Mucin-producing tumors of the ovary--preoperative differentiation between metastatic ovarian mucinous carcinoma and primary mucinous malignant tumors.

OBJECTIVE: To investigate the clinical and magnetic resonance imaging (MRI) features for preoperatively discriminating  primary ovarian mucinous malignant tumors (POMTs) and metastatic mucinous carcinomas involving the ovary (MOMCs). METHODS: This retrospective multicenter study enrolled 61 patients with 22 POMTs and 49 MOMCs, which were pathologically proved between November 2014 to Jane 2023. The clinical and MRI features were evaluated and compared between POMTs and MOMCs. Univariate and multivariate analyses were performed to identify the significant variables between the two groups, which were then incorporated into a predictive nomogram, and ROC curve analysis was subsequently carried out to evaluate diagnostic performance. RESULTS: 35.9% patients with MOMCs were discovered synchronously with the primary carcinomas; 25.6% patients with MOMCs were bilateral, and all of the patients with POMTs were unilateral. The biomarker CEA was significantly different between the two groups (p = 0.002). There were significant differences in the following MRI features: tumor size, configuration, enhanced pattern, the number of cysts, honeycomb sign, stained-glass appearance, ascites, size diversity ratio, signal diversity ratio. The locular size diversity ratio (p = 0.005, OR = 1.31), and signal intensity diversity ratio (p = 0.10, OR = 4.01) were independent predictors for MOMCs. The combination of above independent criteria yielded the largest area under curve of 0.922 with a sensitivity of 82.3% and specificity of 88.9%. CONCLUSIONS: Patients with MOMCs were more commonly bilaterally and having higher levels of CEA, but did not always had a malignant tumor history. For ovarian mucin-producing tumors, the uniform locular sizes and signal intensities were more predict MOMCs.

An automated ICU agitation monitoring system for video streaming using deep learning classification.

OBJECTIVE: To address the challenge of assessing sedation status in critically ill patients in the intensive care unit (ICU), we aimed to develop a non-contact automatic classifier of agitation using artificial intelligence and deep learning. METHODS: We collected the video recordings of ICU patients and cut them into 30-second (30-s) and 2-second (2-s) segments. All of the segments were annotated with the status of agitation as "Attention" and "Non-attention". After transforming the video segments into movement quantification, we constructed the models of agitation classifiers with Threshold, Random Forest, and LSTM and evaluated their performances. RESULTS: The video recording segmentation yielded 427 30-s and 6405 2-s segments from 61 patients for model construction. The LSTM model achieved remarkable accuracy (ACC 0.92, AUC 0.91), outperforming other methods. CONCLUSION: Our study proposes an advanced monitoring system combining LSTM and image processing to ensure mild patient sedation in ICU care. LSTM proves to be the optimal choice for accurate monitoring. Future efforts should prioritize expanding data collection and enhancing system integration for practical application.

Dual intervention on the gut and skin microbiota attenuates facial cutaneous aging.

The gut and skin microbiota are microbial barriers, resisting harmful foreign microorganisms and maintaining internal homeostasis. Dysbiosis of the gut and skin microbiota is involved in aging progression. However, interventions targeting facial skin wellness taking into account the gut-skin axis are scarce. In this study, the impact of an eight-week intervention with oral (O), topical (T), and both oral and topical (OT) xylo-oligosaccharides (XOS) by regulating gut and skin microbiota on facial cutaneous aging was investigated in a double-blind placebo-controlled trial in females. An increase in the proportion of participants with skin rejuvenation was observed, along with a significant reduction in facial pores after OT intervention. The reduction of cutaneous Cutibacterium by OT intervention was greater than that in the O and T groups. These interventions can change the skin microbial structure. Intestinal Bifidobacterium was enriched only by dual treatment with oral and topical XOS. Function prediction analysis revealed a decrease in K02770 encoding fructose-1-phosphate kinase involved in de novo lipid synthesis from fructose with dual intervention, suggesting that inhibition of lipophilic Cutibacterium may contribute to reducing facial pores. Overall, the dual XOS intervention approach is most effective for improving both gut and skin microbiota, as well as facial skin aging.

Comprehensive analysis revealed the immunoinflammatory targets of rheumatoid arthritis based on intestinal flora, miRNA, transcription factors, and RNA-binding proteins databases, GSEA and GSVA pathway observations, and immunoinfiltration typing.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory arthritis. This study aimed to identify potential biomarkers and possible pathogenesis of RA using various bioinformatics analysis tools. METHODS: The GMrepo database provided a visual representation of the analysis of intestinal flora. We selected the GSE55235 and GSE55457 datasets from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) separately. With the intersection of these DEGs with the target genes associated with RA found in the GeneCards database, we obtained the DEGs targeted by RA (DERATGs). Subsequently, Disease Ontology, Gene Ontology, and the Kyoto Encyclopedia of Genes and Genomes were used to analyze DERATGs functionally. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were performed on the data from the gene expression matrix. Additionally, the protein-protein interaction network, transcription factor (TF)-targets, target-drug, microRNA (miRNA)-mRNA networks, and RNA-binding proteins (RBPs)-DERATGs correlation analyses were built. The CIBERSORT was used to evaluate the inflammatory immune state. The single-sample GSEA (ssGSEA) algorithm and differential analysis of DERATGs were used among the infiltration degree subtypes. RESULTS: There were some correlations between the abundance of gut flora and the prevalence of RA. A total of 54 DERATGs were identified, mainly related to immune and inflammatory responses and immunodeficiency diseases. Through GSEA and GSVA analysis, we found pathway alterations related to metabolic regulations, autoimmune diseases, and immunodeficiency-related disorders. We obtained 20 hub genes and 2 subnetworks. Additionally, we found that 39 TFs, 174 drugs, 2310 miRNAs, and several RBPs were related to DERATGs. Mast, plasma, and naive B cells differed during immune infiltration. We discovered DERATGs' differences among subtypes using the ssGSEA algorithm and subtype grouping. CONCLUSIONS: The findings of this study could help with RA diagnosis, prognosis, and targeted molecular treatment.

Dynamic biomechanical changes of clear aligners during extraction space closure: Finite element analysis.

INTRODUCTION: Clear aligners (CAs) have recently become popular and widely used orthodontic appliances. Research on CA biomechanics has become a focal point in orthodontics to improve the efficiency of CA treatment and address challenging issues, such as extraction. The biomechanical characteristics of CAs in space closure have been reported. However, previous studies have mainly focused on static biomechanical analysis that cannot demonstrate the dynamic biomechanical changes in CAs during space-closing. Given that these biomechanical changes can be significant and have considerable clinical value, this study aimed to investigate these characteristics. METHODS: Sequential extraction space-closing models were derived from included patient data and refined using modeling and CA design software. A finite element analysis was performed to obtain biomechanical raw data. This study introduced a dual coordinate system and space geometry analysis to demonstrate the biomechanical properties accurately. RESULTS: As space closure progressed, the instantaneous tooth displacements increased, indicating an enhanced space closure force because of the increased strain in the CA extraction area. Meanwhile, the central axis of rotation of the anterior teeth continuously moved toward the labial-apical direction, showing a gradually enhanced vertical and torque control effect. CONCLUSIONS: During space closure, CAs undergo specific biomechanical changes, including increased contraction and control forces on both sides of the gap. These biomechanical effects are beneficial to alleviate the roller coaster effect gradually. Meanwhile, more reasonable staging design strategies can be proposed on the basis of this biomechanical mechanism.

Rapamycin can alleviate the submandibular gland pathology of Sjögren's syndrome by limiting the activation of cGAS-STING signaling pathway.

BACKGROUND: Sjögren's Syndrome (SS) is also known as autoimmune exocrine gland disease. Previous studies have confirmed that adaptive immunity plays an important role in the development of this disease. But less is known about the role of the innate immune system. METHODS: To identify the core pathways, and local infiltrated immune cells in the local immune microenvironment of SS. We verified the activation of these core genes and core signaling pathways in SS model mice by in vivo experiment and transcriptome sequencing. RESULTS: Finally, we identified 6 core genes EPSTI1, IFI44L, MX1, CXCL10, IFIT3, and IFI44. All the 6 genes had good diagnostic value. Based on multi-omics sequencing results and experimental studies, we found that cGAS-STING signaling pathway is most relevant to the pathogenesis of SS. By in vivo experiments, we verified that autophagy is the key brake to limit the activation of cGAS-STING signaling pathway. CONCLUSIONS: Maladaptive activation of autophagy and cGAS-STING signaling pathway are central contributors to the SG pathogenesis of pSS patient. Regulating autophagy by rapamycin may be a possible treatment for Sjögren's syndrome in the future.

Identification of the six-hormone secretion-related gene signature as a prognostic biomarker for colon adenocarcinoma.

BACKGROUND: Colon adenocarcinoma (COAD) is a globally prevalent cancer, with hormone secretion playing a crucial role in its progression. Despite this, there is limited understanding of the impact of hormone secretion on COAD prognosis. This study aimed to establish a prognostic signature based on hormone secretion-related genes and to elucidate the potential functional mechanisms of these genes in COAD. METHODS: Using data from The Cancer Genome Atlas COAD cohort (TCGA-COAD), six hormone secretion-related genes were identified (CYP19A1, FOXD1, GRP, INHBB, SPP1, and UCN). These genes were used to develop a Hormone secretion score (HSS), which was then evaluated using the Kaplan-Meier curve and multivariable Cox analysis. The HSS model was further validated with external GEO cohorts (GSE41258, GSE39582, and GSE87211). Functional enrichment analyses were performed, and the CIBERSORT and TIDE algorithms were used to assess tumor infiltration. RESULTS: The study developed a prognostic signature, dividing patients into HSS-high and HSS-low groups. The HSS-high group showed a notably worse prognosis within the TCGA-COAD dataset and in three independent datasets: GSE41258, GSE39582, and GSE87211. Moreover, the HSS-high group predicted a shorter overall survival rate in patients maintaining microsatellite stability (MSS). The functional analysis associated HSS-high with the hypoxic, epithelial-mesenchymal transition (EMT), and TGF-ß signaling pathways and correlated with distant and lymph node metastases. The tumor immune microenvironment analysis revealed an elevated CIBERSORT score in the HSS-high group, suggesting an association with tumor metastasis. Further, the HSS-high group showed a higher TIDE score, indicating that patients with high HSS scores are less likely to benefit from Immune Checkpoint Inhibitor (ICI) therapy. CONCLUSIONS: This study demonstrated the prognostic significance of a HSS signature based on six hormone secretion-related genes in COAD. The findings suggest that this gene signature may serve as a reliable biomarker for predicting survival outcomes in COAD patients.

Biosynthesis of Cosmosporasides Reveals the Assembly Line for Fungal Hybrid Terpenoid Saccharides.

Fungal hybrid terpenoid saccharides constitute a new and growing family of natural products with significant biomedical and agricultural activities. One representative family is the cosmosporasides, which feature oxidized terpenoid units and saccharide moieties; however, the assembly line of these building blocks has been elusive. Herein, a cos cluster from Fusarium orthoceras was discovered for the synthesis of cosmosporaside C (1) by genome mining. A UbiA family intramembrane prenyltransferase (UbiA-type PT), a multifunctional cytochrome P450, an α,ß-hydrolase, an acetyltransferase, a dimethylallyl transferase (DMAT-type PT) and a glycosyltransferase function cooperatively in the assembly of the scaffold of 1 using primary central metabolites. The absolute configuration at C4, C6 and C7 of 1 was also established. Our work clarifies the unexpected functions of UbiA-type and DMAT-type PTs and provides an example for understanding the synthetic logic of hybrid terpenoid saccharides in fungi.

CXCL10 as a shared specific marker in rheumatoid arthritis and inflammatory bowel disease and a clue involved in the mechanism of intestinal flora in rheumatoid arthritis.

This study aimed to identify shared specific genes associated with rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) through bioinformatic analysis and to examine the role of the gut microbiome in RA. The data were extracted from the 3 RA and 1 IBD gene expression datasets and 1 RA gut microbiome metagenomic dataset. Weighted correlation network analysis (WGCNA) and machine learnings was performed to identify candidate genes associated with RA and IBD. Differential analysis and two different machine learning algorithms were used to investigate RA's gut microbiome characteristics. Subsequently, the shared specific genes related to the gut microbiome in RA were identified, and an interaction network was constructed utilizing the gutMGene, STITCH, and STRING databases. We identified 15 candidates shared genes through a joint analysis of the WGCNA for RA and IBD. The candidate gene CXCL10 was identified as the shared hub gene by the interaction network analysis of the corresponding WGCNA module gene to each disease, and CXCL10 was further identified as the shared specific gene by two machine learning algorithms. Additionally, we identified 3 RA-associated characteristic intestinal flora (Prevotella, Ruminococcus, and Ruminococcus bromii) and built a network of interactions between the microbiomes, genes, and pathways. Finally, it was discovered that the gene CXCL10 shared between IBD and RA was associated with the three gut microbiomes mentioned above. This study demonstrates the relationship between RA and IBD and provides a reference for research into the role of the gut microbiome in RA.

Reshaping the Diversity of Oxidized Polyquinane Sesquiterpenoids by Cytochrome P450s.

Polyquinane sesquiterpenoids (PQSTs) are complex compounds with two or three fused cabocyclopentane ring systems, and the biocatalysts for direct C-H bond oxidation on these scaffolds have rarely been discovered. In this study, we discovered two versatile fungal CYP450s capable of performing diverse oxidations on seven PQST scaffolds, resulting in the generation of 20 unique products. Our findings significantly expand the diversity of oxidized PQST scaffolds and provide important biocatalysts for the selective oxidation of inert carbons of terpenoids in future research.

Different biomechanical effects of clear aligners in closing maxillary and mandibular extraction spaces: Finite element analysis.

INTRODUCTION: Compared with fixed treatments, clear aligners (CAs) have the advantages of comfort, esthetics, and hygiene, and are popular among patients and orthodontists. However, CAs exhibit control deficiencies in extraction patients because of insufficient root control and retention effects. These deficiencies can magnify biomechanical differences in bimaxillary dentition, further causing different orthodontic requirements between maxillary and mandibular dentition. This study aimed to elaborate on the biomechanical characteristics of bimaxillary dentition in extraction space closure and provided feasible biomechanical compensation strategies for use in clinical practice. METHODS: We constructed a 3-dimensional (3D) bimaxillary model based on patient data. Several 3D modeling-related software was used to generate a standard first premolar extraction model, CAs, and attachments. Subsequently, finite element analysis was performed to demonstrate the biomechanical effects. RESULTS: The maxillary and mandibular dentition showed a roller coaster effect during space closure. Compared with the maxillary dentition, the mandibular posterior teeth exhibited stronger relative anchorage causing greater anterior teeth retraction. The tipping and vertical movements of the anterior teeth were related to tooth length. The longer the anterior tooth, the less tipping and greater vertical displacement occurred. Generally, when having the same retraction distance, the mandibular dentition exhibited greater retroclination and fewer extrusions. Both mechanical and retention compensations should be considered to prevent these unwanted tipping movements. Adding specific attachments to bimaxillary dentitions compensated for the retention and root control deficiencies of CAs. CONCLUSIONS: When applying CAs to extraction patients, different biomechanical effects can present in the bimaxillary dentition because of specific dentition morphologies. To effectively treat these patients, mechanical compensation through overcorrection of the target position should be designed on the basis of bimaxillary control deficiencies, and retention compensation by adding specific attachments should also be considered according to the overcorrections.

Finite element analysis of the biomechanical effect of clear aligners in extraction space closure under different anchorage controls.

INTRODUCTION: Clear aligners (CAs) have attracted increasing attention from patients and orthodontists because of their excellent esthetics and comfort. However, treating tooth extraction patients with CAs is difficult because their biomechanical effects are more complicated than those of traditional appliances. This study aimed to analyze the biomechanical effect of CAs in extraction space closure under different anchorage controls, including moderate, direct strong, and indirect strong anchorage. It could provide several new cognitions for anchorage control with CAs through finite element analysis, further directing clinical practice. METHODS: A 3-dimensional maxillary model was generated by combining cone-beam computed tomography and intraoral scan data. Three-dimensional modeling software was used to construct a standard first premolar extraction model, temporary anchorage devices, and CAs. Subsequently, finite element analysis was performed to simulate space closure under different anchorage controls. RESULTS: Direct strong anchorage was beneficial for reducing the clockwise occlusal plane rotation, whereas indirect anchorage was conducive for anterior teeth inclination control. In the direct strong anchorage group, an increase in the retraction force would require more specific anterior teeth overcorrection to resist the tipping movement, mainly including lingual root control of the central incisor, followed by distal root control of the canine, lingual root control of the lateral incisor, distal root control of the lateral incisor, and distal root control of the central incisor. However, the retraction force could not eliminate the mesial movement of the posterior teeth, possibly causing a reciprocating motion during treatment. In indirect strong groups, when the button was close to the center of the crown, the second premolar presented less mesial and buccal tipping but more intrusion. CONCLUSIONS: The 3 anchorage groups showed significantly different biomechanical effects in both the anterior and posterior teeth. Specific overcorrection or compensation forces should be considered when using different anchorage types. The moderate and indirect strong anchorages have a more stable and single-force system and could be reliable models in investigating the precise control of future tooth extraction patients.

Case report: Unique FLT4 variants associated with differential response to anlotinib in angiosarcoma.

Angiosarcoma (AS) is a rare, clinically aggressive tumor with limited treatment options and a poor prognosis. Mutations involving the angiogenesis-related genesTP53, PTPRB, PLCG1, KDR as well as FLT4 amplification have been observed in AS. There is a potential therapeutic value of inhibition of the VEGF pathway against angiosarcoma. Our case first described a patient with two sites of cutaneous angiosarcomas (cASs) that responded differently to anlotinib. And genetic analysis revealed that those two sites had different FLT4 variants, suggesting that FLT4 amplification could be the cause of anlotinib non-response.

Different biomechanical effects of clear aligners in bimaxillary space closure under two strong anchorages: finite element analysis.

BACKGROUND: Clear aligner (CA) treatment has been gaining popularity, but the biomechanical effects of CAs in bimaxillary dentition have not been thoroughly investigated. Direct and indirect strong anchorages are two common anchorage control methods, but the underlying biomechanical mechanism has not yet been elucidated. This study aimed to investigate the different biomechanical effects of CAs in closing the bimaxillary space under different anchorage controls, further instructing the compensation strategies design and strong anchorage choice in clinical practice. METHODS: Three-dimensional (3D) bimaxillary models of different anchorage controls were created based on cone-beam computed tomography and intraoral scan data. Four first premolars were extracted using 3D modeling software. Finite element analysis was conducted to simulate the space closure process of the CAs. RESULTS: In the two strong anchorage groups, the bimaxillary dentition presented different movement patterns during the space closure process, and the lower dentition was more vulnerable to elastic force. From the vertical view, direct strong anchorage with elastic force had the advantage of flattening the longitudinal occlusal curve and resisting the roller-coaster effects, whereas indirect strong anchorage could lead to a deep longitudinal occlusal curve. From the sagittal view, indirect strong anchorage with metallic ligaments had a greater instantaneous anchorage protection effect, particularly in the lower dentition, which reduced the mesial movement of the posterior teeth by nearly four times that of the direct anchorage group. In addition, indirect strong anchorage presented better anterior teeth torque/tipping control, while direct strong anchorage could aggravate lingual tipping of the upper central incisors. Due to the differences in anterior-posterior anchorage and arch shape, compared with the upper dentition, anchorage preservation and vertical control effects were amplified in the lower dentition. CONCLUSIONS: The biomechanical effects of CAs differed between the two strong anchorage groups. Due to the differences in dentition morphology, anterior-posterior anchorage, and dental arch shape, CAs present different biomechanical effects in bimaxillary space closure. Orthodontists should consider the corresponding mechanical compensation according to specific anchorage control methods and dentitions.

White common bean extract remodels the gut microbiota and ameliorates type 2 diabetes and its complications: A randomized double-blinded placebo-controlled trial.

Objective: Excessive carbohydrate intake is a high risk factor for increased morbidity of type 2 diabetes (T2D). A novel regimen for the dietary care of diabetes that consists of a highly active α-amylase inhibitor derived from white common bean extract (WCBE) and sufficient carbohydrates intake was applied to attenuate T2D and its complications. Furthermore, the role of gut microbiota in this remission was also investigated. Methods: We conducted a 4-month randomized double-blinded placebo-controlled trial. During the intense intervention period, ninety subjects were randomly assigned to the control group (Group C) and WCBE group (Group W). Subjects in Group C were supplemented with 1.5 g of maltodextrin as a placebo. Subjects in Group W took 1.5 g of WCBE half an hour before a meal. Fifty-five participants continued the maintenance intervention receiving the previous dietary intervention whereas less frequent follow-up. The variation in biochemical, vasculopathy and neuropathy indicators and the structure of the fecal microbiota during the intervention was analyzed. Result: Glucose metabolism and diabetic complications showed superior remission in Group W with a 0.721 ± 0.742% decline of glycosylated hemoglobin after 4 months. The proportion of patients with diabetic peripheral neuropathy (Toronto Clinical Scoring System, TCSS ≥ 6) was significantly lower in Group W than in Group C. Both the left and right sural sensory nerve conduction velocity (SNCV-left sural and SNCV-right sural) slightly decreased in Group C and slightly increased in Group W. Additionally, the abundances of Bifidobacterium, Faecalibacterium and Anaerostipes were higher in Group W, and the abundances of Weissella, Klebsiella, Cronobacter and Enterobacteriaceae_unclassified were lower than those in Group C at month 2. At the end of month 4, Bifidobacterium remained more abundant in Group W. Conclusion: To our knowledge, this is the first report of improvement to diabetes complications by using a dietary supplement in such a short-term period. The enrichment of SCFA-producing bacteria might be responsible for the attenuation of T2D and its complications. Clinical trial registration number: http://www.chictr.org.cn/edit.aspx?pid=23309&htm=4, identifier ChiCTR-IOR-17013656.

Molecular and clinicopathological characteristics of ERBB2 gene fusions in 32,131 Chinese patients with solid tumors.

ERBB2 amplification is one of the most important and mature targets for HER2-targeted drug therapy. Somatic mutations of ERBB2 in the tyrosine kinase domain have been studied extensively, and play a role in response to anti-HER2 therapy among different cancer types. However, ERBB2 fusion has not been got attention and its relevance to HER2-targeted therapy is unclear. We comprehensively characterized ERBB2 fusions from next-generation sequencing (NGS) data between May 2018 and October 2021 in 32,131 various solid tumors. Among the tumors, 0.28% harbored ERBB2 fusions, which occurred more commonly in gastroesophageal junction cancer (3.12%; 3/96), breast cancer (1.89%; 8/422), urothelial carcinoma (1.72%; 1/58), and gastric cancer (1.60%; 23/1,437). Our population presented with a median age of 65 years (range 28 to 88 years), a high proportion of men (55 men vs 34 women; 61.80%). Among the patients with ERBB2 fusions, TP53 (82%), APC (18%), and CDK4 (15%) were the top3 co-mutant genes. What's more, most patients with ERBB2 fusion also had ERBB2 amplification (75.28%; 67/89), which was similar to the data in the TCGA database (88.00%; 44/50). Furthermore, TCGA database shows that patients with ERBB2 fusions in pan-cancer had a worse prognosis than those without ERBB2 fusions, as well as in breast cancer. Besides, ERBB2 amplification combined with ERBB2 fusion had worse prognosis than those with only ERBB2 amplification. ERBB2 fusion may interfere the effect of anti-HER2-targeted antibody drugs and influence the prognosis of patients with ERBB2 amplification. Prospective clinical trials are warranted to confirm the results in the future.

Predictive Value of Serum Cholic Acid and Lithocholic Acid for the Diagnosis in an Intrahepatic Cholestasis of Pregnancy Population with High Levels of Total Bile Acids and the Correlation with Placental Hypoxia-Inducible Factor-1α.

Objective: This study aimed to investigate the ability of serum cholic acid (CA) and lithocholic acid (LCA) in the diagnosis and perinatal prognosis assessment of intrahepatic cholestasis of pregnancy (ICP), and the relationship between both indicators and hypoxia-inducible factor-1α (HIF-1α). Methods: Between March 2020 and March 2021, pregnant women with high levels of total bile acid (TBA) in the late pregnancy with TBA ≥10 µmol/L and TBA <10 µmol/L (control group) were included for the retrospective study. Those with TBA ≥10 µmol/L were divided into the ICP group and the asymptomatic hypercholanaemia of pregnancy (AHP) group based on ICP symptoms. The comparison of the bile acid profiles, the receiver operating characteristic (ROC) curve analysis, and Pearson correlation analysis were conducted successively. Results: Nine types of bile acids were significantly higher in ICP and AHP than in the control group, while CA and LCA serum levels in the AHP group were significantly lower than those in the ICP group (P < 0.05). The ROC curve analysis showed that LCA, CA, and LCA+CA were all diagnostic indicators for ICP, and LCA+CA displayed the greatest diagnostic value (area under the curve (AUC), 0.923). Subgroup analysis using the LCA+CA cut-off point (3.28 µmol/L) as the subgroup indicator proved that the incidence of adverse perinatal outcomes and the placental HIF-1α positivity were significantly higher in the high LCA+CA group than in the low LCA+CA group (P < 0.05). Pearson correlation analysis revealed significant positive correlations of HIF-1α expression levels to LCA, CA and LCA+CA (r = 0.473, 0.537, 0.619, respectively. P < 0.05 in all). Conclusion: This study confirmed that CA and LCA have a predictive diagnostic value for ICP in pregnant women, and the combined evaluation is associated with adverse perinatal outcomes, and LCA+CA positively correlates to placental HIF-1α expression levels.

The effect of UV exposure on conventional and degradable microplastics adsorption for Pb (II) in sediment.

Plastic discharged into the environment would break down into microplastics (MPs). However, the possible impact of MPs on heavy metals in the aquatic sediment remains unknown. In order to evaluate the potential role of MPs as carriers of coexisting pollutants, the adsorption capacity of lead ions from sediment onto aged degradable and conventional MPs were investigated as a function of lead ions concentration, contact time, temperature, MPs dosage, aging time, and fulvic acid concentration. MPs were exposed to UV to obtain aged polyethylene (A-PE) and aged polylactic acid (A-PLA). The aging treatment increased the oxygen content, specific surface area and hydrophilicity of MPs. The adsorption capacity of A-PE for Pb(II) in sediment increased from 10.1525 to 10.4642 mg g-1 with the increasing aging time. However, the adsorption capacity of A-PLA for Pb(II) in sediment decreased from 9.3199 to 8.7231 mg g-1 with the increasing aging time. The adsorption capacity of MPs in sediment for Pb(II) was in the following order: A-PE > PLA > PE > A-PLA. Fulvic acid could promote the adsorption of Pb(II) by MPs in sediment. These results indicated that the aging process of the plastics in the environment would affect its role as a carrier of coexisting pollutants.

Topographic Cues Guiding Cell Polarization via Distinct Cellular Mechanosensing Pathways.

Cell polarization exists in a variety of tissues to regulate cell behaviors and functions. Space constraint (spatially limiting cell extension) and adhesion induction (guiding adhesome growth) are two main ways to induce cell polarization according to the microenvironment topographies. However, the mechanism of cell polarization induced by these two ways and the downstream effects on cell functions are yet to be understood. Here, space constraint and adhesion induction guiding cell polarization are achieved by substrate groove arrays in micro and nano size, respectively. Although the morphology of polarized cells is similar on both structures, the signaling pathways to induce the cell polarization and the downstream functions are distinctly different. The adhesion induction (nano-groove) leads to the formation of focal adhesions and activates the RhoA/ROCK pathway to enhance the myosin-based intracellular force, while the space constraint (micro-groove) only activates the formation of pseudopodia. The enhanced intracellular force caused by adhesion induction inhibits the chromatin condensation, which promotes the osteogenic differentiation of stem cells. This study presents an overview of cell polarization and mechanosensing at biointerface to aid in the design of novel biomaterials.

Surface Epitaxial Nano-Topography Facilitates Biomineralization to Promote Osteogenic Differentiation and Osteogenesis.

Biomimetic modification of hydroxyapatite on a polymer surface is a potent strategy for activating biological functions in bone tissue engineering applications. However, the polymer surface is bioinert, and it is difficult to introduce a uniform calcium phosphate (CaP) layer. To overcome this limitation, we constructed a specific nano-topographical structure onto a poly(ε-caprolactone) substrate via surface-directed epitaxial crystallization. Formation of the CaP layer on the nano-topological surface was enhanced by 2.34-fold compared to that on a smooth surface. This effect was attributed to the abundant crystallization sites for CaP deposition because of the increased surface area and roughness. Bone marrow mesenchymal stromal cells (BMSCs) were used to examine the biological effect of biomineralized surfaces. We clearly demonstrated that BMSCs responded to surface biomineralization. Osteogenic differentiation and proliferation of BMSCs were significantly promoted on the biomineralized nano-topological surface. The expression of alkaline phosphatase and osteogenic-related genes as well as extracellular matrix mineralization was significantly enhanced. The proposed strategy shows potential for designing bone repair scaffolds.