Application of deep learning in isolated tooth identification.

BACKGROUND: Teeth identification has a pivotal role in the dental curriculum and provides one of the important foundations of clinical practice. Accurately identifying teeth is a vital aspect of dental education and clinical practice, but can be challenging due to the anatomical similarities between categories. In this study, we aim to explore the possibility of using a deep learning model to classify isolated tooth by a set of photographs. METHODS: A collection of 5,100 photographs from 850 isolated human tooth specimens were assembled to serve as the dataset for this study. Each tooth was carefully labeled during the data collection phase through direct observation. We developed a deep learning model that incorporates the state-of-the-art feature extractor and attention mechanism to classify each tooth based on a set of 6 photographs captured from multiple angles. To increase the validity of model evaluation, a voting-based strategy was applied to refine the test set to generate a more reliable label, and the model was evaluated under different types of classification granularities. RESULTS: This deep learning model achieved top-3 accuracies of over 90% in all classification types, with an average AUC of 0.95. The Cohen's Kappa demonstrated good agreement between model prediction and the test set. CONCLUSIONS: This deep learning model can achieve performance comparable to that of human experts and has the potential to become a valuable tool for dental education and various applications in accurately identifying isolated tooth.

Knocking Down PIAS3 Reduces H2O2-induced Oxidative Stress Injury in HT22 Cells.

Oxidative stress is involved in the pathological processes of many neurodegenerative diseases. Protein modification by small ubiquitin-like modifiers (SUMOs) has been implicated in oxidative stress injury. By conjugating SUMOs to their selective protein substrates, SUMO ligases play critical roles in regulating functions of proteins involved in oxidative stress injury. In this study, we screened siRNAs to knockdown the SUMO ligase PIAS3 to assess its role in H2O2-induced injury in HT22 cells. H2O2 stimulation increased total protein SUMOylation, facilitated intracellular reactive oxygen species (ROS) release, increased cleaved caspase-3 levels, promoted p38 and JNK activation (phosphorylation), upregulated apoptosis, and decreased cell viability. The siRNA against PIAS3 329-347 (siPIAS3-329) markedly downregulated the protein expression of PIAS3 and reversed these effects, whereas siNC (negative control) had no effect. Our findings demonstrate that PIAS3-mediated SUMOylation facilitates oxidative stress injury and p38/JNK-mediated cell apoptosis and that PIAS3 is a potential target to protect against oxidative stress injury.

PM2.5-induced ferroptosis by Nrf2/Hmox1 signaling pathway led to inflammation in microglia.

Particulate matter (PM) has been a dominant contributor to air contamination, which will enter the central nervous system (CNS), causing neurotoxicity. However, the biological mechanism is poorly identified. In this study, C57BL/6J mice were applied to evaluate the neurotoxicity of collected fine particulate matter (PM2.5), via oropharyngeal aspiration at two ambient equivalent concentrations. The Y-maze results showed that PM2.5 exposure in mice would lead to the damage in hippocampal-dependent working memory. In addition, cell neuroinflammation, microglial activation were detected in hippocampus of PM2.5-exposure mice. To confirm the underlying mechanism, the microarray assay was conducted to screen the differentially expressed genes (DEGs) in microglia after PM2.5 exposure, and the results indicated the enrichment of DEGs in ferroptosis pathways. Furthermore, Heme oxygenase-1 (Hmox1) was found to be one of the most remarkably upregulated genes after PM2.5 exposure for 24 h. And PM2.5 exposure induced ferroptosis with iron accumulation through heme degradation by Nrf2-mediated Hmox1 upregulation, which could be eliminated by Nrf2-inhibition. Meanwhile, Hmox1 antagonist zinc protoporphyrin IX (ZnPP) could protect BV2 cells from ferroptosis. The results taken together indicated that PM2.5 resulted in the ferroptosis by causing iron overload through Nrf2/Hmox1 signaling pathway, which could account for the inflammation in microglia.

A time-resolved multi-omics atlas of transcriptional regulation in response to high-altitude hypoxia across whole-body tissues.

High-altitude hypoxia acclimatization requires whole-body physiological regulation in highland immigrants, but the underlying genetic mechanism has not been clarified. Here we use sheep as an animal model for low-to-high altitude translocation. We generate multi-omics data including whole-genome sequences, time-resolved bulk RNA-Seq, ATAC-Seq and single-cell RNA-Seq from multiple tissues as well as phenotypic data from 20 bio-indicators. We characterize transcriptional changes of all genes in each tissue, and examine multi-tissue temporal dynamics and transcriptional interactions among genes. Particularly, we identify critical functional genes regulating the short response to hypoxia in each tissue (e.g., PARG in the cerebellum and HMOX1 in the colon). We further identify TAD-constrained cis-regulatory elements, which suppress the transcriptional activity of most genes under hypoxia. Phenotypic and transcriptional evidence indicate that antenatal hypoxia could improve hypoxia tolerance in offspring. Furthermore, we provide time-series expression data of candidate genes associated with human mountain sickness (e.g., BMPR2) and high-altitude adaptation (e.g., HIF1A). Our study provides valuable resources and insights for future hypoxia-related studies in mammals.

Recovery of nutrients from fish sludge to enhance the growth of microalga Chlorella sorokiniana CMBB276.

Intensive aquaculture production generates large amounts of sludge. This waste could be considered as a potential source of nutrients that can be recovered and utilized. Little attention has been paid to nutrient recovery from fish sludge. In this study, bioconversion of sludge was evaluated in lab scale under anaerobic (AN), facultative anaerobic (FA) and aerobic (AE) conditions. After 40 days of fermentation, AN recovered the highest values of dissolved total nitrogen (82.7 mg L-1), while AE showed the highest dissolved total phosphorus (11.8 mg L-1) and the highest reduction of total suspended solids (36.0 %). Microbial analysis showed that AN exhibited a distinct bacterial community than that of FA and AE. Furthermore, C. sorokiniana grown in AN effluents collected after 12 days of fermentation achieved the highest biomass production (1.96 g L-1). These results suggest that AN has the best potential to recover nutrients from sludge for production of C. sorokiniana.

Green and efficient extraction of flavonoids from Perilla frutescens (L.) Britt. leaves based on natural deep eutectic solvents: Process optimization, component identification, and biological activity.

In this study, an ultrasonic-assisted natural deep eutectic solvent (NaDES) was used to extract flavonoids from Perilla frutescens (L.) Britt. leaves. Of 10 tested NaDESs, that comprising D-(+)-glucose and glycerol exhibited the best total flavonoid extraction rate. Response surface methodology (RSM) was used for extraction modeling and optimization, and the total flavonoid content reached 87.48 ± 1.61 mg RE/g DW, which was a significant increase of 5.36% compared with that of 80% ethanol extraction. Morphological changes in P. frutescens leaves before and after extraction were analyzed by scanning electron microscopy (SEM), and the mechanism of NaDES formation was studied by Fourier transform infrared (FT-IR) spectroscopy. Furthermore, 10 flavonoids were identified by UPLC-Q-TOF-MS. In addition, the NaDES extract had better biological activity according to five kinds of antioxidant capacity measurements, cyclooxygenase-2 (COX-2) and hyaluronidase (Hyal) inhibition experiments. Moreover, the stability test revealed that the total flavonoid loss rate of the NaDES extract after four weeks was 37.75% lower than that of the ethanol extract. These results indicate that the NaDES can effectively extract flavonoids from P. frutescens leaves and provide a reference for further applications in the food, medicine, health product and cosmetic industries.

Associations between immune cells signatures and osteoarthritis: An integrated analysis of bidirectional Mendelian randomization and Bayesian colocalization.

BACKGROUND: Previous investigations have explored the associations between immune cell signatures and osteoarthritis (OA); however, causality remains unclear. This study employs an integrated analysis, combining bidirectional Mendelian randomization (MR) and Bayesian colocalization (Coloc), to investigate causal relationships between 731 immune cells signatures and OA, identifying shared causal variants. METHODS: Utilizing publicly available summary data, this study primarily employs inverse variance weighting (IVW). Supplementary methods include MR-Egger regression, weighted median, weight mode, and simple mode. Various sensitivity tests, including Cochran's Q test, MR pleiotropy Residual Sum and Outlier, and leave-one-out tests, were conducted to assess the robustness of the analysis results. Coloc was employed to identify shared causal genetic variants among potential associations. RESULTS: IVW analysis revealed 196 immune cell signatures potentially linked to OA across diverse subtypes. Reverse MR analyses indicated the causal impact of OA on the levels of 140 immune cell signatures, with subtype-specific variations. Notably, several specific associations, including CD64 on CD14-CD16 + monocyte for Hip OA (OR = 1.0593, 95 % CI: 1.0260-1.0938, P = 0.0004), HLA-DR on CD14 + CD16- monocyte (OR = 0.9664, 95 % CI: 0.9497-0.9834, P = 0.0001), HLA-DR on CD14 + monocyte (OR = 0.9680, 95 % CI: 0.9509-0.9853, P = 0.0003) in the Knee or Hip OA, PDL-1 on CD14-CD16 + monocyte by All OA (OR = 1.7091, 95 %CI:1.2494-2.3378, P = 0.0008), and herpesvirus entry mediator on effector memory CD4 + T cell by Spine OA (OR = 0.5200, 95 %CI:0.3577-0.7561, P = 0.0006) remained significant post-Bonferroni correction. Sensitivity tests validated the credibility of the IVW analysis. Additionally, Coloc revealed several potential associations among shared genetic variants, including rs115328872, rs1800973, and rs317667. CONCLUSIONS: Our findings provide evidence for the potential involvement of immune cell signatures in OA development, revealing avenues for early prevention and innovative therapeutic strategies.

A submicron forest-like silicon surface promotes bone regeneration by regulating macrophage polarization.

Introduction: Silicon is a major trace element in humans and a prospective supporting biomaterial to bone regeneration. Submicron silicon pillars, as a representative surface topography of silicon-based biomaterials, can regulate macrophage and osteoblastic cell responses. However, the design of submicron silicon pillars for promoting bone regeneration still needs to be optimized. In this study, we proposed a submicron forest-like (Fore) silicon surface (Fore) based on photoetching. The smooth (Smo) silicon surface and photoetched regular (Regu) silicon pillar surface were used for comparison in the bone regeneration evaluation. Methods: Surface parameters were investigated using a field emission scanning electron microscope, atomic force microscope, and contact angle instrument. The regulatory effect of macrophage polarization and succedent osteogenesis was studied using Raw264.7, MC3T3-E1, and rBMSCs. Finally, a mouse calvarial defect model was used for evaluating the promoting effect of bone regeneration on the three surfaces. Results: The results showed that the Fore surface can increase the expression of M2-polarized markers (CD163 and CD206) and decrease the expression of inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Fore surface can promote the osteogenesis in MC3T3-E1 cells and osteoblastic differentiation of rBMSCs. Furthermore, the volume fraction of new bone and the thickness of trabeculae on the Fore surface were significantly increased, and the expression of RANKL was downregulated. In summary, the upregulation of macrophage M2 polarization on the Fore surface contributed to enhanced osteogenesis in vitro and accelerated bone regeneration in vivo. Discussion: This study strengthens our understanding of the topographic design for developing future silicon-based biomaterials.

Tumor Microenvironment-Responsive Nanocapsule Delivery CRISPR/Cas9 to Reprogram the Immunosuppressive Microenvironment in Hepatoma Carcinoma.

Cancer immunotherapy has demonstrated significant efficacy in various tumors, but its effectiveness in treating Hepatocellular Carcinoma (HCC) remains limited. Therefore, there is an urgent need to identify a new immunotherapy target and develop corresponding intervention strategies. Bioinformatics analysis has revealed that growth differentiation factor 15 (GDF15) is highly expressed in HCC and is closely related to poor prognosis of HCC patients. The previous study revealed that GDF15 can promote immunosuppression in the tumor microenvironment. Therefore, knocking out GDF15 through gene editing could potentially reverse the suppressive tumor immune microenvironment permanently. To deliver the CRISPR/Cas9 system specifically to HCC, nanocapsules (SNC) coated with HCC targeting peptides (SP94) on their surface is utilized. These nanocapsules incorporate disulfide bonds (SNCSS) that release their contents in the tumor microenvironment characterized by high levels of glutathione (GSH). In vivo, the SNCSS target HCC cells, exert a marked inhibitory effect on HCC progression, and promote HCC immunotherapy. Mechanistically, CyTOF analysis showed favorable changes in the immune microenvironment of HCC, immunocytes with killer function increased and immunocytes with inhibitive function decreased. These findings highlight the potential of the CRISPR-Cas9 gene editing system in modulating the immune microenvironment and improving the effectiveness of existing immunotherapy approaches for HCC.

The finite element analysis study of the impact of single and double lag screw fixation on ankle fractures of different sizes.

In clinical practice, the choice of single vs. double screw fixation for posterior malleolus fractures (PMF) is theoretically unclear, particularly concerning the size-stability relationship. This study, employing Finite Element Analysis (FEA), assesses biomechanical stability in PMF of varying sizes under both fixation methods. Utilizing a 3D model based on CT scans, we simulated fractures with 10-50% fragment sizes and applied a 600 N force to mimic the single-leg stance. Our evaluation focused on screw Von Mises stress (VMS) and fracture relative displacement (RD). Results show that stability increases with fragment size for both fixation types. Single screw fixation is comparable to double screw in fragments up to 25%, but in larger fragments, double screw significantly enhances stability. This suggests that for fragments over 25%, double screw fixation is preferable, marking a critical threshold for PMF stability.

Establishment and application of a TaqMan-based multiplex real-time PCR for simultaneous detection of three porcine diarrhea viruses.

Introduction: Porcine viral diarrhea is a common clinical disease, which results in high mortality and economic losses in the pig industry. Porcine epidemic diarrhea virus (PEDV), porcine rotavirus (PoRV), and porcine deltacoronavirus (PDCoV) are important diarrhea viruses in pig herds. The similarities of their clinical symptoms and pathological changes make it difficult to distinguish these three viruses clinically. Therefore, there is a need for a highly sensitive and specific method to simultaneously detect and differentiate these viruses. Methods: A multiplex real-time PCR assay using TaqMan probes was developed to simultaneously detect PEDV, PoRV, and PDCoV. To assess the efficacy of the established assay, 30 clinical samples with diarrhea symptoms were used to compare the results obtained from the multiplex real-time PCR assay with those obtained from commercial singleplex real-time PCR kit. Importantly, a total of 4,800 diarrhea samples were tested and analyzed to validate the utility of the assay. Results: This multiplex real-time PCR assay showed high sensitivity, specificity, and excellent repeatability with a detection limit of 1 × 102 copies/µL. Comparing the results of the commercial singleplex real-time PCR kit and the multiplex real-time PCR method for detecting PEDV, PoRV, and PDCoV, there was complete agreement between the two approaches. Clinical data revealed single infection rates of 6.56% for PEDV, 21.69% for PoRV, and 6.65% for PDCoV. The co-infection rates were 11.83% for PEDV + PoRV, 0.29% for PEDV + PDCoV, 5.71% for PoRV + PDCoV, and 1.29% for PEDV + PDCoV + PoRV, respectively. Discussion: The multiplex real-time PCR method established in this study is a valuable diagnostic tool for simultaneously differentiating PEDV, PoRV, and PDCoV. This method is expected to significantly contribute to prevent and control the spread of infectious diseases, as well as aid in conducting epidemiological investigations.

Care Needs of Older Adults With Urinary Incontinence: A Cross-Sectional Study.

PURPOSE: To explore care requirements of older adults with urinary incontinence (UI) and contributing factors. METHOD: This cross-sectional study used the Older Adults Urinary Incontinence Care Needs Inventory to survey participants with UI in three large-scale tertiary hospitals located in Guangzhou City, China, from January 2023 to November 2023. Statistical analyses, including analysis of variance, t tests, correlation analyses, and linear regression models, were conducted to assess factors influencing participants' care needs. RESULTS: A total of 530 older adults with UI participated in the survey and mean standardized score for overall care needs was 78.65 (SD = 5.01), with mean scores for each dimension ranging from 70.88 (SD = 10.55) for social participation needs to 82.45 (SD = 7.11) for health education needs. Factors that were found to influence incontinence care needs in older adults included age, literacy level, number of leaks, and type of disease (F = 37.07, adjusted R2 = 0.290, p < 0.001). CONCLUSION: Comprehensive care for older adults with UI, encompassing physiological, psychological, and social aspects, is crucial. It is essential to tailor care to individual needs and characteristics, taking into account factors, such as age and education, to ensure effective care. [Journal of Gerontological Nursing, 50(5), 43-49.].

Elucidating the association of obstructive sleep apnea with brain structure and cognitive performance.

BACKGROUND: Obstructive sleep apnea (OSA) is a pervasive, chronic sleep-related respiratory condition that causes brain structural alterations and cognitive impairments. However, the causal association of OSA with brain morphology and cognitive performance has not been determined. METHODS: We conducted a two-sample bidirectional Mendelian randomization (MR) analysis to investigate the causal relationship between OSA and a range of neurocognitive characteristics, including brain cortical structure, brain subcortical structure, brain structural change across the lifespan, and cognitive performance. Summary-level GWAS data for OSA from the FinnGen consortium was used to identify genetically predicted OSA. Data regarding neurocognitive characteristics were obtained from published meta-analysis studies. Linkage disequilibrium score regression analysis was employed to reveal genetic correlations between OSA and related traits. RESULTS: Our MR study provided evidence that OSA was found to significantly increase the volume of the hippocampus (IVW ß (95% CI) = 158.997 (76.768 to 241.227), P = 1.51e-04), with no heterogeneity and pleiotropy detected. Nominally causal effects of OSA on brain structures, such as the thickness of the temporal pole with or without global weighted, amygdala structure change, and cerebellum white matter change covering lifespan, were observed. Bidirectional causal links were also detected between brain cortical structure, brain subcortical, cognitive performance, and OSA risk. LDSC regression analysis showed no significant correlation between OSA and hippocampus volume. CONCLUSIONS: Overall, we observed a positive association between genetically predicted OSA and hippocampus volume. These findings may provide new insights into the bidirectional links between OSA and neurocognitive features, including brain morphology and cognitive performance.

CT-derived Radiomics Predicts the Efficacy of Tyrosine Kinase Inhibitors in Osteosarcoma Patients with Pulmonary Metastasis.

BACKGROUND: To construct and validate the CT-based radiomics model for predicting the tyrosine kinase inhibitors (TKIs) effects in osteosarcoma (OS) patients with pulmonary metastasis. METHODS: OS patients with pulmonary metastasis treated with TKIs were randomly separated into training and testing cohorts (2:1 ratio). Radiomic features were extracted from the baseline unenhanced chest CT images. The random survival forest (RSF) and Kaplan-Meier survival analyses were performed to construct and evaluate radiomics signatures (R-model-derived). The univariant and multivariant Cox regression analyses were conducted to establish clinical (C-model) and combined models (RC-model). The discrimination abilities, goodness of fit and clinical benefits of the three models were assessed and validated in both training and testing cohorts. RESULTS: A total of 90 patients, 57 men and 33 women, with a mean age of 18 years and median progression-free survival (PFS) of 7.2 months, were enrolled. The R-model was developed with nine radiomic features and demonstrated significant predictive and prognostic values. In both training and testing cohorts, the time-dependent area under the receiver operating characteristic curves (AUC) of the R-model and RC-model exhibited obvious superiority over C-model. The calibration and decision curve analysis (DCA) curves indicated that the accuracy of the R-model was comparable to RC-model, which exhibited significantly better performance than C-model. CONCLUSIONS: The R-model showed promising potential as a predictor for TKI responses in OS patients with pulmonary metastasis. It can potentially identify pulmonary metastatic OS patients most likely to benefit from TKIs treatment and help guide optimized clinical decisions.

Analysis of nearly 3000 archaeal genomes from terrestrial geothermal springs sheds light on interconnected biogeochemical processes.

Terrestrial geothermal springs are physicochemically diverse and host abundant populations of Archaea. However, the diversity, functionality, and geological influences of these Archaea are not well understood. Here we explore the genomic diversity of Archaea in 152 metagenomes from 48 geothermal springs in Tengchong, China, collected from 2016 to 2021. Our dataset is comprised of 2949 archaeal metagenome-assembled genomes spanning 12 phyla and 392 newly identified species, which increases the known species diversity of Archaea by ~48.6%. The structures and potential functions of the archaeal communities are strongly influenced by temperature and pH, with high-temperature acidic and alkaline springs favoring archaeal abundance over Bacteria. Genome-resolved metagenomics and metatranscriptomics provide insights into the potential ecological niches of these Archaea and their potential roles in carbon, sulfur, nitrogen, and hydrogen metabolism. Furthermore, our findings illustrate the interplay of competition and cooperation among Archaea in biogeochemical cycles, possibly arising from overlapping functional niches and metabolic handoffs. Taken together, our study expands the genomic diversity of Archaea inhabiting geothermal springs and provides a foundation for more incisive study of biogeochemical processes mediated by Archaea in geothermal ecosystems.

Effects of elastic band resistance training on the physical and mental health of elderly individuals: A mixed methods systematic review.

OBJECTIVES: Elastic band resistance training in elderly individuals can improve physical fitness and promote mental health in addition to other benefits. This systematic review aimed to review, summarize, and evaluate quantitative, qualitative, and mixed methodological studies on the use of elastic band resistance training in elderly individuals, and to investigate the influence of elastic band resistance training on the physical and mental health of elderly individuals, as well as their preferences and obstacles in training. METHODS: A convergent separation approach was used to synthesize and integrate the results, specifically the mixed systematic review approach recommended by the Joanna Briggs Institute. The extensive search strategy included electronic database searches in the Cochrane Library, PubMed, Embase, Web of Science, Google Scholar, MEDLINE, and CINAHL. The researchers rigorously screened the literature, extracted and analyzed the data, and evaluated the quality of the included studies using the Mixed Methods Appraisal Tool (MMAT). RESULTS: Twenty-eight studies were included, of which 25 were quantitative studies, 2 were qualitative studies, and 1 was a mixed-methods study. A total of 1,697 subjects were investigated across all studies. Quantitative evidence supports the notion that elastic band resistance training can improve upper and lower limb flexibility, endurance, upper strength, physical balance, and cardiopulmonary function and enhance the mental health of elderly individuals. Participants in the qualitative study reported some preferences and obstacles with band resistance training, but most participants reported physical benefits. CONCLUSIONS: Despite the heterogeneity between studies, this review is the first systematic review to comprehensively evaluate the effectiveness of elastic band resistance training in older adults. It not only shows the influence of elastic band resistance training on the physical and mental health of the elderly, but also emphasizes the preference and obstacles of elderly individuals face.

A new model of portal vein thrombosis in rats with cirrhosis induced by partial portal vein ligation plus carbon tetrachloride and intervened with rivaroxaban.

BACKGROUND AND AIMS: Portal vein thrombosis (PVT) is a common complication of liver cirrhosis that can aggravate portal hypertension. However, there are features of both PVT and cirrhosis that are not recapitulated in most current animal models. In this study, we aimed to establish a stable animal model of PVT and cirrhosis, intervene with anticoagulant, and explore the related mechanism. METHODS: First, 49 male SD rats received partial portal vein ligation (PPVL), and 44 survival rats were divided into 6 groups: PPVL control group; 4-week, 6 -week, 8-week, and 10-week model group; and the rivaroxaban (RIVA)-treated group. The rats were intoxicated with or without carbon tetrachloride (CCl4) for 4-10 weeks. Seven normal rats were used as the normal controls. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and parameters for blood coagulation were all assayed with kits. Liver inflammation, collagen deposition and hydroxyproline (Hyp) levels were also measured. The extrahepatic macro-PVT was observed via portal vein HE staining, etc. The intrahepatic microthrombi was stained via fibrin immunohistochemistry. The portal blood flow velocity (PBFV) and diameter were detected via color Doppler ultrasound. Vascular endothelial injury was evaluated by von Willebrand Factor (vWF) immunofluorescence. Fibrinolytic activity was estimated by western blot analysis of fibrin and plasminogen activator inhibitor-1 (PAI-1). RESULTS: After PPVL surgery and 10 weeks of CCl4 intoxication, a rat model that exhibited characteristics of both cirrhosis and extra and intrahepatic thrombi was established. In cirrhotic rats with PVT, the PBFV decreased, both factors of pro- and anti-coagulation decreased, but with relative hypercoagulable state, vascular endothelial injured, and fibrinolytic activity decreased. RIVA-treated rats had improved coagulation function, increased PBFV and attenuated thrombi. This effect was related to the improvements in endothelial injury and fibrinolytic activity. CONCLUSIONS: A new rat model of PVT with cirrhosis was established through partial portal vein ligation plus CCl4 intoxication, with the characteristics of macrothrombi at portal veins and microthrombi in hepatic sinusoids, as well as liver cirrhosis. Rivaroxaban could attenuate PVT in cirrhosis in the model rats. The underlying mechanisms of PVT formation in the rat model and pharmacological action of rivaroxaban are related to the regulation of portal blood flow, coagulant factors, and vascular endothelial cell function.

Adaptive Response to Solvation in Flexible Molecules: Oligo Hydrates of 4-hydroxy-2-butanone.

Structural changes induced by water play a pivotal role in chemistry and biology but remain challenging to predict, measure, and control at molecular level. Here we explore size-governed gas-phase water aggregation in the flexible molecule 4-hydroxy-2-butanone, modeling the conformational adaptability of flexible substrates to host water scaffolds and the preference for sequential droplet growth. The experiment was conducted using broadband rotational spectroscopy, rationalized with quantum chemical calculations. Two different isomers were observed experimentally from the di- to the pentahydrates (4-hydroxy-2-butanone-(water)n = 2-5), including the 18O isotopologues for the di- and trihydrates. Interestingly, to accommodate water molecules effectively, the heavy atom skeleton of 4-hydroxy-2-butanone reshapes in every observed isomer and does not correspond to the stable conformer of the free monomer. All solvates initiate from the (proton donor) alcohol group but retain the carbonyl group as secondary binding point. The water scaffolds closely resemble those found in the pure water clusters, balancing between the capability of 4-hydroxy-2-butanone for steering the orientation and position of the water molecules and the ability of water to modulate the monomer's conformation. The present work thus provides an accurate molecular answer on how torsionally flexible molecules dynamically adapt to water along progressing solvation.

Iron controls the development of airway hyperreactivity by regulating ILC2 metabolism and effector function.

Group 2 innate lymphoid cells (ILC2s) rapidly induce a type 2 inflammation in the lungs in response to allergens. Here, we focused on the role of iron, a critical nutritional trace element, on ILC2 function and asthma pathogenesis. We found that transferrin receptor 1 (TfR1) is rapidly up-regulated and functional during ILC2 activation in the lungs, and blocking transferrin uptake reduces ILC2 expansion and activation. Iron deprivation reprogrammed ILC2 metabolism, inducing a HIF-1α-driven up-regulation of glycolysis and inhibition of oxidative mitochondrial activity. Consequently, we observed that in vivo iron chelation or induction of hypoferremia reduced the development of airway hyperreactivity in experimental models of ILC2-driven allergic asthma. Human circulating ILC2s rapidly induced TfR1 during activation, whereas inhibition of iron uptake or iron deprivation reduced effector functions. Last, we found a negative relationship between circulating ILC2 TfR1 expression and airway function in cohorts of patients with asthma. Collectively, our studies define cellular iron as a critical regulator of ILC2 function.

Label-free OIRD detection of protein microarrays on high dielectric constant substrate with enhanced intrinsic sensitivity.

Oblique-incidence reflectivity difference (OIRD) is a dielectric constant-sensitive technique and exhibits intriguing applications in label-free and high-throughput detection of protein microarrays. With the outstanding advantage of being compatible with arbitrary substrates, however, the effect of the substrate, particularly its dielectric constant on the OIRD sensitivity has not been fully disclosed. In this paper, for the first time we investigated the dependence of OIRD sensitivity on the dielectric constant of the substrate under top-incident OIRD configuration by combining theoretical modeling and experimental evaluation. Optical modeling suggested that the higher dielectric constant substrate exhibits a higher intrinsic sensitivity. Experimentally, three substrates including glass, fluorine-doped tin oxide (FTO) and silicon (Si) with different dielectric constants were selected as microarray substrates and their detection performances were evaluated. In good agreement with the modeling, high dielectric constant Si-based microarray exhibited the highest sensitivity among three chips, reaching a detection limit of as low as 5 ng mL-1 with streptavidin as the model target. Quantification of captured targets on three chips with on-chip enzyme-linked immunosorbent assay (ELISA) further confirmed that the enhanced performance originates from the high dielectric constant enhanced intrinsic OIRD sensitivity. This work thus provides a new way to OIRD-based label-free microarrays with improved sensitivity.