SAFB restricts contact domain boundaries associated with L1 chimeric transcription.

Long interspersed element-1 (LINE-1 or L1) comprises 17% of the human genome, continuously generates genetic variations, and causes disease in certain cases. However, the regulation and function of L1 remain poorly understood. Here, we uncover that L1 can enrich RNA polymerase IIs (RNA Pol IIs), express L1 chimeric transcripts, and create contact domain boundaries in human cells. This impact of L1 is restricted by a nuclear matrix protein scaffold attachment factor B (SAFB) that recognizes transcriptionally active L1s by binding L1 transcripts to inhibit RNA Pol II enrichment. Acute inhibition of RNA Pol II transcription abolishes the domain boundaries associated with L1 chimeric transcripts, indicating a transcription-dependent mechanism. Deleting L1 impairs domain boundary formation, and L1 insertions during evolution have introduced species-specific domain boundaries. Our data show that L1 can create RNA Pol II-enriched regions that alter genome organization and that SAFB regulates L1 and RNA Pol II activity to preserve gene regulation.

Quantitative Lipid Imaging Reveals a New Signaling Function of Phosphatidylinositol-3,4-Bisphophate: Isoform- and Site-Specific Activation of Akt.

Activation of class I phosphatidylinositol 3-kinase (PI3K) leads to formation of phosphatidylinositol-3,4,5-trisphophate (PIP3) and phosphatidylinositol-3,4-bisphophate (PI34P2), which spatiotemporally coordinate and regulate a myriad of cellular processes. By simultaneous quantitative imaging of PIP3 and PI34P2 in live cells, we here show that they have a distinctively different spatiotemporal distribution and history in response to growth factor stimulation, which allows them to selectively induce the membrane recruitment and activation of Akt isoforms. PI34P2 selectively activates Akt2 at both the plasma membrane and early endosomes, whereas PIP3 selectively stimulates Akt1 and Akt3 exclusively at the plasma membrane. These spatiotemporally distinct activation patterns of Akt isoforms provide a mechanism for their differential regulation of downstream signaling molecules. Collectively, our studies show that different spatiotemporal dynamics of PIP3 and PI34P2 and their ability to selectively activate key signaling proteins allow them to mediate class I PI3K signaling pathways in a spatiotemporally specific manner.

Multiplex chromatin interactions with single-molecule precision.

The genomes of multicellular organisms are extensively folded into 3D chromosome territories within the nucleus1. Advanced 3D genome-mapping methods that combine proximity ligation and high-throughput sequencing (such as chromosome conformation capture, Hi-C)2, and chromatin immunoprecipitation techniques (such as chromatin interaction analysis by paired-end tag sequencing, ChIA-PET)3, have revealed topologically associating domains4 with frequent chromatin contacts, and have identified chromatin loops mediated by specific protein factors for insulation and regulation of transcription5-7. However, these methods rely on pairwise proximity ligation and reflect population-level views, and thus cannot reveal the detailed nature of chromatin interactions. Although single-cell Hi-C8 potentially overcomes this issue, this method may be limited by the sparsity of data that is inherent to current single-cell assays. Recent advances in microfluidics have opened opportunities for droplet-based genomic analysis9 but this approach has not yet been adapted for chromatin interaction analysis. Here we describe a strategy for multiplex chromatin-interaction analysis via droplet-based and barcode-linked sequencing, which we name ChIA-Drop. We demonstrate the robustness of ChIA-Drop in capturing complex chromatin interactions with single-molecule precision, which has not been possible using methods based on population-level pairwise contacts. By applying ChIA-Drop to Drosophila cells, we show that chromatin topological structures predominantly consist of multiplex chromatin interactions with high heterogeneity; ChIA-Drop also reveals promoter-centred multivalent interactions, which provide topological insights into transcription.

The SphK1/S1P Axis Regulates Synaptic Vesicle Endocytosis via TRPC5 Channels.

Sphingosine-1-phosphate (S1P), a bioactive sphingolipid concentrated in the brain, is essential for normal brain functions, such as learning and memory and feeding behaviors. Sphingosine kinase 1 (SphK1), the primary kinase responsible for S1P production in the brain, is abundant within presynaptic terminals, indicating a potential role of the SphK1/S1P axis in presynaptic physiology. Altered S1P levels have been highlighted in many neurologic diseases with endocytic malfunctions. However, it remains unknown whether the SphK1/S1P axis may regulate synaptic vesicle endocytosis in neurons. The present study evaluates potential functions of the SphK1/S1P axis in synaptic vesicle endocytosis by determining effects of a dominant negative catalytically inactive SphK1. Our data for the first time identify a critical role of the SphK1/S1P axis in endocytosis in both neuroendocrine chromaffin cells and neurons from mice of both sexes. Furthermore, our Ca2+ imaging data indicate that the SphK1/S1P axis may be important for presynaptic Ca2+ increases during prolonged stimulations by regulating the Ca2+ permeable TRPC5 channels, which per se regulate synaptic vesicle endocytosis. Collectively, our data point out a critical role of the regulation of TRPC5 by the SphK1/S1P axis in synaptic vesicle endocytosis.SIGNIFICANCE STATEMENT Sphingosine kinase 1 (SphK1), the primary kinase responsible for brain sphingosine-1-phosphate (S1P) production, is abundant within presynaptic terminals. Altered SphK1/S1P metabolisms has been highlighted in many neurologic disorders with defective synaptic vesicle endocytosis. However, whether the SphK1/S1P axis may regulate synaptic vesicle endocytosis is unknown. Here, we identify that the SphK1/S1P axis regulates the kinetics of synaptic vesicle endocytosis in neurons, in addition to controlling fission-pore duration during single vesicle endocytosis in neuroendocrine chromaffin cells. The regulation of the SphK1/S1P axis in synaptic vesicle endocytosis is specific since it has a distinguished signaling pathway, which involves regulation of Ca2+ influx via TRPC5 channels. This discovery may provide novel mechanistic implications for the SphK1/S1P axis in brain functions under physiological and pathologic conditions.

Endogenous Protein-Protein Interaction Network of the NPC Cholesterol Transporter 1 in the Cerebral Cortex.

NPC intracellular cholesterol transporter 1 (NPC1) is a multipass, transmembrane glycoprotein mostly recognized for its key role in facilitating cholesterol efflux. Mutations in the NPC1 gene result in Niemann-Pick disease, type C (NPC), a fatal, lysosomal storage disease. Due to the progressively expanding implications of NPC1-related disorders, we investigated endogenous NPC1 protein-protein interactions in the mouse cortex and human-derived iPSCs neuronal models of the disease through coimmunoprecipitation-coupled with LC-MS based proteomics. The current study investigated protein-protein interactions specific to the wild-type and the most prevalent NPC1 mutation (NPC1I1061T) while filtering out any protein interactor identified in the Npc1-/- mouse model. Additionally, the results were matched across the two species to map the parallel interactome of wild-type and mutant NPC1I1061T. Most of the identified wild-type NPC1 interactors were related to cytoskeleton organization, synaptic vesicle activity, and translation. We found many putative NPC1 interactors not previously reported, including two SCAR/WAVE complex proteins that regulate ARP 2/3 complex actin nucleation and multiple membrane proteins important for neuronal activity at synapse. Moreover, we identified proteins important in trafficking specific to wild-type and mutant NPC1I1061T. Together, the findings are essential for a comprehensive understanding of NPC1 biological functions in addition to its classical role in sterol efflux.

ELOVL6 promotes the progression of head and neck squamous cell carcinoma via activating WNT/ß-catenin pathway.

This study was to explore the role of ELOVL6 in the development of head and neck squamous cell carcinoma (HNSCC). Considering its previously identified oncogenic role in hepatocellular carcinoma. ELOVL6 gene expression, clinicopathological analysis, enrichment analysis, and immune infiltration analysis were based on the data from Gene Expression Omnibus and The Cancer Genome Atlas, with additional bioinformatics analyses performed. Human HNSCC tissue microarray and cell lines were used. The expression of ELOVL6 in HNSCC was detected by quantitative polymerase chain reaction, immunohistochemistry assay, and western blot analysis. The proliferation ability of HNSCC cells, invasion, and apoptosis were evaluated using cell counting kit-8 method, Transwell assay, and flow cytometry, respectively. Based on the data derived from the cancer databases and our HNSCC cell and tissue studies, we found that ELOVL6 was overexpressed in HNSCC. Moreover, ELOVL6 expression level had a positive correlation with clinicopathology of HNSCC. Gene set enrichment analysis showed that ELOVL6 affected the occurrence of HNSCC through WNT signaling pathway. Functional experiments demonstrated that ELOVL6 knockdown inhibited the proliferation and invasion of HNSCC cells while promoting apoptosis. Additionally, compound 3f, an agonist of WNT/ß-catenin signaling pathway, enhances the effect of ELOVL6 on the progression of HNSCC cells. ELOVL6 is upregulated in HNSCC and promotes the development of HNSCC cells by inducing WNT/ß-catenin signaling pathway. ELOVL6 stands a potential target for the treatment of HNSCC and a prognosis indicator of human HNSCC.

Sustainable utilization of fruit and vegetable waste bioresources for bioplastics production.

Nowadays, rapidly increasing production, use and disposable of plastic products has become one of the utmost environmental issues. Our current circumstances in which the food supply chain is demonstrated as containing plastic particles and other plastic-based impurities, represents a significant health risk to humans, animals, and environmental alike. According to this point of view, biodegradable plastic material aims to produce a more sustainable and greener world with a lower ecological impact. Bioplastics are being investigated as an environmentally friendly candidate to address this problem and hence global bioplastic production has seen significant growth and expansion in recent years. This article focuses on a few critical issues that must be addressed for bioplastic production to become commercially viable. Although the reduction of fruit and vegetable waste biomass has an apparent value in terms of environmental benefits and sustainability, commercial success at industrial scale has remained flat. This is due to various factors, including biomass feedstocks, pretreatment technologies, enzymatic hydrolysis, and scale-up issues in the industry, all of which contribute to high capital and operating costs. This review paper summarizes the global overview of bioplastics derived from fruit and vegetable waste biomass. Furthermore, economic and technical challenges associated with industrialization and diverse applications of bioplastics in biomedical, agricultural, and food-packaging fields due to their excellent biocompatibility properties are reviewed.HighlightsReview of the diverse types and characteristics of sustainability of biobased plasticsImproved pretreatment technologies can develop to enhance greater yieldEnzyme hydrolysis process used for bioplastic extraction & hasten industrial scale-upFocus on technical challenges facing commercialized the bioplasticsDetailed discussion on the application for sustainability of biodegradable plastics.

Effects of Inorganic Salts on the Phase Separation of Partially Miscible Solutes.

Partially miscible solutions with a lower critical solution temperature have promising applications in the field of physical chemistry. To better guide the utilization of these solutions in practice, we conduct an in-depth study about the phase separation behavior of the solution added with inorganic salts. The addition of the inorganic salts into the solution is found to consequently reduce the phase separation temperature. The variation of concentrations of inorganic salts does not notably affect the mass fraction of the separation. Moreover, the addition of inorganic salts in the solutions at lower mass fractions improves the separation mass fraction, while the addition of inorganic salts decreases the separation mass fraction at the mass fractions above 30%. It sheds light on selecting the proper mass fractions and inorganic salt concentrations. Furthermore, we explore the phase separation behavior of mixed solutions under different inorganic salt additions by means of a high-speed camera. The phase separation behavior under different inorganic salt systems shows a similar trend. However, calcium ions and Fe3+ ions in the solutions can greatly decrease the rate of droplet coalescence and result in an increase in phase separation. For better regulating the solutions with a lower critical solution temperature through inorganic salts, sodium chloride or potassium chloride is recommended with an appropriate concentration.

Association of serum vitamin C levels with Asthma in adults: results of NHANES 2003-2006 and mendelian randomization study.

BACKGROUND: The protective effect of vitamin C as an antioxidant against asthma in adults remains controversial. This study used an observational study and Mendelian randomization (MR) analysis to investigate the association between adult asthma and serum vitamin C levels. METHODS: Using information from the National Health and Nutrition Examination Survey (NHANES) 2003-2006, we carried out an observational study. A multivariate logistic regression model was employed to examine the connection between adult asthma and serum vitamin C levels. We used the inverse-variance weighted (IVW) method of MR analysis as the primary method to analyze the causal effect of serum vitamin C levels on asthma in adults. RESULTS: A total of 8,504 participants were included in the observational study, including 639 in the asthma group and 7,865 in the non-asthma group. Before sample weighting, serum vitamin C was associated with a reduced risk of asthma in adults (OR = 0.798, 95% CI: 0.673-0.945, P = 0.009). After sample weighting, serum vitamin C was not associated with adult asthma risk (OR = 0.829, 95% CI: 0.660 ~ 1.042, P = 0.104). MR analysis showed no causal relationship between serum vitamin C and adult asthma in either the UK Biobank (OR = 0.957, 95% CI: 0.871 ~ 1.053, P = 0.370) or FinnGen (OR = 0.973, 95% CI: 0.824 ~ 1.149, P = 0.750) cohorts. CONCLUSION: Our study did not support a causal association between serum vitamin C levels and adult asthma risk. The relationship between serum vitamin C and adult asthma requires further research.

Robust and Precise Quantitative Real-Time Polymerase Chain Reaction with an Amplification Efficiency-Aware Reaction Kinetics Model.

Quantitative real-time PCR (qPCR) is a method extensively used in nucleic acid testing for plants and animals. During the coronavirus disease 2019 (COVID-19) pandemic, high-precision qPCR analysis was urgently needed since quantitative results obtained from conventional qPCR methods were not accurate and precise, causing misdiagnoses and high rates of false-negative. To achieve more accurate results, we propose a new qPCR data analysis method with an amplification efficiency-aware reaction kinetics model (AERKM). Our reaction kinetics model (RKM) mathematically describes the tendency of the amplification efficiency during the whole qPCR process inferred by biochemical reaction dynamics. Amplification efficiency (AE) was introduced to rectify the fitted data so as to match the real reaction process for individual tests, thus reducing errors. The 5-point 10-fold gradient qPCR tests of 63 genes have been verified. The results of a 0.9% slope bias and an 8.2% ratio bias using AERKM exceed 4.1 and 39.4%, respectively, of the best performance of existing models, which demonstrates higher precision, less fluctuation, and better robustness among different nucleic acids. AERKM also provides a better understanding of the real qPCR process and gives insights into the detection, treatment, and prevention of severe diseases.

The role of ascending arousal network in patients with chronic insomnia disorder.

The ascending arousal system plays a crucial role in individuals' consciousness. Recently, advanced functional magnetic resonance imaging (fMRI) has made it possible to investigate the ascending arousal network (AAN) in vivo. However, the role of AAN in the neuropathology of human insomnia remains unclear. Our study aimed to explore alterations in AAN and its connections with cortical networks in chronic insomnia disorder (CID). Resting-state fMRI data were acquired from 60 patients with CID and 60 good sleeper controls (GSCs). Changes in the brain's functional connectivity (FC) between the AAN and eight cortical networks were detected in patients with CID and GSCs. Multivariate pattern analysis (MVPA) was employed to differentiate CID patients from GSCs and predict clinical symptoms in patients with CID. Finally, these MVPA findings were further verified using an external data set (32 patients with CID and 33 GSCs). Compared to GSCs, patients with CID exhibited increased FC within the AAN, as well as increased FC between the AAN and default mode, cerebellar, sensorimotor, and dorsal attention networks. These AAN-related FC patterns and the MVPA classification model could be used to differentiate CID patients from GSCs with 88% accuracy in the first cohort and 77% accuracy in the validation cohort. Moreover, the MVPA prediction models could separately predict insomnia (data set 1, R2  = .34; data set 2, R2  = .15) and anxiety symptoms (data set 1, R2  = .35; data set 2, R2  = .34) in the two independent cohorts of patients. Our findings indicated that AAN contributed to the neurobiological mechanism of insomnia and highlighted that fMRI-based markers and machine learning techniques might facilitate the evaluation of insomnia and its comorbid mental symptoms.

Bacteroides rhinocerotis sp. nov., isolated from the fresh feces of rhinoceros in Beijing Zoo.

A Gram-negative strain, anaerobic, non-motile, non-spore-forming, rod-shaped bacterial strain named as NGMCC 1.200684 T was isolated from the fresh feces of rhinoceros in Beijing Zoo. Based on 16S rRNA gene sequences, phylogenetic analysis indicated that strain NGMCC 1.200684 T belonged to the genus Bacteroides and was most strongly related to the type strain of Bacteroides uniformis ATCC 8492 T (96.88%). The G + C content of the genomic DNA was determined to be 46.62%. Between strains NGMCC 1.200684 T and B. uniformis ATCC 8492 T, the average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) were 93.89 and 67.60%, respectively. Strain NGMCC 1.200684 T can produce acid from fermentation of several substrates, including glucose, mannitol, lactose, saccharose, maltose, salicin, xylose, cellobiose, mannose, raffinose, sorbitol, trehalose, D-galactose, and maltotriose. The major cellular fatty acids (> 10%) were identified as anteiso-C15:0, iso-C15:0, iso-C14:0, and iso-C17:0 3-OH. The polar lipid profiles of strain NGMCC 1.200684 T were determined to contain diphosphatidyl glycerol, phosphatidylglycerol, phosphatidylethanolamine, three unknown phospholipids, and two unknown amino-phospholipids. Based on phenotypic, phylogenetic, and chemotaxonomic characteristics, a novel species of the genus Bacteroides, Bacteroides rhinocerotis sp. nov. is proposed. The type strain is NGMCC 1.200684 T (= CGMCC 1.18013 T = JCM 35702 T).

Early impairment of right ventricular systolic function in patients with prediabetes and type 2 diabetes mellitus: An analysis of two-dimensional speckle tracking echocardiography.

BACKGROUND: Type 2 diabetes mellitus is a metabolic disease that affects multiple target organs. Current data on right ventricular damage in type 2 diabetes, especially in prediabetes, are limited. Due to the anatomical characteristics of the right ventricle, the assessment of the right ventricle by conventional echocardiography is difficult, whereas the ultrasound two-dimensional speckle tracking echocardiography can provide information on myocardial systolic function by tracking the motion information of myocardial speckles, which can sensitively reflect myocardial mechanical changes. AIMS: To assess the effect of prediabetes and diabetes with preserved left ventricular ejection fraction on right ventricular myocardial systolic function and to identify independent risk factors affecting right ventricular systolic function. METHODS: A total of 49 normoglycaemic (NG) healthy individuals, 43 prediabetics (PDM), and 52 type 2 diabetics (T2DM) were recruited. All study subjects underwent conventional echocardiography and two-dimensional speckle tracking echocardiography (2D-STE). RESULTS: The right ventricular global longitudinal strain (RVGLS) (20.80 ± 1.96% vs. 18.99 ± 3.20% vs. 16.85 ± 4.01%), left ventricular global longitudinal strain (LVGLS), and interventricular septal longitudinal strain (IVS-LS) (17.28 ± 2. 35% vs. 16.14 ± 3.22% vs. 15.53 ± 3.33%) gradually decreased from the controls, through patients with prediabetes, to those with diabetes (p < .001). Right ventricular free wall strain (RVFW-LS) was higher in the control group (25.63 ± 4.58% vs. 22.83 ± 4.83% vs. 20.79 ± 4.92%) than in the other two groups with a statistically significant difference (p < .001), while RVFW-LS was not statistically different between the prediabetic and diabetic groups. Multivariate regression analysis showed that HbA1c (ß = -.626, p < .001), IVS-LS (ß = .417, p < .001), and left ventricular end-diastolic diameter (LVEDd) (ß = .191, p = .011) were independently correlated with RVGLS. CONCLUSIONS: Two-dimensional speckle tracking echocardiography can sensitively detect subtle changes in the early impairment of right ventricular systolic function in patients with abnormal glucose metabolism. Type 2 diabetes is the common mechanism causing impaired myocardial mechanics in the right and left ventricles. The reduced global systolic longitudinal strain of the right ventricle was associated with reduced global septal longitudinal strain and left ventricular remodeling. HbA1c is an independent predictor of the global longitudinal strain of the right ventricle, and controlling blood glucose levels may be expected to improve the extent of myocardial damage.

The value of radiomics-based CT combined with machine learning in the diagnosis of occult vertebral fractures.

PURPOSE: To develop and evaluate the performance of radiomics-based computed tomography (CT) combined with machine learning algorithms in detecting occult vertebral fractures (OVFs). MATERIALS AND METHODS: 128 vertebrae including 64 with OVF confirmed by magnetic resonance imaging and 64 corresponding control vertebrae from 57 patients who underwent chest/abdominal CT scans, were included. The CT radiomics features on mid-axial and mid-sagittal plane of each vertebra were extracted. The fractured and normal vertebrae were randomly divided into training set and validation set at a ratio of 8:2. Pearson correlation analyses and least absolute shrinkage and selection operator were used for selecting sagittal and axial features, respectively. Three machine-learning algorithms were used to construct the radiomics models based on the residual features. Receiver operating characteristic (ROC) analysis was used to verify the performance of model. RESULTS: For mid-axial CT imaging, 6 radiomics parameters were obtained and used for building the models. The logistic regression (LR) algorithm showed the best performance with area under the ROC curves (AUC) of training and validation sets of 0.682 and 0.775. For mid-sagittal CT imaging, 5 parameters were selected, and LR algorithms showed the best performance with AUC of training and validation sets of 0.832 and 0.882. The LR model based on sagittal CT yielded the best performance, with an accuracy of 0.846, sensitivity of 0.846, and specificity of 0.846. CONCLUSION: Machine learning based on CT radiomics features allows for the detection of OVFs, especially the LR model based on the radiomics of sagittal imaging, which indicates it is promising to further combine with deep learning to achieve automatic recognition of OVFs to reduce the associated secondary injury.

Atomistic Insights into the Effect of Functional Groups on the Adsorption of Water by Activated Carbon for Heat Energy Storage.

Adsorption heat storage holds great promise for solar energy applications. The development of new adsorbent materials is currently the research focus in this area. The present work designs several activated carbon models with different functional groups, including -OH, -NH2, -COOH, and -SO3H, and explores the influence of functional groups' categories and numbers on the water adsorption capacity of the activated carbon using the GCMC method. The adsorption mechanism between functional groups and water molecules is analyzed using density functional theory. The results show that the functional groups could significantly improve the water adsorption capacity of activated carbon due to the hydrogen bond between functional groups and water molecules. In the scope of this paper, under low pressure, the activated carbon with -SO3H exhibits the best adsorption capacity, followed by the activated carbon with -COOH. Under low and medium pressure, increasing the number of -SO3H functional groups could increase the water adsorption capacity; however, when the pressure is high, increasing the functional group numbers might decrease the water adsorption capacity. As the temperature increases, the water adsorption capacity of activated carbons decreases, and the activated carbon with -SO3H is proven to have excellent application prospects in heat energy storage.

A novel high-risk subpopulation identified by CTSL and ZBTB7B in gastric cancer.

BACKGROUND: Gastric cancer (GC) is characterised by a heterogeneous tumour microenvironment (TME) that is closely associated with the response to treatment, especially immunotherapies. However, most previous GC molecular subtyping systems need complex gene signatures and examination methods, restricting their clinical applications. Thus, we developed a new TME-based molecular subtype using only two genes. METHODS: Nine independent GC cohorts at the tissue- or single-cell level with more than 2000 patients were used in this study, including data we examined by single-cell sequencing, quantitative RT-PCR and immunochemistry/immunofluorescence staining. Nine different methods, five existing molecular subtypes and a series of signatures were used to evaluate the TME and molecular characteristics of GC. RESULTS: We established a CTSL/ZBTB7B subtyping system and uncovered the novel CTSLHighZBTB7BLow high-risk subgroup, but characterised by relative higher immune cell infiltration and lower tumour purity. This subgroup demonstrate higher levels of immune checkpoints and more enrichment of cancer-related pathways compared with other cases. CONCLUSIONS: We identified a high-risk subpopulation with unique TME features based on expressions of CTSL and ZBTB7B, suggesting a counterbalancing phenotype between immunostimulatory and immunosuppressive mechanisms. This subtyping system could be used to select treatment and management strategies for GC.

Irisin attenuates lipopolysaccharide-induced acute lung injury by downregulating inflammatory cytokine expression through miR-199a-mediated Rad23b overexpression.

AIMS: Acute lung injury (ALI) is a leading cause of mortality as a result of inflammatory cytokine overexpression and increased rates of apoptosis. Therapies for ALI are yet to be thoroughly investigated. Recent evidence has shown that irisin exerts protective effects against many types of pathologies. The present study aimed to determine the function of irisin in an ALI mouse model induced by lipopolysaccharide (LPS) and the corresponding underlying mechanisms at the tissue, cellular, and molecular levels. MAIN METHODS: We assessed irisin function in A549 cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays. The cell apoptosis was evaluated by flow cytometry. Western blotting and RT-PCR were used to test expression level. Animal models of ALI was established. KEY FINDINGS: We found that irisin treatment maintained lung weight, significantly reduced inflammatory cytokine expression, and alleviated lung injury by downregulating miR-199a. In LPS-stimulated cells, forced miR-199a expression downregulated Rad23b expression by targeting its 3' untranslated region, indicating that Rad23b is a direct target of miR-199a. SIGNIFICANCE: These findings reveal that irisin can alleviate ALI by inhibiting miR-199a and upregulating Rad23b expression, suggesting that irisin has clinical potential for the treatment of ALI.

Protective Effects of Vitamin C against Neomycin-Induced Apoptosis in HEI-OC1 Auditory Cell.

Ototoxic hearing loss results from hair cell death via reactive oxygen species (ROS) overproduction and consequent apoptosis. We investigated the effects of vitamin C (VC) on neomycin-induced HEI-OC1 cell damage, as well as the mechanism of inhibition. HEI-OC1 cells were treated with neomycin or with vitamin C (VC). The results indicated that VC had a protective effect on neomycin-induced HEI-OC1 cell death. Mechanistically, VC decreased neomycin-induced ROS generation, suppressed cell death, and increased cell viability. VC inhibited neomycin-induced apoptosis, ameliorated neomycin reduced antiapoptotic Bcl-2 expression, and suppressed neomycin increased expression of proapoptotic Bax, caspase-3 cleavage and caspase-8. TUNEL labeling demonstrated that VC blocked neomycin-induced apoptosis. Further study revealed that the effect of VC on neomycin-induced hair cell death was through interference with JNK activation and p38 phosphorylation. These results indicate that VC via suppressed ROS generation, which inhibited cell death by counteracting apoptotic signaling induced by neomycin in cells. Hence, VC is a potential candidate for protection agent against neomycin-induced HEI-OC1 cell ototoxicity.

Surgical strategies for patients with second primary non-small cell lung cancer lesions 2 cm or less in diameter.

BACKGROUND AND PURPOSE: The wide application of low-dose computed tomography (CT) has led to an increase in the detection of small lung cancer lesions. Moreover, surgical recommendations for second primary non-small cell lung cancer (NSCLC) lesions ≤ 2 cm are obscure. This study compares the efficacy of wedge resection, lobectomy, and segmentectomy for small second primary NSCLC lesions. METHODS: The cohort was established based on the SEER database. Univariate and multivariate cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression, and restricted mean survival time (RMST) values were applied to identify prognostic factors. We used the Kaplan-Meier method to plot the survival curves of the different subgroups according to propensity score matching (PSM) analysis to then compare the therapeutic efficacy of the surgical procedures. RESULTS: A total of 568 patients were enrolled in this study. Age, sex, grade, and lymph node ratio were selected as independent prognostic factors (p < 0.05). No significant differences were observed in survival probabilities among the groups of patients who underwent segmentectomy, wedge resection, or lobectomy (p > 0.05). We also established a nomogram model based on the four prognostic factors to guide clinical treatment. CONCLUSIONS: Based on the findings of our study, segmentectomy was more appropriate than lobectomy for patients with a second primary NSCLC lesion ≤ 2 cm in diameter. The evidence to support other recommendations is insufficient.

Motion Similarity Evaluation between Human and a Tri-Co Robot during Real-Time Imitation with a Trajectory Dynamic Time Warping Model.

Precisely imitating human motions in real-time poses a challenge for the robots due to difference in their physical structures. This paper proposes a human-computer interaction method for remotely manipulating life-size humanoid robots with a new metrics for evaluating motion similarity. First, we establish a motion capture system to acquire the operator's motion data and retarget it to the standard bone model. Secondly, we develop a fast mapping algorithm, by mapping the BVH (BioVision Hierarchy) data collected by the motion capture system to each joint motion angle of the robot to realize the imitated motion control of the humanoid robot. Thirdly, a DTW (Dynamic Time Warping)-based trajectory evaluation method is proposed to quantitatively evaluate the difference between robot trajectory and human motion, and meanwhile, visualization terminals render it more convenient to make comparisons between two different but simultaneous motion systems. We design a complex gesture simulation experiment to verify the feasibility and real-time performance of the control method. The proposed human-in-the-loop imitation control method addresses a prominent non-isostructural retargeting problem between human and robot, enhances robot interaction capability in a more natural way, and improves robot adaptability to uncertain and dynamic environments.