R2-DDI: relation-aware feature refinement for drug-drug interaction prediction.

Precisely predicting the drug-drug interaction (DDI) is an important application and host research topic in drug discovery, especially for avoiding the adverse effect when using drug combination treatment for patients. Nowadays, machine learning and deep learning methods have achieved great success in DDI prediction. However, we notice that most of the works ignore the importance of the relation type when building the DDI prediction models. In this work, we propose a novel R$^2$-DDI framework, which introduces a relation-aware feature refinement module for drug representation learning. The relation feature is integrated into drug representation and refined in the framework. With the refinement features, we also incorporate the consistency training method to regularize the multi-branch predictions for better generalization. Through extensive experiments and studies, we demonstrate our R$^2$-DDI approach can significantly improve the DDI prediction performance over multiple real-world datasets and settings, and our method shows better generalization ability with the help of the feature refinement design.

Baicalein alleviates intrahepatic cholestasis by regulating bile acid metabolism via an FXR-dependent manner.

Cholestasis is characterized by impaired bile secretion and flow, leading to the accumulation of toxic bile acids in the liver, further causing inflammatory reaction, fibrosis, and ultimately liver transplantation. Although first-line clinical agents such as Ursodeoxycholic acid (UDCA) and Obeticholic acid (OCA) are available, serious side effects still exist. Therefore, pharmacologic treatment of cholestatic liver disease remains challenging. Here, we used a murine model of cholestasis treated with or without intraperitoneal injection of baicalein and found that baicalein could attenuate 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet-induced inflammatory response, ductular reaction, liver fibrosis, and bile acid metabolism disorders. Furthermore, the therapeutic effect of baicalein was hampered in the presence of Guggulsterone (GS), an Farnesoid X receptor (FXR) antagonist. These results indicated that baicalein alleviated DDC diet-induced cholestatic liver injury in an FXR-dependent manner.

Bay41-4109-induced aberrant polymers of hepatitis b capsid proteins are removed via STUB1-promoted p62-mediated macroautophagy.

The hepatitis B virus (HBV) core protein (HBc) functions in multiple steps of the viral life cycle. Heteroaryldihydropyrimidine compounds (HAPs) such as Bay41-4109 are capsid protein allosteric modulators that accelerate HBc degradation and inhibit the virion secretion of HBV, specifically by misleading HBc assembly into aberrant non-capsid polymers. However, the subsequent cellular fates of these HAP-induced aberrant non-capsid polymers are not well understood. Here, we discovered that that the chaperone-binding E3 ubiquitin ligase protein STUB1 is required for the removal of Bay41-4109-induced aberrant non-capsid polymers from HepAD38 cells. Specifically, STUB1 recruits BAG3 to transport Bay41-4109-induced aberrant non-capsid polymers to the perinuclear region of cells, thereby initiating p62-mediated macroautophagy and lysosomal degradation. We also demonstrate that elevating the STUB1 level enhances the inhibitory effect of Bay41-4109 on the production of HBeAg and HBV virions in HepAD38 cells, in HBV-infected HepG2-NTCP cells, and in HBV transgenic mice. STUB1 overexpression also facilitates the inhibition of Bay41-4109 on the cccDNA formation in de novo infection of HBV. Understanding these molecular details paves the way for applying HAPs as a potentially curative regimen (or a component of a combination treatment) for eradicating HBV from hepatocytes of chronic infection patients.

Network pharmacology analysis and clinical efficacy of the traditional Chinese medicine Bu-Shen-Jian-Pi. Part 1: Biogenic components and identification of targets and signaling pathways in amyotrophic lateral sclerosis patients.

BACKGROUND: There is evidence that Bu-Shen-Jian-Pi (BSJP), a traditional Chinese medicine, has curative effects in patients suffering from amyotrophic lateral sclerosis (ALS), a progressive and potentially fatal hypoxic condition. OBJECTIVE: To identify biogenic components in BSJP extracts having potential pharmacological efficacy in ALS. MATERIALS AND METHODS: Biogenic components in BSJP and their potential pharmacological targets and signaling pathways in ALS were identified and assessed using network pharmacology/hub node analysis. RESULTS: Network pharmacology analysis identified icariin, naringenin, kaempferol, quercetin, and formononetin as core components in BSJP with potential activity involving mitochondrial protection in patients with ALS. CONCLUSION: Network pharmacology analysis proved to be a successful screening tool for obtaining information from scientific databases on the pharmacology of biogenic components in BSJP showing potential therapeutic activity in ALS.

Network pharmacology analysis and clinical efficacy of the traditional Chinese medicine Bu-Shen-Jian-Pi. Part 2: Modulation of hypoxia, redox status, and mitochondrial protection in a neuroblastoma cell line, SH-SY5Y.

OBJECTIVE: To examine the mitochondrial protective effects of icariin, naringenin, kaempferol, and formononetin, potentially active agents in Bu-Shen-Jian-Pi formula (BSJP) identified using network pharmacology analysis. MATERIALS AND METHODS: Mitochondrial protection activity was determined using a hypoxia-reoxygenation in vitro model based on the neuroblastoma cell line SH-SY5Y and measurements of anti-ferroptotic activity. RESULTS: Icariin, naringenin, kaempferol, and formononetin showed mitochondrial protective activity involving diverse signaling pathways. The cytoprotective effects of formononetin depended on the inhibition of ferroptosis. Hypoxia-reoxygenation stimulation induced ferroptosis in SH-SY5Y cells. DISCUSSION: Ferroptosis is a key mechanism in nervous system diseases and is associated with hypoxia-reoxygenation injury. Naringenin and kaempferol were devoid of anti-ferroptotic activity. CONCLUSION: Evidence has been obtained showing that the core components: icariin, naringenin, kaempferol, and formononetin in BSJP formula have anti-hypoxic and mitochondrial protective activity of potential clinical importance in the treatment of amyotrophic lateral sclerosis and patients with symptoms of hypoxia.

C-C motif chemokine ligand 5 confines liver regeneration by down-regulating reparative macrophage-derived hepatocyte growth factor in a forkhead box O 3a-dependent manner.

BACKGROUND AND AIMS: Liver regeneration (LR) is vital for the recovery of liver function after hepatectomy. Limited regeneration capacity, together with insufficient remnant liver volume, is a risk factor for posthepatectomy liver failure (PHLF) resulting from small-for-size syndrome. Although inflammation plays an important role in controlling LR, the underlying mechanisms still remain obscure. APPROACH AND RESULTS: We identified C-C motif chemokine ligand (CCL) 5 as an important negative regulator for LR. CCL5 levels were elevated after partial hepatectomy (PHx), both in healthy donors of living donor liver transplantation (LT) and PHx mouse models. Ccl5 knockout mice displayed improved survival after 90% PHx and enhanced LR 36 h after 70% PHx. However, primary hepatocytes from Ccl5-/- mice exposed to growth factors in vitro showed no proliferation advantage compared to those from wild-type (WT) mice. Flow cytometry analysis showed that proportions of Ly6Clo macrophages were significantly increased in Ccl5-/- mice after 70% PHx. RNA-sequencing analysis revealed that sorted macrophages (CD11b+ Ly6Clo&hi ) manifested enhanced expression of reparative genes in Ccl5-/- mice compared to WT mice. Mechanistically, CCL5 induced macrophages toward proinflammatory Ly6Chi phenotype, thereby inhibiting the production of hepatocyte growth factor (HGF) through the C-C motif chemokine receptor (CCR) 1- and CCR5-mediated forkhead box O (FoxO) 3a pathways. Finally, blockade of CCL5 greatly optimized survival and boosted LR in the mouse PHx model. CONCLUSIONS: Our findings suggest that inhibition of CCL5 is a promising strategy to improve regeneration restoration by enhancing HGF secretion from reparative macrophages through the FoxO3a pathway, which may potentially reduce the mortality of PHLF.

Improved performance of InGaAs/AlGaAs quantum well lasers on silicon using InAlAs trapping layers.

InGaAs/AlGaAs multiple quantum well lasers grown on silicon (001) by molecular beam epitaxy have been demonstrated. By inserting InAlAs trapping layers into AlGaAs cladding layers, misfit dislocations easily located in the active region can be effectively transferred out of the active region. For comparison, the same laser structure without the InAlAs trapping layers was also grown. All these as-grown materials were fabricated into Fabry-Perot lasers with the same cavity size of 20 × 1000 µm2. The laser with trapping layers achieved a 2.7-fold reduction in threshold current density under pulsed operation (5 µs-pulsed width, 1%-duty cycle) compared to the counterpart, and further realized a room-temperature continuous-wave lasing with a threshold current of 537 mA which corresponds to a threshold current density of 2.7 kA/cm2. When the injection current reached 1000 mA, the single-facet maximum output power and slope efficiency were 45.3 mW and 0.143 W/A, respectively. This work demonstrates significantly improved performances of InGaAs/AlGaAs quantum well lasers monolithically grown on silicon, providing a feasible solution to optimize the InGaAs quantum well structure.

Amygdalin protects against acetaminophen-induced acute liver failure by reducing inflammatory response and inhibiting hepatocyte death.

Amygdalin is a natural compound from Bitter Apricot Seed which is reported to have anti-inflammatory activity. Acetaminophen (APAP) resulted in drug-induced liver injury is the main cause of acute liver failure (ALI) worldwide and only N-acetylcysteine is the accepted detoxification drug. However, there is no effective medicine to perfect the hepatocyte death and secondary inflammation injury. In this study, we aim to investigate the protective effect of Amygdalin in the APAP-induced acute liver failure mice model. We establish the ALI model via intraperitoneal APAP injection and mice were treated with Amygdalin with intraperitoneal injection. We detected liver enzyme and histological change to evaluate the liver injury. We measured oxidative damage markers and inflammatory cell infiltration of liver tissues. At last, we investigated the mechanism of Amygdalin on protecting hepatocytes. Results showed that Amygdalin reduced ALT/AST level and decreased necrotic area of liver tissue. In addition, Amygdalin reduced the count of MPO+(neutrophils) and F4/80+(macrophages) of the liver and inhibited IL-6, TNF-a, and IL-1b expression. Amygdalin reduced liver SOD and MDA levels and increased Nrf2/NQO1/HO1 protein expression. Moreover, Amygdalin reduced TUNEL+ and P-MLKL + staining cells in liver tissue. Mechanically, Amygdalin promoted phosphorylation of AKT and suppressed JNK/RIP3/MLKL signaling.

Effect analysis of a virtual simulation experimental platform in teaching pulpotomy.

BACKGROUND: The experimental teaching of pediatric dentistry is a bridge between theoretical study and clinical practice, and virtual simulation technology provides a new method of instruction. METHODS: We built an experimental teaching platform using virtual simulation technology for vital pulpotomy that includes learning and examination modes. A total of 199 students majoring in stomatology in the fourth year at Sun Yat-Sen University were randomly divided into a control group (conventional teaching mode) and an experimental group (virtual simulation experimental teaching model). The teaching effect was evaluated by theoretical and experimental examination. RESULTS: We found that both the theoretical and experimental scores of the experimental group were higher than those of the control group, and the theoretical scores of the experimental group after exposure to the virtual simulation experimental teaching platform were also higher than those before the class, with significant differences (P < 0.05). Feedback from the experimental group after the class indicated that the platform reinforced their theoretical knowledge and greatly improved their mastery of operational skills. CONCLUSIONS: The application of a virtual simulation experimental teaching platform can effectively improve the teaching of pulpotomy.

Radiographic outcomes and prognostic factors in nonvital immature permanent teeth after apexification with modified calcium hydroxide paste: a retrospective study.

OBJECTIVE: To assess the radiographic outcomes and prognostic factors in nonvital immature permanent teeth after apexification with modified calcium hydroxide paste. MATERIALS AND METHODS: Clinical and radiographic data were collected from 115 necrotic immature permanent teeth (71 caused by trauma and 44 caused by dens evaginatus) treated with apexification using a modified calcium hydroxide. Postoperative root morphology and changes in radiographic root area (RRA) on periapical radiographs were determined and statistically evaluated. Regression analysis was performed to identify factors associated with the outcomes of apexification. RESULTS: The average time for a calcified barrier formation was 10.66 ± 6.37 months. The root morphology after apexification with calcium hydroxide + iodoform paste was similar to that previously described after calcium hydroxide apexification. Compared with the trauma cases, the dens evaginatus cases revealed more type I (40.91% vs 16.9%) and less type II morphology (45.45% vs 67.61%). Although the changes in RRA were limited, the dens evaginatus cases showed greater increment of RRA than the trauma cases (4.12% ± 5.58% vs 0.70% ± 5.21%, P < 0.001). A significant association was found between the preoperative stage of root development and postoperative percentage change in RRA (P < 0.001). CONCLUSIONS: Teeth caused by dens evaginatus had better outcomes after apexification than teeth caused by trauma. Early stages of root development were associated with superior radiographic outcomes. CLINICAL RELEVANCE: Apexification provided reliable outcomes in the treatment of immature teeth with pulp necrosis and apical periodontitis, even though the root development is limited. Treatment decision should be made with comprehensive evaluation of prognostic factors.

One-Step Carbonization Synthesis of Magnetic Biochar with 3D Network Structure and Its Application in Organic Pollutant Control.

In this study, a magnetic biochar with a unique 3D network structure was synthesized by using a simple and controllable method. In brief, the microbial filamentous fungus Trichoderma reesei was used as a template, and Fe3+ was added to the culture process, which resulted in uniform recombination through the bio-assembly property of fungal hyphae. Finally, magnetic biochar (BMFH/Fe3O4) was synthesized by controlling different heating conditions in a high temperature process. The adsorption and Fenton-like catalytic performance of BMFH/Fe3O4 were investigated by using the synthetic dye malachite green (MG) and the antibiotic tetracycline hydrochloride (TH) as organic pollutant models. The results showed that the adsorption capacity of BMFH/Fe3O4 for MG and TH was 158.2 and 171.26 mg/g, respectively, which was higher than that of most biochar adsorbents, and the Fenton-like catalytic degradation effect of organic pollutants was also better than that of most catalysts. This study provides a magnetic biochar with excellent performance, but more importantly, the method used can be effective in further improving the performance of biochar for better control of organic pollutants.

Preoperative factors analysis on root development after regenerative endodontic procedures: a retrospective study.

BACKGROUND: Regenerative endodontic procedures (REPs) have achieved clinical success on the immature permanent teeth with pulp necrosis, and can promote root development. However, preoperative factors and their effects on root development of REPs have not been definitely concluded. The aim of this study was to investigate the preoperative factors that may influence the root development of REPs. METHODS: A total of 116 teeth in 110 patients treated with REPs in the Paediatric Dentistry Department and Endodontics Department from 2013 to 2017 were included in this study. Preoperative factors including aetiology, age, diagnosis and initial root morphology were collected retrospectively, and the associations between these factors and root development after REPs were analysed by Fisher's exact test and multivariate logistic regression model. RESULTS: The overall rate of root development after REPs was 89.7%. The dens evaginatus group showed a higher rate (98.8%) in root development than the trauma group (67.6%) (P < 0.01). There was no significant difference among the different age groups (7-13 years old) or among different diagnoses groups (P > 0.05). And it showed in the trauma group that the teeth with apical foramen sizes larger than 3 mm significantly promoted root development than those smaller than 3 mm (P < 0.01). Multivariate logistic regression indicated that aetiology was significantly correlated with root development of REPs (OR: 0.07, 95% CI 0.007, 0.627, P < 0.05). CONCLUSIONS: The REPs promoted more root developments in the dens evaginatus group than the trauma group, indicating that aetiology may be correlated with the root development of REPs.

Role of cellular, molecular and tumor microenvironment in hepatocellular carcinoma: Possible targets and future directions in the regorafenib era.

Hepatocellular carcinoma (HCC) remains as one of the major causes of cancer-related mortality, despite the recent development of new therapeutic options. Regorafenib, an oral multikinase inhibitor, is the first systemic therapy that has a survival benefit for patients with advanced HCC that have a poor response to sorafenib. Even though regorafenib has been approved by the FDA, the clinical trial for regorafenib treatment does not show significant improvement in overall survival. The impaired efficacy of regorafenib caused by various resistance mechanisms, including epithelial-mesenchymal transitions, inflammation, angiogenesis, hypoxia, oxidative stress, fibrosis and autophagy, still needs to be resolved. In this review, we provide insight on regorafenib microenvironmental, molecular and cellular mechanisms and interactions in HCC treatment. The aim of this review is to help physicians select patients that would obtain the maximal benefits from regorafenib in HCC therapy.

iTRAQ-based quantitative analysis reveals the mechanism underlying the changes in physiological activity in a glutamate racemase mutant strain of Streptococcus mutans UA159.

Streptococcus mutans UA159 is responsible for human dental caries with robust cariogenic potential. Our previous study noted that a glutamate racemase (MurI) mutant strain (designated S. mutans FW1718), with the hereditary background of UA159, displayed alterations of morphogenesis, attenuated stress tolerance, and weakened biofilm-forming capabilities, accompanying with unclear mechanisms. In this study, we applied isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics to characterize the proteome profiles of the murI mutant strain vs. the wild-type strain in chemically defined media to elucidate the mechanisms by which S. mutans copes with MurI deficiency. Whole-cell proteins of S. mutans FW1718 and UA159 were assessed by iTRAQ-coupled LC-ESI-MS/MS. Furthermore, differentially expressed proteins (DEPs) were identified by Mascot, Gene Ontology (GO) annotation, Cluster of Orthologous Groups of proteins (COG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Finally, a protein-protein interaction (PPI) network was established using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Among 1173 total bacterial proteins identified, 112 DEPs exhibited altered expression patterns in S. mutans UA159 with or without the murI mutation. The ΔmurI cells displayed an increase in the relative expression of 93 proteins (fold change ≥ 1.2, p < 0.05) and a decrease in 29 proteins (fold change ≤ 0.833, p < 0.05) compared with the wild-type cells. PPI analysis revealed a complex network of DEPs containing 191 edges and 122 nodes. The DEPs significantly upregulated after murI knockout had roles in diverse functional processes spanning cell-wall biosynthesis, energy production, and DNA replication and repair. We identified distinct variations and diverse modulators caused by murI mutation in the proteome of S. mutans, indicating that the modification of cell membrane structure, redistribution of energy metabolism and enhanced nucleic acid machinery contributed to the S. mutans response to specific environmental contexts.

Trans-cinnamaldehyde shows anti-depression effect in the forced swimming test and possible involvement of the endocannabinoid system.

Depression is a mental disease that significantly reduces the quality of patients' life. Around 322 million people of all ages carry the heavy burden of depression on a worldwide scale, with a life-time prevalence of 20% according to the WHO. Trans-cinnamaldehyde (TCA) is an excellent COX-2 inhibitor in central nervous system which is a main constituent of GUIZHI as a member of traditional Chinese herb. Furthermore, previous studies demonstrated that TCA suppressed depression-like behavior in chronic unexpected mild stress, plus maze test and open field test. However, the molecular mechanism of TCA anti-depression effect is not clear. We examined the immobility of TCA pretreated male BALB/c mice in the forced swimming test (FST). Results show that TCA (50 mg/kg, po) revealed a significant effect on reduced immobility in the FST, compared with SAL group which indicated that TCA suppressed depression-like behavior. Moreover, TCA elevated the level of 5-HT and decreased the ratio of Glu/GABA in mice hippocampus. Compared with SAL + FST group, TCA + FST group significantly decreased COX-2, TRPV1 and CB1 protein level in mice hippocampus (p < 0.05, p < 0.05, p < 0.01). These findings suggest that TCA treatment exerted anti-depressive effect and was able to regulate neurotransmitters in the FST. This effect may have positive influence on the endocannabinoid (eCB) system.

A negative feedback modulator of antigen processing evolved from a frameshift in the cowpox virus genome.

Coevolution of viruses and their hosts represents a dynamic molecular battle between the immune system and viral factors that mediate immune evasion. After the abandonment of smallpox vaccination, cowpox virus infections are an emerging zoonotic health threat, especially for immunocompromised patients. Here we delineate the mechanistic basis of how cowpox viral CPXV012 interferes with MHC class I antigen processing. This type II membrane protein inhibits the coreTAP complex at the step after peptide binding and peptide-induced conformational change, in blocking ATP binding and hydrolysis. Distinct from other immune evasion mechanisms, TAP inhibition is mediated by a short ER-lumenal fragment of CPXV012, which results from a frameshift in the cowpox virus genome. Tethered to the ER membrane, this fragment mimics a high ER-lumenal peptide concentration, thus provoking a trans-inhibition of antigen translocation as supply for MHC I loading. These findings illuminate the evolution of viral immune modulators and the basis of a fine-balanced regulation of antigen processing.

Comparison of mineral trioxide aggregate and calcium hydroxide for apexification of immature permanent teeth: A systematic review and meta-analysis.

BACKGROUND/PURPOSE: Calcium hydroxide and mineral trioxide aggregate (MTA) are used for inducing a calcific barrier at an open tooth root (apexification). The purpose of this study was to compare the efficacy of calcium hydroxide and MTA for apexification of immature permanent teeth. METHODS: Medline, Cochrane, EMBASE, and Google Scholar were searched until November 24, 2015, using the keywords apexification, permanent teeth, MTA, and calcium hydroxide. RESULTS: Of 216 studies identified, four studies were included. There were no differences in the clinical success rate [pooled odds ratio (OR) = 3.03, 95% confidence interval (CI): 0.42-21.72, p = 0.271], radiographic success rate (pooled OR = 4.30, 95% CI: 0.45-41.36, p = 0.206), or apical barrier formation rate (pooled OR = 1.71, 95% CI: 0.59-4.96, p = 0.322) between calcium hydroxide and MTA groups. The time required for apical barrier formation was significantly less in the MTA group (pooled difference in means = -3.58, 95% CI: from -4.91 to -2.25, p < 0.001). CONCLUSION: While both materials provide similar success rates, the shorter treatment time with MTA may translate into higher overall success rates because of better patient compliance.

Retinoic acid induces macrophage cholesterol efflux and inhibits atherosclerotic plaque formation in apoE-deficient mice.

It has been suggested that retinoic acid (RA) has a potential role in the prevention of atherosclerotic CVD. In the present study, we used J774A.1 cell lines and primary peritoneal macrophages to investigate the protective effects of RA on foam cell formation and atherogenesis in apoE-deficient (apoE- / -) mice. A total of twenty male apoE- / - mice (n 10 animals per group), aged 8 weeks, were fed on a high-fat diet (HFD) and treated with vehicle or 9-cis-RA for 8 weeks. The atherosclerotic plaque area in the aortic sinus of mice in the 9-cis-RA group was 40·7 % less than that of mice in the control group (P< 0·01). Mouse peritoneal macrophages from the 9-cis-RA group had higher protein expression levels of ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) than those from the control group. Serum total and LDL-cholesterol concentrations were lower in the 9-cis-RA group than in the control group (P< 0·05). In vitro studies showed that incubation of cholesterol-loaded J774A.1 macrophages with 9-cis-RA (0·1, 1 and 10 µmol/l) induced cholesterol efflux in a dose-dependent manner. The 9-cis-RA treatment markedly attenuated lipid accumulation in macrophages exposed to oxidised LDL. Moreover, treatment with 9-cis-RA significantly increased the protein expression levels of ABCA1 and ABCG1 in J774A.1 macrophages in a dose-dependent manner. Furthermore, 9-cis-RA dose-dependently enhanced the protein expression level of liver X receptor-α (LXRα), the upstream regulator of ABCA1 and ABCG1. Taken together, the present results show that 9-cis-RA suppresses foam cell formation and prevents HFD-induced atherogenesis via the LXRα-dependent up-regulation of ABCA1 and ABCG1.

Role of Candida albicans-secreted aspartyl proteinases (Saps) in severe early childhood caries.

Candida albicans is strongly associated with severe early childhood caries (S-ECC). However, the roles of secreted aspartyl proteinases (Saps), an important virulence factor of C. albicans, in the progress of S-ECC are not clear. In our study, the Saps activities were evaluated by the yeast nitrogen base-bovine serum albumi (YNB-BSA) agar plate method and by the MTT method with bovine serum albumin (BSA) as the substrate. Genotypes of C. albicans and gene expression of Sap1-5 were evaluated. The relationships of Saps activities and genotypes with S-ECC were analyzed. The results showed that enzyme activities of Saps in the S-ECC group were significantly higher than those in the caries free (CF) group (p<0.05). Genotypes A, B and C were detected in the S-ECC group, and genotypes A and C were detected in the CF group. In the genotype A group, Saps activity in the S-ECC group was significantly different from that in the CF group (p<0.05). The gene expression level of Sap1 in the S-ECC group was significantly higher than that in the CF group (p=0.001), while Sap4 expression was significantly lower than that in the CF group (p=0.029). It can be concluded that Sap1-5 are the predominant proteinase genes expressed in C. albicans from dental biofilm and Sap1 may play an important role in the development of S-ECC.

Unsupervised Imbalanced Registration for Enhancing Accuracy and Stability in Medical Image Registration.

BACKGROUND: Medical image registration plays an important role in several applications. Existing approaches using unsupervised learning encounter issues due to the data imbalance problem, as their target is usually a continuous variable. OBJECTIVE: In this study, we introduce a novel approach known as Unsupervised Imbalanced Registration, to address the challenge of data imbalance and prevent overconfidence while increasing the accuracy and stability of 4D image registration. METHODS: Our approach involves performing unsupervised image mixtures to smooth the input space, followed by unsupervised image registration to learn the continual target. We evaluated our method on 4D-Lung using two widely used unsupervised methods, namely VoxelMorph and ViT-V-Net. RESULTS: Our findings demonstrate that our proposed method significantly enhances the mean accuracy of registration by 3%-10% on a small dataset while also reducing the accuracy variance by 10%. CONCLUSION: Unsupervised Imbalanced Registration is a promising approach that is compatible with current unsupervised image registration methods applied to 4D images.