UTP11 promotes the growth of hepatocellular carcinoma by enhancing the mRNA stability of Oct4.

BACKGROUND: Several publications suggest that UTP11 may be a promising gene engaged for involvement of hepatocellular carcinoma (HCC) pathology. However, there are extremely limited biological, mechanistic and clinical studies of UTP11 in HCC. METHODS: To anayze the UTP11 mRNA expression in HCC and normal clinical samples and further investigate the correlation between UTP11 expression and pathology and clinical prognosis via the Cancer Tissue Gene Atlas (TCGA) database. The protein levels of UTP11 were checked using the Human Protein Atlas (HPA) database. GO-KEGG enrichment was performed from Cancer Cell Line Encyclopedia (CCLE) database and TCGA dataset. The levels of UTP11 were tested with qRT-PCR and western blotting assays. Cell viability, immunofluorescence and flow cytometry assays and animal models were used to explore the potential involvement of UTP11 in regulating HCC growth in vitro and in vivo. The correlation of UTP11 and tumor stemness scores and stemness-associated proteins from TCGA database. The mRNA stability was treated with Actinomycin D, followed by testing the mRNA expression using qRT-PCR assay. RESULTS: UTP11 was highly expressed in HCC samples compared to normal tissues from TCGA database. Similarly, UTP11 protein expression levels were obviously elevated in HCC tissue samples from HPA database. Furthermore, UTP11 levels were correlated with poor prognosis in HCC patient samples in TCGA dataset. In addition, the UTP11 mRNA levels was notably enhanced in different HCC cell lines than in normal liver cells and knocking down UTP11 was obviously reduced the viability and cell death of HCC cells. UTP11 knockdown suppressed the tumor growth of HCC in vivo experiment and extended the mice survival time. GO-KEEG analysis from CCLE and TCGA database suggested that UTP11 might involve in RNA splicing and the stability of mRNA. Further, UTP11 was positively correlated with tumor stemness scores and stemness-associated proteins from TCGA database. Knockdown of UTP11 was reduced the expression of stem cell-related genes and regulated the mRNA stability of Oct4. CONCLUSIONS: UTP11 is potentially a diagnostic molecule and a therapeutic candidate for treatment of HCC.

Mechanical Strain Induces and Increases Vesicular Release Monitored by Microfabricated Stretchable Electrodes.

Exocytosis involving the fusion of intracellular vesicles with cell membrane, is thought to be modulated by the mechanical cues in the microenvironment. Single-cell electrochemistry can offer unique information about the quantification and kinetics of exocytotic events; however, the effects of mechanical force on vesicular release have been poorly explored. Herein, we developed a stretchable microelectrode with excellent electrochemical stability under mechanical deformation by microfabrication of functionalized poly(3,4-ethylenedioxythiophene) conductive ink, which achieved real-time quantitation of strain-induced vesicular exocytosis from a single cell for the first time. We found that mechanical strain could cause calcium influx via the activation of Piezo1 channels in chromaffin cell, initiating the vesicular exocytosis process. Interestingly, mechanical strain increases the amount of catecholamines released by accelerating the opening and prolonging the closing of fusion pore during exocytosis. This work is expected to provide revealing insights into the regulatory effects of mechanical stimuli on vesicular exocytosis.

Three-Dimensional Stretchable Sensor-Hydrogel Integrated Platform for Cardiomyocyte Culture and Mechanotransduction Monitoring.

Cardiomyocytes are responsible for generating contractile force to pump blood throughout the body and are very sensitive to mechanical forces and can initiate mechano-electric coupling and mechano-chemo-transduction. Remarkable progress has been made in constructing heart tissue by engineered three-dimensional (3D) culture models and in recording the electrical signals of cardiomyocytes. However, it remains a severe challenge for real-time acquiring of the transient biochemical information in cardiomyocyte mechano-chemo-transduction. Herein, we reported a multifunctional platform by integrating a 3D stretchable electrochemical sensor with collagen hydrogel for the culture, electrical stimulation, and electrochemical monitoring of cardiomyocytes. The 3D stretchable electrochemical sensor was prepared by assembling functionalized conductive polymer PEDOT:PSS on an elastic scaffold, which showed excellent electrochemical sensing performance and stability under mechanical deformations. The integration of a 3D stretchable electrochemical sensor with collagen hydrogel provided an in vivo-like microenvironment for cardiomyocyte culture and promoted cell orientation via in situ electrical stimulation. Furthermore, this multifunctional platform allowed real-time monitoring of stretch-induced H2O2 release from cardiomyocytes under their normal and pathological conditions, as well as pharmacological interventions.

Homeostasis inside Single Activated Phagolysosomes: Quantitative and Selective Measurements of Submillisecond Dynamics of Reactive Oxygen and Nitrogen Species Production with a Nanoelectrochemical Sensor.

Reactive oxygen and nitrogen species (ROS/RNS) are generated by macrophages inside their phagolysosomes. This production is essential for phagocytosis of damaged cells and pathogens, i.e., protecting the organism and maintaining immune homeostasis. The ability to quantitatively and individually monitor the four primary ROS/RNS (ONOO-, H2O2, NO, and NO2-) with submillisecond resolution is clearly warranted to elucidate the still unclear mechanisms of their rapid generation and to track their concentration variations over time inside phagolysosomes, in particular, to document the origin of ROS/RNS homeostasis during phagocytosis. A novel nanowire electrode has been specifically developed for this purpose. It consisted of wrapping a SiC nanowire with a mat of 3 nm platinum nanoparticles whose high electrocatalytic performances allow the characterization and individual measurements of each of the four primary ROS/RNS. This allowed, for the first time, a quantitative, selective, and statistically robust determination of the individual amounts of ROS/RNS present in single dormant phagolysosomes. Additionally, the submillisecond resolution of the nanosensor allowed confirmation and measurement of the rapid ability of phagolysosomes to differentially mobilize their enzyme pools of NADPH oxidases and inducible nitric oxide synthases to finely regulate their homeostasis. This reveals an essential key to immune responses and immunotherapies and rationalizes its biomolecular origin.

Redox Homeostasis Alteration in Endothelial Mechanotransduction Monitored by Dual Stretchable Electrochemical Sensors.

In vivo, endothelial cells are permanently subjected to dynamic cyclic stretch and adapt to it through the release of vasoactive substances. Among them, reactive oxygen species (ROS) and nitric oxide (NO) are indispensable redox molecules, the contents of which and their ratio are closely implicated with endothelial redox homeostasis. However, simultaneous and quantitative monitoring of ROS and NO release in endothelial mechanotransduction remains a great challenge. Herein, a stretchable electrochemical device is developed with a dual electrode based on gold nanotubes decorated with uniform and tiny platinum nanoparticles. This hybrid nanostructure endows the sensor with high sensitivity toward both hydrogen peroxide (H2O2) (as the most stable ROS) and NO electrooxidation. Importantly, the two species can be well discriminated by applying different potentials, which allows simultaneous monitoring of H2O2 and NO release in stretch-induced endothelial mechanotransduction by the same device. The results of quantitative analysis suggest that endothelial redox homeostasis and its alteration are strongly related to vascular biomechanical and biochemical milieus. Further investigation reveals that the interplay of ROS and NO signaling has an important role in the regulation of endothelial redox state. This work will greatly facilitate the deep understanding of the molecular mechanism of endothelial dysfunction and vascular disorder.

Versatile Construction of Biomimetic Nanosensors for Electrochemical Monitoring of Intracellular Glutathione.

The current strategies for nanoelectrode functionalization usually involve sophisticated modification procedures, uncontrollable and unstable modifier assembly, as well as a limited variety of modifiers. To address this issue, we propose a versatile strategy for large-scale synthesis of biomimetic molecular catalysts (BMCs) modified nanowires (NWs) to construct functionalized electrochemical nanosensors. This design protocol employs an easy, controllable and stable assembly of diverse BMCs-poly(3,4-ethylenedioxythiophene) (PEDOT) composites on conductive NWs. The intrinsic catalytic activity of BMCs combined with outstanding electron transfer ability of conductive polymer enables the nanosensors to sensitively and selectively detect various biomolecules. Further application of sulfonated cobalt phthalocyanine functionalized nanosensors achieves real-time electrochemical monitoring of intracellular glutathione levels and its redox homeostasis in single living cells for the first time.

Soft Electrodes for Electrochemical and Electrophysiological Monitoring of Beating Cardiomyocytes.

Many cells in vivo have their inherent motions, which involve numerous biochemical and biophysical signals synergistically regulating cell behavior and function. However, existing methods offer little information about the concurrently chemical and physical responses of dynamically pulsing cells. Here, we report a soft electrode with an electrospun poly(3,4-ethylenedioxythiophene) (PEDOT)-based nanomesh to fully comply with spontaneous motions of cells. Moreover, this electrode demonstrated excellent electrical conductivity, electrochemical performance and cellular biocompatibility. Cardiomyocytes cultured thereon exhibited autonomous and rhythmic contractility, and synchronously induced mechanical deformation of the underlying electrode, which allowed real-time monitoring of nitric oxide release and electrophysiological activity of cardiomyocytes. This work provides a promising way toward recording chemical and electrical signals of biological systems with their natural motions.

A Three-Dimensional Electrochemical Biosensor Integrated with Hydrogel Enables Real-Time Monitoring of Cells under Their In Vivo-like Microenvironment.

Three-dimensional (3D) cell culture can better reproduce the in vivo cell environment and has been extensively used in fields such as tissue engineering, drug screening, and pathological research. Despite the tremendous advancement of 3D cultures, an analysis technique that could collect real-time information of the biological processes therein is sorely lacking. Electrochemical sensing with fast response and high sensitivity has played a vital role in real-time monitoring of living cells, but most current sensors are based on planar electrodes and fail to perfectly match the 3D cell culture matrix. Herein, we developed a robust 3D electrochemical sensor based on functionalized graphene foam (GF), which could be integrated with hydrogels for the 3D culture and in situ monitoring of cells for the first time. Specifically, platinum nanoparticles (Pt NPs) electrodeposited on GF (GF/Pt NPs) conferred the prominent electrochemical sensing performance, and the anti-fouling coating of poly(3,4-ethylenedioxythiophene) (PEDOT) endowed the GF/Pt NPs electrode with greatly improved stability. As a proof of concept, collagen hydrogel with microglia seeded in was filled into the interspace of the 3D GF/Pt NPs/PEDOT sensor to establish an integrated platform, which allowed the successful real-time monitoring of reactive oxygen species released from microglia in the collagen matrix. Given the versatility, our proposed biosensor in conjunction with various 3D culture models will serve as an excellent tool to provide biochemical information of cells under their in vivo-like microenvironment.

Large-Scale Synthesis of Functionalized Nanowires to Construct Nanoelectrodes for Intracellular Sensing.

A strategy for one-pot and large-scale synthesis of functionalized core-shell nanowires (NWs) to high-efficiently construct single nanowire electrodes is proposed. Based on the polymerization reaction between 3,4-ethylenedioxythiophene (EDOT) and noble metal cations, manifold noble metal nanoparticles-polyEDOT (PEDOT) nanocomposites can be uniformly modified on the surface of any nonconductive NWs. This provides a facile and versatile approach to produce massive number of core-shell NWs with excellent conductivity, adjustable size, and well-designed properties. Nanoelectrodes manufactured with such core-shell NWs exhibit excellent electrochemical performance and mechanical stability as well as favorable antifouling properties, which are demonstrated by in situ intracellular monitoring of biological molecules (nitric oxide) and unraveling its relevant unclear signaling pathway inside single living cells.

Stretchable Electrode Based on Au@Pt Nanotube Networks for Real-Time Monitoring of ROS Signaling in Endothelial Mechanotransduction.

Vascular endothelial cells (ECs) are natively exposed to dynamic cyclic stretch and respond to it by the production of vasoactive molecules. Among them, reactive oxygen species (ROS) are closely implicated to the endothelial function and vascular homeostasis. However, the dynamic monitoring of ROS release during endothelial mechanotransduction remains a steep challenge. Herein, we developed a stretchable electrochemical sensor by decoration of uniform and ultrasmall platinum nanoparticles (Pt NPs) on gold nanotube (Au NT) networks (denoted as Au@Pt NTs). The orchestrated structure exhibited prominent electrocatalytic property toward the oxidation of hydrogen peroxide (H2O2) (as the most stable ROS) while maintaining excellent mechanical compliance of Au NT networks. Moreover, the favorable biocompatibility of Au NTs and Pt NPs promoted the adhesion and proliferation of ECs cultured thereon. These allowed in situ inducing ECs mechanotransduction and synchronously real-time monitoring of H2O2 release. Further investigation revealed that the production of H2O2 was positively correlated with the applied mechanical strains and could be boosted by other coexisting pathogenic factors. This indicates the great prospect of our proposed sensor in exploring ROS-related signaling for the deep understanding of cell mechanotransduction and vascular disorder.

Integrating Flexible Electrochemical Sensor into Microfluidic Chip for Simulating and Monitoring Vascular Mechanotransduction.

As an interface between the blood flow and vessel wall, endothelial cells (ECs) are exposed to hemodynamic forces, and the biochemical molecules released from ECs-blood flow interaction are important determinants of vascular homeostasis. Versatile microfluidic chips have been designed to simulate the biological and physiological parameters of the human vascular system, but in situ and real-time monitoring of the mechanical force-triggered signals during vascular mechanotransduction still remains a significant challenge. Here, such challenge is fulfilled for the first time, by preparation of a flexible and stretchable electrochemical sensor and its incorporation into a microfluidic vascular chip. This allows simulating of in vivo physiological and biomechanical parameters of blood vessels, and simultaneously monitoring the mechanically induced biochemical signals in real time. Specifically, the cyclic circumferential stretch that is actually exerted on endothelium but is hard to reproduce in vitro is successfully recapitulated, and nitric oxide signals under normal blood pressure, as well as reactive oxygen species signals under hypertensive states, are well documented. Here, the first integration of a flexible electrochemical sensor into a microfluidic chip is reported, therefore paving a way to evaluate in vitro organs by built-in flexible sensors.

The Household Structure Transition in China: 1982-2015.

Chinese society has experienced a dramatic change over the past several decades, which has had a profound impact on its household system. Utilizing the Chinese national census and 1% population survey data from 1982 to 2015, this study demonstrates the transition of the Chinese household structure through typology analyses. Five typical regional household structure types-large lineal, large nuclear, small nuclear, mixed lineal, and small and diverse-are identified. Our findings demonstrate that since the 1980s, the household system in almost all Chinese regions has evolved from a large unitary model to a small diversified one. However, this evolutionary path diverged after 2000 and formed two distinct household structure systems. There are also significant regional differences in the transition trajectory. Influenced by developmental, cultural, and demographic factors, the regions exhibit four distinct transition paths: lineal tradition, nuclear retardation, smooth transition, and fast transition. On the basis of these results, we discuss family modernization and other theories in explaining the transition of the Chinese household structure.

Mechanical Distension Induces Serotonin Release from Intestine as Revealed by Stretchable Electrochemical Sensing.

The role of endogenous serotonin (5-HT) in gastrointestinal motility is still highly controversial. Although electrochemical techniques allow for direct and real-time recording of biomolecules, the dynamic monitoring of 5-HT release from elastic and tubular intestine during motor reflexes remains a great challenge because of the specific peristalsis patterns and inevitable passivation of the sensing interface. A stretchable sensor with antifouling and decontamination properties was assembled from gold nanotubes, titanium dioxide nanoparticles, and carbon nanotubes. The sandwich-like structure endowed the sensor with satisfying mechanical stability and electrochemical performance, high resistance against physical adsorption, and superior efficiency in the photodegradation of biofouling molecules. Insertion of the sensor into the lumen of rat ileum (the last section of the small intestine) successfully mimics intestinal peristalsis, and simultaneous real-time monitoring of distension-evoked 5-HT release was possible for the first time. Our results unambiguously reveal that mechanical distension of the intestine induces endogenous 5-HT overflow, and 5-HT level is closely associated with the physiological or pathological states of the intestine.

Probiotics decrease depressive behaviors induced by constipation via activating the AKT signaling pathway.

Chronic constipation is often accompanied by emotional disorders such as depression and anxiety. The aim of this study was to determine whether administration of a multispecies probiotic can decrease depressive behaviors through the gut-brain axis and identify any underlying mechanisms. A mouse model of constipation induced by loperamide (5 mg·kg-1,i.p.) was used. For that purpose, 36 ICR male mice were divided into three groups: control, constipation and probiotic groups. The probiotic group received treatment with a probiotic once per day for 14 days via a gavage. All other groups were given an equal volume of normal saline. The fecal parameters and intestinal transit ratio were recorded. The forced swimming test and tail suspension test were used to detect changes in depressive behaviors. Total superoxide dismutase (T-SOD) activity and malondialdehyde (MDA) levels were measured by assay kits. We also detected neuronal survival, as well as phosphorylated Ser/Thr protein kinase (p-AKT), Bcl-2, Bcl-2 associated X protein (Bax) and cleaved caspase-3 levels in the hippocampus. The results showed that administration of a probiotic could ameliorate depressive behaviors and relieve neuronal cell injury in the hippocampal CA3 regions. Moreover, probiotic treatment decreased MDA levels and increased SOD activity. Furthermore, probiotic administration increased p-AKT and Bcl-2 levels in the hippocampus of the constipated mice, while decreasing the concentrations of Bax and cleaved caspase-3, so as to inhibit the neural apoptosis. In the present study, we confirm that probiotics can alleviate depression induced by constipation through protecting neuronal health via activation of the AKT signaling pathway.

Real-Time Quantification of Nanoplastics-Induced Oxidative Stress in Stretching Alveolar Cells.

Nanoplastics from air pollutants can be directly inhaled into the alveoli in the lungs and further enter blood circulation, and numerous studies have revealed the close relation between internalized nanoplastics with many physiological disorders via intracellular oxidative stress. However, the dynamic process of nanoplastics-induced oxidative stress in lung cells under breath-mimicked conditions is still unclear, due to the lack of methods that can reproduce the mechanical stretching of the alveolar and simultaneously monitor the oxidative stress response. Here, we describe a biomimetic platform by culturing alveoli epithelial cells on a stretchable electrochemical sensor and integrating them into a microfluidic device. This allows reproducing the respiration of alveoli by cyclic stretching of the alveoli epithelial cells and monitoring the nanoplastics-induced oxidative stress by the built-in sensor. By this device, we prove that cyclic stretches can greatly enhance the cellular uptake of nanoplastics with the dependencies of strain amplitude. Importantly, oxidative stress evoked by internalized nanoplastics can be quantitatively monitored in real time. This work will promote the deep understanding about the cytotoxicity of inhaled nanoplastics in the pulmonary mechanical microenvironment.

Bass detection model based on improved YOLOv5 in circulating water system.

The feeding amount of bass farming is closely related to the number of bass. It is of great significance to master the number of bass to achieve accurate feeding and improve the economic benefits of the farm. In view of the interference caused by the problems of multiple targets and target occlusion in bass data for bass detection, this paper proposes a bass target detection model based on improved YOLOV5 in circulating water system. Firstly, acquiring by HD cameras, Mosaic-8, a data augmentation method, is utilized to expand datasets and improve the generalization ability of the model. And K-means clustering algorithm is applied to generate suitable coordinates of prior boxes to improve training efficiency. Secondly, Coordinate Attention mechanism (CA) is introduced into backbone feature extraction network and neck feature fusion network to enhance attention to targets of interest. Finally, Soft-NMS algorithm replaces Non-Maximum Suppression algorithm (NMS) to re-screen prediction boxes and keep targets with higher overlap, which effectively solves the problems of missed detection and false detection. The experiments show that the proposed model can reach 98.09% in detection accuracy and detection speed reaches 13.4ms. The proposed model can help bass farmers under the circulating water system to accurately grasp the number of bass, which has important application value to realize accurate feeding and water conservation.

Boosting performance of gene mention tagging system by hybrid methods.

NER (Named Entity Recognition) in biomedical literature is presently one of the internationally concerned NLP (Natural Language Processing) research questions. In order to get higher performance, a hybrid experimental framework is presented for the gene mention tagging task. Six classifiers are firstly constructed by four toolkits (CRF++, YamCha, Maximum Entropy (ME) and MALLET) with different training methods and features sets, and then combined with three different hybrid methods respectively: simple set operation method, voting method and two layer stacking method. Experiments carried out on the corpus of BioCreative II GM task show that the three hybrid methods get the F-measure of 87.40%, 87.31% and 87.70% separately without any post-processing, which are all higher than those of any single ones. Our best hybrid method (two layer stacking method) achieves an F-measure of 88.42% after post-processing, which outperforms most of the state-of-the-art systems. We also discuss the influence on the performance of the ensemble system by the number, performance and divergence of single classifiers in each hybrid method, and give the corresponding analysis why our hybrid models can improve the performance.

Influence of Psychological Supervision on Athletes' Compliance, Mental Elasticity Characteristics and Acute Stress Disorder in Traumatic Fracture Rehabilitation Training.

BACKGROUND: We aimed to explore the effect of psychological supervision on rehabilitation training compliance, mental elasticity characteristics, and acute stress disorder. METHODS: From March 2018 to March 2020, 128 athletes with traumatic fractures in Zhoukou Sports Club in China were divided into two groups using the random number table method, The intervention group (64 athletes) received psychological supervision during the rehabilitation training, while the control group (64 athletes) without psychological supervision. The rehabilitation training compliance in the two groups was observed, and the mental elasticity characteristics and acute stress disorder changes were compared between the two groups before and post-intervention. RESULTS: The compliance rate during postoperative rehabilitation training in the intervention group is 92.19%, which was significantly higher than 73.44% in the control group (P<0.05). Compared with the scores before intervention, the CD-RISC score and SASRD score of the two groups were significantly lower than the scores post-intervention. The SMFA function and vexation indexes of the intervention group in three months after operation were significantly lower than those of the control group (P<0.05). The QOL scores of the intervention group in social, environmental, psychological, and physiological fields were significantly higher than those of the control group in three months after operation (P<0.05). CONCLUSION: The implementation of psychological supervision for athletes with traumatic fractures could improve rehabilitation training compliance, increase the level of mental elasticity, and relieve acute stress disorder.

Predictive role of ultrasound remission for progressive ultrasonography-detected structural damage in patients with rheumatoid arthritis.

Regarding the persistence of subclinical synovitis, the concept of ultrasound remission has been proposed in addition to clinical remission. However, there have been no studies that explored the different time points of ultrasound remission to predict non-progressive structural damage. Given this, the aim of our study is to explore whether early ultrasound remission in patients with rheumatoid arthritis (RA) has predictive value for non-progressive structural damage in the subsequent 12 months. Sixty-one patients with RA were prospectively studied. Synovial hypertrophy, power Doppler (PD) signal, and bone erosions of bilateral wrists, metacarpophalangeal joints I-V, and proximal interphalangeal joints II-III were assessed by ultrasonography at baseline and at 3, 6, and 12 months. Ultrasound remission was defined as no PD signal. Clinical remission was defined as Disease Activity Score in 28 Joints <2.6. Ultrasonography-detected joint damage progression was defined as increase in bone erosion score of ≥1 in the subsequent 12 months. Baseline ultrasonographic factors were not significantly correlated with progressive ultrasonography-detected joint damage in patients with RA at 12 months (all p>0.05). Ultrasound remission at 3 and 6 months was significantly correlated with non-progressive ultrasonography-detected structural damage at 12 months (p=0.006 and p=0.004), with relatively low sensitivity and high specificity. Clinical remission at 3 months was significantly correlated with non-progression of ultrasonography-detected structural damage at 12 months (p=0.029), with relatively low sensitivity and moderate specificity. Ultrasound remission at 3 and 6 months has high specificity in predicting non-progressive structural damage in patients with RA at 12 months; however, the sensitivity is limited.

Sonographic imaging features of alveolar soft part sarcoma: Case series and literature review.

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare tumor but potentially fatal condition. Understanding the imaging and clinical features of ASPS is of certain value for preoperative qualitative diagnosis and clinical treatment of tumors. Nevertheless, there have been only 11 documented case reports describing the sonographic features in the English literature. METHODS: Three patients with confirmed ASPS occurring primarily in the limbs were enrolled in this study. Complete surgical excision was performed with conservative limb function. We pay particular attention to the ultrasonographic features and performed a literature review of ASPS cases. RESULTS: With regular surveillance, one patient had no symptom recurrence and two developed lung and/or breast metastasis later. The specific sonographic findings were heterogeneous hypoechoic, well-circumscribed, and lobulated or round contours on grayscale images, abundant flow signals of intratumoral and extratumoral tubular structures on color Doppler images. CONCLUSION SUBSECTIONS: Its low incidence rate and lack of characteristic clinical manifestations often result in misdiagnosis of ASPS. The specific sonographic findings may add useful diagnostic information.