Genomic analysis of Cobetia sp. D5 reveals its role in marine sulfur cycling.

Dimethylsulfoniopropionate (DMSP) is one of the most abundant sulfur-containing organic compounds on the earth, which is an important carbon and sulfur source and plays an important role in the global sulfur cycle. Marine microorganisms are an important group involved in DMSP metabolism. The strain Cobetia sp. D5 was isolated from seawater samples in the Yellow Sea area of Qingdao during an algal bloom. There is still limited knowledge on the capacity of DMSP utilization of Cobetia bacteria. The study reports the whole genome sequence of Cobetia sp. D5 to understand its DMSP metabolism pathway. The genome of Cobetia sp. D5 consists of a circular chromosome with a length of 4,233,985 bp and the GC content is 62.56%. Genomic analysis showed that Cobetia sp. D5 contains a set of genes to transport and metabolize DMSP, which can cleave DMSP to produce dimethyl sulphide (DMS) and 3-Hydroxypropionyl-Coenzyme A (3-HP-CoA). DMS diffuses into the environment to enter the global sulfur cycle, whereas 3-HP-CoA is catabolized to acetyl CoA to enter central carbon metabolism. Thus, this study provides genetic insights into the DMSP metabolic processes of Cobetia sp. D5 during a marine algal bloom, and contributes to the understanding of the important role played by marine bacteria in the global sulfur cycle.

An Innovative SbIII-WVI-Cotemplated Antimonotungstate with Potential in Sensing Paroxetine Electrochemically.

Advances in polyoxometalate (POM) self-assembly chemistry are always accompanied by new developments in molecular blocks. The exploration and discovery of uncommon building blocks offer great possibilities for generating unprecedented POM clusters. An intriguing SbIII-WVI-cotemplated antimonotungstate [H2N(CH3)2]11Na[SbW9O33]Er2(H2O)2Sb2[SbWVIW15O57]·22H2O (1) was synthesized, which comprises a classical trivacant Keggin [SbW9O33]9- ({SbW9}) fragment and an unclassical lacunary Dawson-like [SbWVIW15O57]15- ({SbWVIW15}) subunit. Notably, the Dawson-like {SbWVIW15} subunit is the first example of a [SbO3]3- and [WVIO6]6- mixed-heteroatom-directing POM segment. Hexacoordinated [WVIO6]6- can not only serve as the heteroatom function but its additional oxygen sites can also link to lanthanide, main-group metal, and transition-metal centers to form the innovative structure. {SbWVIW15} and {SbW9} subunits are joined by the heterometallic [Er2(H2O)2Sb2O17]22- cluster to give rise to an asymmetric sandwich-type architecture. To further realize its potential application in electrochemical sensing, a conductive 1@rGO composite was obtained by the electrochemical deposition of 1 with graphene oxide (GO). Using a 1@rGO-modified glassy carbon electrode as the working electrode, an electrochemical biosensor for detecting the antidepressant drug paroxetine (PRX) was successfully constructed. This work can provide a viable strategy for synthesizing mixed-heteroatom-directing POMs and demonstrates the application of POM-based materials for the electrochemical detection of drug molecules.

Deep lymph node enlargement and renal failure caused by hypercalcemia­associated sarcoidosis: A case report.

Sarcoidosis is a rare disease that severely affects the lungs and superficial lymph nodes. In addition, this disease can also affect the skin, eyes and kidneys to varying degrees. The present report described a 32-year-old male patient who was admitted to Renmin Hospital of Wuhan University (Wuhan, China) due to joint pain in the extremities. He was diagnosed with uncorrectable hypercalcemia. A lymph node biopsy revealed the hypercalcemia to be associated with sarcoidosis, with the patient also demonstrating renal failure and lymph node enlargement. Administration of glucocorticoids provided benefits in terms of both primary and recurrent sarcoidosis, which also improved and preserved renal function. After being prescribed with oral prednisone treatment, blood calcium levels returned to normal, which indicated markedly improving renal function. However, the discontinuation of glucocorticoids for 2 months resulted in increased serum calcium and creatinine levels, both of which returned to abnormal levels. Overall, the present case report suggests that clinicians should actively perform sarcoidosis treatment in clinical practice to overcome any unexpected results associated with organ damage.

Follistatin-like 1 protects against doxorubicin-induced cardiotoxicity by preventing mitochondrial dysfunction through the SIRT6/Nrf2 signaling pathway.

Mitochondrial dysfunction and myocardial remodeling have been reported to be the main underlying molecular mechanisms of doxorubicin-induced cardiotoxicity. SIRT6 is a nicotinamide adenine dinucleotide-dependent enzyme that plays a vital role in cardiac protection against various stresses. Moreover, previous studies have demonstrated that FSTL1 could alleviate doxorubicin-induced cardiotoxicity by inhibiting autophagy. The present study investigated the probable mechanisms of FSTL1 on doxorubicin-induced cardiotoxicity in vivo and in vitro. We confirmed that FSTL1 exerted a pivotal protective role on cardiac tissue in vivo and on doxorubicin-induced cell injury in vitro. Furthermore, FSTL1 can alleviate doxorubicin-induced mitochondrial dysfunction by inhibiting autophagy and apoptosis. Further studies demonstrated that FSTL1 can activate SIRT6 signaling by restoring the SIRT6 protein expression in doxorubicin-induced myocardial injury. SIRT6 activation elevated the protein expression of Nrf2 in doxorubicin-induced H9C2 injury. Treatment with the Nrf2 inhibitor ML385 partially antagonized the cardioprotective role of SIRT6 on doxorubicin-induced autophagy or apoptosis. These results suggested that the protective mechanism of FSTL1 on doxorubicin-induced cardiotoxicity may be related with the inhibition of autophagy and apoptosis, partly through the activation of SIRT6/Nrf2.

Herbal compound cepharanthine attenuates inflammatory arthritis by blocking macrophage M1 polarization.

OBJECTIVE: Cepharanthine (CEP) is a drug candidate for tumor, viral infection, and some inflammatory diseases, but its effect on rheumatoid arthritis (RA) and the underlying mechanism are incompletely understood. METHODS: CEP was administered intraperitoneally to a collagen-induced arthritis (CIA) model. Joints went radiological and histological examination and serum cytokines were examined with cytometry-based analysis. M1 macrophages were induced from THP-1 cells or mouse bone marrow-derived macrophages with LPS and IFN-γ. Bulk RNA-seq was performed on macrophage undergoing M1-polarizatioin. Western blotting was applied to determine pathways involved in monocyte chemotaxis and polarization. Glycolysis metabolites were measured by chemiluminescence while glycolytic enzymes were examined by quantitative PCR. RESULTS: We found CEP significantly ameliorated synovial inflammation and joint destruction of CIA mice. It downregulated TNF-α levels in serum and in joints. The number of M1 macrophages were reduced in CEP-treated mice. In vitro, CEP inhibited monocyte chemotaxis to MCP-1 by downregulating CCR2 and reducing ERK1/2 signaling. Additionally, CEP suppressed M1 polarization of macrophages induced by LPS and IFN-γ. Genes involved in IFN-γ signaling, IL-6-JAK/STAT3 signaling, glycolysis, and oxidative phosphorylation process were downregulated by CEP. Several enzymes critically involved in glycolytic metabolism were suppressed by CEP, which resulted in reduced citrate in M1-polarizing macrophages. The inhibitory effect of CEP on macrophage polarization might be attributed to the blockage of TLRs-MyD88/IRAK4-IRF5 signaling pathway together with suppression of overactivated glycolytic metabolism in M1-polarizing macrophages. CONCLUSION: CEP attenuated joint inflammation by suppressing monocyte chemotaxis and proinflammatory differentiation. It has the potential to be developed into a complementary or alternative therapy for RA.

Role of soluble epoxide hydrolase in the abnormal activation of fibroblast-like synoviocytes from patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by enigmatic pathogenesis. Polyunsaturated fatty acids (PUFAs) are implicated in RA's development and progression, yet their exact mechanisms of influence are not fully understood. Soluble epoxide hydrolase (sEH) is an enzyme that metabolizes anti-inflammatory epoxy fatty acids (EpFAs), derivatives of PUFAs. In this study, we report elevated sEH expression in the joints of CIA (collagen-induced arthritis) rats, concomitant with diminished levels of two significant EpFAs. Additionally, increased sEH expression was detected in both the synovium of CIA rats and in the synovium and fibroblast-like synoviocytes (FLS) of RA patients. The sEH inhibitor TPPU attenuated the migration and invasion capabilities of FLS derived from RA patients and to reduce the secretion of inflammatory factors by these cells. Our findings indicate a pivotal role for sEH in RA pathogenesis and suggest that sEH inhibitors offer a promising new therapeutic strategy for managing RA.

Cerium-Encapsulated SbIII-SeIV-Templating Polyoxotungstate for Electrochemically Sensing Human Multidrug Resistance Gene Segment.

A tower-like SbIII-SeIV-templating polyoxotungstate [H2N(CH3)2]12Na7H3[Ce0.5/Na0.5(H2O)5]2[SbSe2W21O75]2·50H2O (1) was synthesized, whose skeleton is assembled from two prolonged lacunary Dawson [SbSe2W21O75]13- units and two [Ce0.5/Na0.5(H2O)5]2+ linkers. The uncommon [SbSe2W21O75]13- unit can be viewed as a combination of one [SeW6O21]2- group grafted onto a trivacant Dawson [SbSeW15O54]11- subunit. The conductive composite 1-Au@rGO containing 1, gold nanoparticles, and reduced graphene oxide (rGO) was conveniently prepared, using which the 1-Au@rGO-based electrochemical genosensor was constructed for detecting human multidrug resistance gene segment. This work enriches structural types of dual-heteroatom-inserted polyoxometalates and promotes the application of polyoxometalates in genosensors.

Single-cell transcriptome analysis and protein profiling reveal broad immune system activation in IgG4-related disease.

IgG4-related disease (IgG4-RD) is a systemic autoimmune disease with unclear pathogenesis. We performed single-cell RNA-seq and surface proteome analyses on 61,379 PBMCs from 9 treatment-naive IgG4-RD patients and 7 age- and sex-matched healthy controls. Integrative analyses were performed for altered gene expression in IgG4-RD, and flow cytometry and immunofluorescence were used for validation. We observed expansion of plasmablasts with enhanced protein processing and activation, which correlated with the number of involved organs in IgG4-RD. Increased proportions of CD4+ cytotoxic T lymphocytes (CTLs), CD8+ CTLs-GNLY (granulysin), and γδT cells with enhanced chemotaxis and cytotoxicity but with suppressed inhibitory receptors characterize IgG4-RD. Prominent infiltration of lymphocytes with distinct compositions were found in different organs of IgG4-RD patients. Transcription factors (TFs), including PRDM1/XBP1 and RUNX3, were upregulated in IgG4-RD, promoting the differentiation of plasmablasts and CTLs, respectively. Monocytes in IgG4-RD have stronger expression of genes related to cell adhesion and chemotaxis, which may give rise to profibrotic macrophages in lesions. The gene activation pattern in peripheral immune cells indicated activation of multiple interaction pathways between cell types, in part through chemokines or growth factors and their receptors. Specific upregulation of TFs and expansion of plasmablasts and CTLs may be involved in the pathogenesis of IgG4-RD, and each of these populations are candidate targets for therapeutic interventions in this disease.

Effects of second-line anti-tuberculosis drugs on the intestinal microbiota of patients with rifampicin-resistant tuberculosis.

Objective: To determine the effects of second-line anti-tuberculosis (TB) drugs on the composition and functions of intestinal microbiota in patients with rifampicin-resistant TB (RR-TB). Methods: In this cross-sectional study, stool samples and relevant clinical information were collected from patients with RR-TB admitted to the Drug-resistant Specialty Department at Hunan Chest Hospital (Hunan Institute For Tuberculosis Control). The composition and functions of intestinal microbiota were analyzed using metagenomic sequencing and bioinformatics methods. Results: Altered structural composition of the intestinal microbiota was found when patients from the control, intensive phase treatment, and continuation phase treatment groups were compared (P<0.05). Second-line anti-TB treatment resulted in a decrease in the relative abundance of species, such as Prevotella copri, compared with control treatment. However, the relative abundance of Escherichia coli, Salmonella enterica, and 11 other conditionally pathogenic species increased significantly in the intensive phase treatment group. Based on differential functional analysis, some metabolism-related functions, such as the biosynthesises of phenylalanine, tyrosine, and tryptophan, were significantly inhibited during second-line anti-TB drug treatment, while other functions, such as phenylalanine metabolism, were significantly promoted during the intensive phase of treatment. Conclusion: Second-line anti-TB drug treatment caused changes in the structural composition of the intestinal microbiota in patients with RR-TB. In particular, this treatment induced a significant increase in the relative abundance of 11 conditionally pathogenic species, including Escherichia coli. Functional analysis revealed significantly decreased biosynthesises of phenylalanine, tyrosine, and tryptophan and significantly increased phenylalanine metabolism.

Neglected Aspects of SARS-CoV-2 Aerosol Transmission in Bathrooms of Multistory and High-Rise Buildings - Beijing Municipality, China, October 2022.

What is already known about this topic?: There is a toilet flush-soil stack-floor drain pathway of aerosol transmission in multistory and high-rise buildings, but the influencing factors are not completely clear. What is added by this report?: The poor airtightness of the connecting parts of the floor drain, as well as pressure fluctuations in the sewage pipe during toilet flushing caused by blockage of the soil stack vent, may lead to the cross-floor transmission of viral aerosols through the soil stack and floor drains. What are the implications for public health practice?: In multistory and high-rise buildings, the bathroom floor drains should be kept sealed, and floor drain connecting parts should be airtight. Furthermore, the soil stack vent should not be blocked. In this way, the cross-floor transmission of viral aerosols can be effectively reduced.

Role of endoscopic ultrasound in the evaluation of unexplained extrahepatic bile duct dilatation.

OBJECTIVE: This study was performed to assess the diagnostic performance of endoscopic ultrasonography (EUS) in patients with extrahepatic bile duct (EBD) dilatation and develop a novel model incorporating EUS-based signature with clinical parameters for distinguishing the malignant dilation of EBD. METHODS: The EUS data and clinical parameters of the patients were collected and analyzed retrospectively. First, we evaluated the diagnostic performance of EUS in detecting the cause of EBD dilatation. Then, we performed univariate and multivariate binary logistic regression analyses based on clinical and EUS features. Finally, a nomogram was established to aid in distinguishing between malignant dilation and noncalculous benign dilatation of EBD in patients. RESULTS: A total of 184 patients were enrolled. For the diagnosis of malignant dilation, EUS achieved an accuracy of 90.76%, sensitivity of 85.96%, and specificity of 92.91%. For the diagnosis of calculous dilation, EUS achieved an accuracy of 100%, sensitivity of 100%, and specificity of 100%. For the diagnosis of noncalculous benign dilatation, EUS achieved an accuracy of 90.76%, sensitivity of 90.90%, and specificity of 90.58%. Multivariable logistic regression analyses indicated that abnormal liver function test, elevated tumor markers, and EUS findings were the well-diagnostic factors of malignant EBD dilation. The nomogram established by these factors showed good calibration and discrimination. CONCLUSION: EUS is a useful examinational modality in the work-up of EBD dilatation. In combination with abnormal liver function test and elevated tumor markers, EUS may provide additional information for the detection of malignant dilation of EBD and should be further investigated.

N6 -methyladenosine RNA demethylase FTO regulates extracellular matrix-related genes and promotes pancreatic cancer cell migration and invasion.

Pancreatic cancer (PC) is a deadly disease, and its post-transcriptional gene regulation mechanism remains unclear. The abundant extracellular matrix (ECM) in PC plays an important role in tumor progression. This study is the first to focus on the role of N6 -methyladenosine (m6 A) RNA methylation, an emerging post-transcriptional regulatory mechanism, in the regulation of the ECM in PC. Here, we found that ADAMTS2, COL12A1, and THBS2 were associated with the prognosis of PC by comprehensive analysis of differentially expressed genes from two independent GEO expression profile datasets and m6 A-related genes in RMVar database (PAAD). GO and KEGG enrichment analysis found that these m6 A-related targets are chiefly functionally concentrated in the ECM region and participate in ECM signal transduction. Correlation analysis revealed that these genes can be regulated by the demethylase FTO. Cell biology function assays showed that knockdown of FTO-inhibited PC cell abilities to migrate and invade in vitro. qRT-PCR and MeRIP experiments showed that after knockdown of FTO, the mRNA levels of ADAMTS2, COL12A1, and THBS2 and their m6 A modification levels were significantly reduced. These results indicate that m6 A RNA demethylation is associated with the regulation of ECM in PC. In conclusion, m6 A RNA demethylase FTO regulates ECM-related genes and promotes PC cell abilities to migrate and invade, our work provides a new perspective on the molecular mechanism of PC progression.

CASC9 potentiates gemcitabine resistance in pancreatic cancer by reciprocally activating NRF2 and the NF-κB signaling pathway.

Gemcitabine resistance is a frequently occurring and intractable obstacle in pancreatic cancer treatment. However, the underlying mechanisms require further investigation. Adaptive regulation of oxidative stress and aberrant activation of the NF-κB signaling pathway are associated with resistance to chemotherapy. Here, we found that gemcitabine upregulated the expression of CASC9 in a dose-dependent manner, partially via induction of reactive oxygen species, whereas inhibition of CASC9 expression enhanced gemcitabine-induced oxidative stress and apoptosis in pancreatic cancer cells. Furthermore, suppression of CASC9 level inhibited the expression of NRF2 and the downstream genes NQO1 and HO-1, and vice versa, indicating that CASC9 forms a positive feedback loop with NRF2 signaling and modulates the level of oxidative stress. Silencing CASC9 attenuated NF-κB pathway activation in pancreatic cancer cells and synergistically enhanced the cytotoxic effect of gemcitabine chemotherapy in vivo. In conclusion, our findings suggest that CASC9 plays a key role in driving resistance to gemcitabine through a reciprocal loop with the NRF2-antioxidant signaling pathway and by activating NF-κB signaling. Our study reveals potential targets that can effectively reverse resistance to gemcitabine chemotherapy.

Prevalence, Causes, and Risk Factors of Presenting Visual Impairment and Presenting Blindness in Adults Presenting to an Examination Center in Suzhou, China.

Purpose: To evaluate the prevalence, causes, and risk factors of presenting visual impairment (PVI) and presenting blindness among adults in Suzhou, China. Methods: A total of 43927 subjects were included in this cross-sectional study. Each subject underwent ophthalmic examinations, including presenting visual acuity (PVA), intraocular pressure (IOP), slit-lamp examination, and fundus examination under the small pupils of each eye. Results: Using the World Health Organization (WHO) definition, the prevalence of bilateral PVI, bilateral presenting blindness, monocular PVI, and monocular presenting blindness was 1.59% (95% CI, 1.51-1.67), 0.002% (95% CI, 0.0019-0.0021), 3.87% (95% CI, 3.68-4.06), and 0.19% (95% CI, 0.18-0.20), respectively. Using the United States (US) definition, the prevalence of bilateral PVI, bilateral presenting blindness, monocular PVI, and monocular presenting blindness was 5.83% (95% CI, 5.54-6.12), 0.04% (95% CI, 0.038-0.042), 7.43% (95% CI, 7.06-7.80), and 0.45% (95% CI, 0.43-0.47), respectively. The prevalence of PVI was higher in females (WHO criteria, 2.06%, 95% CI, 1.96-2.16; US criteria, 7.27%, 95% CI, 6.91-7.63) than in males (WHO criteria, 1.2%, 95 CI%, 1.14-1.26; US criteria, 4.65%, 95% CI, 4.42-4.89). The leading cause of PVI is an uncorrected refractive error, followed by cataracts and age-related macular degeneration (AMD). Multivariate analysis proved that the prevalence of visual impairment (PVA, better eye, WHO criteria) increased significantly with older age, higher mean arterial pressure (MAP), higher globulin level, and higher fasting blood glucose (FBG). In addition, it also increased significantly with lower hemoglobin, a lower body mass index (BMI), and a lower arterial stiffness index. In this study, serum creatinine, blood urea nitrogen, uric acid, triglycerides, and the systemic immune-inflammation index (SII) showed no association with visual impairment. Conclusion: The leading causes of PVI in Suzhou were uncorrected refractive error and cataracts. The prevalence of PVI increased with females, older age, higher MAP, higher FBG, higher globulin, lower hemoglobin, lower BMI, and lower arterial stiffness index.

Nomogram for Predicting Distant Metastasis of Pancreatic Ductal Adenocarcinoma: A SEER-Based Population Study.

(1) Background: The aim of this study was to identify risk factors for distant metastasis of pancreatic ductal adenocarcinoma (PDAC) and develop a valid predictive model to guide clinical practice; (2) Methods: We screened 14328 PDAC patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. Lasso regression analysis combined with logistic regression analysis were used to determine the independent risk factors for PDAC with distant metastasis. A nomogram predicting the risk of distant metastasis in PDAC was constructed. A receiver operating characteristic (ROC) curve and consistency-index (C-index) were used to determine the accuracy and discriminate ability of the nomogram. A calibration curve was used to assess the agreement between the predicted probability of the model and the actual probability. Additionally, decision curve analysis (DCA) and clinical influence curve were employed to assess the clinical utility of the nomogram; (3) Results: Multivariate logistic regression analysis revealed that risk factors for distant metastasis of PDAC included age, primary site, histological grade, and lymph node status. A nomogram was successfully constructed, with an area under the curve (AUC) of 0.871 for ROC and a C-index of 0.871 (95% CI: 0.860-0.882). The calibration curve showed that the predicted probability of the model was in high agreement with the actual predicted probability. The DCA and clinical influence curve showed that the model had great potential clinical utility; (4) Conclusions: The risk model established in this study has a good predictive performance and a promising potential application, which can provide personalized clinical decisions for future clinical work.

SIRPα maintains macrophage homeostasis by interacting with PTK2B kinase in Mycobacterium tuberculosis infection and through autophagy and necroptosis.

BACKGROUND: To determine whether SIRPα can be a diagnostic marker of pulmonary tuberculosis (PTB) and the molecular mechanism of SIRPα regulating macrophages to kill Mycobacterium tuberculosis (MTB). METHODS: Meta-analysis combined with subsequent qRT-PCR, western-blotting and flow cytometry assay were used to detect SIRPα expression in PTB patients. Cell-based assays were used to explore the regulation of macrophage function by SIRPα. SIRPα-/- and wide type macrophages transplanted C57BL/6J mice were used to determine the function of SIRPα on MTB infection in vivo. FINDINGS: SIRPα levels are closely correlated with the treatment outcomes among PTB patients. Cell-based assay demonstrated that MTB significantly induces the expression of SIRPα on macrophages. SIRPα deficiency enhances the killing ability of macrophages against MTB through processes that involve enhanced autophagy and reduced necroptosis of macrophages. Mechanistically, SIRPα forms a direct interaction with PTK2B through its intracellular C-terminal domain, thus inhibiting PTK2B activation in macrophages. Necroptosis inhibition due to SIRPα deficiency requires PTK2B activity. The transfer of SIRPα-deficient bone marrow-derived macrophages (BMDMs) into wild type mice resulted in a drop of bacterial load in the lungs but an enhancement of inflammatory lung damage, and the combination of ulinastatin and SIRPα-/-→WT treatment could decrease the inflammation and maintain the bactericidal capacity. INTERPRETATION: Our data define SIRPα a novel biomarker for tuberculosis infection and underlying mechanisms for maintaining macrophage homeostasis. FUNDING: This work was financially supported by the Chinese National Natural Science Foundation project (No.81401635). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Organophosphonic Acid-Regulating Assembly of PV-SbIII Polyoxotungstate and Its Potential in Building a Dual-Signal Readout Electrochemical Aptasensor for Carcinogen Detection.

Template-directed assembly of giant cluster-based nanomaterials is an everlasting theme in cluster science. In this work, ethylenediamine tetramethylphosphonic acid [H8EDTPA = (POCH2(OH)2)4C2H4N2] and [B-α-SbW9O33]9- were, respectively, used as an organic template and an inorganic template to prepare an organophosphonic acid-regulating PV-SbIII-heteroatom-inserted polyoxotungstate aggregate [H2N(CH3)2]5Na11H9[CeW4O10(HEDTPA)SbW15O50][B-α-SbW9O33]2·36H2O (1). Noteworthily, organophosphonic acid ligand not only works as an organic template leading to the assembly of a [HEDTPASbW15O50]14- building block but also further bridges the sandwich-type [CeW4O10(B-α-SbW9O33)2]11- entity. To extend its potential application in electrochemical sensing properties, we prepared a three-dimensional 1@EGO composite (EGO = reduced graphene oxide functionalized by ethylenediamine) with porous architecture and a prominent conducting ability. Furthermore, the 1@EGO composite was explored as a modification material for glassy carbon electrodes to build a dual-signal readout electrochemical aptasensor for carcinogens, which shows much better detection performance for aflatoxin B1 compared with traditional single-signal biosensors.

Long non­coding RNA 01614 hyperactivates WNT/ß­catenin signaling to promote pancreatic cancer progression by suppressing GSK­3ß.

Pancreatic cancer (PC) is a lethal type of cancer for which effective therapies are limited. Long non­coding RNAs (lncRNAs) represent a critical type of regulator category, mediating the tumorigenesis and development of various tumor types, including PC. However, the expression patterns and functions of numerous lncRNAs in PC remain poorly understood. In the present study, linc01614 was identified as a PC­related lncRNA. linc01614 was notably upregulated in PC tissues and cell lines and was associated with the poor disease­free survival of patients with PC according to the analysis of The Cancer Genome Atlas­derived datasets. Functionally, linc01614 knockdown suppressed PC cell proliferation, migration and invasion in vitro, and inhibited tumor proliferation in vitro and in vivo. Mechanistically, linc01614 overexpression stabilized the level of ß­catenin protein to hyperactivate the WNT/ß­catenin signaling pathway in PC cells. Further analyses revealed that linc01614 bound to GSK­3ß and perturbed the interaction between GSK­3ß and AXIN1, thereby preventing the formation of the ß­catenin degradation complex and reducing the degradation of ß­catenin. In summary, the present findings reveal that linc01614 may function as an oncogene and promote the progression of PC and may thus be considered as a potential therapeutic target in the future.

Tumorigenic and immunological roles of Heat shock protein A2 in pancreatic cancer: a bioinformatics analysis.

OBJECTIVE: Heat shock protein A2 has been reported to be tightly associated with tumorigenesis and tumor progression. This study aimed to determine the oncogenic and immunological roles of Heat shock protein A2 in pancreatic cancer by bioinformatics. METHODS: Expression of Heat shock protein A2 in tumorous and normal specimens of pancreatic cancer was analyzed using the Cancer Genome Atlas and the Cancer Genome Atlas + Genotype-Tissue Expression data sets, respectively. Relationships of Heat shock protein A2 expression with immune infiltrates in pancreatic cancer were assessed. Heat shock protein A2-associated coexpressed genes in pancreatic cancer were obtained, followed by the implementation of enrichment analysis. RESULTS: The data demonstrated that Heat shock protein A2 was significantly overexpressed in tumorous samples compared with normal samples. Heat shock protein A2 expression was remarkably positively interrelated with CD8+ T cell, neutrophil, dendritic cell, and macrophage, but not with CD4+ T and B cells. Heat shock protein A2 expression was markedly positively relevant to both cancer-associated fibroblast and endothelial cell. Enrichment data revealed that Heat shock protein A2 was intimately involved in the tumorigenesis and progression of pancreatic cancer. CONCLUSION: Heat shock protein A2 is upregulated in pancreatic cancer and is closely associated with tumor immunity and aggressive progression.