Interspecies/Intergroup Complementation of Orthotospovirus Replication and Movement through Reverse Genetics Systems.

Orthotospoviruses, the plant-infecting bunyaviruses, cause serious diseases in agronomic crops and pose major threats to global food security. The family of Tospoviridae contains more than 30 members that are classified into two geographic groups, American-type and Euro/Asian-type orthotospovirus. However, the genetic interaction between different species and the possibility, during mixed infections, for transcomplementation of gene functions by orthotospoviruses from different geographic groups remains underexplored. In this study, minireplicon-based reverse genetics (RG) systems have been established for Impatiens necrotic spot virus (INSV) (an American-type orthotospovirus) and for Calla lily chlorotic spot virus and Tomato zonate spot virus (CCSV and TZSV) (two representative Euro/Asian orthotospoviruses). Together with the earlier established RG system for Tomato spotted wilt virus (TSWV), a type species of the Orthotospovirus American-clade, viral replicase/movement proteins were exchanged and analyzed on interspecies transcomplementation. Whereas the homologous RNA-dependent RNA polymerase (RdRp) and nucleocapsid (N) protein supported the replication of orthotospoviruses from both geographic groups, heterologous combinations of RdRp from one group and N from the other group were unable to support the replication of viruses from both groups. Furthermore, the NSm movement protein (MP), from both geographic groups of orthotospoviruses, was able to transcomplement heterologous orthotospoviruses or a positive-strand Cucumber mosaic virus (CMV) in their movement, albeit with varying efficiency. MP from Rice stripe tenuivirus (RSV), a plant-infecting bunyavirus that is distinct from orthotospoviruses, or MP from CMV also moves orthotospoviruses. Our findings gain insights into the genetic interaction/reassortant potentials for the segmented plant orthotospoviruses. IMPORTANCE Orthotospoviruses are agriculturally important negative-strand RNA viruses and cause severe yield-losses on many crops worldwide. Whereas the emergence of new animal-infecting bunyaviruses is frequently associated with genetic reassortants, this issue remains underexposed with the plant-infecting orthotospovirus. With the development of reverse genetics systems for orthotospoviruses from different geographic regions, the interspecies/intergroup replication/movement complementation between American- and Euro/Asian-type orthotospoviruses were investigated. Genomic RNAs from American orthotospoviruses can be replicated by the RdRp and N from those of Euro/Asia-group orthotospoviruses, and vice versa. However, their genomic RNAs cannot be replicated by a heterologous combination of RdRp from one geographic group and N from another geographic group. Cell-to-cell movement of viral entity is supported by NSm from both geographic groups, with highest efficiency by NSm from viruses belonging to the same group. Our findings provide important insights into the genetic interaction and exchange ability of viral gene functions between different species of orthotospovirus.

Bile acids promote the caveolae-associated entry of swine acute diarrhea syndrome coronavirus in porcine intestinal enteroids.

Intestinal microbial metabolites have been increasingly recognized as important regulators of enteric viral infection. However, very little information is available about which specific microbiota-derived metabolites are crucial for swine enteric coronavirus (SECoV) infection in vivo. Using swine acute diarrhea syndrome (SADS)-CoV as a model, we were able to identify a greatly altered bile acid (BA) profile in the small intestine of infected piglets by untargeted metabolomic analysis. Using a newly established ex vivo model-the stem cell-derived porcine intestinal enteroid (PIE) culture-we demonstrated that certain BAs, cholic acid (CA) in particular, enhance SADS-CoV replication by acting on PIEs at the early phase of infection. We ruled out the possibility that CA exerts an augmenting effect on viral replication through classic farnesoid X receptor or Takeda G protein-coupled receptor 5 signaling, innate immune suppression or viral attachment. BA induced multiple cellular responses including rapid changes in caveolae-mediated endocytosis, endosomal acidification and dynamics of the endosomal/lysosomal system that are critical for SADS-CoV replication. Thus, our findings shed light on how SECoVs exploit microbiome-derived metabolite BAs to swiftly establish viral infection and accelerate replication within the intestinal microenvironment.

Programmed death of cardiomyocytes in cardiovascular disease and new therapeutic approaches.

Cardiovascular diseases (CVDs) have a complex pathogenesis and pose a major threat to human health. Cardiomyocytes have a low regenerative capacity, and their death is a key factor in the morbidity and mortality of many CVDs. Cardiomyocyte death can be regulated by specific signaling pathways known as programmed cell death (PCD), including apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis, etc. Abnormalities in PCD can lead to the development of a variety of cardiovascular diseases, and there are also molecular-level interconnections between different PCD pathways under the same cardiovascular disease model. Currently, the link between programmed cell death in cardiomyocytes and cardiovascular disease is not fully understood. This review describes the molecular mechanisms of programmed death and the impact of cardiomyocyte death on cardiovascular disease development. Emphasis is placed on a summary of drugs and potential therapeutic approaches that can be used to treat cardiovascular disease by targeting and blocking programmed cell death in cardiomyocytes.

The role of glycolytic metabolic pathways in cardiovascular disease and potential therapeutic approaches.

Cardiovascular disease (CVD) is a major threat to human health, accounting for 46% of non-communicable disease deaths. Glycolysis is a conserved and rigorous biological process that breaks down glucose into pyruvate, and its primary function is to provide the body with the energy and intermediate products needed for life activities. The non-glycolytic actions of enzymes associated with the glycolytic pathway have long been found to be associated with the development of CVD, typically exemplified by metabolic remodeling in heart failure, which is a condition in which the heart exhibits a rapid adaptive response to hypoxic and hypoxic conditions, occurring early in the course of heart failure. It is mainly characterized by a decrease in oxidative phosphorylation and a rise in the glycolytic pathway, and the rise in glycolysis is considered a hallmark of metabolic remodeling. In addition to this, the glycolytic metabolic pathway is the main source of energy for cardiomyocytes during ischemia-reperfusion. Not only that, the auxiliary pathways of glycolysis, such as the polyol pathway, hexosamine pathway, and pentose phosphate pathway, are also closely related to CVD. Therefore, targeting glycolysis is very attractive for therapeutic intervention in CVD. However, the relationship between glycolytic pathway and CVD is very complex, and some preclinical studies have confirmed that targeting glycolysis does have a certain degree of efficacy, but its specific role in the development of CVD has yet to be explored. This article aims to summarize the current knowledge regarding the glycolytic pathway and its key enzymes (including hexokinase (HK), phosphoglucose isomerase (PGI), phosphofructokinase-1 (PFK1), aldolase (Aldolase), phosphoglycerate metatase (PGAM), enolase (ENO) pyruvate kinase (PKM) lactate dehydrogenase (LDH)) for their role in cardiovascular diseases (e.g., heart failure, myocardial infarction, atherosclerosis) and possible emerging therapeutic targets.

Biological treatment processes for saline organic wastewater and related inhibition mechanisms and facilitation techniques: A comprehensive review.

Owing to its profound pollution-inducing properties and resistance to biodegradation, saline organic wastewater (SOW) has unavoidably emerged as a predominant focal point within the wastewater treatment domain. Substantial quantities of SOW are discharged by diverse industries encompassing food processing, pharmaceuticals, leather manufacturing, petrochemicals, and textiles. Within this review, the inhibitory repercussions of elevated salinity upon biological water treatment systems are subject to methodical scrutiny spanning from sludge characteristics, microbial consortia to the physiological functionality of microorganisms have been investigated. This exposition elucidates the application of both anaerobic and aerobic biological technologies for SOW treatment, which noting that conventional bioreactors can effectually treat SOW through microbial adaptation, and elaborating that cultivation of salt-tolerant bacteria and the design of advanced bioreactors represents a promising avenue for SOW treatment. Furthermore, the mechanisms underpinning microbial acclimatization to hypersaline milieus and the methodologies aimed at amplifying the efficacy of biological SOW treatment are delved into, which point out that microorganism exhibit salt tolerance via extracellular polymeric substance accumulation or by facilitating the influx of osmolarity-regulating agents into the bacterial matrix. Finally, the projections for future inquiry are proffered, encompassing the proliferation and deployment of high salt-tolerant strains, as well as the development of techniques enhancing the salt tolerance of microflora engaged in wastewater treatment.

Coupling of Fenton reaction and white rot fungi for the degradation of organic pollutants.

Advanced oxidation processes (AOPs) are a class of highly efficient pollution remediation technologies that produce oxidising radicals under specific conditions to degrade organic pollutants. The Fenton reaction is a commonly applied AOP. To combine the advantages of AOPs and biodegradation in the remediation of organic pollutants, some studies have developed coupled systems between Fenton AOPs and white rot fungi (WRF) for environmental organic pollutant remediation and have achieved some success. Moreover, a promising system, termed as advanced bio-oxidation processes (ABOPs), mediated by the quinone redox cycling of WRF, has attracted increasing attention in the field. In this ABOP system, the radicals and H2O2 produced through the quinone redox cycling of WRF can strengthen Fenton reaction. Meanwhile, in this process, the reduction of Fe3+ to Fe2+ ensures the maintenance of Fenton reaction, leading to a promising application potential for the remediation of environmental organic pollutants. ABOPs combine the advantages of bioremediation and advanced oxidation remediation. Further understanding the coupling of Fenton reaction and WRF in the degradation of organic pollutants will be of great significance for the remediation of organic pollutants. Therefore, in this study, we reviewed recent remediation techniques for organic pollutants involving the coupled application of WRF and the Fenton reaction, focusing on the application of new ABOPs mediated by WRF, and discussed the reaction mechanism and conditions of ABOPs. Finally, we discussed the application prospects and future research directions of the joint application of WRF and advanced oxidation technologies for the remediation of environmental organic pollutants.

ZIF-67-Derived Co/N-Doped Carbon-Functionalized MXene for Enhanced Electrochemical Sensing of Carbendazim.

Herein, ZIF-67-derived Co and N-doped carbon (Co/NC) particle-modified multilayer MXene (MXene@Co/NC) was developed as remarkable electrode material for carbendazim (CBZ) detection. MXene as a substrate provides an excellent conductive framework and plentiful accessibility sites. Co/NC particles embedding in MXene can not only prevent the interlayer stacking of MXene but also contribute a great deal of metal catalytic active sites and finally improve the adsorption and catalytic properties of the composite. Accordingly, the MXene@Co/NC electrode displays excellent electrocatalytic activity toward CBZ oxidation. Experimental parameters such as pH value, accumulation time, MXene@Co/NC modification volume and constituent materials' mass ratios were optimized. Under optimal conditions, the as-prepared sensor based on MXene@Co/NC holds a broad linearity range from 0.01 µM to 45.0 µM with a low limit of detection (LOD) of 3.3 nM (S/N = 3, S means the detection signal, while N represents the noise of the instrument). Moreover, the proposed sensor displays excellent anti-interference ability, superior reproducibility, excellent stability, and successfully achieves actual applications for CBZ detection in a lettuce sample.

A pair of G-type lectin receptor-like kinases modulates nlp20-mediated immune responses by coupling to the RLP23 receptor complex.

Plant cells recognize microbial patterns with the plasma-membrane-localized pattern-recognition receptors consisting mainly of receptor kinases (RKs) and receptor-like proteins (RLPs). RKs, such as bacterial flagellin receptor FLS2, and their downstream signaling components have been studied extensively. However, newly discovered regulatory components of RLP-mediated immune signaling, such as the nlp20 receptor RLP23, await identification. Unlike RKs, RLPs lack a cytoplasmic kinase domain, instead recruiting the receptor-like kinases (RLKs) BAK1 and SOBIR1. SOBIR1 specifically works as an adapter for RLP-mediated immunity. To identify new regulators of RLP-mediated signaling, we looked for SOBIR1-binding proteins (SBPs) in Arabidopsis thaliana using protein immunoprecipitation and mass spectrometry, identifying two G-type lectin RLKs, SBP1 and SBP2, that physically interacted with SOBIR1. SBP1 and SBP2 showed high sequence similarity, were tandemly repeated on chromosome 4, and also interacted with both RLP23 and BAK1. sbp1 sbp2 double mutants obtained via CRISPR-Cas9 gene editing showed severely impaired nlp20-induced reactive oxygen species burst, mitogen-activated protein kinase (MAPK) activation, and defense gene expression, but normal flg22-induced immune responses. We showed that SBP1 regulated nlp20-induced immunity in a kinase activity-independent manner. Furthermore, the nlp20-induced the RLP23-BAK1 interaction, although not the flg22-induced FLS2-BAK1 interaction, was significantly reduced in sbp1 sbp2. This study identified SBPs as new regulatory components in RLP23 receptor complex that may specifically modulate RLP23-mediated immunity by positively regulating the interaction between the RLP23 receptor and the BAK1 co-receptor.

Multiple plasmon-induced transparency based on black phosphorus and graphene for high-sensitivity refractive index sensing.

A hybrid bilayer black phosphorus (BP) and graphene structure with high sensitivity is proposed for obtaining plasmon-induced transparency (PIT). By means of surface plasmon resonance in the rectangular-ring BP structure and ribbon graphene structure, a PIT effect with high refractive index sensitivity is achieved, and the surface plasmon hybridization between graphene and anisotropic BP is analyzed theoretically. Meanwhile, the PIT effect is quantitatively described using the coupled oscillator model and the strong coherent coupling phenomena are analyzed by adjusting the coupling distance between BP and graphene, the Fermi level of graphene, and the crystal orientation of BP, respectively. The simulation results show that the refractive index sensitivity S = 7.343 THz/RIU has been achieved. More importantly, this is the first report of tunable PIT effects that can produce up to quintuple PIT windows by using the BP and graphene hybrid structure. The high refractive index sensitivity of the quintuple PIT system for each peak is 3.467 THz/RIU, 3.467 THz/RIU, 3.600 THz/RIU, 4.267 THz/RIU, 4.733 THz/RIU and 6.133 THz/RIU, respectively, which can be used for multiple refractive index sensing function.

Amplified electrochemical determination of niclosamide in food based on carbon nanohorn@MWCNT composite.

In this work, carbon nanohorn (CNH)-decorated multi-walled carbon nanotube (MWCNT) (CNH@MWCNT) composite was prepared and used to modify glass carbon electrode (GCE) as sensitive electrochemical sensor for niclosamide (NA) determination. Herein, the decoration of CNHs induces higher dispersibility for MWCNTs, and endows the composite with better conductivity, larger surface area, and higher catalytic activity, which leads to significantly enhanced electrochemical behavior toward NA oxidation. The parameters such as mass ratios of CNHs and MWCHTs, the amount of composite materials, the accumulation time, and the solution pH are systematically optimized. Under optimized conditions, the developed electrochemical sensor exhibits a low detection limit of 2.0 nM with a wide linear range of 7.0 nM-10.0 µM and high anti-interference ability. In addition, the sensor displays good stability, repeatability, and reproducibility. The feasibility of the assay was verified by testing NA in brown rice and rice field water samples.

Expression and prognostic roles of PRDXs gene family in hepatocellular carcinoma.

BACKGROUND: As the fourth leading cause of cancer-related death in the world, the therapeutic effect and 5-year overall survival of hepatocellular carcinoma (HCC) are not optimistic. Previous researches indicated that the disorder of PRDXs was related to the occurrence and development of cancers. METHODS: In this study, PRDXs were found in various tumor cell lines by CCLE database analysis. The analysis results of UALCAN, HCCDB and Human Protein Atlas databases showed the expression of PRDXs mRNA and protein in HCC tissues was dysregulated. Besides, UALCAN was used to assess the correlations between PRDXs mRNA as well as methylation levels and clinical characterization. RESULTS: High expression of PRDX1 or low expression of PRDX2/3 suggested poor prognosis for HCC patients which was demonstrated by Kaplan-Meier Plotter. The genetic alterations and biological interaction network of PRDXs in HCC samples were obtained from c-Bioportal. In addition, LinkedOmics was employed to analyze PRDXs related differentially expressed genes, and on this basis, enrichment of KEGG pathway and miRNAs targets of PRDXs were conducted. The results indicated that these genes were involved in several canonical pathways and certain amino acid metabolism, some of which may effect on the progression of HCC. CONCLUSIONS: In conclusion, the disordered expression of some PRDX family members was associated with the prognosis of HCC patients, suggesting that these PRDX family members may become new molecular targets for the treatment and prognosis prediction of HCC.

Difficulty with Taking Medications Is Associated with Future Diagnosis of Alzheimer's Disease and Related Dementias.

BACKGROUND: Medication management requires complex cognitive functioning, and therefore, difficulty taking medications might be an early sign of cognitive impairment and could be a risk factor for Alzheimer's disease and related dementias (ADRD). Accordingly, people with difficulty taking medications may benefit from more detailed cognitive screening, potentially aiding in the diagnosis of ADRD, which is underdiagnosed. We are unaware of evidence on medication management difficulties that precede a real-world ADRD diagnosis in the USA. OBJECTIVE: Examine the association between difficulty taking medications and subsequent real-world ADRD diagnoses. DESIGN: Case-control study, using Health and Retirement Study (HRS) survey data linked to Medicare claims. PARTICIPANTS: A total of 1461 HRS respondents with an ADRD diagnosis observed from 1993 to 2012 (cases), matched by year of birth, wave of HRS entry, and sex to 3771 controls with no ADRD diagnosis. MAIN MEASURES: We examined the association between diagnosis of ADRD and self-reported difficulty taking medications in the preceding years (1-2 and 3-4 years prior to case definition). Control individuals were assigned the index date from their matched case. Conditional logistic regressions adjusted for age, sex, race, education, and comorbidities. KEY RESULTS: Compared with matched controls, cases had higher prevalence of difficulty taking medications 1-2 years prior to diagnosis (11.0% versus 2.3%), and 3-4 years prior to diagnosis (5.8% versus 2.3%). Adjusted analyses showed that compared with individuals without ADRD, those with an ADRD diagnosis had more than four times higher odds of difficulty taking medications 1-2 years prior (OR = 4.56 (CI 3.30-6.31)), and more than two times higher odds of difficulty taking medications 3-4 years prior (OR = 2.41 (CI 1.61-3.59)). CONCLUSIONS: Odds of medication difficulty 1-2 years prior were more than four times greater for individuals with ADRD diagnoses compared with those without ADRD. Medication management difficulties may prompt further cognitive screening, potentially aiding in earlier recognition of ADRD.

Ti3C2TxMXene/nitrogen-doped reduced graphene oxide composite: a high-performance electrochemical sensing platform for adrenaline detection.

Herein, Ti3C2TxMXene/N-doped reduced graphene oxide (MXene/N-rGO) composite was employed as the electrocatalyst to construct a new electrochemical sensing platform for the determination of adrenaline (AD). The MXene/N-rGO was synthesized via a facile one-step hydrothermal method, where ethylenediamine acted as a reducing agent and N source. The doped N in rGO served as a bridge between MXene and rGO through tight hydrogen bonds. Scanning electron microscopy showed that large numbers of MXenes with accordion-like morphology were distributed on the surface of the N-rGO. The MXene/N-rGO composite displayed a synergetic catalytic effect for oxidizing AD, originating from the unique catalytic activity of N-rGO and the large surface area and satisfactory conductivity of MXene. These characteristics of composite material led to a remarkable effect on signal amplification for the detection of AD, with a wide linear range from 10.0 nM to 90.0µM and a low detection limit of 3.0 nM based on a signal to noise ratio of 3. Moreover, the MXene/N-rGO electrode displayed good stability, repeatability, and reproducibility. Additionally, the proposed sensor was successfully applied for voltammetric sensing of AD in urine with recoveries from 97.75% to 103.0%.

Predicting the Risk of Acute Kidney Injury in Patients After Percutaneous Coronary Intervention (PCI) or Cardiopulmonary Bypass (CPB) Surgery: Development and Assessment of a Nomogram Prediction Model.

BACKGROUND We sought to create a model that incorporated ultrasound examinations to predict the risk of acute kidney injury (AKI) after percutaneous coronary intervention (PCI) or cardiopulmonary bypass (CPB) surgery. MATERIAL AND METHODS A total of 292 patients with AKI after PCI or CPB surgery were enrolled for the study. Afterwards, treatment-related information, including data pertaining to ultrasound examination, was collected. A random forest model and multivariate logistic regression analysis were then used to establish a predictive model for the risk of AKI. Finally, the predictive quality and clinical utility of the model were assessed using calibration plots, receiver-operating characteristic curve, C-index, and decision curve analysis. RESULTS Predictive factors were screened and the model was established with a C-index of 0.955 in the overall sample set. Additionally, an area under the curve of 0.967 was obtained in the training group. Moreover, decision curve analysis also revealed that the prediction model had good clinical applicability. CONCLUSIONS The prediction model was efficient in predicting the risk of AKI by incorporating ultrasound examinations and a number of factors. Such included operation methods, age, congestive heart failure, body mass index, heart rate, white blood cell count, platelet count, hemoglobin, uric acid, and peak intensity (kidney cortex as well as kidney medulla).

MXene/carbon nanohorns decorated with conductive molecularly imprinted poly(hydroxymethyl-3,4-ethylenedioxythiophene) for voltammetric detection of adrenaline.

A novel molecularly imprinted sensor was developed for the voltammetric determination of adrenaline (AD). MXene/carbon nanohorn (MXene/CNH) composite with good electric conductivity and enormous accessible active sites was firstly introduced as catalytic substrate. Subsequently, molecularly imprinted polymer (MIP) film was fabricated in mixed solutions containing hydroxymethyl-3,4-ethylenedioxythiophene (functional monomer) and AD (template) through electro-polymerization process. A molecularly imprinted sensor was formed after removing the template. The morphology and elemental composition of the prepared composites were studied by scanning electron microscopy and X-ray photoelectron spectroscopy. Cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS) were used to investigate the electrochemical performance of the molecularly imprinted sensors. Under optimized conditions, the designed sensor displays a wide linear range from 1.0 nM to 60.0 µM and a low limit of detection of 0.3 nM. The developed sensor also presents good selectivity, reproducibility and long-term stability, and satisfactory feasibility in practical sample analysis. MXene/carbon nanohorns decorated with conductive molecularly imprinted poly(hydroxymethyl-3,4-ethylenedioxythiophene) was proposed for highly sensitive and selective detection of adrenaline.

Preparation and Antibacterial Activity of Thermo-Responsive Nanohydrogels from Qiai Essential Oil and Pluronic F108.

Essential oils (EOs) have been used in cosmetics and food due to their antimicrobial and antiviral effects. However, the applications of EOs are compromised because of their poor aqueous solubility and high volatility. Qiai (Artemisia argyi Levl. et Van. var. argyi cv. Qiai) is a traditional Chinese herb and possesses strong antibacterial activity. Herein, we report an innovative formulation of EO as nanohydrogels, which were prepared through co-assembly of Qiai EO (QEO) and Pluronic F108 (PEG-b-PPG-b-PEG, or PF108) in aqueous solution. QEO was efficiently loaded in the PF108 micelles and formed nanohydrogels by heating the QEO/PF108 mixture solution to 37 °C, by the innate thermo-responsive property of PF108. The encapsulation efficiency and loading capacity of QEO reached 80.2% and 6.8%, respectively. QEO nanohydrogels were more stable than the free QEO with respect to volatilization. Sustained QEO release was achieved at body temperature using the QEO nanohydrogels, with the cumulative release rate reaching 95% in 35 h. In vitro antibacterial test indicated that the QEO nanohydrogels showed stronger antimicrobial activity against S. aureus and E. coli than the free QEO due to the enhanced stability and sustained-release characteristics. It has been attested that thermo-responsive QEO nanohydrogels have good potential as antibacterial cosmetics.

Activated hepatic stellate cells promote angiogenesis in hepatocellular carcinoma by secreting angiopoietin-1.

Angiogenesis is the central pathological process in hepatocellular carcinoma (HCC), and its progression is affected by tumor cells and the microenvironment. Activated hepatic stellate cells (aHSCs) are the most significant stromal cells involved in HCC. This study was aimed to explore the effects and mechanisms of aHSCs on angiogenesis in HCC. We isolated primary hepatoma cells, aHSCs, and hepatic vascular endothelial cells from human HCC samples. Then, we performed a novel in vitro assay and in vivo experiment in a nude mouse HCC model to investigate the functions of aHSCs on angiogenesis in HCC. Our results demonstrated that aHSCs are the primary sources of angiopoietin-1 (Ang-1) in human HCC in vitro, and aHSCs could promote hepatic vascular endothelial cell (HVEC) growth by secreting Ang-1. Furthermore, aHSCs could induce HVEC microtubule formation, and this ability was reduced when Ang-1 expression was silenced in aHSCs. In addition, CD34 expression in a nude mouse HCC model was downregulated when Ang-1 messenger RNA was silenced in aHSCs. Our data also indicated that HSC Ang-1 expression could be inhibited by overexpressing Raf kinase inhibitor protein. Therefore, we suggest that aHSCs promote angiogenesis through secreting Ang-1, potentially providing an interesting target for antiangiogenic therapies for HCC.

Cyclopamine Suppresses Human Esophageal Carcinoma Cell Growth by Inhibiting Glioma-Associated Oncogene Protein-1, a Marker of Human Esophageal Carcinoma Progression.

BACKGROUND Esophageal carcinoma is a common gastrointestinal tumor in humans. Cyclopamine, a Hedgehog (Hh)-pathway-specific inhibitor, is an effective chemotherapeutic drug for suppressing tumor cell differentiation, with unclear mechanisms. We investigated glioma-associated oncogene protein-1 (Gli-1) expression in human esophageal carcinoma tissue and the inhibition of cyclopamine on EC9706 esophageal carcinoma cell growth. MATERIAL AND METHODS Gli-1 in tumor tissue was measured by immunohistochemistry (IHC). EC9706 cells were treated with different concentrations of cyclopamine and incubated for different times. MTT method, flow cytometry, and Acridine orange/ethidium bromide (AO/EB) double-fluorescence staining were applied to detect cell proliferation and apoptosis. Western blot (WB) analysis was performed to assess Gli-1 expression. RESULTS Gli-1 was associated with patient age, gender, lymphatic metastasis, tumor recurrence, and stage, with significantly (P<0.05) positive correlations with age, lymphatic metastasis, tumor recurrence, and stage. At 12 h (F=214.57), 24 h (F=76.832), 48 h (F=236.90), and 72 h (F=164.55), the higher the concentration of cyclopamine, the higher the inhibition rate of suppressing EC9706 proliferation, and this effect was significant (P<0.05). The number of early-apoptosis cells increased as the concentration of cyclopamine increased. Morphology of EC9706 cells appeared as round with rough edges, karyopyknosis, and karyorrhexis. After 48 h, apoptosis rates of EC9706 cells treated with different concentrations of cyclopamine were (7.73±1.25)% at 2.5 µM, (13.37±1.42)% at 5.0 µM, (22.3±2.92)% at 10.0 µM, and (33.57±1.75)% at 20.0 µM, and the effect was dose-dependent. Gli-1 was obviously reduced after cyclopamine treatment and the effect was dose-dependent. CONCLUSIONS Gli-1 is highly expressed in human esophageal carcinoma, and could be a marker for use in assessing tumor stage and the deciding on treatment target.

A novel colorimetric immunosensor based on platinum colloid nanoparticles immobilized on PowerVision as signal probes and Fe3 O4 @ß-cyclodextrin as capture probes for ractopamine detection in pork.

BACKGROUND: A novel colorimetric immunosensor was developed for the simple, sensitive and selective detection of ractopamine (RAC) based on using ß-cyclodextrin-modified Fe3 O4 particles (Fe3 O4 @ß-CD) as capture probes and complex platinum colloid nanoparticles (PtNPs-PV) composed of platinum colloid nanoparticles (PtNPs) and polymerase chelate PowerVision (PV) as signal probes. RESULTS: PtNPs-PV double catalyzed the chromogenic substrate 3,3'-diaminobenzidine (DAB), which induced changes in the color of DAB and chromogenic absorbance. Incubation temperature, pH and incubation time were systematically optimized and, under optimum conditions, the measured absorbance values showed a linear relationship with the RAC concentrations in the range 0.03-8.1 ng mL-1 . The detection limit was 0.01 ng mL-1 . The sensor exhibited high sensitivity and specificity, as demonstrated by testing structurally similar organic compounds such as salbutamol, clenbuterol and dopamine. The practicality of the developed colorimetric immunosensor was supported by the successful detection of RAC in pork samples with recovery ranging from 94.00% to 106.00%. CONCLUSION: We designed a novel sandwich-type noncompetitive colorimetric immunoassay for the detection of trace levels of RAC in pork. The proposed method can also be used for the detection of toxins in food products via PtNPs-PV amplification. © 2018 Society of Chemical Industry.

LncRNA XIST functions as a molecular sponge of miR-194-5p to regulate MAPK1 expression in hepatocellular carcinoma cell.

Increasing evidence highlights the important role of XIST, a long non-coding RNA (lncRNA), in the regulation of multiple cancers. However, the underlying mechanism of XIST in human hepatocellular carcinoma (HCC) still remains to be explored. Herein, intended to investigate the functional role of XIST in HCC initiation and progression. We first detected that XIST was significantly upregulated in HCC tissues and associated with tumor size and vascular invasion. Gain- and loss-of-function of XIST further presented that XIST promoted the progression of HCC cells, including proliferation, migration, and invasion. Moreover, silencing of XIST could inhibit tumor growth in vivo. We also found that XIST could target miR-194-5p and thus decrease miR-194-5p expression. Besides that, restoring XIST could reverse the inhibitory effect of miR-194-5p on the proliferation and invasion of HCC cells. We further elucidated such rescue role might through derepressing MAPK1 expression, the target of miR-194-5p. In brief, the above results elucidate the important role of XIST in HCC tumorigenesis, suggesting that XIST might be a candidate prognostic biomarker and a novel therapeutic target for treating HCC.