Patterns of health care interactions of individuals with alcohol use disorder: A latent class analysis.

INTRODUCTION: Given the high rates at which individuals with alcohol use disorder (AUD) utilize health care for co-existing conditions, health systems are promising venues for interventions that will facilitate access to AUD treatment. However, how individuals with AUD interact with such systems and, thus, how systems should intervene is unclear. In this study, we seek to identify patterns in how individuals diagnosed with AUD within an academic health system interacted with the system prior to diagnosis. METHODS: We use electronic health records from a single academic health system in a major US metropolitan area to create a deidentified retrospective cohort including all individuals age 18+ diagnosed with AUD 2010-2019 (n = 26,899). Latent class analysis (LCA) identified subgroups defined by aspects of previous system interaction and health status, including having an in-system primary care provider, previous utilization of primary and specialty care, diagnosis setting, payer, and presence of other chronic conditions. We then assessed subgroup differences in demographics and associations with in-system AUD treatment receipt in the year following diagnosis, adjusting for demographics. RESULTS: The population was on average 38.6 years old (standard deviation = 15.4) and predominantly male (66.1 %), White (64.5 %), and not of Hispanic/Latino ethnicity (87.8 %). Only 4.7 % received in-system treatment following diagnosis. We deemed the four-class model the optimal LCA model. This model identified subgroups that can be described as 1) average utilization (20.7 % of population), 2) low utilization (54.5 %), 3) high health burden and low utilization (14.2 %), and 4) high health burden and high utilization (10.6 %). Predicted membership in the high health burden and high utilization subgroup and low utilization subgroup were associated with higher and lower odds of treatment receipt, respectively, compared with predicted membership in the average utilization subgroup (odds ratio (OR) for high/high subgroup = 1.21, 95 % confidence interval (CI) = 1.01, 1.27; OR for low subgroup = 0.29 95 % CI = 0.24, 0.34). CONCLUSION: Individuals diagnosed with AUD within a health system interact with that system in markedly different ways and are unlikely to benefit uniformly from system-based interventions to facilitate treatment. Group-tailored interventions are more likely to have impact and provide returns on investments for systems.

Identification of combinatorial miRNA panels derived from extracellular vesicles as biomarkers for esophageal squamous cell carcinoma.

MicroRNAs (miRNAs) are relatively stable in blood, emerging as one of the most promising biomarkers in tumor liquid biopsy. Both total and extracellular vesicles (EVs) encapsulated miRNA have been studied for prognostic potential in a variety of cancers. Here, we systematically compared and verified the total and vesicle-derived miRNA expression profiles from plasma samples in healthy controls and patients with esophageal squamous cell carcinoma (ESCC). In the present study, four miRNA species miR-636, miR-7641, miR-28-3p, and miR-1246 that were differentially expressed in ESCC patients were chosen for further study. We first elucidated their essential function in ESCC progression and further explored their preliminary mechanism by identifying target proteins and involving signal pathways. Subsequently, the prognostic miRNA panels including miR-636, miR-7641, miR-1246, and miR-28-3p for ESCC diagnosis were constructed and validated using different cohort. Our results showed that the panel including the above four miRNAs derived from plasma EVs was most effective in distinguishing tumor patients from normal subjects, while integrated plasma EVs-derived miR-1246, miR-28-3p and total plasma miRNAs miR-636, miR-7641 showed the best capability in predicting lymph node metastasis. In summary, our studies revealed that plasma EVs-derived miRNAs could be emerged as promising biomarkers for ESCC diagnosis.

Molecular basis of Mg2+ permeation through the human mitochondrial Mrs2 channel.

Mitochondrial RNA splicing 2 (Mrs2), a eukaryotic CorA ortholog, enables Mg2+ to permeate the inner mitochondrial membrane and plays an important role in mitochondrial metabolic function. However, the mechanism by which Mrs2 permeates Mg2+ remains unclear. Here, we report four cryo-electron microscopy (cryo-EM) reconstructions of Homo sapiens Mrs2 (hMrs2) under various conditions. All of these hMrs2 structures form symmetrical pentamers with very similar pentamer and protomer conformations. A special structural feature of Cl--bound R-ring, which consists of five Arg332 residues, was found in the hMrs2 structure. Molecular dynamics simulations and mitochondrial Mg2+ uptake assays show that the R-ring may function as a charge repulsion barrier, and Cl- may function as a ferry to jointly gate Mg2+ permeation in hMrs2. In addition, the membrane potential is likely to be the driving force for Mg2+ permeation. Our results provide insights into the channel assembly and Mg2+ permeation of hMrs2.

Race- and Sex-Specific Factors Associated With Age-Related Slopes in Systolic Blood Pressure: Findings From the CARDIA Study.

BACKGROUND: Although blood pressure (BP) increases throughout young adulthood for most individuals, the age-related slope is not uniform. This study aimed to assess associations of demographic, clinical, behavioral, psychosocial, and neighborhood characteristics with age-related BP slope among 4 race-sex groups who participated in the Coronary Artery Risk Development in Young Adults study. METHODS: Individuals (n=3554) aged 18 to 30 years were included in this analysis if they had normal BP at baseline and ≥2 BP measurements during the years 1985/1986 to 2015/2016. Associations of exposure variables with systolic BP slope were assessed using multivariate linear models. RESULTS: Over a mean follow-up of ~30 years, greater decade increases in systolic BP were estimated among Black than White participants (mean difference between Black females and White females: 3.0 mm Hg/decade; between Black males and White males: 4.7 mm Hg/decade). The exposure risk factors associated with greater increases in systolic BP throughout adulthood varied by race and sex. None of these factors were associated with increases in systolic BP in all race-sex groups. Parent history of high BP was associated with a steeper positive slope among Black females (effect size per decade: 1.1 [95% CI, 0.6-1.6]; P<0.01), Black males (0.6 [95% CI, 0.02-1.2]; P<0.05), and White females (0.6 [95% CI, 0.2-1.0]; P<0.01). Other risk factors were associated with greater age-related yearly increases in systolic BP among 1 or 2 of the 4 race-sex groups or were not statistically significant. CONCLUSIONS: Culturally tailored BP reduction approach should be considered in conjunction with primordial prevention, to moderate increases in BP throughout adulthood.

A shallow mirror transformer for subject-independent motor imagery BCI.

OBJECTIVE: Motor imagery BCI plays an increasingly important role in motor disorders rehabilitation. However, the position and duration of the discriminative segment in an EEG trial vary from subject to subject and even trial to trial, and this leads to poor performance of subject-independent motor imagery classification. Thus, determining how to detect and utilize the discriminative signal segments is crucial for improving the performance of subject-independent motor imagery BCI. APPROACH: In this paper, a shallow mirror transformer is proposed for subject-independent motor imagery EEG classification. Specifically, a multihead self-attention layer with a global receptive field is employed to detect and utilize the discriminative segment from the entire input EEG trial. Furthermore, the mirror EEG signal and the mirror network structure are constructed to improve the classification precision based on ensemble learning. Finally, the subject-independent setup was used to evaluate the shallow mirror transformer on motor imagery EEG signals from subjects existing in the training set and new subjects. MAIN RESULTS: The experiments results on BCI Competition IV datasets 2a and 2b and the OpenBMI dataset demonstrated the promising effectiveness of the proposed shallow mirror transformer. The shallow mirror transformer obtained average accuracies of 74.48% and 76.1% for new subjects and existing subjects, respectively, which were highest among the compared state-of-the-art methods. In addition, visualization of the attention score showed the ability of discriminative EEG segment detection. This paper demonstrated that multihead self-attention is effective in capturing global EEG signal information in motor imagery classification. SIGNIFICANCE: This study provides an effective model based on a multihead self-attention layer for subject-independent motor imagery-based BCIs. To the best of our knowledge, this is the shallowest transformer model available, in which a small number of parameters promotes the performance in motor imagery EEG classification for such a small sample problem.

Cardiovascular health trajectories from age 2-12: a pediatric electronic health record study.

PURPOSE: Many children have non-ideal cardiovascular health (CVH), but little is known about the course of CVH in early childhood. We identified CVH trajectories in children and assess the generalizability of these trajectories in an external sample. METHODS: We used data spanning 2010-2018 from children aged 2-12 years within the Chicago Area Patient-Centered Outcomes Research Network-an electronic health record network. Four clinical systems comprised the derivation sample and a fifth the validation sample. Body mass index, blood pressure, cholesterol, and blood glucose were categorized as ideal, intermediate, and poor using clinical measurements, laboratory readings, and International Classification of Diseases diagnosis codes and summed for an overall CVH score. Group-based trajectory modeling was used to create CVH score trajectories which were assessed for classification accuracy in the validation sample. RESULTS: Using data from 122,363 children (47% female, 47% non-Hispanic White) three trajectories were identified: 59.5% maintained high levels of clinical CVH, 23.4% had high levels of CVH that declined, and 17.1% had intermediate levels of CVH that further declined with age. A similar classification emerged when the trajectories were fitted in the validation sample. CONCLUSIONS: Stratification of CVH was present by age 2, implicating the need for early life and preconception prevention strategies.

Combination of size-exclusion chromatography and ion exchange adsorption for improving the proteomic analysis of plasma-derived extracellular vesicles.

Extracellular vesicles (EVs) are lipid membrane vesicles released by live cells that carry a variety of biomolecules, including nucleic acids, lipids, and proteins. Recently, proteins in plasma-derived EVs have emerged as novel biomarkers with essential functions in the diagnosis and prognosis of human diseases. However, the current methods of isolating EVs from plasma often lead to coisolated impurities in biological fluids. Therefore, before performing any research protocol, the process of extracting EVs from plasma for proteomic analysis must be optimized. In this study, two EV isolation strategies, size exclusion chromatography (SEC) and SEC combined with ion exchange adsorption (SEC + IEA), were compared in terms of the purity and quantity of protein in EVs. Our results demonstrated that, compared to single-step SEC, SEC combined with IEA could produce plasma-derived EVs with a higher purity by decreasing the abundance of lipoprotein. Additionally, with MS analysis, we demonstrated that the combination approach maintained the stability and improved the purity of EVs in many plasma samples. Furthermore, by combining SEC with IEA, more cancer-associated proteins were detected in the plasma of various cancer samples.

Assessment of risk factors associated with outpatient parenteral antimicrobial therapy (OPAT) complications: A retrospective cohort study.

Objective: To characterize factors associated with increased risk of outpatient parenteral antimicrobial therapy (OPAT) complication. Design: Retrospective cohort study. Setting: Four hospitals within NYU Langone Health (NYULH). Patients: All patients aged ≥18 years with OPAT episodes who were admitted to an acute-care facility at NYULH between January 1, 2017, and December 31, 2020, who had an infectious diseases consultation during admission. Results: Overall, 8.45% of OPAT patients suffered a vascular complication and 6.04% suffered an antimicrobial complication. Among these patients, 19.95% had a 30-day readmission and 3.35% had OPAT-related readmission. Also, 1.58% of patients developed a catheter-related bloodstream infection (CRBSI). After adjusting for key confounders, we found that patients discharged to a subacute rehabilitation center (SARC) were more likely to develop a CRBSI (odds ratio [OR], 4.75; P = .005) and to be readmitted for OPAT complications (OR, 2.89; P = .002). Loss to follow-up with the infectious diseases service was associated with increased risks of CRBSI (OR, 3.78; P = .007) and 30-day readmission (OR, 2.59; P < .001). Conclusions: Discharge to an SARC is strongly associated with increased risks of readmission for OPAT-related complications and CRBSI. Loss to follow-up with the infectious diseases service is strongly associated with increased risk of readmission and CRBSI. CRBSI prevention during SARC admission is a critically needed public health intervention. Further work must be done for patients undergoing OPAT to improve their follow-up retention with the infectious diseases service.

HMGB1 overexpression promotes a malignant phenotype and radioresistance in ESCC.

Esophageal cancer is a common malignant disease that is generally treated with radiotherapy. High mobility group box 1 (HMGB1) plays an essential role in tumor cell proliferation, migration, and cell cycle progression. Here, we aimed to clarify the effects of HMGB1 on radioresistance in esophageal squamous cell carcinoma (ESCC) cell lines and patient survival. We performed immunohistochemistry for HMGB1 in biopsy samples of 39 stage I-III ESCC patients grouped by HMGB1 expression status. Then, 1-, 3-, 5-, and 10-year overall survival outcomes were calculated by Kaplan-Meier survival analysis. The cellular localization of HMGB1 was examined before and after irradiation by Immunofluorescence staining. Stable cell lines (KYSE30 and KYSE510) with differential HMGB1 expression were constructed using lentiviruses. Furthermore, we examined phosphorylated histone H2AX (γ-H2AX) expression in both HMGB1 overexpression and negative control groups by western blotting. HMGB1-negative expression was associated with superior ESCC patient 10-year survival (P=0.016). HMGB1 overexpression promoted cell migration, proliferation, and radioresistance and mitigated cell cycle arrest at the G0/G1 phase induced by irradiation. This demonstrates that HMGB1-positive expression is correlated with unfavorable clinical outcomes, and HMGB1 overexpression may promote the malignant phenotype of ESCC cells and induce radioresistance by regulating cell cycle distribution in ESCC.

Interferon­stimulated gene 15 promotes progression of endometrial carcinoma and weakens antitumor immune response.

Endometrial carcinoma (EC) is one of the most common gynecological cancers with a poor prognosis. Therefore, clarifying the details of the molecular mechanisms is of great importance for EC diagnosis and clinical management. Interferon­stimulated gene 15 (ISG15) plays an important role in the development of various cancers. However, its role in EC remains unclear. High ISG15 expression was observed in EC, which was associated with poor clinical outcomes and pathological stage of patients with EC, thus representing a promising marker for EC progression. Further exploratory analysis revealed that the elevated ISG15 levels in EC were driven by aberrant DNA methylation, independent of copy number variation and specific transcription factor aberrations. Accordingly, knockdown of ISG15 by small interfering RNA attenuated the malignant cellular phenotype of EC cell lines, including proliferation and colony formation in vitro. Finally, investigation of the molecular mechanisms indicated that ISG15 promoted the cell cycle G1/S transition in EC. Furthermore, ISG15 promoted EC progression by activating the MYC proto­oncogene protein signaling pathway. Moreover, ECs with high levels of ISG15 harbored a more vital immune escape ability, evidenced not only by significantly less invasive CD8+ T cells, but also higher expression of T cell inhibitory factors, such as programmed death­ligand 1. These results suggest a tumor­promoting role of ISG15 in EC, which may be a promising marker for diagnosis, prognosis and therapeutic immunity.

Cryo-EM structure of the heptameric calcium homeostasis modulator 1 channel.

Calcium homeostasis modulator 1 (CALHM1) is a voltage- and Ca2+-gated ATP channel that plays an important role in neuronal signaling. However, as the previously reported CALHM structures are all in the ATP-conducting state, the gating mechanism of ATP permeation is still elusive. Here, we report cryo-EM reconstructions of two Danio rerio CALHM1 heptamers with ordered or flexible long C-terminal helices at resolutions of 3.2 Å and 2.9 Å, respectively, and one D. rerio CALHM1 octamer with flexible long C-terminal helices at a resolution of 3.5 Å. Structural analysis shows that the heptameric CALHM1s are in an ATP-nonconducting state with a central pore diameter of approximately 6.6 Å. Compared with those inside the octameric CALHM1, the N-helix inside the heptameric CALHM1 is in the "down" position to avoid steric clashing with the adjacent TM1 helix. Molecular dynamics simulations show that as the N-helix moves from the "down" position to the "up" position, the pore size of ATP molecule permeation increases significantly. Our results provide important information for elucidating the mechanism of ATP molecule permeation in the CALHM1 channel.

Cryo-EM structure of the human TACAN in a closed state.

TACAN is an ion channel-like protein that may be involved in sensing mechanical pain. Here, we present the cryo-electron microscopic structure of human TACAN (hTACAN). hTACAN forms a dimer in which each protomer consists of a transmembrane globular domain (TMD) containing six helices and an intracellular domain (ICD) containing two helices. Molecular dynamic simulations suggest that each protomer contains a putative ion conduction pore. A single-point mutation of the key residue Met207 greatly increases membrane pressure-activated currents. In addition, each hTACAN subunit binds one cholesterol molecule. Our data show the molecular assembly of hTACAN and suggest that wild-type hTACAN is in a closed state.

Outer Membrane Vesicles Secreted by Helicobacter pylori Transmitting Gastric Pathogenic Virulence Factors.

Helicobacter pylori (H. pylori) is known to be a major pathogen causing gastric diseases through its direct localization in gastric epithelium cells. H. pylori releases outer membrane vesicles (OMVs) throughout the growth process. The content, function, and mechanism of H. pylori OMVs in gastric epithelial cells remain unclear. In this study, we extracted and characterized H. pylori OMVs of two strains (standard strain NCTC11637 and clinical strain Hp-400) and analyzed the specific content by proteomic technology. We identified more than 400 proteins in H. pylori OMVs. In addition, we investigated the impact of H. pylori OMVs on cellular functions by detecting proteomic changes in GES1 cells. GES1 cells cocultured with increasing concentrations of H. pylori OMVs were subjected to quantitative proteomic analyses using label-free methods for relative quantitation. The results showed that a total of 4261 proteins were verified, 153 of which were significantly altered in abundance when cocultured with NCTC11637 OMVs, and a total of 4234 proteins in Hp-400 OMVs, 390 of which were significantly altered. Gene ontology analysis and Kyoto encyclopedia of genes and genomes pathway mapping identified significantly altered inflammatory and cancer signaling pathways, including metabolic pathways and the PI3K-Akt signaling pathway. Furthermore, we explored the proteomic changes in GES1 cells induced by H. pylori. Bioinformatics analysis showed that changes in multiple pathways coincided with OMV-mediated proteomic changes. Based on these results, H. pylori induced pathogenicity in epithelial cells at least partially by secreting OMVs that mediated dramatic and specific proteomic changes in host cells. Data are available via ProteomeXchange with identifiers PXD025216, PXD025259, and PXD025281.

[The expression and role of interleukin-8 in chronic rhinosinusitis].

Interleukin-8（IL-8） is an inflammatory factor secreted by multiple cells. It has a variety of biological effects such as trending inflammatory cells and promoting angiogenesis in the body. Currently, it is found to play an important role in promoting airway inflammation. Chronic rhinosinusitis is a chronic inflammatory disease of the nasal cavity and sinus mucosa. Under the stimulation of a variety of factors, the secretion of IL-8 in the nasal mucosa and nasal polyps of CRS patients could increase. Therefore, it can cause inflammation and mucosal damage by trending chemotaxis neutrophils and eosinophils.

Inhibitory Effects of Periplocin on Lymphoma Cells: A Network Pharmacology Approach and Experimental Validation.

PURPOSE: Lymphoma is considered to be one of the most pressing health problems worldwide owing to its high incidence and mortality. Previous studies have shown that periplocin, a naturally occurring compound, inhibits growth and induces apoptosis in several cancers. However, the effects of periplocin on lymphoma and the underlying mechanisms of action remain unclear. METHODS: The PharmMapper database was used to predict the potential targets of periplocin. The GeneCard database was used to identify lymphoma-related genes. A few intersecting genes were obtained, and the protein-protein interaction network was visualized using STRING Gene ontology analysis. Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed using R project. MTS assay, flow cytometry, real-time quantitative polymerase chain reaction (qPCR), and Western blotting were used to verify whether periplocin possesses anti-lymphoma activity. RESULTS: A total of 216 intersecting genes were identified. Numerous cancer-related signaling pathways were visualized using Cytoscape software, with the PI3K-Akt signaling pathway being the highest-ranked pathway related to cell proliferation, apoptosis, and cell cycle progression. HuT 78 and Jurkat cell lines were used to verify the predictions. Periplocin significantly inhibited their proliferation in a dose- and time-dependent manner, but had no effect on the viability of peripheral blood lymphocytes. Flow cytometry revealed that treatment with periplocin increased the apoptotic rate and ratio of HuT 78 and Jurkat cells in the G2/M phase. CDK1 and cyclin B1 complex formation is a key gatekeeper to mitotic division in the G2/M phase. Western blot analysis revealed that periplocin significantly decreased the protein levels of CDK1 and cyclin B1; however, real-time qPCR revealed no effect on gene expression. CONCLUSION: Periplocin showed anti-tumor effects in lymphoma cells through multiple targets and signaling pathways, and could be a novel therapeutic agent for the treatment of lymphoma.

Extracellular vesicles isolated by size-exclusion chromatography present suitability for RNomics analysis in plasma.

BACKGROUND: Extracellular vesicles (EVs), known as cell-derived membranous structures harboring a variety of biomolecules, have been widely used in liquid biopsy. Due to the complex biological composition of plasma, plasma RNA omics analysis (RNomics) is easily affected, thus it is necessary to select an optimal strategy from exiting methods according to the performance for intended application. METHODS: In this study, four different strategies for EVs isolation were performed and compared (i.e. ultracentrifugation (UC), size exclusion chromatography (SEC), and two most frequently-used commercially available isolation kit (ExoQuick and exoEasy). We compared the yield, purity, PCR quantification of RNAs, miRNA-seq analyses and mRNA-seq analyses of RNAs from EVs isolated using four methods. RESULTS: The results showed that the lowest miRNA binding protein AGO2 (Argonaute-2) and the highest EVs-specific miRNA and lncRNA were observed in EVs obtained through SEC, meanwhile the content of the non-specific miRNA was the lowest. Further RNA-Seq data revealed that RNAs obtained via SEC presented more useful reads for both miRNA and mRNA. Furthermore, the mRNA delivered via SEC tended to have a concentration comparable to the ideal FPKM (Fragments Per Kilobase Million) value. CONCLUSIONS: SEC shall be used as an optimal strategy for the isolation of EVs in plasma RNomics analysis.

Improving the performance of multisubject motor imagery-based BCIs using twin cascaded softmax CNNs.

Objective.Motor imagery (MI) EEG signals vary greatly among subjects, so scholarly research on motor imagery-based brain-computer interfaces (BCIs) has mainly focused on single-subject systems or subject-dependent systems. However, the single-subject model is applicable only to the target subject, and the small sample number greatly limits the performance of the model. This paper aims to study a convolutional neural network to achieve an adaptable MI-BCI that is applicable to multiple subjects.Approach.In this paper, a twin cascaded softmax convolutional neural network (TCSCNN) is proposed for multisubject MI-BCIs. The proposed TCSCNN is independent and can be applied to any single-subject MI classification convolutional neural network (CNN) model. First, to reduce the influence of individual differences, subject recognition and MI recognition are accomplished simultaneously. A cascaded softmax structure consisting of two softmax layers, related to subject recognition and MI recognition, is subsequently applied. Second, to improve the MI classification precision, a twin network structure is proposed on the basis of ensemble learning. TCSCNN is built by combining a cascaded softmax structure and twin network structure.Main results.Experiments were conducted on three popular CNN models (EEGNet and Shallow ConvNet and Deep ConvNet from EEGDecoding) and three public datasets (BCI Competition IV datasets 2a and 2b and the high-gamma dataset) to verify the performance of the proposed TCSCNN. The results show that compared with the state-of-the-art CNN model, the proposed TCSCNN obviously improves the precision and convergence of multisubject MI recognition.Significance.This study provides a promising scheme for multisubject MI-BCI, reflecting the progress made in the development and application of MI-BCIs.

SNHG5 inhibits the progression of EMT through the ubiquitin-degradation of MTA2 in oesophageal cancer.

A substantial fraction of transcripts are known as long noncoding RNAs (lncRNAs), and these transcripts play pivotal roles in the development of cancer. However, little information has been published regarding the functions of lncRNAs in oesophageal squamous cell carcinoma (ESCC) and the underlying mechanisms. In our previous studies, we demonstrated that small nucleolar RNA host gene 5 (SNHG5), a known lncRNA, is dysregulated in gastric cancer (GC). In this study, we explored the expression and function of SNHG5 in development of ESCC. SNHG5 was found to be downregulated in human ESCC tissues and cell lines, and this downregulation was associated with cancer progression, clinical outcomes and survival rates of ESCC patients. Furthermore, we also found that overexpression of SNHG5 significantly inhibited the proliferation, migration and invasion of ESCC cells in vivo and in vitro. Notably, we found that metastasis-associated protein 2 (MTA2) was pulled down by SNHG5 in ESCC cells using RNA pulldown assay. We also found that SNHG5 reversed the epithelial-mesenchymal transition by interacting with MTA2. In addition, overexpression of SNHG5 downregulated the transcription of MTA2 and caused its ubiquitin-mediated degradation. Thus, overexpression of MTA2 partially abrogated the effect of SNHG5 in ESCC cell lines. Furthermore, we found that MTA2 mRNA expression was significantly elevated in ESCC specimens, and a negative correlation between SNHG5 and MTA2 expression was detected. Overall, this study demonstrated, for the first time, that SNHG5-regulated MTA2 functions as an important player in the progression of ESCC and provide a new potential therapeutic strategy for ESCC.

Long non-coding RNA FOXD3-AS1 regulates the expression and secretion of IL-25 in nasal epithelial cells to inhibit Th2 type immunoreaction in allergic rhinitis.

Long non-coding RNA FOXD3-AS1 is associated with allergic rhinitis (AR). This article aims to demystify the role of FOXD3-AS1 in AR. We compared FOXD3-AS1 expression in nasal mucosas between AR patients and healthy control. Next, nasal epithelial cells (NECs) were incubated with lipopolysaccharide or recombinant IL-25, and then the supernatant of the NECs was incubated with CD4+ T cells. Th2 cell proportions were assessed by flow cytometry. The levels of gene and cytokines were detected by real-time quantitative PCR or enzyme linked immunosorbent assay. FOXD3-AS1 was downregulated in nasal mucosas of AR patients, whereas Th2 cell proportions and the levels of IL-25, IL-4, and IL-13 were enhanced in peripheral blood of AR patients. FOXD3-AS1 overexpression inhibited the expression and secretion of IL-25 in NECs. The levels of IL-4 and IL-13 and Th2 cell proportions in CD4+ T cells were enhanced by recombinant IL-25, which was effectively abolished by the supernatant of FOXD3-AS1-overexpressed NECs treatment. Our study demonstrates that FOXD3-AS1 is downregulated in nasal mucosas of AR patients, and FOXD3-AS1 represses the expression and secretion IL-25 in NECs, thereby inhibiting Th2 type immunoreaction in AR. Thus, our data provide a novel target gene for AR treatment.

High expression of TCN1 is a negative prognostic biomarker and can predict neoadjuvant chemosensitivity of colon cancer.

Transcobalamin (TCN1) is a vitamin B12 (cobalamin)-binding protein that regulates cobalamin homeostasis. Recent studies and bioinformatic analyses have found that TCN1 is highly expressed in cancer tissues and is associated with tumour aggressiveness and poor prognosis. The present study aimed to detect TCN1 as a novel biomarker for prognosis and chemosensitivity of colon cancer. Next-generation sequencing showed that TCN1 was one of several upregulated mRNAs in colon cancer, which was verified by further bioinformatics analyses. Western blotting (n = 9) and quantitative real time polymerase chain reaction (qRT-PCR, n = 30) revealed that TCN1 was highly expressed in colon cancer tissues at both the protein and mRNA level. A total of 194 cases of colon cancer were examined by immunohistochemistry and revealed that TCN1 expression level was related to advanced stages (P < 0.005). Kaplan-Meier analysis verified that patients with lower TCN1 expression usually had longer overall survival (P = 0.008). In addition, TCN1 was highly expressed in pulmonary metastatic tumour tissues (n = 37, P = 0.025) and exhibited higher levels in right-sided colon cancer than in left-sided colon cancer (P = 0.029). TCN1 expression in specimens that had received neoadjuvant chemotherapy decreased compared with that in colonoscopy biopsy tissues (n = 42, P = 0.009). Further bioinformatics analyses verified that apoptosis pathways might have a role in high TCN1 expression. All the studies revealed that TCN1 expression in colon cancer was significantly associated with malignant biological behaviour. Therefore, TCN1 could be used as a novel biomarker for colon cancer aggressiveness and prognosis and might also be a potential biomarker for predicting neoadjuvant chemosensitivity.