and germination under osmotic stress. Furthermore, osal7.1 and osal11 mutants have larger seeds and are more sensitive to abscisic acid and mannitol during germination stage. Overexpressing of OsAL7.1 and OsAL11 in rice weakened the tolerance to drought in the adult stage. Thus, our work provides informative knowledge for exploring and harnessing haplotype diversity of OsALs to improve yield stability under drought stress.

Detecting Submicromolar Analytes in Mixtures with a 5 min Acquisition on 600 MHz NMR Spectrometers.

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 1H-13C HSQC 2D-NMR (PRISE-NUS-HSQC). We introduced two 13CH3 tags for each analyte to respectively increase the 1H and 13C 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 1H-13C 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.

Gold Microbeads Enabled Proximity Electrochemiluminescence for Highly Sensitive and Size-Encoded Multiplex Immunoassays.

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.

Nanocages and cell-membrane display technology as smart biomaterials.

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.

Two Purely Inorganic Cationic Tellurite Materials Based on Group IB Metal Tetrafluoroborates with Similar Lamellar Cationic Layers: [Cu2F(Te2O5)](BF4) and [Ag18O2(Te4O9)4(Te3O8)(BF4)2]·2HBF4.

Two new purely inorganic cationic tellurite networks of Group IB metal-based tetrafluoroborates, namely, [Cu2F(Te2O5)](BF4), 1, and [Ag18O2(Te4O9)4(Te3O8)(BF4)2]·2HBF4, 2, have been hydrothermally synthesized under mild conditions. The prepared materials have been characterized by single-crystal X-ray diffraction, powder X-ray diffraction, IR and Raman spectroscopy, SEM-energy-dispersive spectroscopy, UV-vis-NIR diffuse reflectance, magnetic study, and TG analyses. Single-crystal diffraction studies show that both materials have similar cationic Cu/Ag tellurite layers with tetrafluoroborates as interlamellar charge-balancing anions. Magnetic results indicate that [Cu2F(Te2O5)](BF4), 1, exhibits a mainly short-range antiferromagnetic ordering within the 2D layer, and further detailed analysis of magnetic susceptibility analysis confirms a spin-singlet ground state with an energy gap of 85 K.

CIL-ExPMRM: An Ultrasensitive Chemical Isotope Labeling Assisted Pseudo-MRM Platform to Accelerate Exposomic Suspect Screening.

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.

Comparative microcomputed tomography and histological analysis of the effects of a horizontal platelet-rich fibrin bone block on maxillary sinus augmentation: A preclinical in vivo study.

BACKGROUND: While suggested to be effective in tissue regeneration, the effects of horizontal platelet-rich fibrin (H-PRF) bone block in sinus augmentation have not been verified in an animal model. METHODS: A total of 12 male New Zealand white rabbits that underwent sinus augmentation were divided into two groups: deproteinized bovine bone mineral (DBBM) only and H-PRF bone block. H-PRF was prepared at 700 × g for 8 min using a horizontal centrifuge. The H-PRF bone block was prepared by mixing 0.1 g DBBM with H-PRF fragments and then adding liquid H-PRF. Samples were collected after 4 and 8 weeks and analyzed using microcomputed tomography (micro-CT) for vertical bone gain of the sinus, bone volume/total volume (BV/TV) percentage, trabecular number (Tb.N), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp). Then, histological analyses were performed to investigate new blood vessels, material residue, bone formation and osteoclasts. RESULTS: Higher vertical bone gain of the sinus floor, BV/TV percentage, Tb.Th, and Tb.N and lower Tb.Sp were found in the H-PRF bone block group at both time points compared with the DBBM group. Higher amounts of new blood vessels and more osteoclasts were found in the H-PRF bone block group than in the DBBM group at both time points, especially in the regions close to the bone plate. More new bone formation and less material residue were observed in the H-PRF bone block group at 8 weeks. CONCLUSIONS: H-PRF bone block showed greater potential for sinus augmentation by promoting angiogenesis, bone formation and bone remodeling in a rabbit model.