Myosin II mediates Shh signals to shape dental epithelia via control of cell adhesion and movement.

The development of ectodermal organs begins with the formation of a stratified epithelial placode that progressively invaginates into the underlying mesenchyme as the organ takes its shape. Signaling by secreted molecules is critical for epithelial morphogenesis, but how that information leads to cell rearrangement and tissue shape changes remains an open question. Using the mouse dentition as a model, we first establish that non-muscle myosin II is essential for dental epithelial invagination and show that it functions by promoting cell-cell adhesion and persistent convergent cell movements in the suprabasal layer. Shh signaling controls these processes by inducing myosin II activation via AKT. Pharmacological induction of AKT and myosin II can also rescue defects caused by the inhibition of Shh. Together, our results support a model in which the Shh signal is transmitted through myosin II to power effective cellular rearrangement for proper dental epithelial invagination.

Genomic anatomy of homozygous XX females and YY males reveals early evolutionary trajectory of sex-determining gene and sex chromosomes in Silurus fishes.

Sex chromosomes display remarkable diversity and variability among vertebrates. Compared with research on the X/Y and Z/W chromosomes, which have long evolutionary histories in mammals and birds, studies on the sex chromosomes at early evolutionary stages are limited. Here, we precisely assembled the genomes of homozygous XX female and YY male Lanzhou catfish (Silurus lanzhouensis) derived from an artificial gynogenetic family and a self-fertilized family, respectively. Chromosome 24 (Chr24) was identified as the sex chromosome based on resequencing data. Comparative analysis of the X and Y chromosomes showed an approximate 320 kb Y-specific region with a Y-specific duplicate of anti-Mullerian hormone type-II receptor (amhr2y), which is consistent with findings in two other Silurus species but on different chromosomes (Chr24 of S. meridionalis and Chr5 of S. asotus). Deficiency of amhr2y resulted in male-to-female sex reversal, indicating that amhr2y plays a male-determining role in S. lanzhouensis. Phylogenetic analysis and comparative genomics revealed that the common sex-determining gene amhr2y was initially translocated to Chr24 of the Silurus ancestor along with the expansion of transposable elements. Chr24 was maintained as the sex chromosome in S. meridionalis and S. lanzhouensis, whereas a sex-determining region transition triggered sex chromosome turnover from Chr24 to Chr5 in S. asotus. Additionally, gene duplication, translocation, and degeneration were observed in the Y-specific regions of Silurus species. These findings present a clear case for the early evolutionary trajectory of sex chromosomes, including sex-determining gene origin, repeat sequence expansion, gene gathering and degeneration in sex-determining region, and sex chromosome turnover.

Tauroursodeoxycholic acid ameliorates renal injury induced by COL4A3 mutation.

COL4A3/A4/A5 mutations have been identified as critical causes of Alport syndrome and other genetic chronic kidney diseases. However, the underlying pathogenesis remains unclear, and specific treatments are lacking. Here, we constructed a transgenic Alport syndrome mouse model by generating a mutation (Col4a3 p.G799R) identified previously from one large Alport syndrome family into mice. We observed that the mutation caused a pathological decrease in intracellular and secreted collagen IV α3α4α5 heterotrimers. The mutant collagen IV α3 chains abnormally accumulated in the endoplasmic reticulum and exhibited defective secretion, leading to persistent endoplasmic reticulum stress in vivo and in vitro. RNA-seq analysis revealed that the MyD88/p38 MAPK pathway plays key roles in mediating subsequent inflammation and apoptosis signaling activation. Treatment with tauroursodeoxycholic acid, a chemical chaperone drug that functions as an endoplasmic reticulum stress inhibitor, effectively suppressed endoplasmic reticulum stress, promoted secretion of the α3 chains, and inhibited the activation of the MyD88/p38 MAPK pathway. Tauroursodeoxycholic acid treatment significantly improved kidney function in vivo. These results partly clarified the pathogenesis of kidney injuries associated with Alport syndrome, especially in glomeruli, and suggested that tauroursodeoxycholic acid might be useful for the early clinical treatment of Alport syndrome.

Association between autonomic dysfunction with motor and non-motor symptoms in patients with Parkinson's disease.

To investigate the association between autonomic dysfunction (AutD) and motor as well as non-motor symptoms (NMS) in patients with Parkinson's disease (PD). Fifty-three PD patients were divided into two groups based on the number of domains affected by AutD: a multi-domain AutD group (AutD-M) and a single-domain AutD group (AutD-S), as evaluated using the Scale for Outcomes in Parkinson's disease-Autonomic (SCOPA-AUT), which assesses autonomic symptoms, one of the NMS. A comprehensive comparison was conducted between the two groups, including clinical measures such as clinical scales, quantitative evaluations of motor function and exercise capacity. Spearman correlation analysis was employed to investigate the relationship between AutD severity and PD symptoms. Additionally, we performed multiple linear regression model analysis to determine whether associations between SCOPA-AUT scores and clinical assessments remained significant after adjusting for Hoehn and Yahr stage, sex, and age. PD patients in the AutD-M group exhibited significantly more severe NMS and motor symptoms compared to those in the AutD-S group. In correlation analysis, SCOPA-AUT scores showed significant correlations with multiple clinical symptoms, such as most of the NMS, 10-MWT and CPET parameters. Furthermore, regression analysis also revealed that more pronounced fatigue, anxiety, depressive symptoms, worse walking speed and impaired exercise capacity were associated with higher SCOPA-AUT scores. The presence of AutD is correlated with emotional disturbances, decreased exercise endurance, and impaired gait function in patients with PD. Early management of AutD may prove beneficial in alleviating some NMS and motor symptoms in PD.

Computational Insights into SARS-CoV-2 Main Protease Mutations and Nirmatrelvir Efficacy: The Effects of P132H and P132H-A173V.

Nirmatrelvir, a pivotal component of the oral antiviral Paxlovid for COVID-19, targets the SARS-CoV-2 main protease (Mpro) as a covalent inhibitor. Here, we employed combined computational methods to explore how the prevalent Omicron variant mutation P132H, alone and in combination with A173V (P132H-A173V), affects nirmatrelvir's efficacy. Our findings suggest that P132H enhances the noncovalent binding affinity of Mpro for nirmatrelvir, whereas P132H-A173V diminishes it. Although both mutants catalyze the rate-limiting step more efficiently than the wild-type (WT) Mpro, P132H slows the overall rate of covalent bond formation, whereas P132H-A173V accelerates it. Comprehensive analysis of noncovalent and covalent contributions to the overall binding free energy of the covalent complex suggests that P132H likely enhances Mpro sensitivity to nirmatrelvir, while P132H-A173V may confer resistance. Per-residue decompositions of the binding and activation free energies pinpoint key residues that significantly affect the binding affinity and reaction rates, revealing how the mutations modulate these effects. The mutation-induced conformational perturbations alter drug-protein local contact intensities and the electrostatic preorganization of the protein, affecting noncovalent binding affinity and the stability of key reaction states, respectively. Our findings inform the mechanisms of nirmatrelvir resistance and sensitivity, facilitating improved drug design and the detection of resistant strains.

Transcriptome analysis of Kluyveromyces marxianus under succinic acid stress and development of robust strains.

Kluyveromyces marxianus has become an attractive non-conventional yeast cell factory due to its advantageous properties such as high thermal tolerance and rapid growth. Succinic acid (SA) is an important platform molecule that has been applied in various industries such as food, material, cosmetics, and pharmaceuticals. SA bioproduction may be compromised by its toxicity. Besides, metabolite-responsive promoters are known to be important for dynamic control of gene transcription. Therefore, studies on global gene transcription under various SA concentrations are of great importance. Here, comparative transcriptome changes of K. marxianus exposed to various concentrations of SA were analyzed. Enrichment and analysis of gene clusters revealed repression of the tricarboxylic acid cycle and glyoxylate cycle, also activation of the glycolysis pathway and genes related to ergosterol synthesis. Based on the analyses, potential SA-responsive promoters were investigated, among which the promoter strength of IMTCP2 and KLMA_50231 increased 43.4% and 154.7% in response to 15 g/L SA. In addition, overexpression of the transcription factors Gcr1, Upc2, and Ndt80 significantly increased growth under SA stress. Our results benefit understanding SA toxicity mechanisms and the development of robust yeast for organic acid production. KEY POINTS: • Global gene transcription of K. marxianus is changed by succinic acid (SA) • Promoter activities of IMTCP2 and KLMA_50123 are regulated by SA • Overexpression of Gcr1, Upc2, and Ndt80 enhanced SA tolerance.

Optimal exercise intensity for improving executive function in patients with attention deficit hyperactivity disorder: systematic review and network meta-analysis.

This study aimed to compare and rank the effectiveness of optimal exercise intensity in improving executive function in patients with ADHD (Attention deficit hyperactivity disorder, ADHD) through a comprehensive comparison of direct and indirect evidence. A systematic search was performed in five electronic databases to explore the optimal exercise intensity for improving executive function in patients with ADHD by directly and indirectly comparing a variety of exercise intervention intensities. In addition, the isolated effects of exercise on improving executive function in patients with ADHD were explored through classical meta-analysis of paired direct comparisons. Twenty-nine studies were retrieved and included in this study. Classical paired meta-analysis showed that for the patients with ADHD in the age group of 7-17 years, statistical difference was observed for all the parameters of exercise interventions (intensity, frequency, period, and training method), the three dimensions of executive function, the use of medication or not, the high and low quality of the methodological approach. Network meta-analysis showed that high-intensity exercise training was optimal for improving working memory (97.4%) and inhibitory function (85.7%) in patients with ADHD. Meanwhile, moderate-intensity exercise training was optimal for improving cognitive flexibility (77.3%) in patients with ADHD. Moderate to high intensity exercise training shows potential for improving executive function in these patients. Therefore, we recommend applying high-intensity exercise intervention to improve executive function in patients with ADHD to achieve substantial improvement.

Machine learning-based decision support system for orthognathic diagnosis and treatment planning.

BACKGROUND: Dento-maxillofacial deformities are common problems. Orthodontic-orthognathic surgery is the primary treatment but accurate diagnosis and careful surgical planning are essential for optimum outcomes. This study aimed to establish and verify a machine learning-based decision support system for treatment of dento-maxillofacial malformations. METHODS: Patients (n = 574) with dento-maxillofacial deformities undergoing spiral CT during January 2015 to August 2020 were enrolled to train diagnostic models based on five different machine learning algorithms; the diagnostic performances were compared with expert diagnoses. Accuracy, sensitivity, specificity, and area under the curve (AUC) were calculated. The adaptive artificial bee colony algorithm was employed to formulate the orthognathic surgical plan, and subsequently evaluated by maxillofacial surgeons in a cohort of 50 patients. The objective evaluation included the difference in bone position between the artificial intelligence (AI) generated and actual surgical plans for the patient, along with discrepancies in postoperative cephalometric analysis outcomes. RESULTS: The binary relevance extreme gradient boosting model performed best, with diagnostic success rates > 90% for six different kinds of dento-maxillofacial deformities; the exception was maxillary overdevelopment (89.27%). AUC was > 0.88 for all diagnostic types. Median score for the surgical plans was 9, and was improved after human-computer interaction. There was no statistically significant difference between the actual and AI- groups. CONCLUSIONS: Machine learning algorithms are effective for diagnosis and surgical planning of dento-maxillofacial deformities and help improve diagnostic efficiency, especially in lower medical centers.

The clinical value of serum-related indexes in differentiating simple premature thelarche from idiopathic central precocious puberty.

Objective: To explore the changes of serum-related indexes at different time points, so as to identify the critical time of converting from simple premature thelarche (PT) to idiopathic central precocious puberty (ICPP). Methods: This is a retrospective study. The subjects of the study were 50 girls with PT who were admitted to the Children's Hospital of Hebei Province from January 2019 to September 2020. The enrolled 50 children were divided into the conversion group(n=12) and the non-conversion group(n=38) according to whether PT was converted into ICPP during follow-up. Furthermore, the levels of serum-related indexes and uterine and ovarian volumes were compared after the diagnosis of PT. Results: The IGF-1 and IGFBP-3 levels of children in the conversion group began to change significantly from six months after the diagnosis, with statistically significant differences when compared with the levels of children at the initial diagnosis, three months and those of the non-conversion group at the same time points (p<0.05). The levels of vitamin-D, DHEA and leptin began to change significantly at nine months after the diagnosis (p<0.05). Besides, uterine and ovarian volumes in the conversion group began to increase significantly six months after the diagnosis, with statistically significant differences when compared with those in the non-conversion group (p<0.05). Conclusion: Findings in our study suggest that regular monitoring of vitamin-D, IGF-1, IGFBP-3, DHEA and leptin levels, and uterine and ovarian volumes can predict the conversion from PT to ICPP at an early stage.

A deep learning and radiomics fusion model based on contrast-enhanced computer tomography improves preoperative identification of cervical lymph node metastasis of oral squamous cell carcinoma.

OBJECTIVES: In this study, we constructed and validated models based on deep learning and radiomics to facilitate preoperative diagnosis of cervical lymph node metastasis (LNM) using contrast-enhanced computed tomography (CECT). MATERIALS AND METHODS: CECT scans of 100 patients with OSCC (217 metastatic and 1973 non-metastatic cervical lymph nodes: development set, 76 patients; internally independent test set, 24 patients) who received treatment at the Peking University School and Hospital of Stomatology between 2012 and 2016 were retrospectively collected. Clinical diagnoses and pathological findings were used to establish the gold standard for metastatic cervical LNs. A reader study with two clinicians was also performed to evaluate the lymph node status in the test set. The performance of the proposed models and the clinicians was evaluated and compared by measuring using the area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity (SEN), and specificity (SPE). RESULTS: A fusion model combining deep learning with radiomics showed the best performance (ACC, 89.2%; SEN, 92.0%; SPE, 88.9%; and AUC, 0.950 [95% confidence interval: 0.908-0.993, P < 0.001]) in the test set. In comparison with the clinicians, the fusion model showed higher sensitivity (92.0 vs. 72.0% and 60.0%) but lower specificity (88.9 vs. 97.5% and 98.8%). CONCLUSION: A fusion model combining radiomics and deep learning approaches outperformed other single-technique models and showed great potential to accurately predict cervical LNM in patients with OSCC. CLINICAL RELEVANCE: The fusion model can complement the preoperative identification of LNM of OSCC performed by the clinicians.

Identification and functional study of AA11 family polysaccharide monooxygenase genes in filamentous fungus Podospora anserina.

The lytic polysaccharide monooxygenase (LPMO) in the auxiliary active protein family (AA family) catalyzes the oxidative depolymerization of various refractory carbohydrates including cellulose, chitin and starch. While accumulating studies investigate the enzymology of LPMO, the research on the inactivation of LPMO genes has been rarely explored. In this study, five LPMO genes PaLPMO11A (Pa_4_4790), PaLPMO11B (Pa_1_5310), PaLPMO11C (Pa_2_7840), PaLPMO11D (Pa_2_8610) and PaLPMO11E (Pa_3_9420) of the AA11 family in the filamentous fungus Podospora anserina were knocked out by homologous recombination. Single mutants ΔPaLPMO11A (ΔA), ΔPaLPMO11B (ΔB), ΔPaLPMO11C (ΔC), ΔPaLPMO11D (ΔD) and ΔPaLPMO11E (ΔE) were constructed, and then all polygenic mutants were constructed via genetic crosses. The differences in the growth rate and sexual reproduction between wild type and mutant strains were observed on different carbon source media. The alteration of oxidative stress and cellulose degradation ability were found on DAB and NBT staining and cellulase activity determination. These results implicated that LPMO11 genes play a key role in the growth, development, and lignocellulose degradation of P. anserina. The results showed that the spore germination efficiency, growth rate and reproductive capacity of mutant strains including ΔBΔCΔE, ΔAΔBΔCΔE, ΔAΔCΔDΔE and ΔAΔBΔCΔDΔE was significantly decreased on different cellulose carbon sources and the remaining strains have no difference. The reduced utilization of various carbon sources, the growth rate, the spore germination rate, the number of fruiting bodies, the normal fruiting bodies, the shortened life span and the ability to degrade cellulose were found in strains which all five genes in the PaLPMO11 family were deleted. However, the strain still had 45% cellulase activity compared to wild type. These results suggest that LPMO11 genes may be involved in the growth and development, sexual reproduction, senescence and cellulose degradation of P. anserina. This study provides information for systematically elucidating the regulatory mechanism of lignocellulose degradation in filamentous fungus P. anserina.

The First Case Report of Inactive Nontuberculous Mycobacterial Pulmonary Disease (NTM-PD) in a Pneumoconiosis Patient Caused by Mycobacterium europaeum in China.

We reported a 51-year-old male electric welder with stage I pneumoconiosis, who had no significant cough, sputum, fever, chest pain, or other discomfort. However, regular physical examination at our hospital revealed bilateral pulmonary nodules with cavity formation. Blood routine, liver or kidney function, and infection-related biomarkers, including interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and procalcitonin (PCT), were normal. Sputum and alveolar lavage fluid (BALF) acid-fast bacilli (AFB) smears, BALF Mycobacterium tuberculosis (TB) PCR, and T-SPOT.TB were negative. The nucleic acid sequence of Mycobacterium europaeum was detected by BALF metagenomic next-generation sequencing (mNGS), which was confirmed by the subsequent positive culture for NTM. Considering stable conditions, no significant discomfort, and no significant changes in the lung lesion, the patient was diagnosed with inactive nontuberculous mycobacterial pulmonary disease (NTM-PD).

Network meta-analysis of the effects of different cognitive trainings on the cognitive function of patients with mild cognitive impairment.

OBJECTIVE: Examining the relationship between the responses of a number of different cognitive trainings on cognitive functioning in middle-aged and elderly patients with mild cognitive impairment. METHODS: Randomized controlled experimental studies published publicly from the time of inception to October 30, 2023 were searched through Web of Science, PubMed, Embase, and Cochrane library databases. Traditional and network meta-analyses were performed using Stata 17.0 software. RESULTS: Fifty papers on 4 types of cognitive training were included. Traditional meta-analysis showed that virtual reality training (SMD = 0.53, 95%CI: [0.36,0.70], P = 0.00), neuropsychological training (SMD = 0.44, 95%CI: [0.18,0.70], P = 0.00), cognitive strategy training (SMD = 0.26, 95%CI: [0.16,0.36], P = 0.00), and cognitive behavioral therapy (SMD = 0.25, 95%CI: [0.08,0.41], P = 0.00) all had significant improvement effects on the cognitive function of middle-aged and elderly patients with mild cognitive impairment. Network meta-analysis revealed neuropsychological training as the best cognitive training, and subgroup analysis of cognitive function subdimensions showed that neuropsychological training had the best effects on working memory, lobal cognitive function, memory, and cognitive flexibility improvement. Meanwhile, virtual reality training had the best effects on processing speed, verbal ability, overall executive function, spatial cognitive ability, and attention improvement. CONCLUSION: Cognitive training can significantly improve the cognitive function of middle-aged and elderly patients with mild cognitive impairment, and neuropsychological training is the best intervention, most effective in interventions lasting more than 8 weeks.

Comparison of the gastrointestinal bacterial microbiota between dairy cows with and without mastitis.

Mastitis causes significant losses in the global dairy industry, and the health of animals has been linked to their intestinal microbiota. To better understand the relationship between gastrointestinal microbiota and mastitis in dairy cows, we collected blood, rumen fluid, and fecal samples from 23 dairy cows, including 13 cows with mastitis and 10 healthy cows. Using ELISA kit and high-throughput sequencing, we found that cows with mastitis had higher concentrations of TNF-α, IL-1, and LPS than healthy cows (p < 0.05), but no significant differences in microbiota abundance or diversity (p > 0.05). Principal coordinate analysis (PCOA) revealed significant differences in rumen microbial structure between the two groups (p < 0.05), with Moryella as the signature for rumen in cows with mastitis. In contrast, fecal microbial structure showed no significant differences (p > 0.05), with Aeriscardovia, Lactococcus, and Bacillus as the signature for feces in healthy cows. Furthermore, the results showed distinct microbial interaction patterns in the rumen and feces of cows with mastitis compared to healthy cows. Additionally, we observed correlations between the microbiota in both the rumen and feces of cows and blood inflammatory indicators. Our study sheds new light on the prevention of mastitis in dairy cows by highlighting the relationship between gastrointestinal microbiota and mastitis.

Development of a Rapid and Sensitive CANARY Biosensor Assay for the Detection of Shiga Toxin 2 from Escherichia coli.

Shiga-toxin-producing Escherichia coli (STEC) causes a wide spectrum of diseases including hemorrhagic colitis and hemolytic uremic syndrome (HUS). The current Food Safety Inspection Service (FSIS) testing methods for STEC use the Food and Drug Administration (FDA) Bacteriological Analytical Manual (BAM) protocol, which includes enrichment, cell plating, and genomic sequencing and takes time to complete, thus delaying diagnosis and treatment. We wanted to develop a rapid, sensitive, and potentially portable assay that can identify STEC by detecting Shiga toxin (Stx) using the CANARY (Cellular Analysis and Notification of Antigen Risks and Yields) B-cell based biosensor technology. Five potential biosensor cell lines were evaluated for their ability to detect Stx2. The results using the best biosensor cell line (T5) indicated that this biosensor was stable after reconstitution with assay buffer covered in foil at 4 °C for up to 10 days with an estimated limit of detection (LOD) of ≈0.1-0.2 ng/mL for days up to day 5 and ≈0.4 ng/mL on day 10. The assay detected a broad range of Stx2 subtypes, including Stx2a, Stx2b, Stx2c, Stx2d, and Stx2g but did not cross-react with closely related Stx1, abrin, or ricin. Additionally, this assay was able to detect Stx2 in culture supernatants of STEC grown in media with mitomycin C at 8 and 24 h post-inoculation. These results indicate that the STEC CANARY biosensor developed in this study is sensitive, reproducible, specific, rapid (≈3 min), and may be applicable for surveillance of the environment and food to protect public health.

Flow field analysis of cigarette filter through micro-CT-based geometries and CFD simulation.

The cigarette filter is an essential component of modern cigarettes and studying the flow distribution within the cigarette filter is of great significance in reducing the harm of cigarettes and optimizing smoking sensations. As the object of numerical simulation research, a three-dimensional model of the cigarette was accurately constructed through micro-CT reverse engineering, achieving a scanning accuracy of 4.05 µm. An overall porous media model of the cigarette filter was established to characterize the pressure distribution inside the filter. Based on the three-dimensional reconstruction, a local simulation model of the cavity-filtered filter was created by extracting a 1/36 geometric model. The simulation results of the overall porous media model of the cigarette filter were used as the pressure boundary conditions for the local simulation model of the cavity-filtered filter, and the effects of the wrapped paper and cavity on the flow field were analyzed. The results show that the simulated pressure drop in the overall porous media model of the cigarette filter had a deviation of less than 3.5% compared to the experimental results. This suggests that the porous media model can effectively predict the changes in pressure drop within the filter. When both wrapped paper and cavity were present, the velocity at the interface between acetate fiber and wrapped paper increased by 141.54%, while the pressure approached 0 Pa. Similarly, at the interface between acetate fiber and cavity, the velocity increased by 130.77%. It indicates that both wrapped paper and cavity significantly influenced the flow field characteristics within the cigarette filter. Additionally, as the porosity of the wrapped paper gradually increased from 0.69 to 0.99 in the radial direction, the fluid velocity increased by 14.46%, while the fluid pressure decreased by 29.09%. These changes were particularly evident when the porosity was below 0.87.

IL-33 Enhances the Total Production of IgG, IgG1, and IgG3 in Angiostrongylus cantonensis-Infected Mice.

The purpose of this study is to clarify the role of IL-33 in the immune response to angiostrongyliasis, especially in terms of antibody production and isotype switching. In our experiment, C57BL/6 mice were each infected with 35 infectious larvae and were divided into groups that received an intraperitoneal injection of IL-33, anti-IL-33 monoclonal antibody (mAb), or anti-ST2 mAb 3 days post-infection (dpi) and were subsequently administered booster shots at 5-day intervals with the same dose. Serum samples from each group were collected weekly for ELISA assays. The levels of total IgG, IgG1, and IgG3 were significantly increased in A. cantonensis-infected mice that were treated with IL-33, and the levels decreased significantly in infected groups treated with anti-IL-33 or anti-ST2 mAb. These results suggest that IL-33 may play a critical role in the pathogenesis of human angiostrongyliasis and could be useful for understanding protective immunity against this parasitic infection.

Postoperative facial prediction for mandibular defect based on surface mesh deformation.

OBJECTIVES: This study aims to introduce a novel predictive model for the post-operative facial contours of patients with mandibular defect, addressing limitations in current methodologies that fail to preserve geometric features and lack interpretability. METHODS: Utilizing surface mesh theory and deep learning, our model diverges from traditional point cloud approaches by employing surface triangular mesh grids. We extract latent variables using a Mesh Convolutional Restricted Boltzmann Machines (MCRBM) model to generate a three-dimensional deformation field, aiming to enhance geometric information preservation and interpretability. RESULTS: Experimental evaluations of our model demonstrate a prediction accuracy of 91.2 %, which represents a significant improvement over traditional machine learning-based methods. CONCLUSIONS: The proposed model offers a promising new tool for pre-operative planning in oral and maxillofacial surgery. It significantly enhances the accuracy of post-operative facial contour predictions for mandibular defect reconstructions, providing substantial advancements over previous approaches.

Rapid and Sensitive Detection of Shiga Toxin-Producing Escherichia coli (STEC) from Food Matrices Using the CANARY Biosensor Assay.

Shiga toxin-producing Escherichia coli (STEC) causes a wide spectrum of diseases including hemorrhagic colitis and hemolytic uremic syndrome (HUS). Previously, we developed a rapid, sensitive, and potentially portable assay that identified STEC by detecting Shiga toxin (Stx) using a B-cell based biosensor platform. We applied this assay to detect Stx2 present in food samples that have been implicated in previous STEC foodborne outbreaks (milk, lettuce, and beef). The STEC enrichment medium, modified Tryptone Soy Broth (mTSB), inhibited the biosensor assay, but dilution with the assay buffer relieved this effect. Results with Stx2a toxoid-spiked food samples indicated an estimated limit of detection (LOD) of ≈4 ng/mL. When this assay was applied to food samples inoculated with STEC, it was able to detect 0.4 CFU/g or 0.4 CFU/mL of STEC at 16 h post incubation (hpi) in an enrichment medium containing mitomycin C. Importantly, this assay was even able to detect STEC strains that were high expressors of Stx2 at 8 hpi. These results indicate that the STEC CANARY biosensor assay is a rapid and sensitive assay applicable for detection of STEC contamination in food with minimal sample processing that can complement the current Food Safety Inspection Service (US) methodologies for STEC.

Diabetes treatment by conversion of gut epithelial cells to insulin-producing cells.

Insulin-deficient (type 1) diabetes is treated by providing insulin to maintain euglycemia. The current standard of care is a quasi-closed loop integrating automated insulin delivery with a continuous glucose monitoring sensor. Cell replacement technologies are advancing as an alternative treatment and have been tested as surrogates to cadaveric islets in transplants. In addition, immunomodulatory treatments to delay the onset of type 1 diabetes in high-risk (stage 2) individuals have gained regulatory approval. We have pioneered a cell conversion approach to restore insulin production through pharmacological conversion of intestinal epithelial cells into insulin-producing cells. We have advanced this approach along a translational trajectory through the discovery of small molecule forkhead box protein O1 inhibitors. When administered to different rodent models of insulin-deficient diabetes, these inhibitors have resulted in robust glucose-lowering responses and generation of insulin-producing cells in the gut epithelium. We review past work and delineate a path to human clinical trials.