Comparison of gasless transaxillary endoscopic thyroidectomy, endoscopic thyroidectomy via areola approach and conventional open thyroidectomy in patients with unilateral papillary thyroid carcinoma.

BACKGROUND: Gasless transaxillary endoscopic thyroidectomy (GTET) and endoscopic thyroidectomy via the areola approach (ETA) have emerged as minimally invasive surgical techniques for managing papillary thyroid carcinoma (PTC). This study aimed to assess the surgical efficacy of endoscopic thyroidectomy (ET) as compared to conventional open thyroidectomy (COT) in PTC patients. METHODS: Between 2020 and 2022, 571 PTC patients underwent unilateral thyroidectomy accompanied by ipsilateral central lymph node dissection. This cohort comprised 72 patients who underwent GTET, 105 ETA, and 394 COT. The analysis encompassed a comprehensive examination of patient clinicopathologic characteristics and postoperative complaints. Furthermore, the learning curve of GTET was evaluated using the cumulative summation (CUSUM) method. RESULTS: Patients in the ET group exhibited a lower mean age and a higher proportion of female individuals. Operation time in the ET group was significantly longer. No significant differences were observed in the incidence of postoperative complications among the three groups. With regard to postoperative complaints reported three months after surgery, GTET demonstrated superior alleviation of anterior chest discomfort and swallowing difficulties. Patients who underwent ET reported significantly higher cosmetic satisfaction levels. Additionally, the learning curve of GTET was 27 cases, and the operation time during the mature phase of the learning curve exhibited a significant reduction when compared to ETA. CONCLUSIONS: The findings of this study affirm the safety and feasibility of employing GTET and ETA for the surgical management of PTC. GTET presents an attractive surgical option, particularly for patients with unilateral PTC who place a premium on cosmetic outcomes.

2-Dodecyl-6-Methoxycyclohexa-2, 5-Diene-1, 4-Dione isolated from Averrhoa carambola L. root inhibits high glucose-induced EMT in HK-2 cells through targeting the regulation of miR-21-5p/Smad7 signaling pathway.

OBJECTIVE: 2-Dodecyl-6-Methoxycyclohexa-2, 5-Diene-1, 4-Dione (DMDD) isolated from Averrhoa carambola L. root, has been proven therapeutic effects on diabetic kidney disease (DKD). This research aims to assess DMDD's effects on DKD and to investigate its underlying mechanisms, to establish DMDD as a novel pharmaceutical agent for DKD treatment. METHODS: The human renal tubular epithelial (HK-2) cells were induced by high glucose (HG) to mimic DKD and followed by DMDD treatment. The cytotoxicity of DMDD was assessed using the Cell Counting Kit-8 (CCK-8) assay. The migratory capacity of HK-2 cells was evaluated through transwell and scratch-wound assays. To investigate the effect of Smad7 and miR-21-5p, lentiviral transfection was employed in HK-2 cells. Additionally, the expression of proteins related to epithelial-mesenchymal transition (EMT) and TGFß1/Smad2/3 pathway was checked by QRT-PCR, Western blot, and immunofluorescence techniques. RESULTS: This study has shown that DMDD significantly suppresses cell migration and the expression of Vimentin, α-SMA, TGFß1, and p-Smad2/3 in HK-2 cells under HG conditions. Concurrently, DMDD enhances the protein expression of E-cadherin and Smad7. Intriguingly, the therapeutic effect of DMDD was abrogated upon Smad7 silencing. Further investigations revealed that DMDD effectively inhibits miR-21-5p expression, which is upregulated by HG. Downregulation of miR-21-5p inhibits the activation of the TGFß1/Smad2/3 pathway and EMT induced by HG. In contrast, overexpression of miR-21-5p negates DMDD's therapeutic benefits. CONCLUSION: DMDD mitigates EMT in HG-induced HK-2 cells by modulating the miR-21-5p/Smad7 pathway, thereby inhibiting renal fibrosis in DKD. These findings suggest that DMDD holds promise as a potential therapeutic agent for DKD.

Development and validation of a nomogram model based on pretreatment ultrasound and contrast-enhanced ultrasound to predict the efficacy of neoadjuvant chemotherapy in patients with borderline resectable or locally advanced pancreatic cancer.

OBJECTIVES: To develop a nomogram using pretreatment ultrasound (US) and contrast-enhanced ultrasound (CEUS) to predict the clinical response of neoadjuvant chemotherapy (NAC) in patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC). METHODS: A total of 111 patients with pancreatic ductal adenocarcinoma (PDAC) treated with NAC between October 2017 and February 2022 were retrospectively enrolled. The patients were randomly divided (7:3) into training and validation cohorts. The pretreatment US and CEUS features were reviewed. Univariate and multivariate logistic regression analyses were used to determine the independent predictors of clinical response in the training cohort. Then a prediction nomogram model based on the independent predictors was constructed. The area under the curve (AUC), calibration plot, C-index and decision curve analysis (DCA) were used to assess the nomogram's performance, calibration, discrimination and clinical benefit. RESULTS: The multivariate logistic regression analysis showed that the taller-than-wide shape in the longitudinal plane (odds ratio [OR]:0.20, p = 0.01), time from injection of contrast agent to peak enhancement (OR:3.64; p = 0.05) and Peaktumor/ Peaknormal (OR:1.51; p = 0.03) were independent predictors of clinical response to NAC. The predictive nomogram developed based on the above imaging features showed AUCs were 0.852 and 0.854 in the primary and validation cohorts, respectively. Good calibration was achieved in the training datasets, with C-index of 0.852. DCA verified the clinical usefulness of the nomogram. CONCLUSIONS: The nomogram based on pretreatment US and CEUS can effectively predict the clinical response of NAC in patients with BRPC and LAPC; it may help guide personalized treatment.

Evaluation of the diagnostic efficacy of liquid-based cytology obtained via percutaneous ultrasound-guided fine-needle aspiration for pancreatic masses: a large tertiary center's 8-year experience.

PURPOSE: There were limited data on the diagnostic efficacy of liquid-based cytology (LBC) for pancreatic tissues acquired by percutaneous ultrasound-guided fine-needle aspiration (US-FNA). This study aimed to evaluate the diagnostic value of LBC acquired via percutaneous US-FNA for pancreatic tumors compared with LBC combined with smear cytology (SC). METHODS: A retrospective database search (January 2014 and February 2022) was performed for patients who underwent percutaneous US-FNA with both LBC and SC. Clinical and pathological data were collected from 298 patients; eventually, 251 cases met the inclusion criteria. Diagnostic accuracy, sensitivity (SEN), specificity (SPE), positive predictive value (PPV) and negative predictive value (NPV) were compared. Rapid on-site evaluation (ROSE) was not available in all cases. RESULTS: Based on the pancreaticobiliary cytology guidelines published by the Papanicolaou Society of Cytopathology, 224 (89.2%), 13 (5.2%) and 14 (5.6%) cases were diagnosed as malignant, pre-malignant and benign lesions, respectively. The diagnostic accuracy of the LBC + SC (88.5%) was better than that of LBC (87.3%) but without statistical significance (P = 0.125). The SEN, SPE, PPV and NPV were 87.5%, 85.2%, 98.0% and 45.1%, respectively, in the LBC group and 88.8%, 85.2%, 98.0% and 47.9%, respectively, in the LBC + SC group. According to univariate and multivariate analyses, there were no factors have significant association with the diagnostic sensitivity of LBC. CONCLUSIONS: LBC obtained via percutaneous US-FNA provides good diagnostic value for pancreatic lesions and there was no significant difference between the diagnostic accuracy of LBC and LBC + SC when ROSE was unavailable.

Nanoreactor based on Cu nanoparticles confined in B, N co-doped porous carbon nanotubes for glutathione biosensing.

A cost-effective approach has been developed to synthesize Cu nanoparticles encapsulated into B and N double-doped carbon nanotubes (Cu@BCNNTs) by one-step pyrolysis. According to the specific binding of Cu-Cl and Cu-glutathione (GSH), we employed Cu@BCNNTs to build an electrochemical sensing platform to detect GSH. The unique space-confined structure can prevent Cu nanoparticles from agglomeration. In addition, B and N co-doped porous hollow tubes can improve the electrochemical conductivity, expand the number of active sites, enhance surface adsorption, and shorten the transport path. These favorable characteristics of Cu@BCNNTs make them have excellent electrocatalytic properties. These results display that the prepared sensor can detect GSH from 0.5 to 120 µM with a detection limit of 0.024 µM. The obtained sensors can be successfully applied in the human serum with recovery of GSH ranging from 100.2 to 103.9%. This work provides a new vision to synthesize nanoparticles confined in a hollow tube for the applications in biosensing and medical diagnostics.

Predicting the Efficacy of Neoadjuvant Chemotherapy for Pancreatic Cancer Using Deep Learning of Contrast-Enhanced Ultrasound Videos.

Contrast-enhanced ultrasound (CEUS) is a promising imaging modality in predicting the efficacy of neoadjuvant chemotherapy for pancreatic cancer, a tumor with high mortality. In this study, we proposed a deep-learning-based strategy for analyzing CEUS videos to predict the prognosis of pancreatic cancer neoadjuvant chemotherapy. Pre-trained convolutional neural network (CNN) models were used for binary classification of the chemotherapy as effective or ineffective, with CEUS videos collected before chemotherapy as the model input, and with the efficacy after chemotherapy as the reference standard. We proposed two deep learning models. The first CNN model used videos of ultrasound (US) and CEUS (US+CEUS), while the second CNN model only used videos of selected regions of interest (ROIs) within CEUS (CEUS-ROI). A total of 38 patients with strict restriction of clinical factors were enrolled, with 76 original CEUS videos collected. After data augmentation, 760 and 720 videos were included for the two CNN models, respectively. Seventy-six-fold and 72-fold cross-validations were performed to validate the classification performance of the two CNN models. The areas under the curve were 0.892 and 0.908 for the two models. The accuracy, recall, precision and F1 score were 0.829, 0.759, 0.786, and 0.772 for the first model. Those were 0.864, 0.930, 0.866, and 0.897 for the second model. A total of 38.2% and 40.3% of the original videos could be clearly distinguished by the deep learning models when the naked eye made an inaccurate classification. This study is the first to demonstrate the feasibility and potential of deep learning models based on pre-chemotherapy CEUS videos in predicting the efficacy of neoadjuvant chemotherapy for pancreas cancer.

Asymmetric Heterodimer-Regulated Surface Plasmon Coupling ECL Polarization Strategy for MiRNA-182 Detection.

In this work, a novel plasmonic heterodimer with controllable hot spot was designed and applied to regulate surface plasmon coupling electrochemiluminescence (SPC-ECL) polarization sensing system. The heterodimer nanostructure consisted of individual Au-Ag core-shell nanocubes (Au@Ag NC) and Au nanospheres (Au NS), which were precisely assembled by thiol-DNA and biotin-streptavidin. The asymmetric nanostructure can significantly modulate the ECL intensity and emission polarization angle based on the synergy of the surface plasmon coupling (SPC) effect and the lightning rod effect with extraordinary field enhancement in the hot spot region. As a result, the isotropic ECL signal of zinc-doped nitrogen dots (Zn-N dots) was regulated in the directional emission. Furthermore, the SPC-ECL biosensor was successfully applied to detect miRNA-182 in triple-negative breast cancer (TNBC) tissues. The research on the established relationship between ECL polarization analysis and plasmonic heterodimers can provide a new pathway for the development of ECL sensing platforms.

Effects of frog skin peptide temporin-1CEa and its analogs on ox-LDL induced macrophage-derived foam cells.

Purpose: Atherosclerosis is one of the most important pathological foundations of cardiovascular and cerebrovascular diseases with high morbidity and mortality. Studies have shown that macrophages play important roles in lipid accumulation in the vascular wall and thrombosis formation in atherosclerotic plaques. This study aimed to explore the effect of frog skin antimicrobial peptides (AMPs) temporin-1CEa and its analogs on ox-LDL induced macrophage-derived foam cells. Methods: CCK-8, ORO staining, and intracellular cholesterol measurements were used to study cellular activity, lipid droplet formation and cholesterol levels, respectively. ELISA, real-time quantitative PCR, Western blotting and flow cytometry analysis were used to study the expression of inflammatory factors, mRNA and proteins associated with ox-LDL uptake and cholesterol efflux in macrophage-derived foam cells, respectively. Furthermore, the effects of AMPs on inflammation signaling pathways were studied. Results: Frog skin AMPs could significantly increase the cell viability of the ox-LDL-induced foaming macrophages and decrease the formation of intracellular lipid droplets and the levels of total cholesterol and cholesterol ester (CE). Frog skin AMPs inhibited foaming formation by reducing the protein expression of CD36, which regulates ox-LDL uptake but had no effect on the expression of efflux proteins ATP binding cassette subfamily A/G member 1 (ABCA1/ABCG1). Then, decreased mRNA expression of NF-κB and protein expression of p-NF-κB p65, p-IκB, p-JNK, p-ERK, p-p38 and the release of TNF-α and IL-6 occurred after exposure to the three frog skin AMPs. Conclusion: Frog skin peptide temporin-1CEa and its analogs can improve the ox-LDL induced formation of macrophage-derived foam cells, in addition, inhibit inflammatory cytokine release through inhibiting the NF-κB and MAPK signaling pathways, thereby inhibiting inflammatory responses in atherosclerosis.

[Performance of Contrast-enhanced Ultrasound Liver Imaging Reporting and Data System LR-5 in the Diagnosis of Hepatocellular Carcinoma:A Meta-analysis].

Objective To evaluate the performance of contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system (LI-RADS) LR-5 in the diagnosis of hepatocellular carcinoma (HCC). Methods The clinical research reports with the application of CEUS LI-RADS in the diagnosis of HCC were collected from PubMed,Embase,Cochrane Library,CNKI,and Wanfang Data from inception to November 14,2021.Two researchers respectively screened the literature and extracted relevant information.The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) was used to evaluate the quality of all the included articles.RevMan 5.4,Meta disc 1.4,and Stata 16.0 were employed to analyze the diagnostic performance of LR-5 for HCC in high-risk patients. Results Twenty original studies were included,involving a total of 6131 lesions,of which 5142 were HCC.The results of meta-analysis showed that the LR-5 in CEUS LI-RADS for diagnosing HCC in the high-risk population had the overall sensitivity of 0.72 (95%CI=0.66-0.77),the overall specificity of 0.93 (95%CI=0.87-0.96),the overall positive likelihood ratio of 9.89 (95%CI=5.31-18.41),the overall negative likelihood ratio of 0.30 (95%CI=0.25-0.37),and the area under the summary receiver operating characteristic curve of 0.88 (95%CI=0.85-0.91).There was heterogeneity among the included studies (I2=95.31,P<0.001).The funnel plot indicated the existence of publication bias (P=0.04). Conclusion The CEUS LI-RADS can effectively diagnose HCC in high-risk patients based on the LR-5 criteria.

Transoral endoscopic thyroidectomy vestibular approach for papillary thyroid microcarcinoma: an analysis of clinical outcomes.

OBJECTIVE: To analyze the influence of transoral endoscopic thyroidectomy vestibular approach (TOETVA) on the clinical outcomes of patients with papillary thyroid microcarcinoma (PTMC). METHODS: The clinical data of PTMC patients (n=90) who visited the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University from July 2019 to July 2021 were retrospectively analyzed. Patients who underwent endoscopic thyroidectomy via the transthoracic-areola approach were included in the control group (CG; n=42) and those with TOETVA were assigned to the observation group (OG; n=48). The operative time (OT), length of hospital stay (LOS), postoperative drainage volume, and complications were recorded. Besides, C-reactive protein (CRP), white blood cell count (WBC), erythrocyte sedimentation rate (ESR), as well as scores of the Visual Analogue Scale (VAS), Vancouver Scar Scale (VSS), postoperative patient satisfaction, and the Short-Form 36 Item Health Survey (SF-36) were compared between the two groups. RESULTS: The data showed that the OT and LOS of the OG were not statistically different from those of the CG, and the postoperative drainage volume was less than that of the CG (P<0.05). The two cohorts of patients showed a similar incidence of complications such as postoperative hematoma, transient hoarseness, infection, temporary recurrent laryngeal nerve injury and transient hypothyroidism (all P>0.05). CRP, WBC and ESR increased in both groups after treatment but showing no evident difference between groups. The OG had statistically lower VAS and VSS scores at two days after surgery, a statistical higher satisfaction rate than the CG, and a statistically higher score of SF-36 at three months after surgery than in the CG (all P<0.05). CONCLUSIONS: While ensuring the therapeutic effect, TOETVA can significantly reduce the pain degree of patients and scarring, as well as provide better cosmetic effect, higher patient satisfaction, and better quality of life, which is worthy of clinical promotion.

The diagnostic performance of contrast-enhanced ultrasound versus contrast-enhanced computed tomography for pancreatic carcinoma: a systematic review and meta-analysis.

Background: Pancreatic carcinoma is a highly fatal disease, and early diagnosis is of vital importance. This meta-analysis aimed to compare the diagnostic performances of contrast-enhanced ultrasonography (CEUS) against contrast-enhanced computed tomography (CECT) for pancreatic carcinoma, using pathological results or alternative imaging modality as the gold standard. Methods: A thorough search was conducted in PubMed, EMBASE, Web of Science and Cochrane Library databases. Two investigators selected the studies and extracted the data independently. A bivariate mixed-effects regression model was used to calculate the pooled data. Subgroup analysis and meta-regression were performed to explore the causes of heterogeneity. Results: A total of 1,227 records were identified, of which 7 articles with 588 patients were assessed for eligibility. The overall sensitivity, specificity of CEUS and CECT with their 95% confidential intervals (95% CI) were 0.91 (0.85-0.94) and 0.88 (0.81-0.92), 0.83 (0.70-0.91) and 0.87 (0.73-0.94), respectively. The area under curve (AUC) of CEUS and CECT were 0.94 and 0.93. Subgroup analysis showed CEUS may be good at diagnosing lesions with diameters less than 2 cm. Tumor features, region and study type were the main causes of heterogeneity. Conclusions: CEUS has a satisfying diagnostic performance for pancreatic carcinoma and it has high sensitivity for small pancreatic carcinomas (≤2 cm); besides, it performs well in discriminating pancreatic cancer from chronic pancreatitis. Therefore, CEUS can be a useful supplement to CECT.

A novel AIRE mutation leads to autoimmune polyendocrine syndrome type-1.

Autoimmune polyendocrine syndrome type-1 (APS-1) is a rare inherited monogenic autoimmune disease characterized by the presence of at least two of three following major clinical features: chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency. Mutations in autoimmune regulator (AIRE) gene have been found to contribute to APS-1. In the present study, we reported a 36-years-old male APS-1 patient who presented with hypoparathyroidism and Addison's disease. The proband underwent complete clinical examinations and mutation screening was performed by Sanger sequencing on AIRE gene. A novel homozygous mutation in exon 9 of the AIRE gene (c.1024C>T) was identified. Based on sequencing findings, HEK293T cell-based assays were conducted to analyze the subcellular localization and mutant transcript processing. Our results revealed that p.Q342X mutant localized in nuclear speckles and exerted a dominant-negative effect on wildtype AIRE function. We reported the c.1024C>T mutation of AIRE gene for the first time, which enriched the AIRE mutation database and contributed to further understanding of APS-1.

ALKBH3-dependent m1A demethylation of Aurora A mRNA inhibits ciliogenesis.

Primary cilia are antenna-like subcellular structures to act as signaling platforms to regulate many cellular processes and embryonic development. m1A RNA modification plays key roles in RNA metabolism and gene expression; however, the physiological function of m1A modification remains largely unknown. Here we find that the m1A demethylase ALKBH3 significantly inhibits ciliogenesis in mammalian cells by its demethylation activity. Mechanistically, ALKBH3 removes m1A sites on mRNA of Aurora A, a master suppressor of ciliogenesis. Depletion of ALKBH3 enhances Aurora A mRNA decay and inhibits its translation. Moreover, alkbh3 morphants exhibit ciliary defects, including curved body, pericardial edema, abnormal otoliths, and dilation in pronephric ducts in zebrafish embryos, which are significantly rescued by wild-type alkbh3, but not by its catalytically inactive mutant. The ciliary defects caused by ALKBH3 depletion in both vertebrate cells and embryos are also significantly reversed by ectopic expression of Aurora A mRNA. Together, our data indicate that ALKBH3-dependent m1A demethylation has a crucial role in the regulation of Aurora A mRNA, which is essential for ciliogenesis and cilia-associated developmental events in vertebrates.

Catalytic amplification based on hierarchical heterogeneity bimetal-organic nanostructures with peroxidase-like activity.

In this paper, integrating heterometallic units and nanostructures into metal-organic frameworks (MOFs) were applied to improve the sensitivity of detecting hydrogen peroxide (H2O2) in neutral solution. The bimetal-MOFs (CuCo-BDC) and GO composite (CuCo-BDC/GO) were first synthesized via an ordinary one-step solvothermal synthesis. The CuCo-BDC/GO with admirable peroxidase-like catalytic activity could be applied to detect H2O2. The results have low detection limit of 69 nM (S/N = 3) and a wide linear detection range, from 100 nM to 3.5 mM. This is superior to recently published biosensors based on noble metal nanomaterials, which confirms CuCo-BDC/GO as the MOF electrocatalysts with high performance. The remarkable electroanalytical performance of CuCo-BDC/GO is due to the presence of numerous open metal active sites, the synergistic effect of Cu2+ and Co2+, hierarchical structure with high-specific surface areas and the marvelous electrochemical properties of GO. Therefore, CuCo-BDC/GO is a powerful candidate for detecting H2O2 in electrochemical biosensing fields. Moreover, H2O2 detection in real samples can be done with the CuCo-BDC/GO, including human serum samples. Therefore, the novel CuCo-BDC/GO is a promising catalyst that can be applied in biotechnological and environmental applications.

Centrosomal protein FOR20 knockout mice display embryonic lethality and left-right patterning defects.

Centrosomal protein FOR20 has been reported to be crucial for essential cellular processes, including ciliogenesis, cell migration, and cell cycle in vertebrates. However, the function of FOR20 during mammalian embryonic development remains unknown. To investigate the in vivo function of the For20 gene in mammals, we generated For20 homozygous knockout mice by gene targeting. Our data reveal that homozygous knockout of For20 results in significant embryonic growth arrest and lethality during gestation, while the heterozygotes show no obvious defects. The absence of For20 leads to impaired left-right patterning of embryos and reduced cilia in the embryonic node. Deletion of For20 also disrupts angiogenesis in yolk sacs and embryos. These results highlight a critical role of For20 in early mammalian embryogenesis.

Epithelial expression and role of secreted STC1 on asthma airway hyperresponsiveness through calcium channel modulation.

BACKGROUND: Asthma is characterized by airway hyperresponsiveness (AHR), inflammation, and airway remodeling. Airway hyperresponsiveness results from enhanced airway smooth muscle (ASM) contraction potentially under the control of an epithelium-derived relaxing factor (EpDRF). However, relatively rare is known about EpDRF. We aimed to elucidate the role of epithelium-derived stanniocalcin-1 (STC1) on AHR and ASM contraction. METHODS: Stanniocalcin-1 levels in the serum of asthmatic patients and healthy volunteers and in bronchoalveolar lavage fluid (BALF) from ovalbumin (OVA)-challenged mice were measured by ELISA. The effects of exogenous STC1 on AHR and on inflammation were examined in mice. IL-13 modulation of STC1 mRNA and protein levels was studied in human bronchial epithelial cell lines (16HBE). The function of STC1 on Ca2+ influx and ASM contraction was examined ex vivo. RESULTS: Serum STC1 was decreased in asthma (n = 93) compared with healthy volunteers (1071 ± 30.4 vs 1414 ± 75.1 pg/ml, p < 0.0001, n = 23) and correlated with asthma control (p = 0.0270), lung function (FEV1, p = 0.0130), and serum IL-13 levels (p = 0.0009). Treatment of ten asthmatic subjects with inhaled corticosteroids/long-acting beta2-agonists (ICS/LABA) for 1 year enhanced STC1 expression which correlated with improved asthma control (p = 0.022). STC1 was mainly expressed in bronchial epithelium and intranasal administration of recombinant human STC1 (rhSTC1) reduced AHR and inflammation in mice. IL-13 suppressed STC1 release from 16HBE, whereas rhSTC1 blocked store-operated Ca2+ entry (SOCE) by suppressing stromal interaction molecule 1 (STIM1) and further inhibited ASM cell contractility by suppressing Ca2+ -dependent myosin light chain (MLC) phosphorylation. CONCLUSION: Our data indicate that STC1 deficiency in asthmatic airways promotes STIM1 hyperactivity, enhanced ASM contraction, and AHR. STC1 may be a candidate EpDRF.

Emerging roles of RNA methylation in gastrointestinal cancers.

RNA methylation has emerged as a fundamental process in epigenetic regulation. Accumulating evidences indicate that RNA methylation is essential for many biological functions, and its dysregulation is associated with human cancer progression, particularly in gastrointestinal cancers. RNA methylation has a variety of biological properties, including N6-methyladenosine (m6A), 2-O-dimethyladenosine (m6Am), N1-methyladenosine (m1A), 5-methylcytosine (m5C) and 7-methyl guanosine (m7G). Dynamic and reversible methylation on RNA is mediated by RNA modifying proteins called "writers" (methyltransferases) and "erasers" (demethylases). "Readers" (modified RNA binding proteins) recognize and bind to RNA methylation sites, which influence the splicing, stability or translation of modified RNAs. Herein, we summarize the biological functions and mechanisms of these well-known RNA methylations, especially focusing on the roles of m6A in gastrointestinal cancer development.

Density Functional Theory-Assisted Electrochemical Assay Manipulated by a Donor-Acceptor Structure toward Pharmaceutical Diagnostic.

Oxidative stress is a state of stress injury, which leads to the pathogenesis of most neurodegenerative diseases. Moreover, this is also one of the main reasons for the loss of dopaminergic neurons and the abnormal content of dopamine (DA). In the past decades, a number of studies have found that acetaminophen (AP) is metabolized and distributed in the brain when it is used as a neuroprotective compound. In this context, we proposed an electrochemical sensor based on 9-(4-(10-phenylanthracen-9-yl)phenyl)-9H-carbazole with the goal of diagnosing these two drugs in the body. Carbazole groups can easily be formed into large π-conjugated systems by electropolymerization. The introduction of anthracene exactly combined the carbazole group to establish an efficient electron donor-acceptor pattern, which enhanced π-π interaction with the electrode surface and charge transporting ability. The diagnostic platform showed good sensing activity toward the oxidation of DA and AP. The detection range for DA and AP is from 0.2 to 300 µM and from 0.2 to 400 µM, respectively. The simultaneous detection range is from 0.5 to 250 µM, which is wider than most reports. After a series of electrochemical assessments were determined, the sensor was finally developed to the analysis of pharmaceutical and human serum, displaying a meaningful potential in clinical evaluation.

Non-coding RNAs in gastric cancer.

Non-coding RNAs (ncRNAs) are functional RNA molecules that play crucial regulatory roles in many fundamental biological processes. The dysregulation of ncRNAs is significantly associated with the progression of human cancers, including gastric cancer. In this review, we have summarized the oncogenic or tumor-suppressive roles and the regulatory mechanisms of lncRNAs, miRNAs, circRNAs and piRNAs, and have discussed their potential as biomarkers or therapeutic targets in gastric cancer.