Effect of hysteroscopic surgery on IVF/ICSI pregnancy outcomes for different cesarean scar diverticulum severity: A retrospective cohort study.

OBJECTIVE: To investigate associations between hysteroscopic surgery for patients with varying cesarean scar diverticulum (CSD) severity and in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) embryo transfer (ET) pregnancy outcomes, focusing also on the correlation between the CSD size with its severity, and pregnancy outcomes. METHODS: A retrospective study was conducted on patients with CSD who underwent IVF/ICSI-ET at a university-based hospital between January 2017 and July 2023. Patients were categorized into four groups based on CSD severity and whether they received hysteroscopic surgery: a mild surgical group (Group A, n = 86), a mild non-surgical group (Group B, n = 30), a moderate-to-severe surgical group (Group C, n = 173), and a moderate-to-severe non-surgical group (Group D, n = 96). Baseline characteristics and pregnancy outcomes were compared among these groups. Correlation assessments were conducted to explore relationships between CSD size with its severity, and pregnancy outcomes. RESULTS: Compared with Group D, Group C exhibited significantly increased rates of biochemical pregnancy (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.03-3.51, P = 0.041), clinical pregnancy (OR 2.30; 95% CI1.18-4.45; P = 0.014), and live birth (OR 2.77; 95% CI 1.10-7.00, P = 0.031). However, no differences in pregnancy outcomes were observed between Groups A and B. Correlation analyses revealed significant positive associations between CSD severity and its depth, length, width, and volume. CONCLUSIONS: Patients with moderate-to-severe CSD achieved favorable IVF/ICSI pregnancy outcomes following hysteroscopic surgery. The CSD size was significantly related to its severity.

Fungal-bacteria interactions provide shelter for bacteria in Caesarean section scar diverticulum.

Caesarean section scar diverticulum (CSD) is a significant cause of infertility among women who have previously had a Caesarean section, primarily due to persistent inflammatory exudation associated with this condition. Even though abnormal bacterial composition is identified as a critical factor leading to this chronic inflammation, clinical data suggest that a long-term cure is often unattainable with antibiotic treatment alone. In our study, we employed metagenomic analysis and mass spectrometry techniques to investigate the fungal composition in CSD and its interaction with bacteria. We discovered that local fungal abnormalities in CSD can disrupt the stability of the bacterial population and the entire microbial community by altering bacterial abundance via specific metabolites. For instance, Lachnellula suecica reduces the abundance of several Lactobacillus spp., such as Lactobacillus jensenii, by diminishing the production of metabolites like Goyaglycoside A and Janthitrem E. Concurrently, Clavispora lusitaniae and Ophiocordyceps australis can synergistically impact the abundance of Lactobacillus spp. by modulating metabolite abundance. Our findings underscore that abnormal fungal composition and activity are key drivers of local bacterial dysbiosis in CSD.

Dyadic coping, resilience, and quality of life in young and middle-aged couples after gynecologic cancer: An actor-partner interdependence mediation model.

PURPOSE: To examine the effects of dyadic coping on quality of life (QoL) and the mediating role of resilience in these effects among young and middle-aged couples after gynecologic cancer (GC). METHODS: A cross-sectional study was conducted between July 2022 and June 2023 from one tertiary hospital in Wuhan, China. 240 pairs of young and middle-aged GC couples were recruited. The demographic and clinical characteristics questionnaire, the Dyadic Coping Inventory, the 10-item Connor-Davidson Resilience Scale, and the 12-item Short-Form Health Survey were used to collect data. The process of dyadic analysis was based on the actor-partner interdependence mediation model. RESULTS: GC patients' dyadic coping had an actor effect on both their own physical and mental QoL, while spouses' dyadic coping only exerted an actor effect on their own mental QoL. The mediating effects of resilience on the relationship between dyadic coping and QoL were identified in dyads. Moreover, spouses' dyadic coping could indirectly influence patients' QoL through their own and patients' resilience. CONCLUSION: The findings confirm the dyadic relationships between dyadic coping, resilience, and QoL among young and middle-aged couples facing GC. These results suggest that it is necessary to develop couple-based interventions to improve dyadic coping and resilience, thus enhancing the QoL of both members.

Toxic epidermal necrolysis complicated with primary cutaneous aspergillosis: A report of four cases.

Primary cutaneous aspergillosis (PCA) is a rare opportunistic infection caused by Aspergillus that can be life-threatening. PCA is mainly reported in immunocompromised hosts such as patients with AIDS, those with hematologic malignancy, or infants with occlusive dressings. However, no study has previously reported PCA associated with toxic epidermal necrolysis (TEN). This study reports four cases of TEN complicated with PCA, presenting with discrete gray or black spots over newly formed epithelia. Risk factors of PCA in patients with TEN include host factors, iatrogenic factors, indoor environment, and wound care. Two of the four cases eventually died, highlighting the importance of further exploring PCA in patients with TEN.

Isolation and functional characterization of cold-induced gene (AmCIP) promoter from Ammopiptanthus mongolicus.

AmCIP is a dehydrin-like protein which involved in abiotic stress tolerance in xerophytes evergreen woody plant A. mongolicus. AmCIP could be induced in the cotyledon and radicle during cold acclimation. To further elucidate the regulation of the upstream region of the gene, we isolated and characterized the promoter of AmCIP. Herein, a 1115 bp 5'-flanking region of AmCIP genomic DNA was isolated and cloned by genome walking from A. mongolicus and the segment sequence was identified as "PrAmCIP" promoter. Analysis of the promoter sequence revealed the presences of some basic cis-acting elements, which were related to various environmental stresses and plant hormones. GUS histochemical staining of transgene tobacco showed that PrAmCIP was induced by 4℃, 55℃, NaCl, mannitol and ABA, whereas it could hardly drive GUS gene expression under normal conditions. Furthermore, we constructed three deletion fragments and genetically transformed them into Arabidopsis thaliana. GUS histochemical staining showed that the MYCATERD1 element of the CP7 fragment (-189 âˆ¼ -1) may be a key element in response to drought. In conclusion, we provide an inducible promoter, PrAmCIP, which can be applied to the development of transgenic plants for abiotic stresse tolerance.

Role of genes encoding microbial carbohydrate-active enzymes in the accumulation and dynamics of organic carbon in subtropical forest soils.

Microbial anabolism and catabolism regulate the accumulation and dynamics of soil organic carbon (SOC). However, very little attention has been paid to the role of microbial functional traits in the accumulation and dynamics of SOC in forest soils. In this study, nine forest soils were selected at three altitudes (600 m, 1200 m, and 1500 m) and three soil depths (0-15 cm, 15-30 cm, and 30-45 cm) located in Jiugong Mountain. Vertical traits of functional genes encoding microbial carbohydrate-active enzymes (CAZymes) were observed using metagenomic sequencing. Soil amino sugars were used as biomarkers to indicate microbial residue carbon (MRC). The results showed that GH1 (ß-glucosidase: 147.49 TPM) and GH3 (ß-glucosidase: 109.09 TPM) were the dominant genes for plant residue decomposition, and their abundance increased with soil depth and peaked in the deep soil at 600 m (GH1: 147.89 TPM; GH3: 109.59 TPM). The highest abundance of CAZymes for fungal and bacterial residue decomposition were GH18 (chitinase: 30.81 TPM) and GH23 (lysozyme: 58.02 TPM), respectively. The abundance of GH18 increased with soil depth, while GH23 showed the opposite trend. Moreover, MRC accumulation was significantly positively correlated with CAZymes involved in the degradation of hemicellulose (r = 0.577, p = 0.002). Compared with the soil before incubation, MRC in the topsoil at the low and middle altitudes after incubation increased by 4 % and 8 %, respectively, while MRC in the soils at 1500 m tended to decrease (p > 0.05). The mineralization capacity of SOC at 1500 m was significantly higher than that at 1200 m and 600 m (p < 0.05). Our results suggested that microbial function for degrading plant residue components, especially hemicellulose and lignin, contributed greatly to SOC accumulation and dynamics. These results were vital for understanding the roles of microbial functional traits in C cycling in forest.

Lawsonia intracellularis flagellin protein LfliC stimulates NF-κB and MAPK signaling pathways independently of TLR5 interaction.

Lawsonia intracellularis, a Gram-negative obligate intracellular bacterium and etiologic agent of porcine proliferative enteropathy, was observed to have a long, single, and unipolar flagellum. Bacterial flagellar filament comprises thousands of copies of the protein flagellin (FliC), and has been reported to be recognized by Toll-like receptor (TLR5) to activate the NF-κB and MAPK signaling pathways, thereby inducing the expression of proinflammatory genes. Recently, two L. intracellularis flagellin proteins, LfliC and LFliC, were reported to be involved in bacterial-host interaction and immune response. Here, to further explore the role of LfliC in proinflammatory response, we purified LfliC, and found that its exposure could activate NF-κB signaling pathway in both HEK293T and IPI-FX cells, as well as activate MAPK p38 and ERK1/2 in HEK293T cells but not in IPI-FX cells. However, our yeast two-hybrid and co-immunoprecipitation assay results revealed that LfliC has no interaction with the porcine TLR5 ECD domain though it harbors the conserved D1-like motif required for the interaction. Moreover, LfliC was identified as a substrate of the virulence-associated type III secretion system (T3SS) by using the heterologous Y. enterocolitica system. Transient expression of LfliC also activated the NF-κB and MAPK signaling pathway in HEK293T cells. Collectively, our results suggest that both the exposure and expression of L. intracellularis LfliC can induce the NF-κB and MAPK signaling pathway in mammalian cells. Our findings may provide important implications and resources for the development of diagnostic tools or vaccines and dissection of the pathogenesis of L. intracellularis.

Enantioselective Palladium(II)-Catalyzed Desymmetrizative Coupling of 7-Azabenzonorbornadienes with Alkynylanilines.

A PdII -catalyzed, domino enantioselective desymmetrizative coupling of 7-azabenzonorbornadienes with alkynylanilines is disclosed herein. This operationally simple transformation generates three covalent bonds and two contiguous stereocenters with excellent enantio- and diastereo-selectivity. The resulting functionalized indole-dihydronaphthalene-amine conjugates served as an appealing platform to streamline the diversity-oriented synthesis (DOS) of other valuable enantioenriched compounds. DFT calculations revealed that the two stabilizing non-covalent interactions contributed to the observed enantioselectivity.

Causal effects of gut microbiome on endometriosis: a two-sample mendelian randomization study.

BACKGROUND: Previous studies have shown observational associations between the gut microbiota and endometriosis; however, the causal nature of such associations remains unclear. This study aimed to analyze the genetic causal relationship between the two. METHODS: A gut microbiome genome-wide association study conducted by the MiBioGen consortium was used as exposure data, and summary statistics of endometriosis were obtained from the FinnGen consortium R8 release data. Inverse variance weighted, MR-Egger, weighted median, weighted model, and simple model analyses were applied to examine the causal relationship, and sensitivity analyses were conducted to validate the robustness of the results. RESULTS: The results showed that, out of 211 gut microbiome taxa, Clostridiales_vadin_BB60_group, Oxalobacteraceae, Desulfovibrio, Haemophilus, and Holdemania had protective effects on endometriosis, while Porphyromonadaceae and Anaerotruncus might contribute to the development of endometriosis. Heterogeneity and pleiotropy analyses confirmed the robustness of the results. CONCLUSION: The two-sample Mendelian randomization analysis conducted in this study identified specific intestinal flora with a causal relationship with endometriosis at the genetic level, offering new insights into the gut microbiota-mediated development mechanism of endometriosis.

Breastfeeding needs of mothers of preterm infants in China: a qualitative study informed by the behaviour change wheel.

BACKGROUND: Although breastfeeding is strongly recommended, the breastfeeding rate of preterm infants in China remains significantly low. In addition to the global structural challenges to breastfeeding and the physiological immaturity of preterm infants, Chinese mothers of preterm infants face unique challenges of maternal-infant separation after birth. Moreover, little is known about Chinese mothers' specific needs in coping with the difficulties posed by these challenges. This study utilized the Behaviour Change Wheel to investigate the breastfeeding needs of Chinese preterm mothers that may facilitate its practice in the future. METHOD: A qualitative descriptive design was implemented in Wuhan in 2022. Based on purposeful sampling, 13 preterm mothers were recruited from a NICU in a Grade III Class A hospital in Wuhan, China. Face-to-face semi-structured interviews were conducted to collect data using the interview guide developed by the Theoretical Domains Framework. Theoretical Thematic Analysis was used to review the data in 6 steps to identify themes. RESULTS: Five major themes emerged: (1) capability: ability to interpret infants' cues and identify problems, and need for breastfeeding knowledge and skills training; (2) physical opportunity: cleanliness and quietness in household environment, private lactation spaces and breastfeeding tools in workplaces and hospitals; (3) social opportunity: family support, peer support, and authoritative support from healthcare providers; (4) reflective motivation: information on health impacts of breastfeeding; (5) automatic motivation: maternal-infant bonding, free of aversive stimulus. CONCLUSION: Preterm mothers' needs to enable breastfeeding were diverse, including increasing their capability, physical and social opportunities, and reflective and automatic motivation. People, resources and environments associated with these needs should be engaged together to stablish a conducive structural environment for breastfeeding. The policy change for "zero separation" and implementation of kangaroo care should also be implemented in Chinese neonatal intensive care units. Future studies are needed to design effective interventions according to mothers' specific needs.

Occupational low back pain prevention capacity of nurses in China: A multicenter cross-sectional study.

Introduction: Nurses have a high prevalence of occupational low back pain, especially since the outbreak of the COVID-19 pandemic, which has increased the nurses' workloads. It has brought a huge burden on nurses and their professional development. Nurses' occupational low back pain prevention capacity is the logical starting point and core of interventions to prevent its occurrence. To date, there is no study investigating it with a scientific scale. Therefore, a multicenter cross-sectional study was conducted to explore the current status of nurses' capacity in occupational low back pain prevention and its influencing factors in China. Methods: Using a two-stage, purposive and convenience mixed sampling method, 1331 nurses from 8 hospitals across 5 provinces (Hubei, Zhejiang, Shandong, Henan, and Sichuan) in the southern, western, northern, and central areas of mainland China were involved in this study. The demographic questionnaire and occupational low back pain prevention behavior questionnaire were used for data collection. The descriptive analysis, univariate analysis, and multiple stepwise linear regression were used for data analysis. Results: The results showed that the occupational low back pain prevention behavior questionnaire score was 89.00 (80.00, 103.00) [M (Q1, Q3)], which indicated that nurses' ability was at a moderate level. Participation in prevention training before, perceived stress at work, and working hours per week were predictors for nurses' occupational low back pain prevention capacity. Discussion: To improve nurses' prevention ability, nursing managers should organize various training programs, strengthen regulations to reduce nurses' workload and stress, provide a healthy workplace, and offer incentives to motivate nurses.

Chronic poor healing wounds of post cesarean scar diverticulum: Altered angiogenesis and immunobiology.

Cesarean section (CS) scar diverticula (CSD) is an important cause impede further fecundity, with rather complicated pathophysiologic mechanisms and unclear etiopathogenesis. In this study, we detect the influences of CSD on the pregnancy outcomes in in-vitro fertilization (IVF) or intra-cytoplasmic sperm injection (ICSI) embryo transfer (ET) cycles, and further explore the mechanisms involved based on histopathology and immunology differences in endometrium between CSD and vaginal birth (VB) women. The CS group had significantly lower CLBR compared to NCS group. Histopathological analysis showed that the higher prevalent of CE is accompanied by excessive fibroblast proliferation at the lower segment of uterus and significantly exaggerated vascular proliferation in situ. Intrauterine inflammatory cytokines including IL-1α, IL-1ß, IL-6, IL-8, TNF-α and SDF-1α were also increased in CSD group. The present data suggests impaired fecundity in CSD women undergoing IVF/ICSI treatment. Although the causal relationship is ambiguous, the potential mechanisms may involve persistent inflammatory response in the uterine cavity, active vascular proliferation accompanied with increased fibrosis which are responsible for poor chronic wound healing of CSD.

Integrative bioinformatics analysis to identify novel biomarkers associated with non-obstructive azoospermia.

Aim: This study aimed to identify autophagy-related genes (ARGs) associated with non-obstructive azoospermia and explore the underlying molecular mechanisms. Methods: Two datasets associated with azoospermia were downloaded from the Gene Expression Omnibus database, and ARGs were obtained from the Human Autophagy-dedicated Database. Autophagy-related differentially expressed genes were identified in the azoospermia and control groups. These genes were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, protein-protein interaction (PPI) network, and functional similarity analyses. After identifying the hub genes, immune infiltration and hub gene-RNA-binding protein (RBP)-transcription factor (TF)-miRNA-drug interactions were analyzed. Results: A total 46 differentially expressed ARGs were identified between the azoospermia and control groups. These genes were enriched in autophagy-associated functions and pathways. Eight hub genes were selected from the PPI network. Functional similarity analysis revealed that HSPA5 may play a key role in azoospermia. Immune cell infiltration analysis revealed that activated dendritic cells were significantly decreased in the azoospermia group compared to those in the control groups. Hub genes, especially ATG3, KIAA0652, MAPK1, and EGFR were strongly correlated with immune cell infiltration. Finally, a hub gene-miRNA-TF-RBP-drug network was constructed. Conclusion: The eight hub genes, including EGFR, HSPA5, ATG3, KIAA0652, and MAPK1, may serve as biomarkers for the diagnosis and treatment of azoospermia. The study findings suggest potential targets and mechanisms for the occurrence and development of this disease.

Ste20-Like Kinase TAOK1 Positively Regulates Antiviral Responses by Controlling the TBK1-IRF3 Signaling Axis.

The cytosolic viral nucleic acid-sensing pathways converge on the protein kinase TANK-binding kinase 1 (TBK1) and the transcription factor interferon (IFN)-regulatory factor 3 (IRF3) to induce type I IFN production and antiviral immune responses. However, the mechanism that triggers the binding of TBK1 and IRF3 after virus infection remains not fully understood. Here, we identified that thousand and one kinase 1 (TAOK1), a Ste20-like kinase, positively regulated virus-induced antiviral immune responses by controlling the TBK1-IRF3 signaling axis. Virus invasion downregulated the expression of TAOK1. TAOK1 deficiency resulted in decreased nucleic acid-mediated type I IFN production and increased susceptibility to virus infection. TAOK1 was constitutively associated with TBK1 independently of the mitochondrial antiviral signaling protein MAVS. TAOK1 promoted IRF3 activation by enhancing TBK1-IRF3 complex formation. TAOK1 enhanced virus-induced type I IFN production in a kinase activity-dependent manner. Viral infection induced TAOK1 to bind with dynein instead of microtubule-associated protein 4 (MAP4), leading to the trafficking of TBK1 to the perinuclear region to bind IRF3. Thus, the depolymerization of microtubule impaired virus-mediated IRF3 activation. Our results revealed that TAOK1 functioned as a new interaction partner and regulated antiviral signaling via trafficking TBK1 along microtubules to bind IRF3. These findings provided novel insights into the function of TAOK1 in the antiviral innate immune response and its related clinical significance.

Ni2+ -Directed Anisotropic Growth of PtCu Nested Skeleton Cubes Boosting Electroreduction of Oxygen.

Structure-controlled Pt-based nanocrystals have the great potential to provide a flexible strategy for improving the catalysis of the oxygen reduction reaction (ORR). Here, a new synthetic approach is developed to tune the 3D structure of Pt-based alloys, and switch a synthetic reaction which produces solid PtCu octahedral stars (OSs) to produce PtCu nested skeleton cubes (NSCs) by simple addition of Ni(acac)2 . In particular, Ni2+ -guided anisotropic growth is observed to generate the nested skeleton structure in PtCu NSCs. Ni2+ , though absent from the nanoalloys, not only endows faster Cu reduction kinetics but also acts as a structure-directing agent. Moreover, it is shown that acetic acid treatment of PtCu NSCs/C exposes Pt-rich surface with a fine-tuned Pt d-band center energy and the reduced Cu leaching, resulting in strikingly high activity and stability. Acid-treated PtCu NSCs/C shows a remarkable ORR mass activity of 5.13 A mgPt -1 , about 26 times higher than commercial Pt/C catalyst. This catalyst also exhibits excellent stability with a lower activity decay of 11.5% and the negligible variation in structure after 10 000 cycles.

Engineering miscellaneous particles from media-milled defatted walnut flour as novel food-grade Pickering stabilizers.

Media milling, an efficient and organic solvent-free method without the use of chemical modification, has been developed to engineer novel walnut-based miscellaneous colloidal particles. The defatted walnut flour particles (DWFPs), which were prepared by a novel continuous phase transition extraction method operated under low temperature (i.e., 50-65 °C) followed by 6-h media milling, were spherical shape with an average size of 753.0 ± 27.8 nm. These particles were mainly composed of proteins (55.6 ± 0.2 wt%) and carbohydrates (24.0 ± 0.2 wt%) and demonstrated the ability to form a gel-like network structure in Pickering emulsions (PEs). The visual observation and confocal laser scanning microscopy (CLSM) showed that the PE droplets stabilized by DWFPs had a good stability over a prolonged storage time (i.e., 3-month storage). Increasing particle concentration (c) in aqueous phase led to the increased emulsified phase volume, decreased oil droplet sizes, and increased storage moduli G' for the viscoelastic responses. As the oil volume fraction (ϕ) increased, the emulsified phase volume fraction and droplet size increased while their rheological properties shifted from fluid-like to gel-like behaviors. The method developed in this study is significant in value-added utilization of walnut products and provides a new insight into facile fabrication of stable food-grade Pickering emulsions-based functional foods using miscellaneous particle stabilizers from walnut extracts.

Optimized oxygen reduction activity by tuning shell component in Pd@Pt-based core-shell electrocatalysts.

Combining the interests of core-shell and alloy structures, herein we report the versatile co-reduction synthesis of Pd@Pt-based core-shell nanoparticles. The current strategy can effectively tune the component of shell, from isolated Pt to binary PtNi alloy, then ternary PtNi-M (M = Fe or Cu) alloy. Further, significant improvement of oxygen reduction reaction (ORR) activity is optimized by the change in shell component. Compared to Pd@Pt/C, Pd@PtNi/C catalyst presents the ORR-helpful mass activity of 1.29 A mg-1Pt. By incorporating a third metal (M) into shell layer, the optimized mass activity of Pd@PtNiFe/C and Pd@PtNiCu/C catalysts is 1.1 times and 1.4 times higher than that of Pd@PtNi/C, respectively. Meanwhile, the lower activity decays of 11.0% for Pd@PtNiFe/C and 10.6% for Pd@PtNiCu/C are obtained compared with that of Pd@PtNi/C (12.4%) after 5,000 cycles, respectively.

Indicators and prediction models for the severity of Covid-19.

OBJECTIVES: Coronavirus disease 2019 (Covid-19) is outbreaking globally. We aimed to analyse the clinical characteristics, cardiac injury, electrocardiogram and computed tomography (CT) features of patients confirmed Covid-19 and explored the prediction models for the severity of Covid-19. METHODS: A retrospective and single-centre study enrolled 98 laboratory-confirmed Covid-19 patients. Clinical data, electrocardiogram and CT features were collected and analysed using Statistical Package for the Social Sciences software. RESULTS: There were 46 males and 52 females, with a median age of 44 years, categorised into three groups, including mild, moderate and severe/critical Covid-19. The rate of abnormal electrocardiograms in severe/critical group (79%) was significantly higher than that in the mild group (17%) (P = .027), which (r = 0.392, P = .005) positively related to the severity of Covid-19 (OR: 5.71, 95% CI: 0.45-3.04, P = .008). Age older than 60 years old, comorbidities, whether had symptoms on admission, fatigue, CT features, laboratory test results such as platelet count, lymphocyte cell count, eosinophil cell count, CD3+ cell count, CD4+ cell count, CD8+ cell count, the ratio of albumin/globulin decreased and D-dimer, C-reactive protein (CRP), B-type natriuretic peptide (BNP), cardiac troponin I (cTnI) elevated were the risk factors for the increased severity of Covid-19. The logistic model, adjusted by age, lobular involvement score and lymphocyte cell count, could be applied for assessing the severity of Covid-19 (AUC, 0.903; Sensitivity, 90.9%; Specificity, 78.1%). CONCLUSIONS: Age >60 years old, chronic comorbidities, lymphocytopoenia and lobular involvement score were associated with the Covid-19 severity. The inflammation induced by Covid-19 caused myocardial injury with elevated BNP and cTnI level and abnormal electrocardiograms.

Improving the bioaccessibility and bioavailability of carnosic acid using a lecithin-based nanoemulsion: complementary in vitro and in vivo studies.

Carnosic acid (CA) represents one of the most effective antioxidants that can be applied for the prevention of degenerative and chronic diseases. However, the intrinsic hydrophobic nature of CA results in low solubility and poor dissolution in the gastrointestinal (GI) tract, which limits its applications in a variety of functional food systems. In order to address these issues, we encapsulated CA in a lecithin-based nanoemulsion (CA-NE) to improve its bioaccessibility and bioavailability which are evaluated using in vitro and in vivo digestion models. The CA-NE demonstrated a loading capacity of 2.6-3.0%, an average particle size of 165 nm, a ζ-potential value of -57.2 mV, and good stability during 4-weeks of storage at 4, 25, and 37 °C. The in vitro static pH-stat lipolysis model and dynamic TNO gastrointestinal (TIM-1) model demonstrated a 12.6 and 5.6 fold increase in the total bioaccessibility of CA encapsulated in nanoemulsion, respectively, as opposed to CA in suspension form. Moreover, the in vivo pharmacokinetics study on a rat model (Male Sprague Dawley) confirmed that the bioavailability of CA in nanoemulsion showed a 2.2 fold increase, as compared to that of CA in suspension form. In conclusion, the bioaccessibility and bioavailability of CA were remarkably improved by encapsulation of CA in a lecithin-based nanoemulsion. Moreover, the combined in vitro and in vivo study could serve as a useful approach for the comprehensive evaluation of oral lipid-based delivery systems.

TAOK1 positively regulates TLR4-induced inflammatory responses by promoting ERK1/2 activation in macrophages.

Thousand and one amino acid kinase 1 (TAOK1) is a member of Ste20-like kinases, but its function in regulating inflammatory responses remains largely unknown. In this study, we identify TAOK1 as a positive regulator of TLR4-triggered inflammatory responses in macrophages. TAOK1 increases LPS-induced production of pro-inflammatory cytokine such as IL-6, TNF-α and IL12p40 in macrophages. TAOK1 deficient mice showed decreased susceptibility to endotoxin shock, with less pro-inflammatory cytokine production than control mice. TAOK1 promotes LPS-induced activation of ERK1/2 by constitutively interacting with TRAF6 and TPL2. These finding unravel the important role of TAOK1 as a positive regulator of TLR4-induced inflammatory responses.