The contributions from the progenitor genomes of the mesopolyploid Brassiceae are evolutionarily distinct but functionally compatible.

The members of the tribe Brassiceae share a whole-genome triplication (WGT), and one proposed model for its formation is a two-step pair of hybridizations producing hexaploid descendants. However, evidence for this model is incomplete, and the evolutionary and functional constraints that drove evolution after the hexaploidy are even less understood. Here, we report a new genome sequence of Crambe hispanica, a species sister to most sequenced Brassiceae. Using this new genome and three others that share the hexaploidy, we traced the history of gene loss after the WGT using the Polyploidy Orthology Inference Tool (POInT). We confirm the two-step formation model and infer that there was a significant temporal gap between those two allopolyploidizations, with about a third of the gene losses from the first two subgenomes occurring before the arrival of the third. We also, for the 90,000 individual genes in our study, make parental subgenome assignments, inferring, with measured uncertainty, from which of the progenitor genomes of the allohexaploidy each gene derives. We further show that each subgenome has a statistically distinguishable rate of homoeolog losses. There is little indication of functional distinction between the three subgenomes: the individual subgenomes show no patterns of functional enrichment, no excess of shared protein-protein or metabolic interactions between their members, and no biases in their likelihood of having experienced a recent selective sweep. We propose a "mix and match" model of allopolyploidy, in which subgenome origin drives homoeolog loss propensities but where genes from different subgenomes function together without difficulty.

Chicoric Acid Ameliorated Beta-Amyloid Pathology and Enhanced Expression of Synaptic-Function-Related Markers via L1CAM in Alzheimer's Disease Models.

Alzheimer's disease (AD) is the most common progressive neurodegenerative disease. The accumulation of amyloid-beta (Aß) plaques is a distinctive pathological feature of AD patients. The aims of this study were to evaluate the therapeutic effect of chicoric acid (CA) on AD models and to explore its underlying mechanisms. APPswe/Ind SH-SY5Y cells and 5xFAD mice were treated with CA. Soluble Aß1-42 and Aß plaque levels were analyzed by ELISA and immunohistochemistry, respectively. Transcriptome sequencing was used to compare the changes in hippocampal gene expression profiles among the 5xFAD mouse groups. The specific gene expression levels were quantified by qRT-PCR and Western blot analysis. It was found that CA treatment reduced the Aß1-42 levels in the APPswe/Ind cells and 5xFAD mice. It also reduced the Aß plaque levels as well as the APP and BACE1 levels. Transcriptome analysis showed that CA affected the synaptic-plasticity-related genes in the 5xFAD mice. The levels of L1CAM, PSD-95 and synaptophysin were increased in the APPswe/Ind SH-SY5Y cells and 5xFAD mice treated with CA, which could be inhibited by administering siRNA-L1CAM to the CA-treated APPswe/Ind SH-SY5Y cells. In summary, CA reduced Aß levels and increased the expression levels of synaptic-function-related markers via L1CAM in AD models.

Aerosol liquid water in PM2.5 and its roles in secondary aerosol formation at a regional site of Yangtze River Delta.

Aerosol liquid water content (ALWC) plays an important role in secondary aerosol formation. In this study, a whole year field campaign was conducted at Shanxi in north Zhejiang Province during 2021. ALWC estimated by ISORROPIA-II was then investigated to explore its characteristics and relationship with secondary aerosols. ALWC exhibited a highest value in spring (66.38 µg/m3), followed by winter (45.08 µg/m3), summer (41.64 µg/m3), and autumn (35.01 µg/m3), respectively. It was supposed that the secondary inorganic aerosols (SIA) were facilitated under higher ALWC conditions (RH > 80%), while the secondary organic species tended to form under lower ALWC levels. Higher RH (> 80%) promoted the NO3- formation via gas-particle partitioning, while SO42- was generated at a relative lower RH (> 50%). The ALWC was more sensitive to NO3- (R = 0.94) than SO42- (R = 0.90). Thus, the self-amplifying processes between the ALWC and SIA enhanced the particle mass growth. The sensitivity of ALWC and OX (NO2 + O3) to secondary organic carbon (SOC) varied in different seasons at Shanxi, more sensitive to aqueous-phase reactions (daytime R = 0.84; nighttime R = 0.54) than photochemical oxidation (daytime R = 0.23; nighttime R = 0.41) in wintertime with a high level of OX (daytime: 130-140 µg/m3; nighttime: 100-140 µg/m3). The self-amplifying process of ALWC and SIA and the aqueous-phase formation of SOC will enhance aerosol formation, contributing to air pollution and reduction of visibility.

AQP4-A25Q Point Mutation in Mice Depolymerizes Orthogonal Arrays of Particles and Decreases Polarized Expression of AQP4 Protein in Astrocytic Endfeet at the Blood-Brain Barrier.

Aquaporin-4 (AQP4) is characterized by the formation of orthogonal arrays of particles (OAPs) comprising its M1 and M23 isoforms in the plasma membrane. However, the biological importance of OAP formation is obscure. Here, we developed an OAP depolymerization male mouse model by transgenic knock-in of an AQP4-A25Q mutation. Analyses of the mutant brain tissue using blue native polyacrylamide gel electrophoresis, super-resolution imaging, and immunogold electron microscopy revealed remarkably reduced OAP structures and glial endfeet localization of the AQP4-A25Q mutant protein without effects on its overall mRNA and protein expression. AQP4A25Q/A25Q mice showed better survival and neurologic deficit scores when cerebral edema was induced by water intoxication or middle cerebral artery occlusion/reperfusion. The brain water content and swelling of pericapillary astrocytic endfeet processes in AQP4A25Q/A25Q mice were significantly reduced, functionally supporting decreased AQP4 protein expression at the blood-brain barrier. The infarct volume and neuronal damage were also reduced in AQP4A25Q/A25Q mice in the middle cerebral artery occlusion/reperfusion model. Astrocyte activation in the brain was alleviated in AQP4A25Q/A25Q mice, which may be associated with decreased cell swelling. We conclude that the OAP structure of AQP4 plays a key role in its polarized expression in astrocytic endfeet processes at the blood-brain barrier. Therefore, our study provided new insights into intervention of cerebral cellular edema caused by stroke and traumatic brain injury through regulating AQP4 OAP formation.SIGNIFICANCE STATEMENT Aquaporin-4 (AQP4) is characterized by orthogonal arrays of particles (OAPs) comprising the M1 and M23 isoforms in the membrane. Here, an OAP depolymerization male mouse model induced by AQP4-A25Q mutation was first established, and the functions of OAP depolymerization in cerebral edema have been studied. The results revealed that AQP4 lost its OAP structure without affecting AQP4 mRNA and protein levels in AQP4-A25Q mice. AQP4-A25Q mutation mice has neuroprotective effects on cerebral edema induced by water intoxication and middle cerebral artery occlusion/reperfusion through relieving the activation of astrocytes and suppressed microglia-mediated neuroinflammation. We concluded that the OAP structure of AQP4 plays a key role in its polarized expression in astrocytic endfeet processes at the blood-brain barrier. Therefore, our study provided new insights into intervention of cerebral cellular edema caused by stroke and traumatic brain injury through regulating AQP4 OAP formation.

Sequencing of Camelina neglecta, a diploid progenitor of the hexaploid oilseed Camelina sativa.

Camelina neglecta is a diploid species from the genus Camelina, which includes the versatile oilseed Camelina sativa. These species are closely related to Arabidopsis thaliana and the economically important Brassica crop species, making this genus a useful platform to dissect traits of agronomic importance while providing a tool to study the evolution of polyploids. A highly contiguous chromosome-level genome sequence of C. neglecta with an N50 size of 29.1 Mb was generated utilizing Pacific Biosciences (PacBio, Menlo Park, CA) long-read sequencing followed by chromosome conformation phasing. Comparison of the genome with that of C. sativa shows remarkable coincidence with subgenome 1 of the hexaploid, with only one major chromosomal rearrangement separating the two. Synonymous substitution rate analysis of the predicted 34 061 genes suggested subgenome 1 of C. sativa directly descended from C. neglecta around 1.2 mya. Higher functional divergence of genes in the hexaploid as evidenced by the greater number of unique orthogroups, and differential composition of resistant gene analogs, might suggest an immediate adaptation strategy after genome merger. The absence of genome bias in gene fractionation among the subgenomes of C. sativa in comparison with C. neglecta, and the complete lack of fractionation of meiosis-specific genes attests to the neopolyploid status of C. sativa. The assembled genome will provide a tool to further study genome evolution processes in the Camelina genus and potentially allow for the identification and exploitation of novel variation for Camelina crop improvement.

TREM-1 as a potential prognostic biomarker associated with immune infiltration in clear cell renal cell carcinoma.

BACKGROUND: The tumor immune microenvironment plays a crucial role in the efficacy of various therapeutics. However, their correlation is not yet completely understood in Clear cell renal cell carcinoma (ccRCC). This study aimed to investigate the potential of TREM-1 as a potential novel biomarker for ccRCC. METHODS: We constructed a ccRCC immune prognostic signature. The clinical characteristics, the status of the tumor microenvironment, and immune infiltration were analyzed through the ESTIMATE and CIBERSORT algorithms for the hub gene, while the Gene Set Enrichment Analysis and PPI analysis were performed to predict the function of the hub gene. Immunohistochemical staining was used to detect the expression of TREM-1 in renal clear cell carcinoma tissues. RESULTS: The CIBERSORT and ESTIMATE algorithms revealed that TREM-1 was correlated with the infiltration of 12 types of immune cells. Therefore, it was determined that TREM-1 was involved in numerous classical pathways in the immune response via GSEA analysis. In Immunohistochemical staining, we found that the expression of TREM-1 was significantly upregulated with increasing tumor grade in renal clear cell carcinoma, and elevated TREM-1 expression was associated with poor prognosis. CONCLUSIONS: The results suggest that TREM-1 may act as an implicit novel prognostic biomarker in ccRCC that could be utilized to facilitate immunotherapeutic strategy.

Design and Evaluation of the Extended FBS Model Based Gaze-Control Power Wheelchair for Individuals Facing Manual Control Challenges.

This study addresses the challenges faced by individuals with upper limb disadvantages in operating power wheelchair joysticks by utilizing the extended Function-Behavior-Structure (FBS) model to identify design requirements for an alternative wheelchair control system. A gaze-controlled wheelchair system is proposed based on design requirements from the extended FBS model and prioritized using the MosCow method. This innovative system relies on the user's natural gaze and comprises three levels: perception, decision making, and execution. The perception layer senses and acquires information from the environment, including user eye movements and driving context. The decision-making layer processes this information to determine the user's intended direction, while the execution layer controls the wheelchair's movement accordingly. The system's effectiveness was validated through indoor field testing, with an average driving drift of less than 20 cm for participates. Additionally, the user experience scale revealed overall positive user experiences and perceptions of the system's usability, ease of use, and satisfaction.

Trans-ε-viniferin as an inhibitor of TMEM16A preventing intestinal smooth muscle contraction.

TMEM16A regulator is an important tool to study the physiological functions and pathogenesis related to TMEM16A. In the present study, trans-ε-viniferin (TV) was identified as a TMEM16A inhibitor with inhibitory activity against TMEM16A mediated Cl- currents, which was reversible, without affecting intracytoplasmic Ca2+ concentration and TMEM16A protein expression. TV inhibited intestinal peristalsis and prolonged gastrointestinal transport time. TV could inhibit autonomic and Eact-stimulated intestinal contractility, and was equally effective in ACh- and HA-induced high contractile states. The results indicate that TV significantly inhibits the intestinal smooth muscle contraction, which may be applied in the treatment of TMEM16A-related intestinal dynamic abnormalities.

Visual Identification of Trichosporon asahii, a Gut Yeast Associated with Obesity, Using an Enzymatic NIR Fluorescent Probe.

Lipase found in the gut microbiota participates in the digestion and absorption of dietary fats. As such, the gut microbiota is involved in the regulation of the host metabolism, affecting the levels of lipids and free fatty acids, ultimately resulting in obesity. In this study, an enzymatic activatable near-infrared fluorescent probe, DDAO-C6, was developed for visually sensing endogenous lipase from gut microbes. Using DDAO-C6, a cultivated intestinal yeast strain was rapidly identified from human feces that exhibited high lipase expression and was identified as Trichosporon asahii Y2. We then determined that the colonization of the gut of mice with T. asahii Y2 increased lipase activity in the digestive tract and promoted obesity and hyperlipidemia when the mice were fed high fat diets. Above all, the present research resulted in a fluorescence visualization tool for the functional investigation of gut microbiota associated with obesity and disorders of lipid metabolism.

Design of Audio-Augmented-Reality-Based O&M Orientation Training for Visually Impaired Children.

Orientation and Mobility training (O&M) is a specific program that teaches people with vision loss to orient themselves and travel safely within certain contexts. State-of-the-art research reveals that people with vision loss expect high-quality O&M training, especially at early ages, but the conventional O&M training methods involve tedious programs and require a high participation of professional trainers. However, there is an insufficient number of excellent trainers. In this work, we first interpret and discuss the relevant research in recent years. Then, we discuss the questionnaires and interviews we conducted with visually impaired people. On the basis of field investigation and related research, we propose the design of a training solution for children to operate and maintain direction based on audio augmented reality. We discuss how, within the perceptible scene created by EasyAR's map-aware framework, we created an AR audio source tracing training that simulates a social scene to strengthen the audiometric identification of the subjects, and then to verify the efficiency and feasibility of this scheme, we implemented the application prototype with the required hardware and software and conducted the subsequential experiments with blindfolded children. We confirm the high usability of the designed approach by analyzing the results of the pilot study. Compared with other orientation training studies, the method we propose makes the whole training process flexible and entertaining. At the same time, this training process does not involve excessive economic costs or require professional skills training, allowing users to undergo training at home or on the sports ground rather than having to go to rehabilitation sites or specified schools. Furthermore, according to the feedback from the experiments, the approach is promising in regard to gamification.

Keratin 86 is up-regulated in the uterus during implantation, induced by oestradiol.

BACKGROUND: Uterine receptivity is one of the determinants of embryo implantation, which is responsible for pregnancy success. Aberrant embryo implantation due to disrupted uterine receptivity is usually found in ovarian hyperstimulation induced hyperoestrogen patients. RESULTS: This study identified keratin 86 (KRT86), a fibrous structural protein, which was upregulated in uterine endometrium during peri-implantation. Using a hyperoestrogen mouse model established in a previous study, we found abnormal oestradiol (E2) levels during pre-implantation could trigger high expression of Krt86 in the uterine epithelium. In an ovariectomised mouse model, combining oestrogen receptors ERα and ERß knockout mice models, uterine Krt86 was found to be up-regulated after E2 treatment, mediated by nuclear ERα. Furthermore, we found progesterone (P4) could ameliorate Krt86 expression, induced by abnormal E2. CONCLUSIONS: These results revealed the dynamic expression and regulation of Krt86, especially in hyperoestrogen treated mice, indicating it might act as a marker for non-receptive uterus.

Psychiatric referral is required in children with vaginal foreign body injury: A case-control study from China.

PURPOSE: The rate of vaginal foreign body (VFB) injury has been increasing in recent years. VFB will cause vaginal inflammation, injury and negative psychological impacts in girls. Our study aimed to elucidate the need of psychological referral in children with VFB. DESIGN AND METHODS: A case-control study was performed. A total of 67 girls who visited the clinic due to vaginal foreign bodies were recruited. A questionnaire and Family environment scale-Chinese version (FES-CV) and social anxiety scale for children-Chinese version (SASC-CV) were completed by parents and children. Demographic information, parenting pattern, girls' social anxiety status, and their daily life trajectory and outdoor activities were collected. RESULTS: The mean age of the 67 girls with VFB was 6.6 ± 2.1 years with a range of 2 years10 months-13 years. The 72 girls of the control group were age-matched with the patients. Scorings in two subscales of FES-CV including family cohesion, emotion expression were significantly lower in the VFB group than those in the control group (7.2 ± 2.4 vs. 7.9 ± 1.7, p < 0.05; 5.2 ± 1.6 vs. 6.5 ± 1.3, p < 0.001). Social anxiety level was higher in the VFB group comparing with the control group. Shorter time of outdoor activities (t = 3.205, p = 0.002) and significantly longer screen time were in the VFB group (t = 5.74, p < 0.001). CONCLUSIONS AND IMPLICATIONS: The occurrence of VFB was associated with parenting patterns and social anxiety level. Psychiatric referral is required in children with VFB.

Endoplasmic Reticulum Targeting Ratiometric Fluorescent Probe for Carboxylesterase 2 Detection in Drug-Induced Acute Liver Injury.

Carboxylesterase 2 (CES2), an endoplasmic reticulum (ER) located phase I enzyme, plays a vital role in the metabolism of various endogenous and exogenous substances, and is regarded as an important target for the design of prodrugs. Unfortunately, superior highly selective ER targeting fluorescent probes for monitoring of CES2 are not currently available. Herein, we report an ER targeting CES2 selective and sensitive ratiometric fluorescent probe ERNB based on the ER localizing group p-toluenesulfonamide. ERNB possessed high specificity, sensitivity, and exhibited excellent subcellular localization when compared to commercial ER tracker, and was used to image CES2 in the ER of living cells. Additionally, using ERNB we evaluated the CES2 regulation under d,l-dithiothreitol and tunicamycin-induced ER stress. Furthermore, we determined the down regulation of CES2 activity and expression in the acetaminophen-induced acute liver injury model. On the basis of these results, we conclude that ERNB is a promising tool for highlighting the role of CES2 in the ER and in exploring the role of CES2 in the development of diseases associated with ER stress.

Highly Specific near-Infrared Fluorescent Probe for the Real-Time Detection of ß-Glucuronidase in Various Living Cells and Animals.

ß-Glucuronidase (GLU) is an important biomarker for primary cancers and intestinal metabolism of drugs or endogenous substances; however, an effective optical probe for near-infrared (NIR) monitoring in vivo is still lacking. Herein, we design an enzyme-activated off-on NIR fluorescent probe, HC-glu, based on a hemicyanine keleton, which is conjugated with a d-glucuronic acid residue via a glycosidic bond, for the fluorescent quantification and trapping of endogenous GLU activity in vitro and in vivo. The newly developed NIR probe exhibited prominent features including prominent selectivity, high sensitivity, and ultrahigh imaging resolution. It has been successfully used to detect and image endogenous GLU in various hepatoma carcinoma cells, tumor tissues, and tumor-bearing mouse models, for cancer diagnosis and therapy. Moreover, it could detect the in vivo activity of GLU in the intestinal tracts of animals including mice and zebrafish, where GLU performs a vital biological function and is mainly distributed. It could also evaluate real intestinal distribution and real-time variations of GLU in development and growth, all of which are very helpful to guide rational drug use in the clinic. Our results fully demonstrated that HC-glu may serve as a promising tool for evaluating the biological function and process of GLU in living systems.

Natural constituents from Cortex Mori Radicis as new pancreatic lipase inhibitors.

Pancreatic lipase (PL), a key enzyme responsible for the hydrolysis of triacylglycerides in the gastrointestinal tract, has been identified as the therapeutic target for the regulation of lipid absorption. In the present study, six major constituents from a famous Chinese herbal medicine Cortex Mori Radicis (also named sangbaipi in Chinese), have been collected and their inhibitory effects on PL have been carefully investigated and well characterized by a fluorescence-based assay. The results clearly demonstrated that all tested bioactive constituents from Cortex Mori Radicis including sanggenone C (SC), sanggenone D (SD), kuwanon C (KC), kuwanon G (KG), morin and morusin displayed strong to moderate inhibitory effects towards PL with the IC50 values ranging from 0.77 µM to 20.56 µM. Further investigations on inhibition kinetics demonstrated that SC, SD, KC and KG functioned as potent and mixed inhibitors against PL-mediated 4-MU oleate hydrolysis, with the Ki values less than 5.0 µM. Furthermore, molecular docking simulations demonstrated that SD (the most potent PL inhibitor from Cortex Mori Radicis) could create strong interaction with Ser152 (the key amino acid in the catalytic triad) of PL via hydrogen bonding. All these findings provided a new powerful evidence for explaining the hypolipidemic effect of Cortex Mori Radicis, also suggested that some abundant natural compounds in this herbal medicine could be served as lead compounds for the development of new PL inhibitors.

Computational identification of harmful mutation regions to the activity of transposable elements.

BACKGROUND: Transposable elements (TEs) are interspersed DNA sequences that can move or copy to new positions within a genome. TEs are believed to promote speciation and their activities play a significant role in human disease. In the human genome, the 22 AluY and 6 AluS TE subfamilies have been the most recently active, and their transposition has been implicated in many inherited human diseases and in various forms of cancer. Therefore, understanding their transposition activity is very important and identifying the factors that affect their transpositional activity is of great interest. Recently, there has been some work done to quantify the activity levels of active Alu TEs based on variation in the sequence. Given this activity data, an analysis of TE activity based on the position of mutations is conducted. RESULTS: A method/simulation is created to computationally predict so-called harmful mutation regions in the consensus sequence of a TE; that is, mutations that occur in these regions decrease the transpositional activity dramatically. The methods are applied to the most active subfamily, AluY, to identify the harmful regions, and seven harmful regions are identified within the AluY consensus with q-values less than 0.05. A supplementary simulation also shows that the identified harmful regions covering the AluYa5 RNA functional regions are not occurring by chance. This method is then applied to two additional TE families: the Alu family and the L1 family, to computationally detect the harmful regions in these elements. CONCLUSIONS: We use a computational method to identify a set of harmful mutation regions. Mutations within the identified harmful regions decrease the transpositional activity of active elements. The correlation between the mutations within these regions and the transpositional activity of TEs are shown to be statistically significant. Verifications are presented using the activity of AluY elements and the secondary structure of the AluYa5 RNA, providing evidence that the method is successfully identifying harmful mutation regions.

Abhd2, a Candidate Gene Regulating Airway Remodeling in COPD via TGF-ß.

Purpose: The typical characteristic of COPD is airway remodeling, affected by environmental and genetic factors. However, genetic studies on COPD have been limited. Currently, the Abhd2 gene is found to play a critical role in maintaining alveolar architecture and stability. The research aims to investigate the predictive value of Abhd2 for airway remodeling in COPD and its effect on TGF-ß regulation. Methods: In humans, Abhd2 protein was obtained from peripheral blood monocytes. Peripheral blood TGF-ß, pulmonary surfactant proteins (SPs), metalloproteinases, inflammatory indicators (WBC, NEU, NLR, EOS, CRP, PCT, D-Dimer), chest CT (airway diameter and airway wall thickness), pulmonary function, and blood gas analysis were used to assess airway remodeling. In animals, Abhd2 deficient mice (Abhd2Gt/Gt) using gene trapping and C57BL6 mice were injected intraperitoneally with CSE to construct COPD models. HE staining, Masson staining and immunohistochemistry were used to observe the pathological changes of airway in mice, and RT-PCR, WB, ELISA and immunofluorescence were used to detect the expression of secreted proteins and EMT markers. Results: COPD patients with worse pulmonary function and higher airway remodeling-related inflammatory factors had lower Abhd2 protein expression. Moreover, indicators followed the same trend for COPD patients grouped by prognosis (Group A vs Group B). Serum TGF-ß was negatively correlated with Abhd2 protein expression, FEV1/FVC, FEV1, and FEV1% PRED. In mice, Abhd2 depletion promoted deposition of TGF-ß, leading to more pronounced emphysema, airway thickening, increased alveolar macrophage infiltration, decreased AECII number and SPs, and EMT phenomenon. Conclusion: Downregulation of Abhd2 can promote airway remodeling in COPD by modulating repair after injury and EMT via TGF-ß. This study suggests that Abhd2 may serve as a biomarker for assessing airway remodeling and guiding prognosis in COPD.

Predicting phenotypes from novel genomic markers using deep learning.

Genomic selection (GS) models use single nucleotide polymorphism (SNP) markers to predict phenotypes. However, these predictive models face challenges due to the high dimensionality of genome-wide SNP marker data. Thanks to recent breakthroughs in DNA sequencing and decreased sequencing cost, the study of novel genomic variants such as structural variations (SVs) and transposable elements (TEs) become increasingly prevalent. In this article, we develop a deep convolutional neural network model, NovGMDeep, to predict phenotypes using SVs and TEs markers for GS. The proposed model is trained and tested on samples of Arabidopsis thaliana and Oryza sativa using k-fold cross-validation. The prediction accuracy is evaluated using Pearson's Correlation Coefficient (PCC), mean absolute error (MAE) and SD of MAE. The predicted results showed higher correlation when the model is trained with SVs and TEs than with SNPs. NovGMDeep also has higher prediction accuracy when comparing with conventional statistical models. This work sheds light on the unappreciated function of SVs and TEs in genotype-to-phenotype associations, as well as their extensive significance and value in crop development.

LINC00460 mediates HMGA2 expression through binding to miRNA-143-5p competitively in gastric carcinoma.

Background: Compelling evidence has manifested a strong association between aberrant expression of long noncoding RNAs (lncRNAs) and gastric carcinoma (GC) development. Nonetheless, biological impacts of differentially expressed lncRNAs (DElncRNAs) on GC are not scrutinized. Methods: Bioinformatics methods were employed for differential expression analysis and target gene prediction. MTT, colony formation, and Transwell methods were implemented for GC cell proliferation, migration, and invasion assessment. Western blot was implemented to test the protein level. The binding of genes was tested with dual-luciferase and RNA binding protein immunoprecipitation (RIP) approaches. Results: Noticeably high level of LINC00460 was observed in GC tissues and cells. LINC00460 silencing constrained proliferation, migration, and invasion of GC cells. FISH and nuclear-cytoplasmic separation assays confirmed the main presentation of LINC00460 in the cytoplasm. Bioinformatics predicted that LINC00460 had binding sites to miRNA-143-5p, which was upregulated in GC. Dual luciferase and RIP experiments also confirmed the binding relationship. Concurrent silencing of LINC00460s and miRNA-133-5p rescued the repressive influence of sh-LINC004600 on GC cell proliferation, migration, and invasion. HMGA2 was predicted to be a target gene downstream of miRNA-143-5p, their binding relationship was validated via dual luciferase assays. Silencing HMGA2 constrained GC cell proliferation, invasion, and migration. LINC00460 modulated HMGA2 expression via binding miRNA-143-5p, thereby affecting proliferation, invasion, and migration of GC cells. Conclusion: These findings validated that LINC00460 could regulate HMGA2 via sponging miRNA-143-5p to facilitate GC proliferation, invasion, and migration, which provides a deeper understanding of lncRNAs in the development of GC.

Seabuckthorn Wuwei Pulvis attenuates chronic obstructive pulmonary disease in rat through gut microbiota-short chain fatty acids axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Seabuckthorn Wuwei Pulvis (SWP) is a traditional Mongolian medicine used in China. It is composed of Hippophae rhamnoides (berries, 30 g), Aucklandiae costus Falc. (dry root, 25 g), Vitis vinifera F. Cordifolia (berries, 20 g), Glycyrrhiza uralensis Fisch. (dry root, 15 g), and Gardenia jasminoides J. Ellis (desiccative ripe fruit, 10 g). It is clinically applied in the treatment of chronic cough, shortness of breath and phlegm, and chest distress. Past studies demonstrated that Seabuckthorn Wuwei Pulvis improved lung inflammation and chronic bronchitis in mice. However, the effect of Seabuckthorn Wuwei Pulvis on chronic obstructive pulmonary disease (COPD) in rats and the underlying action mechanism is not fully understood. AIM OF THE STUDY: To evaluate the anti-COPD effect of Seabuckthorn Wuwei Pulvis and investigate whether its ameliorative effect is correlated with the composition of gut microbiota and its metabolites. MATERIALS AND METHODS: The effects of Seabuckthorn Wuwei Pulvis on a COPD rat model were established by exposure to lipopolysaccharide (LPS) and smoking. These effects were then evaluated by monitoring the animal weight, pulmonary function, lung histological alteration, and the levels of inflammatory factors (tumor necrotic factor [TNF]-α, interleukin [IL]-8, IL-6, and IL-17). Furthermore, the serum LPS and fluorescein isothiocyanate-dextran levels were detected by using an enzyme-linked immunosorbent assay and fluorescence microplate reader, respectively. Tight junction proteins (ZO-1 and occludin-1) in the small intestine were detected by performing real-time quantitative polymerase chain reactions and Western blotting to evaluate the intestinal barrier function. The contents of short-chain fatty acids (SCFAs) in the feces of rats were determined by gas chromatography-mass spectrometry. 16S rDNA high throughput sequencing was used to investigate the effect of SWP on the gut microbiota of COPD rats. RESULTS: Treatment with low and median doses of SWP significantly increased the pulmonary function (forced expiratory volume [FEV] 0.3, forced vital capacity [FVC], and FEV0.3/FVC), decreased the levels of TNF-α, IL-8, IL-6, and IL-17 in the lung, and attenuated the infiltration of inflammatory cells into the lung. The low and median doses of SWP shaped the composition of gut microbiota, which increased the abundances of Ruminococcaceae, Christensenellaceae, and Aerococcaceae, increased the productions of acetic acid, propionic acid, and butyric acid, and upregulated the expression of ZO-1 and occludin-1 in the small intestine of COPD rats. CONCLUSION: SWP improved pulmonary functions and inhibited the inflammatory response by shaping the gut microbiota, increasing SCFA production, and strengthening the intestinal barrier function in rats with COPD induced by LPS and smoking.