Insights into the hydrogen generation and catalytic mechanism on Co-based nanocomposites derived from pyrolysis of organic metal precursor.

Hydrogen generation from boron hydride is important for the development of hydrogen economy. Cobalt (Co) element has been widely used in the hydrolysis of boron hydride. Pyrolysis is a common method for materials synthesis in catalytic fields. Herein, Co-based nanocomposites derived from the pyrolysis of organic metal precursors and used for hydrolysis of boron hydride are summarized and discussed. The different precursors consisting of MOF, supported, metal, and metal phosphide precursors are summarized. The catalytic mechanism consisting of dissociation mechanism based on oxidative addition-reduction elimination, pre-activation mechanism, SN2 mechanism, four-membered ring mechanism, and acid-base mechanism is intensively discussed. Finally, conclusions and outlooks are conveyed from the design of high-efficiency catalysts, the characterization of catalyst structure, the enhancement of catalytic activities, the investigation of the catalytic mechanism, and the catalytic stability of active structure. This review can provide guidance for designing high-efficiency catalysts and boosting development of hydrogen economy.

Single-cell calcium monitoring of Caco-2 cell co-cultured with intestinal microbiome through carbon fiber based potentiometric microelectrode.

The Caco-2 cells were used as intestinal epithelial cell model to illustrate the hyperuricemia (HUA) mechanism under the co-culture of the imbalanced intestinal microbiome in this work. The uric acid (UA) concentration in the HUA process was monitored, and could be up to 425 µmol/L at 8 h co-cultured with the imbalanced intestinal microbiome. Single-cell potentiometry based on ion-selective microelectrode was used to study extracellular calcium change, which is hypothesized to play an important role in the UA excretion. The potential signal of the calcium in the extremely limited microenvironment around single Caco-2 cell was recorded through the single-cell analysis platform. The potential signal of sharp decrease and slow increase followed within a few seconds indicates the sudden uptake and gradually excretion process of calcium through the cell membrane. Moreover, the value of the potential decrease increases with the increase of the time co-cultured with the imbalanced intestinal microbiome ranging from 0 to 8 h. The Ca2+ concentration around the cell membrane could decrease from 1.3 mM to 0.4 mM according to the potential decrease of 27.0 mV at the co-culture time of 8 h. The apoptosis ratio of the Caco-2 cells also exhibits time dependent with the co-culture of the imbalanced intestinal microbiome, and was 39.1 ± 3.6 % at the co-culture time of 8 h, which is much higher than the Caco-2 cells without any treatment (3.9 ± 2.9 %). These results firstly provide the links between the UA excretion with the apoptosis of the intestinal epithelial cell under the interaction of the imbalanced intestinal microbiome. Moreover, the apoptosis could be triggered by the calcium signaling.

Pulmonary artery stiffness in fetuses with tetralogy of Fallot.

PURPOSE: This study evaluated the elastic characteristics of the pulmonary trunk and distal branches in fetuses diagnosed with tetralogy of Fallot (TOF) using Doppler echocardiography. METHODS: Data on 42 fetuses diagnosed with TOF and 84 gestational age-matched normal fetuses were prospectively collected from the Second Xiangya Hospital of Central South University between August 2022 and January 2023. The severity of TOF was classified into three categories based on the z-score of the pulmonary annulus diameter: mild (z-score ≥-2), moderate (-40.05). CONCLUSION: Fetuses diagnosed with TOF exhibited increased vascular stiffness in the MPA and reduced stiffness in the distal pulmonary artery (PA). Larger-scale follow-up studies are required to elucidate the relationships between these changes in vascular stiffness and PA development in patients with TOF.

Assessment of Pulmonary Arterial Vascular Impedance in Fetuses With Tetralogy of Fallot.

OBJECTIVE: To evaluate the vascular impedance of the pulmonary arteries in fetuses with tetralogy of Fallot (TOF) by Doppler echocardiography. METHODS: A total of 42 fetuses with TOF (TOF group) and 84 gestational age-matched normal fetuses (control group) were prospectively collected from the Second Xiangya Hospital of Central South University from August 2022 to January 2023. The severity of TOF was classified into mild TOF (z score ≥-2), moderate TOF (-4 < z score < -2), or severe TOF (z score ≤-4) according to the z score value of the pulmonary annulus diameter. The pulsatility index (PI) of the main pulmonary artery (MPA), distal left pulmonary artery (DLPA), and distal right pulmonary artery (DRPA) were measured by pulsed-wave Doppler. The differences in clinical data and echocardiographic parameters between TOF group, control group, and TOF subgroups were compared. RESULTS: Compared with the control group, MPA-PI increased significantly, whereas DLPA-PI and DRPA-PI decreased in TOF group (all P < .001). There were no significant differences in MPA-PI and DRPA-PI among mild TOF, moderate TOF, and severe TOF (all P > .05). However, DLPA-PI decreased significantly in severe TOF compared with mild TOF (P < .05). CONCLUSION: Fetuses with TOF presented increased vascular impedance in the pulmonary trunk and decreased impedance in distal pulmonary artery branches. Further large and follow-up studies are needed to demonstrate the associations between those changed vascular impedances and the development of PA in patients with TOF.

Adjuvant chemotherapy and survival in males aged 70 years or older with breast cancer: a population-based retrospective study.

BACKGROUND: Male breast cancer constitutes a minority of breast cancer diagnoses, yet its incidence has been on the rise in recent decades. However, elderly male breast cancer patients have been inadequately represented in clinical trials, posing challenges in treatment decisions. This study seeks to clarify the efficacy of chemotherapy in this demographic and identify the population most likely to benefit from such intervention. METHODS: We conducted a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database, encompassing a total of 1900 male breast cancer patients aged 70 years or older. Among them, 1652 were categorized in the no-chemotherapy group, while 248 were in the chemotherapy group. A multifactorial logistic regression model was employed to investigate the determinants influencing the administration of chemotherapy in elderly male breast cancer patients. Additionally, the multivariate Cox proportional hazards regression model was applied to identify factors associated with outcomes, with overall survival (OS) as the primary endpoint. RESULTS: Multivariate logistic regression analysis revealed that grade, tumor size, and nodal status were robust predictors for elderly male breast cancer patients receiving chemotherapy. Furthermore, the multivariate analysis demonstrated that chemotherapy conferred benefits compared to the no-chemotherapy group (HR = 0.822, 95% CI: 0.682-0.991, p = 0.040). Stratified analyses indicated that individuals with N+, poorly/undifferentiated grade, and stage II/III disease could derive benefits from chemotherapy. Upon further investigation of progesterone receptor (PR) positive patients, it was found that only stage III patients experienced significant benefits from chemotherapy (HR = 0.571, 95% CI: 0.372-0.875, p = 0.010). Conversely, in PR negative patients, both stage II (HR = 0.201, 95% CI: 0.051-0.792, p = 0.022) and stage III patients (HR = 0.242, 95% CI: 0.060-0.972, p = 0.046) derived benefits from chemotherapy. CONCLUSION: Adjuvant chemotherapy may benefit certain elderly male breast cancer patients, specifically those with positive lymph node status, poorly/undifferentiated grade, and PR-positive in stage III, as well as PR-negative expression in stage II/III. Given favorable physical tolerance, it is advisable not to hastily dismiss chemotherapy for these elderly male breast cancer patients.

MaSMG7-Mediated Degradation of MaERF12 Facilitates Fusarium oxysporum f. sp. cubense Tropical Race 4 Infection in Musa acuminata.

Modern plant breeding relies heavily on the deployment of susceptibility and resistance genes to defend crops against diseases. The expression of these genes is usually regulated by transcription factors including members of the AP2/ERF family. While these factors are a vital component of the plant immune response, little is known of their specific roles in defense against Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4) in banana plants. In this study, we discovered that MaERF12, a pathogen-induced ERF in bananas, acts as a resistance gene against Foc TR4. The yeast two-hybrid assays and protein-protein docking analyses verified the interaction between this gene and MaSMG7, which plays a role in nonsense-mediated RNA decay. The transient expression of MaERF12 in Nicotiana benthamiana was found to induce strong cell death, which could be inhibited by MaSMG7 during co-expression. Furthermore, the immunoblot analyses have revealed the potential degradation of MaERF12 by MaSMG7 through the 26S proteasome pathway. These findings demonstrate that MaSMG7 acts as a susceptibility factor and interferes with MaERF12 to facilitate Foc TR4 infection in banana plants. Our study provides novel insights into the biological functions of the MaERF12 as a resistance gene and MaSMG7 as a susceptibility gene in banana plants. Furthermore, the first discovery of interactions between MaERF12 and MaSMG7 could facilitate future research on disease resistance or susceptibility genes for the genetic improvement of bananas.

Nature-Inspired Gelatin-Based Adhesive Hydrogel: A Rapid and User-Friendly Solution for Hemostatic Applications.

Conventional hemostatic agents face challenges in achieving rapid hemostasis and effective tissue repair due to limited hemostatic scenarios, suboptimal efficacy, and inadequate adhesion to wet tissues. Drawing inspiration from nature-sourced materials, a gelatin-based adhesive hydrogel (AOT)  is designed, easily prepared and quick to form, driven by Schiff base and multiple hydrogen bonds for applications in arterial and liver bleeding models. AOT exhibits exceptional adhesion to wet tissues (48.67 ± 0.16 kPa) and displays superior hemostatic properties with reduced blood loss and hemostatic time compared to other hydrogels and conventional hemostatic materials. Moreover, AOT exhibits good biocompatibility and biodegradability. In summary, this easily prepared adhesive hydrogel has the potential to supplant traditional hemostatic agents, offering a novel approach to achieve swift sealing of hemostasis and facilitate wound healing and repair in broader application scenarios, owing to its unique advantages.

The Autophagy-Related Musa acuminata Protein MaATG8F Interacts with MaATG4B, Regulating Banana Disease Resistance to Fusarium oxysporum f. sp. cubense Tropical Race 4.

Banana is one of the most important fruits in the world due to its status as a major food source for more than 400 million people. Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4) causes substantial losses of banana crops every year, and molecular host resistance mechanisms are currently unknown. We here performed a genomewide analysis of the autophagy-related protein 8 (ATG8) family in a wild banana species. The banana genome was found to contain 10 MaATG8 genes. Four MaATG8s formed a gene cluster in the distal part of chromosome 4. Phylogenetic analysis of ATG8 families in banana, Arabidopsis thaliana, citrus, rice, and ginger revealed five major phylogenetic clades shared by all of these plant species, demonstrating evolutionary conservation of the MaATG8 families. The transcriptomic analysis of plants infected with Foc TR4 showed that nine of the MaATG8 genes were more highly induced in resistant cultivars than in susceptible cultivars. Finally, MaATG8F was found to interact with MaATG4B in vitro (with yeast two-hybrid assays), and MaATG8F and MaATG4B all positively regulated banana resistance to Foc TR4. Our study provides novel insights into the structure, distribution, evolution, and expression of the MaATG8 family in bananas. Furthermore, the discovery of interactions between MaATG8F and MaATG4B could facilitate future research of disease resistance genes for the genetic improvement of bananas.

Research and development of fully enclosed wire-shell support structure technology for deep soft rock roadway based on TRIZ theory.

The TRIZ theory was used to accurately discover the problems to be solved in the design of roadway surrounding rock control technology. This paper tried to solve the complex issue of surrounding rock control in deep roadways from a new perspective. Based on the functional component analysis and causal axis analysis of the problem's primary reason, simultaneously, the surrounding rock control technology was optimized through technical contradiction analysis, physical contradiction analysis, and substance and field model analysis. As a result, a fully enclosed wire-shell support technology was proposed. Finally, taking the typical soft rock roadway engineering of Pansan Coal Mine in Huainan Mining Area, Anhui Province, China, as the engineering background, the engineering application and effect evaluation were completed. This paper provides a reference for controlling the instability of deep soft rock roadways in coal mines. A new idea of optimizing roadway support engineering based on TRIZ theory was proposed.

Synergistic Interfacial Effect of Ru/Co3 O4 Heterojunctions for Boosting Overall Water Splitting.

Low-cost bifunctional electrocatalysts capable of efficiently driving the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) are needed for the growth of a green hydrogen economy. Herein, a Ru/Co3 O4 heterojunction catalyst rich in oxygen vacancies (VO ) and supported on carbon cloth (RCO-VO @CC) is prepared via a solid phase reaction (SPR) strategy. A RuO2 /Co9 S8 @CC precursor (ROC@CC) is first prepared by loading Co9 S8 nanosheets onto CC, following the addition of RuO2 nanoparticles (NPs). After the SPR process in an Ar atmosphere, Ru/Co3 O4 heterojunctions with abundant VO are formed on the CC. The compositionally optimized RCO-VO @CC electrocatalyst with a Ru content of 0.55 wt.% exhibits very low overpotential values of 11 and 253 mV at 10 mA cm-2 for HER and OER, respectively, in 1 m KOH. Further, a low cell voltage of only 1.49 V is required to achieve a current density of 10 mA cm-2 . Density functional theoretical calculations verify that the outstanding bifunctional electrocatalytic performance originates from synergistic charge transfer between Ru metal and VO -rich Co3 O4 . This work reports a novel approach toward a high-efficiency HER/OER electrocatalyst for energy storage and conversion.

Specific and Nonuniform Brain States during Cold Perception in Mice.

The quest to decode the complex supraspinal mechanisms that integrate cutaneous thermal information in the central system is still ongoing. The dorsal horn of the spinal cord is the first hub that encodes thermal input which is then transmitted to brain regions via the spinothalamic and thalamocortical pathways. So far, our knowledge about the strength of the interplay between the brain regions during thermal processing is limited. To address this question, we imaged the brains of adult awake male mice in resting state using functional ultrasound imaging during plantar exposure to constant and varying temperatures. Our study reveals for the first time the following: (1) a dichotomy in the response of the somatomotor-cingulate cortices and the hypothalamus, which was never described before, due to the lack of appropriate tools to study such regions with both good spatial and temporal resolutions. (2) We infer that cingulate areas may be involved in the affective responses to temperature changes. (3) Colder temperatures (ramped down) reinforce the disconnection between the somatomotor-cingulate and hypothalamus networks. (4) Finally, we also confirm the existence in the mouse brain of a brain mode characterized by low cognitive strength present more frequently at resting neutral temperature. The present study points toward the existence of a common hub between somatomotor and cingulate regions, whereas hypothalamus functions are related to a secondary network.

Left Ventricular Vortex Characteristics in Fetuses With Coarctation of the Aorta by Blood Speckle-Tracking Echocardiography.

OBJECTIVES: The aims of this study were to assess the vortex characteristics of left ventricle (LV) in fetuses with coarctation of the aorta (CoA) using high-frame rate ultrasound with blood speckle-tracking (BST) and explore its relationships with cardiac function and morphology parameters. METHODS: Thirty fetuses with CoA and 30 gestational-age matched normal fetuses were included in this cross-sectional study. The area, length, width, and position of the vortex in the LV were recorded and quantitatively analyzed by BST echocardiography. The associations of vortex properties with ventricular function and morphology were also determined. RESULTS: Based on BST imaging, the LV vortex can be observed in 93% of the fetuses. The fetuses with CoA exhibited significantly larger and wider vortex than the controls (P < .05). Linear regression analysis indicated that vortex area was positively related to sphericity index of LV as well as isovolumic relaxation time (r = .52, P = .003 and r = .42, P = .021). There was a negative correlation between vortex area and mitral valve size (r = -.443, P = .014). No significant association was found between vortex area and myocardial performance index and aortic isthmus size. CONCLUSIONS: It is feasible to quantitatively evaluate the left ventricular vortex in fetuses by BST. The fetuses with CoA exhibited greater vortex area and width, and the altered vortex property is associated with geometry of LV. This will facilitate our comprehension of the unique flow patterns and early cardiac remodeling in fetuses with CoA.

EFHD1 expression is correlated with tumor-infiltrating neutrophils and predicts prognosis in gastric cancer.

Background: Gastric cancer (GC) ranks third in terms of mortality worldwide. The tumor microenvironment is critical for the progression of gastric cancer. This study investigated the association between EF-hand domain containing 1 (EFHD1) expression and its clinical significance in the tumor microenvironment (TME) of gastric cancer. Methods: We used bioinformatic analyses to assess the relevance of EFHD1 mRNA in the TME of gastric carcinoma tissues and its relationship with clinical features. Therefore, we performed multiplex immunohistochemistry analyses to determine the potential role of the EFHD1 protein in the TME of gastric cancer. Results: EFHD1 expression increased dramatically in gastric cancer tissues compared to levels in non-cancerous tissue samples (t = 6.246, P < 0.001). The EFHD1 protein presentation was associated with invasion depth (χ2 = 19.120, P < 0.001) and TNM stages (χ2 = 14.468, P = 0.002). Notably, EFHD1 protein expression was significantly related to CD66b + neutrophil infiltration of the intratumoral (r = 0.420, P < 0.001) and stromal (r = 0.367, P < 0.001) TME in gastric cancer. Additionally, Cox regression analysis revealed that EFHD1 was an independent prognostic predictor (hazard ratio [HR] = 2.262, P < 0.001) in patients with gastric cancer. Conclusions: Our study revealed the pattern of EFHD1 overexpression in the TME of patients with gastric cancer and demonstrated its utility as a biomarker for unfavorable clinical outcomes, thereby providing a potential immunotherapy target.

Recent advances in the application and biological mechanism of silicon nitride osteogenic properties: a review.

Silicon nitride, an emerging bioceramic material, is highly sought after in the biomedical industry due to its osteogenesis-promoting properties, which are a result of its unique surface chemistry and excellent mechanical properties. Currently, it is used in clinics as an orthopedic implant material. The osteogenesis-promoting properties of silicon nitride are manifested in its contribution to the formation of a local osteogenic microenvironment, wherein silicon nitride and its hydrolysis products influence osteogenesis by modulating the biological behaviors of the constituents of the osteogenic microenvironment. In particular, silicon nitride regulates redox signaling, cellular autophagy, glycolysis, and bone mineralization in cells involved in bone formation via several mechanisms. Moreover, it may also promote osteogenesis by influencing immune regulation and angiogenesis. In addition, the wettability, surface morphology, and charge of silicon nitride play crucial roles in regulating its osteogenesis-promoting properties. However, as a bioceramic material, the molding process of silicon nitride needs to be optimized, and its osteogenic mechanism must be further investigated. Herein, we summarize the impact of the molding process of silicon nitride on its osteogenic properties and clinical applications. In addition, the mechanisms of silicon nitride in promoting osteogenesis are discussed, followed by a summary of the current gaps in silicon nitride mechanism research. This review, therefore, aims to provide novel ideas for the future development and applications of silicon nitride.

The clinical significance and application of the peri-implant phenotype in dental implant surgery: a narrative review.

Background and Objective: In recent years, the concept of the peri-implant phenotype has become a new standard for the clinical evaluation of the soft and hard tissues surrounding dental implants. Improving this phenotype enhances the likelihood of achieving long-term favorable results and is a necessary consideration during implant planning. Stable peri-implant tissue support is also crucial for the functional and aesthetic value of implant restoration. Herein, the authors review the clinical significance of the peri-implant phenotype and assess the timing of treatment strategies for improving peri-implant phenotype elements. Methods: A literature search was performed to retrieve papers on peri-implant tissue management and clinical outcomes published up to November 24th, 2022 in PubMed, Web of Science, EMBASE, and Scopus. Key Content and Findings: The optimal time to improve peri-implant bone thickness (PBT) is with augmentation procedures before implant surgery or at the same time as first-stage surgery. Similarly, issues associated with keratinized mucosa width (KMW) and mucosal thickness (MT) should be addressed before final restoration. The establishment of supracrestal tissue height (STH) depends on the MT and implant depth of the patient. Furthermore, special attention should be paid to the effect of the peri-implant phenotype on the prognosis of immediate implant placement in the aesthetic zone. Conclusions: The long-term success of implant restoration depends on careful planning that considers appropriate interventions for improving the peri-implant phenotype at different stages of treatment to reduce iatrogenic variables.

Prediction of knee joint pain in Tai Chi practitioners: a cross-sectional machine learning approach.

OBJECTIVE: To build a supervised machine learning-based classifier, which can accurately predict whether Tai Chi practitioners may experience knee pain after years of exercise. DESIGN: A prospective approach was used. Data were collected using face-to-face through a self-designed questionnaire. SETTING: Single centre in Shanghai, China. PARTICIPANTS: A total of 1750 Tai Chi practitioners with a course of Tai Chi exercise over 5 years were randomly selected. MEASURES: All participants were measured by a questionnaire survey including personal information, Tai Chi exercise pattern and Irrgang Knee Outcome Survey Activities of Daily Living Scale. The validity of the questionnaire was analysed by logical analysis and test, and the reliability of this questionnaire was mainly tested by a re-test method. Dataset 1 was established by whether the participant had knee pain, and dataset 2 by whether the participant's knee pain affected daily living function. Then both datasets were randomly assigned to a training and validating dataset and a test dataset in a ratio of 7:3. Six machine learning algorithms were selected and trained by our dataset. The area under the receiver operating characteristic curve was used to evaluate the performance of the trained models, which determined the best prediction model. RESULTS: A total of 1703 practitioners completed the questionnaire and 47 were eliminated for lack of information. The total reliability of the scale is 0.94 and the KMO (Kaiser-Meyer-Olkin measure of sampling adequacy) value of the scale validity was 0.949 (>0.7). The CatBoost algorithm-based machine-learning model achieved the best predictive performance in distinguishing practitioners with different degrees of knee pain after Tai Chi practice. 'Having knee pain before Tai Chi practice', 'knee joint warm-up' and 'duration of each exercise' are the top three factors associated with pain after Tai Chi exercise in the model. 'Having knee pain before Tai Chi practice', 'Having Instructor' and 'Duration of each exercise' were most relevant to whether pain interfered with daily life in the model. CONCLUSION: CatBoost-based machine learning classifier accurately predicts knee pain symptoms after practicing Tai Chi. This study provides an essential reference for practicing Tai Chi scientifically to avoid knee pain.

A Case Report of Cutaneous Anthrax Diagnosed by Using a Metagenomic Next-Generation Sequencing (mNGS) Approach.

Anthrax is caused by Bacillus anthracis. Humans are mainly infected through contact with the fur and meat of livestock. The cutaneous form is the most common form. The skin lesions of typical cutaneous anthrax are characterized by shallow ulcers with black crusts, surrounded by small blisters and nonpitting edema of nearby tissues. Metagenomic next-generation sequencing (mNGS) is a new pathogenic detection method which is rapid and unbiased. We reported the first case of cutaneous anthrax diagnosed by mNGS. Ultimately, the man received prompt antibiotic therapy and had a good prognosis. In conclusion, mNGS is proved to be a good method for etiological diagnosis, especially for rare infectious diseases.

Nicotine Treatment Ameliorates Blood-Brain Barrier Damage After Acute Ischemic Stroke by Regulating Endothelial Scaffolding Protein Pdlim5.

Analysis of a National Institutes of Health (NIH) trial shows that cigarette smoking protected tissue plasminogen activator (tPA)-treated patients from hemorrhage transformation (HT); however, the underlying mechanism is not clear. Damage to the integrity of the blood-brain barrier (BBB) is the pathological basis of HT. Here, we investigated the molecular events of BBB damage after acute ischemic stroke (AIS) using in vitro oxygen-glucose deprivation (OGD) and in vivo mice middle cerebral artery occlusion (MCAO) models. Our results showed that the permeability of bEND.3 monolayer endothelial cells was significantly increased after being exposed to OGD for 2 h. Mice were subjected to 90-min ischemia with 45-min reperfusion, and BBB integrity was significantly damaged, accompanied by tight junction protein occludin degradation, downregulation of microRNA-21 (miR-21), transforming growth factor-ß (TGF-ß), phosphorylated Smad (p-Smad), plasminogen activator inhibitor-1 (PAI-1), and the upregulation of PDZ and LIM domain protein 5 (Pdlim5), an adaptor protein that has been shown to regulate TGF-ß-Smad3 pathway. In addition, pretreatment with two-week nicotine significantly reduced AIS-induced BBB damage and its associated protein dysregulation via downregulating Pdlim5. Notably, AIS did not significantly induce BBB damage in Pdlim5 deficit mice, but overexpression of Pdlim5 in the striatum with adeno-associated virus produced BBB damage and associated protein dysregulation which could be ameliorated by two-week nicotine pretreatment. More important, AIS induced a significant miR-21 decrease, and miR-21 mimics treatment decreased AIS-induced BBB damage by decreasing Pdlim5. Together, these results demonstrate that nicotine treatment alleviates the AIS-compromised integrity of BBB by regulating Pdlim5.

Long noncoding RNA FTX promotes epithelial-mesenchymal transition of epithelial ovarian cancer through modulating miR-7515/TPD52 and activating Met/Akt/mTOR.

Overexpressed long noncoding RNA FTX is associated with low survival rate of epithelial ovarian cancer (EOC) patients, and enhances tumor infiltration. Thus, we aim to illuminate the undefined underlying mechanisms. Real-time quantitative polymerase chain reaction was applied to detect the expressions of FTX, miR-7515, miR-342-3p, miR-940, miR-150-5p, miR-205-5p and tumor protein D52 (TPD52). Cell counting kit-8 and transwell assays were utilized to explore the cell viability, migration or invasion of EOC cells. Western blot was conducted to measure the expressions of E-cadherin, N-cadherin, Met, phosphorylated (p)-Met, Akt, p-Akt, mTOR and p-mTOR. LncBase and TargetScan predicted the binding of miR-7515 with FTX, and the binding of TPD52 with miR-7515, respectively. The two bindings were further validated by dual luciferase reporter assay. As a result, FTX sponged miR-7515 and miR-7515 targeted to TPD52. FTX was overexpressed in four EOC cell lines. Overexpressed FTX enhanced the cell viability, migration or invasion of EOC cells, elevated N-cadherin and TPD52 expressions, phosphorylated Met/Akt/mTOR, and inhibited E-cadherin expression. All these influences were subsequently reversed by miR-7515 mimic. Collectively, FTX regulates miR-7515/TPD52 to facilitate the migration, invasion or epithelial-mesenchymal transition of EOC through activating Met/Akt/mTOR signaling pathway.

Pathological bile acid concentrations in chronic cholestasis cause adipose mitochondrial defects.

Background & Aims: Although fat loss is observed in patients with cholestasis, how chronically elevated bile acids (BAs) impact white and brown fat depots remains obscure. Methods: To determine the direct effect of pathological levels of BAs on lipid accumulation and mitochondrial function, primary white and brown adipocyte cultures along with fat depots from two separate mouse models of cholestatic liver diseases, namely (i) genetic deletion of farnesoid X receptor (Fxr); small heterodimer (Shp) double knockout (DKO) and (ii) injury by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), were used. Results: As expected, cholestatic mice accumulate high systemic BA levels and exhibit fat loss. Here, we demonstrate that chronic exposure to pathological BA levels results in mitochondrial dysfunction and defective thermogenesis. Consistently, both DKO and DDC-fed mice exhibit lower body temperature. Importantly, thermoneutral (30 °C) housing of the cholestatic DKO mice rescues the decrease in brown fat mass, and the expression of genes responsible for lipogenesis and regulation of mitochondrial function. To overcome systemic effects, primary adipocyte cultures were treated with pathological BA concentrations. Mitochondrial permeability and respiration analysis revealed that BA overload is sufficient to reduce mitochondrial function in primary adipocytes, which is not as a result of cytotoxicity. Instead, we found robust reductions in uncoupling protein 1 (Ucp1), PR domain containing 16 (Prdm16), and deiodinase, iodothyronine, type II (Dio2) transcripts in brown adipocytes upon treatment with chenodeoxycholic acid, whereas taurocholic acid led to the suppression of Dio2 transcript. This BA-mediated decrease in transcripts was alleviated by pharmacological activation of UCP1. Conclusions: High concentrations of BAs cause defective thermogenesis by reducing the expression of crucial regulators of mitochondrial function, including UCP1, which may explain the clinical features of hypothermia and fat loss observed in patients with cholestatic liver diseases. Impact and Implications: We uncover a detrimental effect of chronic bile acid overload on adipose mitochondrial function. Pathological concentration of different BAs reduces the expression of distinct genes involved in energy expenditure, which can be mitigated with pharmacological UCP1 activation.