Large-scale foundation model on single-cell transcriptomics.

Large pretrained models have become foundation models leading to breakthroughs in natural language processing and related fields. Developing foundation models for deciphering the 'languages' of cells and facilitating biomedical research is promising yet challenging. Here we developed a large pretrained model scFoundation, also named 'xTrimoscFoundationα', with 100 million parameters covering about 20,000 genes, pretrained on over 50 million human single-cell transcriptomic profiles. scFoundation is a large-scale model in terms of the size of trainable parameters, dimensionality of genes and volume of training data. Its asymmetric transformer-like architecture and pretraining task design empower effectively capturing complex context relations among genes in a variety of cell types and states. Experiments showed its merit as a foundation model that achieved state-of-the-art performances in a diverse array of single-cell analysis tasks such as gene expression enhancement, tissue drug response prediction, single-cell drug response classification, single-cell perturbation prediction, cell type annotation and gene module inference.

Dental Age Estimation in Northern Chinese Han Children and Adolescents Using Demirjian's Method Combined with Machine Learning Algorithms.

OBJECTIVES: To investigate the application value of combining the Demirjian's method with machine learning algorithms for dental age estimation in northern Chinese Han children and adolescents. METHODS: Oral panoramic images of 10 256 Han individuals aged 5 to 24 years in northern China were collected. The development of eight permanent teeth in the left mandibular was classified into different stages using the Demirjian's method. Various machine learning algorithms, including support vector regression (SVR), gradient boosting regression (GBR), linear regression (LR), random forest regression (RFR), and decision tree regression (DTR) were employed. Age estimation models were constructed based on total, female, and male samples respectively using these algorithms. The fitting performance of different machine learning algorithms in these three groups was evaluated. RESULTS: SVR demonstrated superior estimation efficiency among all machine learning models in both total and female samples, while GBR showed the best performance in male samples. The mean absolute error (MAE) of the optimal age estimation model was 1.246 3, 1.281 8 and 1.153 8 years in the total, female and male samples, respectively. The optimal age estimation model exhibited varying levels of accuracy across different age ranges, which provided relatively accurate age estimations in individuals under 18 years old. CONCLUSIONS: The machine learning model developed in this study exhibits good age estimation efficiency in northern Chinese Han children and adolescents. However, its performance is not ideal when applied to adult population. To improve the accuracy in age estimation, the other variables can be considered.

Age-related patterns in mandibular third molar eruption: presenting new forensic age assessment reference data from a Chinese population.

Valid reference data are essential for reliable forensic age assessment procedures in the living, a fact that extends to the trait of mandibular third molar eruption in dental panoramic radiographs (PAN). The objective of this study was to acquire valid reference data for a northern Chinese population. The study was guided by the criteria for reference studies in age assessment.To this end, a study population from China comprising 917 panoramic radiographs obtained from 430 females and 487 males aged between 15.00 and 25.99 years was analysed. Of the 917 PANs, a total of 1230 mandibular third molars were evaluated.The PANs, retrospectively evaluated, were performed for medical indication during the period from 2016 to 2021. The assessment of mandibular third molars was conducted using the staging scale presented by Olze et al. in 2012. Two independent examiners, trained in assessing PANs for forensic age estimation, evaluated the images. In instances where the two examiners diverged in their assessments these were subsequently deliberated, and a consensus stage was assigned.The mean age increased with higher stages for both teeth and both sexes. The minimum age recorded for stage D, indicating complete tooth eruption, was 15.6 years in females and 16.1 years in males. Consequently, the completion of mandibular third molar eruption was observed in both sexes well before reaching the age of 18. In light of our results, it is evident that relying solely on the assessment of mandibular third molar eruption may not be sufficient for accurately determining the age of majority. Contrary to previous literature, this finding of a completed eruption of the mandibular third molars in northern Chinese individuals is only suitable for detecting the completion of the 16th year of life in males according to our results. However, as the results are inconsistent compared to other studies in the literature, the trait should not be used as the only decisive marker to prove this age threshold in males from northern China.

The relevance of taurodontism in forensic dental age estimation.

Taurodontism is a dental morphological anomaly characterized by enlarged pulp cavities repositioned towards the apical region of the tooth, coupled with shortened root structures. Molars are commonly affected by this alteration. Certain populations exhibit up to 48% prevalences for this dental alteration, underscoring its significance in dental age estimation (DAE). In the field of DAE, an individual's chronological age is inferred from specific dental features, frequently employed within the forensic context. The effect of taurodontism on the features of DAE is an unanswered issue. The influence of taurodontism on eruption, mineralization, radiographic visibility of root canals, and radiographic visibility of the periodontal ligament space in mandibular third molars- some of the established criteria for DAE as examples-is currently not systematically examined. Some common staging scales for the dental features of DAE cannot technically be applied to taurodontic teeth. Additionally, given the association of taurodontism with syndromes affecting tooth development, caution is warranted in age assessment procedures. Notably, taurodontic teeth may serve as indicators of syndromes influencing skeletal development, further emphasizing the relevance of taurodontism in forensic age assessment. Presumably taurodontic teeth were included in reference data to some extent due to their partially high prevalence in the past, whereby the influence of taurodontism has been statistically absorbed within the overall spread of the features. Future studies should compare the temporal course of these tooth characteristics in affected and unaffected teeth. Subsequent initiatives should focus on raising awareness among forensic dentists regarding taurodontism, necessitating in-depth exploration of the subject.

Different machine learning methods based on maxillary sinus in sex estimation for northwestern Chinese Han population.

BACKGROUND & OBJECTIVE: Sex estimation is a critical aspect of forensic expertise. Some special anatomical structures, such as the maxillary sinus, can still maintain integrity in harsh environmental conditions and may be served as a basis for sex estimation. Due to the complex nature of sex estimation, several studies have been conducted using different machine learning algorithms to improve the accuracy of sex prediction from anatomical measurements. MATERIAL & METHODS: In this study, linear data of the maxillary sinus in the population of northwest China by using Cone-Beam Computed Tomography (CBCT) were collected and utilized to develop logistic, K-Nearest Neighbor (KNN), Support Vector Machine (SVM) and random forest (RF) models for sex estimation with R 4.3.1. CBCT images from 477 samples of Han population (75 males and 81 females, aged 5-17 years; 162 males and 159 females, aged 18-72) were used to establish and verify the model. Length (MSL), width (MSW), height (MSH) of both the left and right maxillary sinuses and distance of lateral wall between two maxillary sinuses (distance) were measured. 80% of the data were randomly picked as the training set and others were testing set. Besides, these samples were grouped by age bracket and fitted models as an attempt. RESULTS: Overall, the accuracy of the sex estimation for individuals over 18 years old on the testing set was 77.78%, with a slightly higher accuracy rate for males at 78.12% compared to females at 77.42%. However, accuracy of sex estimation for individuals under 18 was challenging. In comparison to logistic, KNN and SVM, RF exhibited higher accuracy rates. Moreover, incorporating age as a variable improved the accuracy of sex estimation, particularly in the 18-27 age group, where the accuracy rate increased to 88.46%. Meanwhile, all variables showed a linear correlation with age. CONCLUSION: The linear measurements of the maxillary sinus could be a valuable tool for sex estimation in individuals aged 18 and over. A robust RF model has been developed for sex estimation within the Han population residing in the northwestern region of China. The accuracy of sex estimation could be higher when age is used as a predictive variable.

Reversible non-volatile electronic switching in a near-room-temperature van der Waals ferromagnet.

Non-volatile phase-change memory devices utilize local heating to toggle between crystalline and amorphous states with distinct electrical properties. Expanding on this kind of switching to two topologically distinct phases requires controlled non-volatile switching between two crystalline phases with distinct symmetries. Here, we report the observation of reversible and non-volatile switching between two stable and closely related crystal structures, with remarkably distinct electronic structures, in the near-room-temperature van der Waals ferromagnet Fe5-δGeTe2. We show that the switching is enabled by the ordering and disordering of Fe site vacancies that results in distinct crystalline symmetries of the two phases, which can be controlled by a thermal annealing and quenching method. The two phases are distinguished by the presence of topological nodal lines due to the preserved global inversion symmetry in the site-disordered phase, flat bands resulting from quantum destructive interference on a bipartite lattice, and broken inversion symmetry in the site-ordered phase.

The Functional Study of Response Regulator ArlR Mutants in Staphylococcus Aureus.

Staphylococcus aureus is a major cause of hospital-associated infections worldwide. The organism's ability to form biofilms has led to resistance against current treatment options such as beta-lactams, glycopeptides, and daptomycin. The ArlRS two-component system is a crucial regulatory system necessary for S. aureus autolysis, biofilm formation, capsule synthesis, and virulence. This study aims to investigate the role of the arlR deletion mutant in the detection and activation of S. aureus. We created an arlR deleted mutant and complementary strains and characterized their impact on the strains using partial growth measurement. The quantitative real-time PCR was performed to determine the expression of icaA, and the microscopic images of adherent cells were captured at the optical density of 600 to determine the primary bacterial adhesion. The biofilm formation assay was utilized to investigate the number of adherent cells using crystal violet staining. Eventually, the Triton X-100 autolysis assay was used to determine the influence of arlR on the cell autolytic activities. Our findings indicate that the deletion of arlR reduced the transcriptional expression of icaA but not icaR in the ica operon, leading to decrease in polysaccharide intercellular adhesin (PIA) synthesis. Compared to the wild-type and the complementary mutants, the arlR mutant exhibited decreased in biofilm production but increased autolysis. It concluded that the S. aureus response regulatory ArlR influences biofilm formation, agglutination, and autolysis. This work has significantly expanded our knowledge of the ArlRS two-component regulatory system and could aid in the development of novel antimicrobial strategies against S. aureus.

"On/off"-switchable crosslinked PTX-nanoformulation with improved precise delivery for NSCLC brain metastases and restrained adverse reaction over nab-PTX.

Non-small cell lung cancer (NSCLC) brain metastases present a significant treatment challenge due to limited drug delivery efficiency and severe adverse reactions. In this study, we address these challenges by designing a "on/off" switchable crosslinked paclitaxel (PTX) nanocarrier, BPM-PD, with novel ultra-pH-sensitive linkages (pH 6.8 to 6.5). BPM-PD demonstrates a distinct "on/off" switchable release of the anti-cancer drug paclitaxel (PTX) in response to the acidic extratumoral microenvironment. The "off" state of BPM-PD@PTX effectively prevents premature drug release in the blood circulation, blood-brain barrier (BBB)/blood-tumor barrier (BTB), and normal brain tissue, surpassing the clinical PTX-nanoformulation (nab-PTX). Meanwhile, the "on" state facilitates precise delivery to NSCLC brain metastases cells. Compared to nab-PTX, BPM-PD@PTX demonstrates improved therapeutic efficacy with a reduced tumor area (only 14.6%) and extended survival duration, while mitigating adverse reactions (over 83.7%) in aspartate aminotransferase (AST) and alanine aminotransferase (ALT), offering a promising approach for the treatment of NSCLC brain metastases. The precise molecular switch also helped to increase the PTX maximum tolerated dose from 25 mg/kg to 45 mg/kg This research contributes to the field of cancer therapeutics and has significant implications for improving the clinical outcomes of NSCLC patients.

Mechanistic and biophysical characterization of polymyxin resistance response regulator PmrA in Acinetobacter baumannii.

Introduction: Acinetobacter baumannii PmrAB is a crucial two-component regulatory system (TCS) that plays a vital role in conferring resistance to polymyxin. PmrA, a response regulator belonging to the OmpR/PhoB family, is composed of a C-terminal DNA-binding effector domain and an N-terminal receiver domain. The receiver domain can be phosphorylated by PmrB, a transmembrane sensor histidine kinase that interacts with PmrA. Once phosphorylated, PmrA undergoes a conformational change, resulting in the formation of a symmetric dimer in the receiver domain. This conformational change facilitates the recognition of promoter DNA by the DNA-binding domain of PmrA, leading to the activation of adaptive responses. Methods: X-ray crystallography was carried out to solve the structure of PmrA receiver domain. Electrophoretic mobility shift assay and Isothermal titration calorimetry were recruited to validate the interaction between the recombinant PmrA protein and target DNA. Field-emission scanning electron microscopy (FE-SEM) was employed to characterize the surface morphology of A. baumannii in both the PmrA knockout and mutation strains. Results: The receiver domain of PmrA follows the canonical α5ß5 response regulator assembly, which undergoes dimerization upon phosphorylation and activation. Beryllium trifluoride is utilized as an aspartate phosphorylation mimic in this process. Mutations involved in phosphorylation and dimerization significantly affected the expression of downstream pmrC and naxD genes. This impact resulted in an enhanced cell surface smoothness with fewer modifications, ultimately contributing to a decrease in colistin (polymyxin E) and polymyxin B resistance. Additionally, a conservative direct-repeat DNA PmrA binding sequence TTTAAGNNNNNTTTAAG was identified at the promoter region of the pmrC and naxD gene. These findings provide structural insights into the PmrA receiver domain and reveal the mechanism of polymyxin resistance, suggesting that PmrA could be a potential drug target to reverse polymyxin resistance in Acinetobacter baumannii.

Sex estimation using maxillary sinus volume for Chinese subjects based on cone-beam computed tomography.

BACKGROUND: Sex estimate is a key stage in forensic science for identifying individuals. Some anatomical structures may be useful for sex estimation since they retain their integrity even after highly severe events. However, few studies are focusing on the Chinese population. Some researchers used teeth for sex estimation, but comparison with maxillary sinus were lack. As a result, the objective of this research is to develop a sex estimation formula for the northwestern Chinese population by the volume of the maxillary sinus and compare with the accuracy of sex estimation based on teeth through cone-beam computed tomography (CBCT). METHODS: CBCT images from 349 samples were used to establish and verify the formula. The volume of both the left and right maxillary sinuses was measured and examined for appropriate formula coefficients. To create the formula, we randomly picked 80% of the data as the training set and 20% of the samples as the testing set. Another set of samples, including 20 males and 20 females, were used to compare the accuracy of maxillary sinuses and teeth. RESULTS: Overall, sex estimation accuracy by volume of the left maxillary sinus can reach 78.57%, while by the volume of the right maxillary sinus can reach 74.29%. The accuracy for females, which can reach 91.43% using the left maxillary sinus, was significantly higher than that for males, which was 65.71%. The result also shows that maxillary sinus volume was higher in males. The comparison with the available results using measurements of teeth for sex estimation performed by our group showed that the accuracy of sex estimation using canines volume was higher than the one using maxillary sinus volume, the accuracies based on mesiodistal diameter of canine and first molar were the same or lower than the volume of maxillary sinus. CONCLUSIONS: The study demonstrates that measurement of maxillary sinus volume based on CBCT scans was an available and alternative method for sex estimation. And we established a method to accurately assess the sex of the northwest Chinese population. The comparison with the results of teeth measurements made the conclusion more reliable.

Bipolar outflows out to 10 kpc for massive galaxies at redshift z ≈ 1.

Galactic outflows are believed to play a critical role in the evolution of galaxies by regulating their mass build-up and star formation1. Theoretical models assume bipolar shapes for the outflows that extend well into the circumgalactic medium (CGM), up to tens of kiloparsecs (kpc) perpendicular to the galaxies. They have been directly observed in the local Universe in several individual galaxies, for example, around the Milky Way and M82 (refs. 2,3). At higher redshifts, cosmological simulations of galaxy formation predict an increase in the frequency and efficiency of galactic outflows owing to the increasing star-formation activity4. Galactic outflows are usually of low gas density and low surface brightness and therefore difficult to observe in emission towards high redshifts. Here we present an ultra-deep Multi-Unit Spectroscopic Explorer (MUSE) image of the mean Mg II emission surrounding a sample of galaxies at z ≈ 1 that strongly suggests the presence of outflowing gas on physical scales of more than 10 kpc. We find a strong dependence of the detected signal on the inclination of the central galaxy, with edge-on galaxies clearly showing enhanced Mg II emission along the minor axis, whereas face-on galaxies show much weaker and more isotropic emission. We interpret these findings as supporting the idea that outflows typically have a bipolar cone geometry perpendicular to the galactic disk. We demonstrate that this CGM-scale outflow is prevalent among galaxies with stellar mass M* ≳ 109.5M⊙.

Accuracy comparison of tooth volume and mesiodistal diameter measurements for sex dimorphism based on cone-beam computed tomography: a study for the northern Chinese population.

Sex estimation based on teeth could help to narrow the scope for individual identification. According to the different teeth morphology among both genders, we plan to establish a sex estimation method for the northern Chinese population through mesiodistal diameter and teeth volume measurements and compare the accuracy of the two methods. In this study, measurements were taken from cone-beam computed tomography images collected from 142 males and 140 females aged 21-59 years. The mesiodistal diameter and volume of the left canines and the first molars in both upper and lower jaws were measured and analyzed for suitable coefficients. We selected 80% samples as the training set to set up the logistic regression formulas and 20% as the test set to obtain accuracy. The accuracy of sex estimation by mesiodistal diameter can reach 87.50%, and the volume is up to 78.57%. The measurement of mesiodistal diameter is less time-consuming. This work established and tested a method to estimate sex for the northern Chinese population. Results showed that sex estimation based on the mesiodistal diameter of teeth has higher accuracy than the method based on teeth volume.

Determination of the preferred epitaxy for III-nitride semiconductors on wet-transferred graphene.

Transferred graphene provides a promising III-nitride semiconductor epitaxial platform for fabricating multifunctional devices beyond the limitation of conventional substrates. Despite its tremendous fundamental and technological importance, it remains an open question on which kind of epitaxy is preferred for single-crystal III-nitrides. Popular answers to this include the remote epitaxy where the III-nitride/graphene interface is coupled by nonchemical bonds, and the quasi-van der Waals epitaxy (quasi-vdWe) where the interface is mainly coupled by covalent bonds. Here, we show the preferred one on wet-transferred graphene is quasi-vdWe. Using aluminum nitride (AlN), a strong polar III-nitride, as an example, we demonstrate that the remote interaction from the graphene/AlN template can inhibit out-of-plane lattice inversion other than in-plane lattice twist of the nuclei, resulting in a polycrystalline AlN film. In contrast, quasi-vdWe always leads to single-crystal film. By answering this long-standing controversy, this work could facilitate the development of III-nitride semiconductor devices on two-dimensional materials such as graphene.

An Uncertainty-Aware and Sex-Prior Guided Biological Age Estimation From Orthopantomogram Images.

Bone age, as a measure of biological age (BA), plays an important role in a variety of fields, including forensics, orthodontics, sports, and immigration. Despite its significance, accurate estimation of BA remains a challenge due to the uncertainty error between BA and chronological age (CA) caused by individual diversity and the difficult integration of multiple factors, such as sex, and identified or measured anatomical structures, into the estimation process. To address problems, we propose an uncertainty-aware and sex-prior guided biological age estimation from orthopantomogram images (OPGs), named UASP-BAE, which models uncertainty errors while setting sex dimorphism as tractive features to enhance age-related specific features, aiming to improve the accuracy of BA estimation. Furthermore, considering the global relevance of the anatomic structure, such as the mandible, teeth, maxillary sinus, etc., a cross-attention module based on CNN and self-attention is proposed to mine the local texture and global semantic features of OPGs. Moreover, we design a novel age composition loss by cross-entropy, probability bias, and regression functions, aiming at evaluating BA's uncertainty errors and results to obtain an accurate and robust model. On 10703 OPGs from 5.00 to 25.00 years of age, our model had a best MAE value of 0.8005 years and higher than the comparison popular algorithms, which also demonstrates the method's potential for improved accuracy in BA estimation.

A semi-independent policies training method with shared representation for heterogeneous multi-agents reinforcement learning.

Humans do not learn everything from the scratch but can connect and associate the upcoming information with the exchanged experience and known knowledge. Such an idea can be extended to cooperated multi-reinforcement learning and has achieved its success on homogeneous agents by means of parameter sharing. However, it is difficult to straightforwardly apply parameter sharing when dealing with heterogeneous agents thanks to their individual forms of input/output and their diverse functions and targets. Neuroscience has provided evidence that our brain creates several levels of experience and knowledge-sharing mechanisms that not only exchange similar experiences but also allow for sharing of abstract concepts to handle unfamiliar situations that others have already encountered. Inspired by such a brain's functions, we propose a semi-independent training policy method that can well tackle the conflict between parameter sharing and specialized training for heterogeneous agents. It employs a shared common representation for both observation and action, enabling the integration of various input and output sources. Additionally, a shared latent space is utilized to maintain a balanced relationship between the upstream policy and downstream functions, benefiting each individual agent's target. From the experiments, it can approve that our proposed method outperforms the current mainstream algorithms, especially when handling heterogeneous agents. Empirically, our proposed method can also be improved as a more general and fundamental heterogeneous agents' reinforcement learning structure for curriculum learning and representation transfer. All our code is open and released on https://gitlab.com/reinforcement/ntype.

Structure and assembly of type VI secretion system cargo delivery vehicle.

Type VI secretion system is widely used in Gram-negative bacteria for injecting toxic effectors into neighboring prokaryotic or eukaryotic cells. Various effectors can be loaded onto the T6SS delivery tube via its core components: Hcp, VgrG, or PAAR. Here, we report 2.8-Å resolution cryo-EM structure of intact T6SS Hcp5-VgrG-PAAR cargo delivery system and crystal structure of unbound Hcp5 from B. fragilis NCTC 9343. Loading of Hcp5 hexameric ring onto VgrG causes expansion of its inner cavity and external surface, explaining how structural changes could be propagated to regulate co-polymerization and surrounding contractile sheath. High-affinity binding between Hcp and VgrG causes entropically unfavorable structuring of long loops. Furthermore, interactions between VgrG trimer and Hcp hexamer are asymmetric, with three of the six Hcp monomers exhibiting a major loop flip. Our study provides insights into the assembly, loading, and firing of T6SS nanomachine that contributes to bacterial inter-species competition and host interactions.

Mechanistic and structural insights into the bifunctional enzyme PaaY from Acinetobacter baumannii.

PaaY is a thioesterase that enables toxic metabolites to be degraded through the bacterial phenylacetic acid (PA) pathway. The Acinetobacter baumannii gene FQU82_01591 encodes PaaY, which we demonstrate to possess γ-carbonic anhydrase activity in addition to thioesterase activity. The crystal structure of AbPaaY in complex with bicarbonate reveals a homotrimer with a canonical γ-carbonic anhydrase active site. Thioesterase activity assays demonstrate a preference for lauroyl-CoA as a substrate. The AbPaaY trimer structure shows a unique domain-swapped C-termini, which increases the stability of the enzyme in vitro and decreases its susceptibility to proteolysis in vivo. The domain-swapped C-termini impact thioesterase substrate specificity and enzyme efficacy without affecting carbonic anhydrase activity. AbPaaY knockout reduced the growth of Acinetobacter in media containing PA, decreased biofilm formation, and impaired hydrogen peroxide resistance. Collectively, AbPaaY is a bifunctional enzyme that plays a key role in the metabolism, growth, and stress response mechanisms of A. baumannii.

Automatic sex estimation using deep convolutional neural network based on orthopantomogram images.

Sex estimation is very important in forensic applications as part of individual identification. Morphological sex estimation methods predominantly focus on anatomical measurements. Based on the close relationship between sex chromosome genes and facial characterization, craniofacial hard tissues morphology shows sex dimorphism. In order to establish a more labor-saving, rapid, and accurate reference for sex estimation, the study investigated a deep learning network-based artificial intelligence (AI) model using orthopantomograms (OPG) to estimate sex in northern Chinese subjects. In total, 10703 OPG images were divided into training (80%), validation (10%), and test sets (10%). At the same time, different age thresholds were selected to compare the accuracy differences between adults and minors. The accuracy of sex estimation using CNN (convolutional neural network) model was higher for adults (90.97%) compared with minors (82.64%). This work demonstrated that the proposed model trained with a large dataset could be used in automatic morphological sex-related identification with favorable performance and practical significance in forensic science for adults in northern China, while also providing a reference for minors to some extent.

A cone-beam computed tomography study of hyoid bone position and airway volume in subjects with obstructive and nonobstructive adenotonsillar hypertrophy.

OBJECTIVES: To investigate hyoid bone position and airway volume in subjects with adenoid hypertrophy, tonsillar hypertrophy, and adenotonsillar hypertrophy compared to subjects with nonobstructive adenoids or tonsils and to assess the correlation between hyoid bone and airway parameters. MATERIALS AND METHODS: A total of 121 subjects were grouped based on adenoid or tonsillar hypertrophy into four groups, as follows: (1) control group (C-group), (2) adenoid hypertrophy group (AH-group), (3) adenotonsillar hypertrophy group (ATH-group), and (4) tonsillar hypertrophy group (TH-group). Hyoid bone position and airway volumes were measured. The Kruskal-Wallis test was used for intergroup comparison, followed by pairwise comparison using the Mann-Whitney U-test. Bivariate correlation was conducted using Spearman correlation coefficients. Multiple linear regression was performed to create a model for airway volume based on hyoid bone predictive variables. RESULTS: No significant difference was found between subjects with isolated adenoid or tonsillar hypertrophy compared to the C-group. However, the ATH-group exhibited a significantly decreased hyoid bone vertical distance (HV), total airway volume (TA volume), and retroglossal airway volume (RG volume) compared to the C-group. HV and age had a high potential in terms of explaining the RG volume, whereas the TA volume and retropalatal airway volume (RP volume) models were not as successful as the RG volume counterpart. CONCLUSIONS: Subjects in ATH-group were characterized by an elevated hyoid bone position and constricted TA volume and RG volume compared to those in the C-group. HV and age were predictor variables that best explained retroglossal airway volume.

Screening and epitope characterization of diagnostic nanobody against total and activated Bacteroides fragilis toxin.

Enterotoxigenic Bacteroides fragilis (ETBF) can rapidly secrete an enterotoxin termed B. fragilis toxin (BFT), which is thought to be the only recognized virulence factor in ETBF. ETBF can cause acute diarrhea, inflammatory bowel disease (IBD), colorectal cancer, and breast cancer. BFT is divided into three subtypes, BFT1, BFT2, and BFT3. BFT1 is the most widely distributed in human B. fragilis isolates. BFT can be used as a biomarker for predicting the inflammation-cancer transformation of intestine and breast. Nanobodies have the advantages of small structure, complete antigen recognition capacity, rapid selection via phage display technology, and can be massively produced in microbial expression systems. Nanobodies have become a powerful tool for medical diagnosis and treatment. This study focuses on screening and structural characterization of nanobodies targeting full length and active BFT. By constructing prokaryotic expression systems to obtain recombinant BFT1 protein, high purity BFT1 protein was used to immunize alpacas. Phage display technology was used to construct a phage display library. The positive clones were selected by bio-panning, and the isothermal titration calorimetry was used to select high-affinity nanobodies. Then the three-dimensional structures of BFT1:Nb2.82 and BFT1:Nb3.27 were solved by crystal X-ray diffraction. We got two kinds of nanobodies, Nb2.82 targeting the BFT1 prodomain and Nb3.27 recognizing the BFT1 catalytic domain. This study provides a new strategy for the early diagnosis of ETBF and the possibility for BFT as a biomarker for diagnosing diseases.