Chronic Stress-Induced Elevation of Melanin-Concentrating Hormone in the Locus Coeruleus Inhibits Norepinephrine Production and Associated With Depression-Like Behaviors in Rats.

BACKGROUND: Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that projects throughout the central nervous system, including the noradrenergic locus coeruleus (LC). Our previous study suggested that MCH/MCH receptor 1 (MCHR1) in the LC may be involved in the regulation of depression. The present study investigated whether the role of MCH/MCHR1 in the LC in depression-like behaviors is associated with the regulation of norepinephrine. METHOD: Chronic unpredictable stress (CUS) and an acute intra-LC microinjection of MCH induced depression-like behaviors in rats. The MCHR1 antagonist SNAP-94847 was also microinjected in the LC in rats that were suffering CUS or treated with MCH. The sucrose preference, forced swim, and locomotor tests were used for behavioral evaluation. Immunofluorescence staining, enzyme-linked immunosorbent assay, western blot, and high-performance liquid chromatography with electrochemical detection were used to explore the mechanism of MCH/MCHR1 in the regulation of depression-like behaviors. RESULTS: CUS induced an abnormal elevation of MCH levels and downregulated MCHR1 in the LC, which was highly correlated with the formation of depression-like behaviors. SNAP-94847 exerted antidepressant effects in CUS-exposed rats by normalizing tyrosine hydroxylase, dopamine ß hydroxylase, and norepinephrine in the LC. An acute microinjection of MCH induced depression-like behaviors through its action on MCHR1. MCHR1 antagonism in the LC significantly reversed the MCH-induced downregulation of norepinephrine production by normalizing MCHR1-medicated cAMP-PKA signaling. CONCLUSIONS: Our study confirmed that the MCH/MCHR1 system in the LC may be involved in depression-like behaviors by downregulating norepinephrine production. These results improve our understanding of the pathogenesis of depression that is related to the MCH/MCHR1 system in the LC.

Separation mixed semen of two individuals using magnetic beads coupled ABH blood group antibody.

In sexual assault cases, one of the most common samples collected is a mixed semen stain, which is often found on the vagina, female underwear, or bed sheets. However, it is usually difficult to identify the perpetrator based on this sample alone. One technique that has been developed to address this issue is magnetic bead-based separation. This method involves using modified magnetic microspheres to capture and enrich specific target cells, in this case, sperm cells. In this study, we utilized magnetic beads coupled with ABH blood group antibody to isolate sperm cells from an individual of a single ABO blood type. Subsequently, polymerase chain reaction amplification and capillary electrophoresis were employed to perform the genotyping the short tandem repeat (STR) loci. This approach allows for the identification of different individuals in a mixed seminal stain sample from two individuals, by first separating sperm cells based on ABH antigen differences and subsequently utilizing autosomal STR typing on the enriched single blood group cells.

N(6)-methyladenosine-binding protein YTHDF1 suppresses EBV replication and promotes EBV RNA decay.

N6 -methyladenosine (m6 A) modification of mRNA mediates diverse cellular and viral functions. Infection with Epstein-Barr virus (EBV) is causally associated with nasopharyngeal carcinoma (NPC), 10% of gastric carcinoma, and various B-cell lymphomas, in which the viral latent and lytic phases both play vital roles. Here, we show that EBV transcripts exhibit differential m6 A modification in human NPC biopsies, patient-derived xenograft tissues, and cells at different EBV infection stages. m6 A-modified EBV transcripts are recognized and destabilized by the YTHDF1 protein, which leads to the m6 A-dependent suppression of EBV infection and replication. Mechanistically, YTHDF1 hastens viral RNA decapping and mediates RNA decay by recruiting RNA degradation complexes, including ZAP, DDX17, and DCP2, thereby post-transcriptionally downregulating the expression of EBV genes. Taken together, our results reveal the critical roles of m6 A modifications and their reader YTHDF1 in EBV replication. These findings contribute novel targets for the treatment of EBV-associated cancers.

Exploration of spatial confinement and ligand effects for the oxygen reduction reaction on Fe-Nx embedded hole-graphene.

In this work, we constructed theoretical models by embedding Fe-TCPP and Fe-(mIM)n (n = 2,3,4) active sites into hole-graphene, and the structural stability was evaluated using molecular dynamics simulations. Based on the theoretical models, we systematically studied the oxygen reduction reaction (ORR) mechanism and the effect of spatial confinement and ligands with DFT calculations. The analysis of the ORR reaction pathway shows that Fe-TCPP and Fe-(mIM)4 have good catalytic activity. Subsequently, the confinement effect (5-14 Å) was introduced to investigate its influence on the catalytic activity. The Fe-TCPP and Fe-(mIM)4 active sites have the lowest overpotential at an axial space of 8 Å and 9 Å, respectively. We select four ligands (bpy, pya, CH3, and bIm) to explore their effect on the catalytic activity of the Fe-TCPP active site. With the modification of bpy, pya, and bIm_N (Fe-N4 sites become Fe-N5 active sites), the overpotential decreases by 26-31%. In the present work, the best catalytic system is Fe-TCPP_pya, which is on the top of the volcano plot.

An evaluation of cervical maturity for Chinese women with labor induction by machine learning and ultrasound images.

BACKGROUND: To evaluate the improvement of evaluation accuracy of cervical maturity for Chinese women with labor induction by adding objective ultrasound data and machine learning models to the existing traditional Bishop method. METHODS: The machine learning model was trained and tested using 101 sets of data from pregnant women who were examined and had their delivery in Peking University Third Hospital in between December 2019 and January 2021. The inputs of the model included cervical length, Bishop score, angle, age, induced labor time, measurement time (MT), measurement time to induced labor time (MTILT), method of induced labor, and primiparity/multiparity. The output of the model is the predicted time from induced labor to labor. Our experiments analyzed the effectiveness of three machine learning models: XGBoost, CatBoost and RF(Random forest). we consider the root-mean-squared error (RMSE) and the mean absolute error (MAE) as the criterion to evaluate the accuracy of the model. Difference was compared using t-test on RMSE between the machine learning model and the traditional Bishop score. RESULTS: The mean absolute error of the prediction result of Bishop scoring method was 19.45 h, and the RMSE was 24.56 h. The prediction error of machine learning model was lower than the Bishop score method. Among the three machine learning models, the MAE of the model with the best prediction effect was 13.49 h and the RMSE was 16.98 h. After selection of feature the prediction accuracy of the XGBoost and RF was slightly improved. After feature selection and artificially removing the Bishop score, the prediction accuracy of the three models decreased slightly. The best model was XGBoost (p = 0.0017). The p-value of the other two models was < 0.01. CONCLUSION: In the evaluation of cervical maturity, the results of machine learning method are more objective and significantly accurate compared with the traditional Bishop scoring method. The machine learning method is a better predictor of cervical maturity than the traditional Bishop method.

Estrogen receptor-related receptor γ uppresses hypoxia-induced angiogenesis by regulating VEGFA in endometrial cancer.

OBJECTIVE: Estrogen receptor-related receptor γ (ERRγ), is implicated in cancer cell proliferation and metastasis. The function of ERRγ in tumor angiogenesis, however, is to be revealed. This study was designed to elaborate the regulatory effect of ERRγ on angiogenesis in endometrial cancer (EC). METHODS: Immunohistochemistry (IHC) was adopted to determine the protein expression of ERRγ, VEGFA, CD31 and hypoxia-inducible factor-1 (HIF-1) in tumor tissues. HEC-1A cells stably expressing ERRγ were established bytransfection, and then an endothelial cell tube formation assay was performed. CCK-8 assay was employed for cell viability, and wound healing assay for cell migration ability. Besides, western blot, ELISA and qRT-PCR were used to examine the VEGFA expression. After hypoxia treatment of ERRγ overexpressing HEC-1A cells, the ERRγ expression and VEGFA expression were determined by western blot. Finally, EC xenografts in nude mice were constructed by subcutaneous injection of ERRγ stably expressing HEC-1A cells and control HEC-1A cells. RESULTS: IHC results revealed a negative correlation between the expression of ERRγ and VEGFA in EC tissues. ERRγ overexpression significantly decreased the level of HIF-1 in tumor tissue of nude mice. ERRγ overexpression down-regulated inhibited angiogenesis capability and inhibited the proliferation and migration of HEC-1A cells. Furthermore, ERRγ expression was suppressed under the condition of hypoxia while restoration of ERRγ partially inhibited hypoxia-induced VEGFA expression in HEC-1A cells. CONCLUSIONS: ERRγ is an angiogenesis suppressor and involved in hypoxia-induced VEGFA expression in EC. Hence, ERRγ might be a promising antiangiogenic target for human EC.

Natural product 1,2,3,4,6-penta-O-galloyl-ß-D-glucopyranose is a reversible inhibitor of glyceraldehyde 3-phosphate dehydrogenase.

Aerobic glycolysis, also known as the Warburg effect, is a hallmark of cancer cell glucose metabolism and plays a crucial role in the activation of various types of immune cells. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) catalyzes the conversion of D-glyceraldehyde 3-phosphate to D-glycerate 1,3-bisphosphate in the 6th critical step in glycolysis. GAPDH exerts metabolic flux control during aerobic glycolysis and therefore is an attractive therapeutic target for cancer and autoimmune diseases. Recently, GAPDH inhibitors were reported to function through common suicide inactivation by covalent binding to the cysteine catalytic residue of GAPDH. Herein, by developing a high-throughput enzymatic screening assay, we discovered that the natural product 1,2,3,4,6-penta-O-galloyl-ß-D-glucopyranose (PGG) is an inhibitor of GAPDH with Ki = 0.5 µM. PGG blocks GAPDH activity by a reversible and NAD+ and Pi competitive mechanism, suggesting that it represents a novel class of GAPDH inhibitors. In-depth hydrogen deuterium exchange mass spectrometry (HDX-MS) analysis revealed that PGG binds to a region that disrupts NAD+ and inorganic phosphate binding, resulting in a distal conformational change at the GAPDH tetramer interface. In addition, structural modeling analysis indicated that PGG probably reversibly binds to the center pocket of GAPDH. Moreover, PGG inhibits LPS-stimulated macrophage activation by specific downregulation of GAPDH-dependent glucose consumption and lactate production. In summary, PGG represents a novel class of GAPDH inhibitors that probably reversibly binds to the center pocket of GAPDH. Our study sheds new light on factors for designing a more potent and specific inhibitor of GAPDH for future therapeutic applications.

mTOR regulates cocaine-induced behavioural sensitization through the SynDIG1-GluA2 interaction in the nucleus accumbens.

Behavioral sensitization is a progressive increase in locomotor or stereotypic behaviours in response to drugs. It is believed to contribute to the reinforcing properties of drugs and to play an important role in relapse after cessation of drug abuse. However, the mechanism underlying this behaviour remains poorly understood. In this study, we showed that mTOR signaling was activated during the expression of behavioral sensitization to cocaine and that intraperitoneal or intra-nucleus accumbens (NAc) treatment with rapamycin, a specific mTOR inhibitor, attenuated cocaine-induced behavioural sensitization. Cocaine significantly modified brain lipid profiles in the NAc of cocaine-sensitized mice and markedly elevated the levels of phosphatidylinositol-4-monophosphates (PIPs), including PIP, PIP2, and PIP3. The behavioural effect of cocaine was attenuated by intra-NAc administration of LY294002, an AKT-specific inhibitor, suggesting that PIPs may contribute to mTOR activation in response to cocaine. An RNA-sequencing analysis of the downstream effectors of mTOR signalling revealed that cocaine significantly decreased the expression of SynDIG1, a known substrate of mTOR signalling, and decreased the surface expression of GluA2. In contrast, AAV-mediated SynDIG1 overexpression in NAc attenuated intracellular GluA2 internalization by promoting the SynDIG1-GluA2 interaction, thus maintaining GluA2 surface expression and repressing cocaine-induced behaviours. In conclusion, NAc SynDIG1 may play a negative regulatory role in cocaine-induced behavioural sensitization by regulating synaptic surface expression of GluA2.

A novel model of controlling PD-L1 expression in ALK+ anaplastic large cell lymphoma revealed by CRISPR screening.

The success of programmed cell death protein 1 (PD-1)/PD-L1-based immunotherapy highlights the critical role played by PD-L1 in cancer progression and reveals an urgent need to develop new approaches to attenuate PD-L1 function by gaining insight into how its expression is controlled. Anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALK+ ALCL) expresses a high level of PD-L1 as a result of the constitutive activation of multiple oncogenic signaling pathways downstream of ALK activity, making it an excellent model in which to define the signaling processes responsible for PD-L1 upregulation in tumor cells. Here, using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 library screening, we sought a comprehensive understanding of the molecular effectors required for PD-L1 regulation in ALK+ ALCL. Indeed, we determined that PD-L1 induction is dependent on the nucleophosmin-ALK oncoprotein activation of STAT3, as well as a signalosome containing GRB2/SOS1, which activates the MEK-ERK and PI3K-AKT signaling pathways. These signaling networks, through STAT3 and the GRB2/SOS1, ultimately induce PD-L1 expression through the action of transcription factors IRF4 and BATF3 on the enhancer region of the PD-L1 gene. IRF4 and BATF3 are essential for PD-L1 upregulation, and IRF4 expression is correlated with PD-L1 levels in primary ALK+ ALCL tissues. Targeting this oncogenic signaling pathway in ALK+ ALCL largely inhibited the ability of PD-L1-mediated tumor immune escape when cocultured with PD-1-positive T cells and natural killer cells. Thus, our identification of this previously unrecognized regulatory hub not only accelerates our understanding of the molecular circuitry that drives tumor immune escape but also provides novel opportunities to improve immunotherapeutic intervention strategies.

Role of calcitonin gene-related peptide in pain regulation in the parabrachial nucleus of naive rats and rats with neuropathic pain.

Researches have shown that calcitonin gene-related peptide (CGRP) plays a pivotal role in pain modulation. Nociceptive information from the periphery is relayed from parabrachial nucleus (PBN) to brain regions implicated involved in pain. This study investigated the effects and mechanisms of CGRP and CGRP receptors in pain regulation in the PBN of naive and neuropathic pain rats. Chronic sciatic nerve ligation was used to model neuropathic pain, CGRP and CGRP 8-37 were injected into the PBN of the rats, and calcitonin receptor-like receptor (CLR), a main structure of CGRP receptor, was knocked down by lentivirus-coated CLR siRNA. The hot plate test (HPT) and the Randall Selitto Test (RST) was used to determine the latency of the rat hindpaw response. The expression of CLR was detected with RT-PCR and western blotting. We found that intra-PBN injecting of CGRP induced an obvious anti-nociceptive effect in naive and neuropathic pain rats in a dose-dependent manner, the CGRP-induced antinociception was significantly reduced after injection of CGRP 8-37, Moreover, the mRNA and protein levels of CLR, in PBN decreased significantly and the antinociception CGRP-induced was also significantly lower in neuropathic pain rats than that in naive rats. Knockdown CLR in PBN decreased the expression of CLR and the antinociception induced by CGRP was observably decreased. Our results demonstrate that CGRP induced antinociception in PBN of naive or neuropathic pain rats, CGRP receptor mediates this effect. Neuropathic pain induced decreases in the expression of CGRP receptor, as well as in CGRP-induced antinociception in PBN.

Combined DFT and kinetic Monte Carlo study of a bridging-spillover mechanism on fluorine-decorated graphene.

In this work, combining first-principles calculations with kinetic Monte Carlo (KMC) simulations, we constructed an irregular carbon bridge on the graphene surface and explored the process of H migration from the Pt catalyst to carbon bridge, and further migration to the graphene surface. The calculated reaction diagrams show that the hydrogen atoms can easily migrate from the Pt cluster to the carbon bridge with a low barrier of 0.22-0.86 eV, and KMC simulations indicate that the migration reactions can take place at intermediate temperatures (91.9-329.5 K). Our research clarified the role of the carbon bridge: (1) the close combination of Pt clusters and carbon bridges reduces H2 adsorption enthalpy, which facilitates the spillover of H atoms from the Pt cluster to the carbon bridges and (2) the unsaturated carbon atoms on the carbon bridges have radical character and tend to bind radical H atoms. The subsequent study shows that the F atoms decorated on graphene can greatly reduce the migration barrier of H atoms from the carbon bridge to graphene. With F atoms decorated, the carbon atoms are in an electron-deficient state, which have a strong ability to bind the hydrogen atoms, and it promotes the migration of H atoms to the graphene surface. The migration barrier and reaction temperature are reduced to 0.72 eV and 279 K, respectively.

Revealing Crystallization-Induced Blue-Shift Emission of a Di-Boron Complex by Enhanced Photoluminescence and Electrochemiluminescence.

Elucidating the effects of crystallization-induced blue-shift emission of a newly synthesized di-boron complex (DBC) by enhanced photoluminescence (PL) and electrochemiluminescence (ECL) in the annihilation pathway was realized for the first time. The 57 nm blue-shift and great enhancement in the crystalline lattice relative to the DBC solution were attributed to the restriction of intramolecular rotation (RIR) and confirmed by PL imaging, X-ray diffraction, as well as DFT calculations. It was discovered that ECL at crystalline film/solution interfaces can be further enhanced by means of both co-reactant route and RIR. The RIR contributions with co-reactant increased ECL up to 5 times more. Very interestingly, the co-reactant system was found to give off a red-shifted light emission. Mechanistic studies reveal that a difference between location of the ECL in the co-reactant route and that in the annihilation pathway leads to an alternative emission wavelength.

Targeting of SPP1 by microRNA-340 inhibits gastric cancer cell epithelial-mesenchymal transition through inhibition of the PI3K/AKT signaling pathway.

Gastric cancer (GC) is a common heterogeneous disease. The critical roles of microRNA-340 (miR-340) in the development and progression of GC were emphasized in accumulating studies. This study aims to examine the regulatory mechanism of miR-340 in GC cellular processes. Initially, microarray technology was used to identify differentially expressed genes and regulatory miRs in GC. After that, the potential role of miR-340 in GC was determined via ectopic expression, depletion, and reporter assay experiments. Expression of secreted phosphoprotein 1 (SPP1), miR-340, phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway, and epithelial-mesenchymal transition (EMT)-related genes was measured. Moreover, to further explore the function of miR-340 in vivo and in vitro, proliferation, apoptosis, migration, invasion, and tumorigenic capacity were evaluated. SPP1 was a target gene of miR-340 which could then mediate the PI3K/AKT signaling pathway by targeting SPP1 in GC. Furthermore, miR-340 levels were reduced and SPP1 was enriched in GC tissues and cells, with the PI3K/AKT signaling pathway being activated. Inhibitory effects of upregulated miR-340 on SPP1 and the PI3K/AKT signaling pathway were confirmed in vivo and in vitro. Overexpression of miR-340 or the silencing of SPP1 inhibited GC cell proliferation, invasion, migration, and EMT process, but promoted apoptosis of GC cells. Typically, targeting of SPP1 by miR-340 may contribute to the inhibition of proliferation, migration, invasion, and EMT of GC cells via suppression of PI3K/AKT signaling pathway.

Phthalideisoquinoline Hemiacetal Alkaloids from Corydalis decumbens That Inhibit Spontaneous Calcium Oscillations, Including Alkyl Derivatives of (+)-Egenine That Are Strikingly Levorotatory.

The new phthalideisoquinoline hemiacetal alkaloids (2-7) and the known analogues (1 and 8) were isolated from the bulbs of Corydalis decumbens. The new compounds were characterized by analysis of their NMR spectroscopic data, chemical degradation syntheses, X-ray crystallography, and comparison of experimental and calculated ECD data. All the isolates were screened in vitro for inhibitory activity of spontaneous calcium oscillations in primary cultured neocortical neurons. Compounds 1-3 and 5-7 were found to be active in the suppression of spontaneous calcium oscillations with IC50 values of 6.8, 5.6, 11.6, 10.2, 8.3, and 3.1 µM, respectively. It was also observed that the presence of hydroxy, methoxy, and ethoxy groups at the remote stereogenic center C-7' of some isolated phthalideisoquinoline hemiacetal alkaloids could alter the preferred conformation and invert the sign of optical rotation, rather than this resulting from configurational isomerism at C-1 or C-9, and that the 3J1,9 coupling constants of these analogues varied accordingly. For example, compounds 1 and 6 are levorotatory, despite these molecules having the same carbon skeleton and absolute configuration as (+)-egenine. This emphasizes the potential risk of incorrectly assigning absolute configuration based only on observed coupling constants or optical rotation when comparing the data of new compounds with literature values for known analogues, especially within this class of molecules.

NLRP3 inflammasome pathway is involved in olfactory bulb pathological alteration induced by MPTP.

Olfactory bulb, as one of sensory organs opening to the outside, is susceptible to toxic environment and easy to deteriorate. Recent studies in Parkinson's disease (PD) patients and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys have shown that abnormal α-synuclein is accumulated in the olfactory glomeruli, suggesting that the lesions of PD are not only confined to the substantia nigra (SN) but also located in the olfactory bulb. Thus, olfactory bulb might be the region of onset in PD pathogenesis and a targeted region for diagnosis and treatment of PD. However, the relationship between olfactory bulb and pathogenesis of PD remains unclear. In the present study, we investigated the inflammatory pathological alterations in olfactory bulb and the underlying mechanisms in chronic MPTP mice. Mice were treated with MPTP/P, i.e., MPTP (25 mg/kg, s.c.) plus probenecid (250 mg/kg, i.p.) every 4 days, for ten times. The mice displayed typical parkinsonian syndrome. Then we examined their olfactory function and the pathologic changes in olfactory bulb. The mice showed obvious olfactory dysfunction in a buried pellet test. Immunohistochemical studies revealed that tyrosine hydroxylase (TH) protein levels were significantly decreased, whereas abnormal α-synuclein was significantly increased in the olfactory bulbs. Furthermore, the olfactory bulbs in MPTP/P-treated mice showed significantly increased levels of interleukin-1ß (IL-1ß), caspase-1, glial fibrillary acidic protein (GFAP), Toll receptor 4 (TLR4), phosphorylation of p65, as well as activated molecules of NOD-like receptor protein 3 (NLRP3) that were associated with neuroinflammation. Our results demonstrate that MPTP/P-caused olfactory bulb damage might be related to NLRP3-mediated inflammation.

Overexpression of dedicator of cytokinesis 2 correlates with good prognosis in colorectal cancer associated with more prominent CD8+ lymphocytes infiltration: a colorectal cancer analysis.

Recently, dedicator of cytokinesis 2 (DOCK2) has been reportedly exhibited high mutation prevalence in the Asian colorectal cancer (CRC) cohort. However, the expression pattern of DOCK2 and its clinical significance in CRC were still unknown. To characterize the role of DOCK2, a tissue microarray (TMA) containing 481 archived paraffin-embedded CRC specimens was performed by immunohistochemistry. Among which, 54 primary CRC tissues showed high expression of DOCK2 protein, while others were negative. Moreover, DOCK2 expression was positively associated with invasion depth (P < .001) and tumor size (P = .016). Significantly, Kaplan-Meier survival analysis revealed that patients with higher DOCK2 expression had a longer overall survival time (P = .017). Furthermore, univariate and multivariate Cox regression analysis confirmed that DOCK2 is an independent prognostic marker in CRC (P = .049,; HR, 0.519; 95% CI, 0.270 to 0.997). In addition, we observed a strong correlation between the infiltration of CD8+ T lymphocytes and DOCK2 expression (P = .0119). Our findings demonstrated that overexpressed DOCK2 might involve in recruiting CD8+ T lymphocytes and serve as a novel prognostic indicator and indicated a potential therapeutic strategy by restoring DOCK2 for CRC.

The Effects of miR-195-5p/MMP14 on Proliferation and Invasion of Cervical Carcinoma Cells Through TNF Signaling Pathway Based on Bioinformatics Analysis of Microarray Profiling.

BACKGROUND/AIMS: This study is aimed at identification of miR-195-5p/MMP14 expression in cervical cancer (CC) and their roles on cell proliferation and invasion profile of CC cells through TNF signaling pathway in CC. METHODS: Microarray analysis, gene set enrichment analysis (GSEA) and DAVID were used to analyze differentially expressed miRNAs, mRNAs and signaling pathways. MiR-195-5p and MMP14 expression levels in CC cell were determined by qRT-PCR. Western blot was employed to measure MMP14 and TNF signaling pathway-relating protein level. Luciferase reporter system was used to confirm the targeting relationship between MMP14 and miR-195-5p. Cell proliferation and invasion was respectively deeded by CCK8, transwell. In vivo experiment was carried out to study the impact of MMP14 and miR-195-5p on CC development in mice. RESULTS: The microarray analysis and the results of qRT-PCR determined that miR-195-5p was under-expressed and MMP14 was over-expressed in CC cells. GSEA and DAVID analysis showed that TNF signaling pathway was regulated by miR-195-5p/MMP14 and activated in cervical carcinoma cells. The miR-195-5p and MMP14 have a negative regulation relation. In vivo experiment found that down-regulated MMP14 and up-regulated miR-195-5p suppressed the tumor development. CONCLUSION: Our results suggest that MMP14 is a direct target of miR-195-5p, and down-regulated MMP14 and up-regulated miR-195-5p suppressed proliferation and invasion of CC cells by inhibiting TNF signaling pathway.

Readily functionalized AAA-DDD triply hydrogen-bonded motifs.

Herein we present a new, readily functionalized AAA-DDD hydrogen bond array. A novel AAA monomeric unit (3a-b) was obtained from a two-step synthetic procedure starting with 2-aminonicotinaldehyde via microwave radiation (overall yield of 52-66%). 1H NMR and fluorescence spectroscopy confirmed the complexation event with a calculated association constant of 1.57 × 107 M-1. Likewise, the usefulness of this triple hydrogen bond motif in supramolecular polymerization was demonstrated through viscosity measurements in a crosslinked supramolecular alternating copolymer.

Supramolecular Polymers Based on Non-Coplanar AAA-DDD Hydrogen-Bonded Complexes.

Non-coplanar triple-hydrogen-bond arrays are connected as telechelic groups to alkyl chains and their properties as AA/BB type supramolecular polymers are examined. Viscosity studies at three temperatures are used to study the ring-chain equilibrium and determine the critical concentrations where polymer chains are formed. It is observed that neither the temperature range studied nor the alkyl chain length of one component significantly affect the polymerization properties in this system.

Nonmuscle myosin heavy chain IIA mediates Epstein-Barr virus infection of nasopharyngeal epithelial cells.

EBV causes B lymphomas and undifferentiated nasopharyngeal carcinoma (NPC). Although the mechanisms by which EBV infects B lymphocytes have been extensively studied, investigation of the mechanisms by which EBV infects nasopharyngeal epithelial cells (NPECs) has only recently been enabled by the successful growth of B lymphoma Mo-MLV insertion region 1 homolog (BMI1)-immortalized NPECs in vitro and the discovery that neuropilin 1 expression positively affects EBV glycoprotein B (gB)-mediated infection and tyrosine kinase activations in enhancing EBV infection of BMI1-immortalized NPECs. We have now found that even though EBV infected NPECs grown as a monolayer at extremely low efficiency (<3%), close to 30% of NPECs grown as sphere-like cells (SLCs) were infected by EBV. We also identified nonmuscle myosin heavy chain IIA (NMHC-IIA) as another NPEC protein important for efficient EBV infection. EBV gH/gL specifically interacted with NMHC-IIA both in vitro and in vivo. NMHC-IIA densely aggregated on the surface of NPEC SLCs and colocalized with EBV. EBV infection of NPEC SLCs was significantly reduced by NMHC-IIA siRNA knock-down. NMHC-IIA antisera also efficiently blocked EBV infection. These data indicate that NMHC-IIA is an important factor for EBV NPEC infection.