Associations of prenatal blood pressure trajectory and variability with child neurodevelopment at 2 years old.

BACKGROUND: The patterns of blood pressure (BP) change throughout the pregnancy were related to adverse birth outcomes. However, little is known about the long-term effect of BP change patterns on child neurodevelopment. This study aimed to explore the relationship between the BP trajectory and BP variability during pregnancy and early childhood neurodevelopment. METHOD: A total of 2797 mother-newborn pairs were derived from the Wuhan Healthy Baby Cohort Study. BP was measured during each antenatal visit, and Mental and Psychomotor Development Indexes (MDI and PDI) were assessed using the Bayley Scales of Infant Development (BSID) when the children were 2 years old. Delayed neurodevelopment was defined as scores of PDI or MDI less than - 1SD relative to the mean score of the study population. A group-based multi-trajectory model was adopted to identify multi-trajectories of systolic blood pressure (SBP) and diastolic blood pressure (DBP). Visit-to-visit BP variability was assessed by the coefficient of variation (CV), standard deviation (SD), and average real variability (ARV). Generalized linear models and multivariate logistic regressions were used to assess the associations of BP trajectories and variability with BSID scores and delayed neurodevelopment, respectively. RESULTS: Five distinct trajectories for SBP and DBP were identified, namely, "Low-increasing," "Low-stable," "Moderate-decreasing," "Moderate-increasing," and "High-stable" groups. Compared with the "Low-stable" group, the children whose mothers' BP fell into the other four groups had lower PDI scores, and mothers in the "Low-increasing," "Moderate-increasing," and "Moderate-decreasing" groups had 43% (OR: 1.43, 95% CI: 1.01, 2.03), 48% (OR: 1.48, 95% CI: 1.05, 2.08) and 45% (OR:1.45, 95% CI: 1.03, 2.04) higher risk of having offspring with delayed psychomotor neurodevelopment, respectively. High DBP variability was associated with lower BSID scores, and delayed psychomotor neurodevelopment (OR = 1.46, 95% CI: 1.10, 1.92 for DBP-SD; OR = 1.53, 95% CI: 1.16, 2.02 for DBP-CV). CONCLUSION: Our findings suggest that BP change patterns assessed by multi-trajectory and visit-to-visit variability were associated with lower BSID scores and delayed neurodevelopment. Health professionals should be aware of the influence of BP level and its oscillations during pregnancy on the risk of delayed neurodevelopment.

Voluntary running wheel exercise induces cognitive improvement post traumatic brain injury in mouse model through redressing aberrant excitation regulated by voltage-gated sodium channels 1.1, 1.3, and 1.6.

Traumatic brain injury (TBI) leads to disturbed brain discharge rhythm, elevated excitability, anxiety-like behaviors, and decreased learning and memory capabilities. Cognitive dysfunctions severely affect the quality of life and prognosis of TBI patients, requiring effective rehabilitation treatment. Evidence indicates that moderate exercise after brain injury decreases TBI-induced cognitive decline. However, the underlying mechanism remains unelucidated. Our results demonstrate that TBI causes cognitive impairment behavior abnormalities and overexpression of Nav1.1, Nav1.3 and Nav1.6 proteins inside the hippocampus of mice models. Three weeks of voluntary running wheel (RW) exercise treatments before or/and post-injury effectively redressed the aberrant changes caused by TBI. Additionally, a 10% exercise-conditioned medium helped recover cell viability, neuronal sodium current and expressions of Nav1.1, Nav1.3 and Nav1.6 proteins across cultured neurons after injury. Therefore, the results validate the neuroprotection induced by voluntary RW exercise treatment before or/and post-TBI. The RW exercise-induced improvement in cognitive behaviors and neuronal excitability could be associated with correcting the Nav1.1, Nav1.3, and Nav1.6 expression levels. The current study proves that voluntary exercise is an effective treatment strategy against TBI. The study also highlights novel potential targets for rehabilitating TBI, including the Navs proteins.

Human amnion-derived mesenchymal stem cells improve subclinical hypothyroidism by immunocompetence mediating apoptosis inhibition on thyroid cells in aged mice.

Subclinical hypothyroidism (SCH) affects 10% of the global population, which is most prevalent in women and the elderly. However, it remains debatable whether the elderly with subclinical hypothyroidism needs thyroxine supplement. Human amnion-derived mesenchymal stem cells (hAMSCs) could play important roles in autoimmune diseases, suggesting that hAMSC be a candidate to regulate the thyroid function of female age-related subclinical hypothyroidism. Herein, we established the model of SCH in the aged female mice. This study was designed to investigate whether human amnion-derived mesenchymal stem cells (hAMSC) could effect on immune regulation, apoptosis inhibition of thyroid cells, thyroid function, blood lipid levels, and heart function. In addition, qualified hAMSCs were intravenously injected into aged female SCH mice via the tail vein on day 0 and day 10. The levels of thyroid hormone and blood lipids as well as cardiac function, serum immunological indexes, and apoptosis of thyroid cells were then analyzed on day 5, 10, 15, and 20; meanwhile, the quantity of Th1, Th2, Th17, and Treg immune cells in peripheral blood was evaluated before and on day 20 post-injection. Our study demonstrated that after hAMSC transplantation, the thyroid functions, blood lipid levels, and heart function indexes of age-related SCH (AR-SCH) mice were significantly improved. Consistent with this, Th1 and Treg cells increased significantly, while Th2 and Th17 cells decreased in peripheral blood. Apoptosis was also suppressed in the thyroid cells. In summary, hAMSC delivery can potentially be a safe and effective therapy for treating SCH in the elderly, improving related complications by immunomodulatory and apoptosis inhibition.

Tumor educated platelet: the novel BioSource for cancer detection.

Platelets, involved in the whole process of tumorigenesis and development, constantly absorb and enrich tumor-specific substances in the circulation during their life span, thus called "Tumor Educated Platelets" (TEPs). The alterations of platelet mRNA profiles have been identified as tumor markers due to the regulatory mechanism of post-transcriptional splicing. Small nuclear RNAs (SnRNAs), the important spliceosome components in platelets, dominate platelet RNA splicing and regulate the splicing intensity of pre-mRNA. Endogenous variation at the snRNA levels leads to widespread differences in alternative splicing, thereby driving the development and progression of neoplastic diseases. This review systematically expounds the bidirectional tumor-platelets interactions, especially the tumor induced alternative splicing in TEP, and further explores whether molecules related to alternative splicing such as snRNAs can serve as novel biomarkers for cancer diagnostics.

Reduced Expression of Voltage-Gated Sodium Channel Beta 2 Restores Neuronal Injury and Improves Cognitive Dysfunction Induced by Aß1-42.

Voltage-gated sodium channel beta 2 (Nav2.2 or Navß2, coded by SCN2B mRNA), a gene involved in maintaining normal physiological functions of the prefrontal cortex and hippocampus, might be associated with prefrontal cortex aging and memory decline. This study investigated the effects of Navß2 in amyloid-ß 1-42- (Aß1-42-) induced neural injury model and the potential underlying molecular mechanism. The results showed that Navß2 knockdown restored neuronal viability of Aß1-42-induced injury in neurons; increased the contents of brain-derived neurotrophic factor (BDNF), enzyme neprilysin (NEP) protein, and NEP enzyme activity; and effectively altered the proportions of the amyloid precursor protein (APP) metabolites including Aß42, sAPPα, and sAPPß, thus ameliorating cognitive dysfunction. This may be achieved through regulating NEP transcription and APP metabolism, accelerating Aß degradation, alleviating neuronal impairment, and regulating BDNF-related signal pathways to repair neuronal synaptic efficiency. This study provides novel evidence indicating that Navß2 plays crucial roles in the repair of neuronal injury induced by Aß1-42 both in vivo and in vitro.

SNORD63 and SNORD96A as the non-invasive diagnostic biomarkers for clear cell renal cell carcinoma.

BACKGROUND: Increasing evidence has demonstrated that snoRNAs play crucial roles in tumorigenesis of various cancer types. However, researches on snoRNAs in ccRCC were very little. This study mainly aimed to validate the differential expression and the potential diagnostic value of SNORD63 and SNORD96A in ccRCC. METHODS: SnoRNAs expression was downloaded from the SNORic and TCGA database including 516 patients with ccRCC and 71 control cases. SNORD63 and SNORD96A expression were further detected in 54 tumor and adjacent FFPE ccRCC tissues, 55 plasma and 75 urinary sediment of ccRCC patients. Then, differential expression and diagnostic value of SNORD63 and SNORD96A were further calculated. RESULTS: SNORD63 and SNORD96A expression were significantly increased in ccRCC tissues compared with normal tissues from the TCGA database (both, P < 0.0001). In addition, we found that SNORD63 and SNORD96A localized in plasma and US stably after treating with RNase A. Meanwhile, SNORD63 and SNORD96A in FFPE and US were elevated in ccRCC patients (all, P < 0.0001). However, plasma SNORD63 expression had no significance while SNORD96A significantly increased in plasma of ccRCC patients. Notably, the AUC of SNORD63 in US was 0.7055, by comparison the AUC of plasma SNORD63 was only 0.5161. However, the AUC of plasma SNORD96A was up to 0.8909, by comparison the AUC of SNORD96A in US was 0.6788. Interestingly, the AUC of plasma SNORD96A in early stage ccRCC was highly up to 0.9359. CONCLUSIONS: Our findings revealed that SNORD63 in US and SNORD96A in plasma could act as the promising non-invasive diagnostic biomarkers for ccRCC patients.

Land-use classification based on high-resolution remote sensing imagery and deep learning models.

High-resolution imagery and deep learning models have gained increasing importance in land-use mapping. In recent years, several new deep learning network modeling methods have surfaced. However, there has been a lack of a clear understanding of the performance of these models. In this study, we applied four well-established and robust deep learning models (FCN-8s, SegNet, U-Net, and Swin-UNet) to an open benchmark high-resolution remote sensing dataset to compare their performance in land-use mapping. The results indicate that FCN-8s, SegNet, U-Net, and Swin-UNet achieved overall accuracies of 80.73%, 89.86%, 91.90%, and 96.01%, respectively, on the test set. Furthermore, we assessed the generalization ability of these models using two measures: intersection of union and F1 score, which highlight Swin-UNet's superior robustness compared to the other three models. In summary, our study provides a systematic analysis of the classification differences among these four deep learning models through experiments. It serves as a valuable reference for selecting models in future research, particularly in scenarios such as land-use mapping, urban functional area recognition, and natural resource management.

Dipolar Microenvironment Engineering Enabled by Electron Beam Irradiation for Boosting Catalytic Performance.

Creating a diverse dipolar microenvironment around the active site is of great significance for the targeted induction of intermediate behaviors to achieve complicated chemical transformations. Herein, an efficient and general strategy is reported to construct hypercross-linked polymers (HCPs) equipped with tunable dipolar microenvironments by knitting arene monomers together with dipolar functional groups into porous network skeletons. Benefiting from the electron beam irradiation modification technique, the catalytic sites are anchored in an efficient way in the vicinity of the microenvironment, which effectively facilitates the processing of the reactants delivered to the catalytic sites. By varying the composition of the microenvironment scaffold structure, the contact and interaction behavior with the reaction participants can be tuned, thereby affecting the catalytic activity and selectivity. As a result, the framework catalysts produced in this way exhibit excellent catalytic performance in the synthesis of glycinate esters and indole derivatives. This manipulation is reminiscent of enzymatic catalysis, which adjusts the internal polarity environment and controls the output of products by altering the scaffold structure.

GATAD2B is required for pre-implantation embryonic development by regulating zygotic genome activation.

Major zygotic genome activation (ZGA) occurs at the late 2-cell stage and involves the activation of thousands of genes, supporting early embryonic development. The reasons underlying the regulation of ZGA are not clear. Acetylation modifications of histone tails promote transcriptional activation, and the maternal deletion of H4K16ac leads to failure in ZGA. GATAD2B is one of the core subunits of the nucleosome remodelling and histone deacetylation (NuRD) complex. Our research has shown that GATAD2B exhibits specific nucleus localization and high protein expression from the late 2-cell stage to the 8-cell stage. This intriguing phenomenon prompted us to investigate the relationship between GATAD2B and the ZGA. We discovered a distinctive pattern of GATAD2B, starting from the late 2-cell stage with nuclear localization. GATAD2B depletion resulted in defective embryonic development, including increased DNA damage at morula, decreased blastocyst formation rate, and abnormal differentiation of ICM/TE lineages. Consistent with the delay during the cleavage stage, the transcriptome analysis of the 2-cell embryo revealed inhibition of the cell cycle G2/M phase transition pathway. Furthermore, the GATAD2B proteomic data provided clear evidence of a certain association between GATAD2B and molecules involved in the cell cycle pathway. As hypothesized, GATAD2B-deficient 2-cell embryos exhibited abnormalities in ZGA during the maternal-to-embryonic transition, with lower expression of the major ZGA marker MERVL. Overall, our results demonstrate that GATAD2B is essential for early embryonic development, in part through facilitating ZGA.

Associations of maternal pre-pregnancy body mass index and gestational weight gain with risk of offspring neurodevelopment at 2 years: A Chinese birth cohort study.

Introduction: In recent decades, there has been a surge in both obesity and developmental impairments. Only a few research have looked at the relationship between gestational weight growth and pre-pregnancy BMI in mothers and the neurobehavioral development of their infants. The current research investigates the associations among maternal pre-pregnancy BMI, GWG, and the risk of child neural development at 2 years of age depending on a Chinese birth prospective study. Methods: The study population was 3,115 mother-infant pairs were registered in the Wuhan Health Baby cohort between September 2013 and October 2018, and data from this cohort was used in this investigation. The Chinese classification was used to group maternal BMI before conception. Based on the 2019 Life Cycle Project-Maternal Obesity and Childhood Outcomes Study Group, categories for GWG were created. The outcome was an assessment of child neural development at age 2 which was measured by employing a Chinese translation of the Bayley scales (BSID-CR). The multivariate regression models were used to calculate the beta (ß) coefficients and 95% confidence intervals (CIs) for estimating the associations between continuous Bayley scores and maternal pre-pregnancy BMI categories, as same as in GWG categories. Results: Infants of overweight and obese moms exhibited lower MDI scores than those of mothers with normal pre-pregnancy BMI (ß = -2.510, 95%CI = -4.821 to -0.200) in the entire sample. Meanwhile, we find among the normal pre-pregnancy BMI mothers, infants of inadequate GWG mothers had lower MDI scores (ß = -3.952, 95%CI = -7.809 to -0.094) compared with the referenced adequate GWG mothers, as well as the infants of excessive GWG mothers among the underweight pre-pregnancy BMI mothers (ß = -5.173, 95%CI = -9.803 to -0.543). The PDI scores of the infants were not affected by the maternal pre-pregnancy BMI or GWG. Conclusion: For Chinese babies aged 2 in this nationally representative sample, aberrant pre-pregnancy BMI and GWG can impair infants' mental development, but not psychomotor development. Such results are significant given the incidence of overweight and obesity as well as the long-term effects of early brain development. In this study we found optimal GWG recommendations proposed by 2019 Life Cycle Project-Maternal Obesity and Childhood Outcomes Study Group were more suitable for Chinese women than 2009 Institute of Medicine(IOM) guidelines. Additionally, women should be given general advice on how to achieve their ideal pre-pregnancy BMI and GWG.

Electron Beam Etching of Cellulose Microgels for Absorptive Separation of DMSO from Reactions of 5-Hydroxymethylfurfural Synthesis.

In this study, an efficient method for the separation of 5-hydroxymethylfurfural by the specific adsorption of dimethyl sulfoxide (DMSO) with cellulose microgels fabricated by electron beam irradiation was developed. The cellulose microgel was recovered and reused although this was accompanied by a decrease in the separation efficiency. A series of characterizations, including ultraviolet and infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry, thermogravimetric analysis, and swelling ability tests, were performed to determine the adsorption behavior of the chemical structures of the microgel toward DMSO. The results showed that after the first run, the chemical structure of the recovered microgel did not change significantly. Electron-beam etching played a pivotal role in conferring a special capacity for enriching DMSO in its matrix on the microgel.

Electron Beam Etching of Cellulose Microgels for Absorptive Separation of DMSO from Reactions of 5-Hydroxymethylfurfural Synthesis.

Invited for this month's cover is the groups of Jiang Huang and Yanlong Gu at Huazhong University of Science and Technology. The image shows a new method for the separation of dimethyl sulfoxide from a reaction solution of synthesizing 5-hydroxymethylfurfural by means of using a cellulose microgel fabricated by electron beam irradiation as a bio-based absorbant. The Research Article itself is available at 10.1002/cssc.202201755.

SPATA2 suppresses epithelial-mesenchymal transition to inhibit metastasis and radiotherapy sensitivity in non-small cell lung cancer via impairing DVL1/ß-catenin signaling.

Metastasis is the major cause of cancer-related death of cancer patients. Epithelial-mesenchymal transition (EMT) is one critical process during the cascade of tumor metastasis. EMT is a developmental program exploited by cancer cells to transition from epithelial state to mesenchymal state and confers metastatic properties as well as treatment resistance. Finding factors to inhibit EMT will greatly improve the prognosis patients. Spermatogenesis associated 2 (SPATA2) was originally isolated from human testis and proved playing a role in spermatogenesis. To date, however, the role of SPATA2 in oncogenesis is unknown. In the current study, by mining the public database and validating in a cohort of collected non-small cell lung cancer (NSCLC) specimens, we uncovered that the expression of SPATA2 positively correlated with the prognosis of patients and was an independent prognosis marker in NSCLC. Functional studies proved that ectopic overexpression of SPATA2 inhibited EMT resulting in impaired motility and invasiveness properties in vitro and metastasis in vivo, and increased radiosensitivity in NSCLC. Mechanistic investigation showed that SPATA2 could suppress the ß-catenin signaling via attenuating DVL1 ubiquitination to achieve the functions. Taken together, the current study revealed an inhibitory role of SPATA2 on EMT and that SPATA2 could be a potential target for therapy of NSCLC.

Establishing a human embryonic stem cell line (SKLRMe005-A) from a blastocyst with congenital heart disease (CHD).

GATA binding protein 6 (GATA6) is an important transcription factor of cardiovascular endothelial cells, has the potential to regulate the process of cardiac development. Consequently, its abnormal expression is related to congenital heart disease.Human GATA6 gene clones were on chromosome 18 q11.1- q 11.2, consists of 7 exons and 6 intron.Now, a human embryonic stem cell line with GATA6 c.620_647del (p.S208Afs*77) mutation was generated. Interestingly, the ESC line displayed a normal karyotype, pluripotency and morphology of stem cells.This cell line has the ability to undergo differentiation into three germ layers in vivo.

Trimester-specific associations of maternal exposure to bisphenols with neonatal thyroid stimulating hormone levels: A birth cohort study.

BACKGROUND: Growing evidence suggests that exposure to bisphenol A (BPA) during pregnancy could interfere with neonatal thyroid function. Bisphenol F (BPF) and bisphenol S (BPS) are increasingly used as the substitutes of BPA. However, little is known about the effects of maternal exposure to BPS and BPF on neonatal thyroid function. The current study was aimed to investigate the trimester-specific associations of maternal exposure to BPA, BPS, and BPF with neonatal thyroid stimulating hormone (TSH) levels. METHODS: Between November 2013 and March 2015, a total of 904 mother-newborn pairs were recruited from the Wuhan Healthy Baby Cohort Study, providing maternal urine samples in the first, second, and third trimesters for bisphenol exposure assessment, and neonatal heel prick blood samples for TSH measurement. Multiple informant model and quantile g-computation were used to evaluate the trimester-specific associations of bisphenols individually and mixture with TSH, respectively. RESULTS: Each doubling concentration increase of maternal urinary BPA in the first trimester was significantly related to a 3.64 % (95% CI: 0.84 %, 6.51 %) increment in neonatal TSH. Each doubling concentration increase of BPS in the first, second and third trimesters were associated with 5.81 % (95 % CI: 2.27 %, 9.46 %), 5.70 % (95 % CI: 1.99 %, 9.55 %), 4.36 % (95 % CI: 0.75 %, 8.11 %) higher neonatal blood TSH, respectively. No significant association between trimester-specific BPF concentration and TSH was observed. The relationships between exposures to BPA/BPS and neonatal TSH were more evident in female infants. Quantile g-computation indicated that maternal co-exposure to bisphenols in the first trimester was significantly associated with neonatal TSH levels in a non-linear fashion. CONCLUSION: Maternal exposure to BPA and BPS were positively associated with neonatal TSH levels. The results indicated the endocrine disrupting effect of prenatal exposure to BPS and BPA, which should be of particular concern.

A background parenchymal enhancement quantification framework of breast magnetic resonance imaging.

Background: Background parenchymal enhancement (BPE) is defined as the enhanced proportion of normal fibroglandular tissue on enhanced magnetic resonance imaging. BPE shows promise as a quantitative imaging biomarker (QIB). However, the lack of consensus among radiologists in their semi-quantitative grading of BPE limits its clinical utility. Methods: The main objective of this study was to develop a BPE quantification model according to clinical expertise, with the BPE integral being used as a QIB to incorporate both the volume and intensity of the enhancement metrics. The model was applied to 2,786 cases to compare our quantitative results with radiologists' semi-quantitative BPE grading to evaluate the effectiveness of using the BPE integral as a QIB for analyzing BPE. Comparisons between multiple groups of nonnormally distributed BPE integrals were performed using the Kruskal-Wallis test. Results: Our study found a considerable degree of concordance between our BPE quantitative integral and radiologists' semi-quantitative assessments. Specifically, our research results revealed significant variability in BPE integral attained through the BPE quantification framework among all semi-quantitative BPE grading groups labeled by experienced radiologists, including mild-moderate (P<0.001), mild-marked (P<0.001), and moderate-marked (P<0.001). Furthermore, there was an apparent correlation between BPE integral and BPE grades, with marked BPE displaying the highest BPE integral, followed by moderate BPE, with mild BPE exhibiting the lowest BPE integral value. Conclusions: The study developed and implemented a BPE quantification framework, which incorporated both the volume and intensity of enhancement and which could serve as a QIB for BPE.

Liensinine Inhibits Cell Growth and Blocks Autophagic Flux in Nonsmall-Cell Lung Cancer.

Liensinine is a bioactive component of Plumula Nelumbinis extracted from the green embryo of the mature seeds of Nelumbonaceae and exhibits therapeutic functions and noteworthy anti-tumor effects in recent studies. However, the potential anti-tumor property and the underlying mechanisms of liensinine in nonsmall-cell lung cancer (NSCLC) have not been illustrated. In this study, we demonstrated that liensinine has the potential anti-tumor property, and it could inhibit growth of NSCLC in vitro and in vivo. In addition, we found that although it induced significant accumulation of autophagosomes, liensinine could quench them for degradation and blocked autophagic flux. Importantly, we observed that liensinine inhibited the normal function of mitochondrial energy supply and impaired the lysosomal function. This research firstly provides a possibility insight that liensinine could be a novel therapeutic strategy for NSCLC.

Zwitterionic/active ester block polymers as multifunctional coatings for polyurethane-based substrates.

Bacterial-associated infection, blood coagulation, and tissue adhesion are severe issues associated with biomedical implants and devices in clinic applications. Here, we report a general strategy to simultaneously tackle these issues on polyurethane (PU)-based substrates. Taking advantage of reversible addition-fragmentation chain transfer (RAFT) polymerization, well-defined zwitterionic/active ester block polymers (pSBMA-b-pNHSMA) with an identical pNHSMA segment (polymerization degree of 15) but varied zwitterionic pSBMA segments (polymerization degrees of 40 and 100) were precisely prepared. The pSBMA-b-pNHSMA block polymers could be easily covalently constructed on PU substrates that were pretreated with a polydopamine coating based on highly efficient anime-active ester chemistry, as evidenced by the water contact angle and XPS tests. The relationship between the length of pSBMA segments in the coating and the antifouling ability of PU substrates was established. The results indicated that block polymers with a pSBMA segment of 40 repeat units could significantly prevent protein adsorption, bacterial/platelet adhesion, and cell attachment on PU substrates within 24 h, while a longer pSBMA segment (repeat units of 100) could endow long-term antibacterial (14 days without biofilm formation) and anti-cell attachment (5 days without cell attachment) properties to the PU substrates. Furthermore, the coating significantly improved the surface lubricating property of PU substrates without compromising on the mechanical property. This strategy may find many applications in PU-based implants and devices.

Development and validation of a deep learning model for breast lesion segmentation and characterization in multiparametric MRI.

Importance: The utilization of artificial intelligence for the differentiation of benign and malignant breast lesions in multiparametric MRI (mpMRI) assists radiologists to improve diagnostic performance. Objectives: To develop an automated deep learning model for breast lesion segmentation and characterization and to evaluate the characterization performance of AI models and radiologists. Materials and methods: For lesion segmentation, 2,823 patients were used for the training, validation, and testing of the VNet-based segmentation models, and the average Dice similarity coefficient (DSC) between the manual segmentation by radiologists and the mask generated by VNet was calculated. For lesion characterization, 3,303 female patients with 3,607 pathologically confirmed lesions (2,213 malignant and 1,394 benign lesions) were used for the three ResNet-based characterization models (two single-input and one multi-input models). Histopathology was used as the diagnostic criterion standard to assess the characterization performance of the AI models and the BI-RADS categorized by the radiologists, in terms of sensitivity, specificity, accuracy, and the area under the receiver operating characteristic curve (AUC). An additional 123 patients with 136 lesions (81 malignant and 55 benign lesions) from another institution were available for external testing. Results: Of the 5,811 patients included in the study, the mean age was 46.14 (range 11-89) years. In the segmentation task, a DSC of 0.860 was obtained between the VNet-generated mask and manual segmentation by radiologists. In the characterization task, the AUCs of the multi-input and the other two single-input models were 0.927, 0.821, and 0.795, respectively. Compared to the single-input DWI or DCE model, the multi-input DCE and DWI model obtained a significant increase in sensitivity, specificity, and accuracy (0.831 vs. 0.772/0.776, 0.874 vs. 0.630/0.709, 0.846 vs. 0.721/0.752). Furthermore, the specificity of the multi-input model was higher than that of the radiologists, whether using BI-RADS category 3 or 4 as a cutoff point (0.874 vs. 0.404/0.841), and the accuracy was intermediate between the two assessment methods (0.846 vs. 0.773/0.882). For the external testing, the performance of the three models remained robust with AUCs of 0.812, 0.831, and 0.885, respectively. Conclusions: Combining DCE with DWI was superior to applying a single sequence for breast lesion characterization. The deep learning computer-aided diagnosis (CADx) model we developed significantly improved specificity and achieved comparable accuracy to the radiologists with promise for clinical application to provide preliminary diagnoses.

Zwitterionic/phosphonate copolymer coatings endow excellent antifouling properties and robust re-mineralization ability of dentine substrates.

Inhibition of biofilm formation and induction of the re-mineralization of damaged dental tissues are two major strategies to combat dental hypersensitivity (DH). However, single component synthetic materials normally cannot fulfil these two functions during the repairing of damaged dental tissues. Here, we report zwitterionic phosphorylcholine based polymers to be a new type of dual functional coating for the repairing of DH. Zwitterionic/phosphonate copolymers, p(DEMMP-co-MPC), bearing varied zwitterionic contents (95 and 75 mol%) were prepared through conventional radical copolymerization. 1H NMR spectroscopy clearly indicated the precise preparation of the copolymers. The copolymers can be easily coated on dentine substrates based on the high affinity between the phosphonate group and the calcium phosphate minerals of the dentine substrates, as evidenced by XPS and water contact angle measurements. Antifouling evaluations indicated that zwitterionic coating can efficiently inhibit protein adsorption (BSA, egg white, and milk, by 85%) and bacterial adhesion (by 97.1%) on dentine substrates. Furthermore, in vitro and in vivo experiments consistently indicated that the zwitterionic coating could not only induce the robust re-mineralization of dentine surfaces, but also template the extensive re-mineralization of dentine tubules to a similar level of pristine dentine. Both the antifouling properties and the re-mineralization potency are positively correlated with the content of zwitterionic pMPC in the coating copolymer. These findings may provide the zwitterionic phosphorylcholine based materials to be a promising candidate to treat dental hypersensitivity and other related dental diseases.