Kinds Of Inhibitors Research Articles

Optimization and evaluation of corrosion inhibitors for N80 steel in sulfamic acid solutions

Sulfamic acid (SA) has a low acid-rock reaction rate and can be used for deep high-temperature acidizing. However, the inhibition effect of existing corrosion inhibitors at deep high temperatures is greatly reduced. Through experiments, it is found that corrosion inhibitors such as imidazoline (OAI), cinnamaldehyde (CA), C14 quaternary ammonium salt (C14-GN), and potassium iodide (KI) have good corrosion inhibition effect, the average corrosion inhibition rate can reach 99 %, and the corrosion rate is less than 2 g/m2 h. The experimental results show that the film formation of a single inhibitor is uneven and the pitting corrosion is serious. In contrast, the mixed-use of many kinds of inhibitors can effectively inhibit the pitting corrosion, and the corrosion rate is less than 1.6 g/m2 h. And it can effectively inhibit pitting corrosion. At 363 K, the corrosion inhibition rate is 99.9 % and the corrosion rate is 1.1 g/m2·h. Through the orthogonal test, it is concluded that the best inhibitor ratio is OAI: CA: C14-GN: KI = 3:3:3:2. The optimized inhibitor has the best synergistic effect, can play an important role at high temperature, make the film uniform and dense, and improve the corrosion inhibition effect of the solution of sulfamic acid with the investigated inhibitor.

Positive feedback regulation between glycolysis and histone lactylation drives oncogenesis in pancreatic ductal adenocarcinoma

BackgroundMetabolic reprogramming and epigenetic alterations contribute to the aggressiveness of pancreatic ductal adenocarcinoma (PDAC). Lactate-dependent histone modification is a new type of histone mark, which links glycolysis metabolite to the epigenetic process of lactylation. However, the role of histone lactylation in PDAC remains unclear.MethodsThe level of histone lactylation in PDAC was identified by western blot and immunohistochemistry, and its relationship with the overall survival was evaluated using a Kaplan-Meier survival plot. The participation of histone lactylation in the growth and progression of PDAC was confirmed through inhibition of histone lactylation by glycolysis inhibitors or lactate dehydrogenase A (LDHA) knockdown both in vitro and in vivo. The potential writers and erasers of histone lactylation in PDAC were identified by western blot and functional experiments. The potential target genes of H3K18 lactylation (H3K18la) were screened by CUT&Tag and RNA-seq analyses. The candidate target genes TTK protein kinase (TTK) and BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) were validated through ChIP-qPCR, RT-qPCR and western blot analyses. Next, the effects of these two genes in PDAC were confirmed by knockdown or overexpression. The interaction between TTK and LDHA was identified by Co-IP assay.ResultsHistone lactylation, especially H3K18la level was elevated in PDAC, and the high level of H3K18la was associated with poor prognosis. The suppression of glycolytic activity by different kinds of inhibitors or LDHA knockdown contributed to the anti-tumor effects of PDAC in vitro and in vivo. E1A binding protein p300 (P300) and histone deacetylase 2 were the potential writer and eraser of histone lactylation in PDAC cells, respectively. H3K18la was enriched at the promoters and activated the transcription of mitotic checkpoint regulators TTK and BUB1B. Interestingly, TTK and BUB1B could elevate the expression of P300 which in turn increased glycolysis. Moreover, TTK phosphorylated LDHA at tyrosine 239 (Y239) and activated LDHA, and subsequently upregulated lactate and H3K18la levels.ConclusionsThe glycolysis-H3K18la-TTK/BUB1B positive feedback loop exacerbates dysfunction in PDAC. These findings delivered a new exploration and significant inter-relationship between lactate metabolic reprogramming and epigenetic regulation, which might pave the way toward novel lactylation treatment strategies in PDAC therapy.

Recent Advances in Enzyme Inhibition: A Pharmacological Review

Abstract: Enzyme inhibition is a crucial mechanism for regulating biological processes and developing therapeutic interventions. This pharmacological review summarizes recent advances in enzyme inhibition, focusing on key developments and their implications for drug discovery and therapeutic strategies. It explains basic ideas, including the different kinds of inhibitors and how they work, and looks at recent advances in small-molecule inhibitor design, fragment-based drug discovery, and virtual screening techniques. The review also highlights the advances in targeting specific enzyme families, explaining the structural basis of enzyme-inhibitor interactions, optimizing inhibitor potency, selectivity, and pharmacokinetic properties, and new trends in enzyme inhibition. The clinical implications of recent advances in enzyme inhibition include the development of novel therapeutic agents for diseases like cancer, infectious diseases, and neurological disorders. The review addresses challenges and future directions in the field, such as optimizing drug safety, resistance mechanisms, and personalized medicine approaches. Overall, the insights provided in this review may inspire further research and collaborations to accelerate the translation of enzyme inhibitors into effective clinical treatments.

Identification of emulsification proteins released from the cells by inhibiting the synthesis of GPI-anchor or β-1,3-glucan in Candida albicans

IntroductionA previous study demonstrated a strong emulsification ability of the culture supernatant obtained by cultivation of Candida albicans in a medium containing a β-1,3-glucan synthesis inhibitor and proposed a novel screening method using emulsification as an indicator for β-1,3-glucan synthesis inhibition (Nerome et al., 2021. Evaluating β-1,3-glucan synthesis inhibition using emulsion formation as an indicator. J Microbiol Methods. 190:106327). The emulsification was presumed to be caused by the proteins released from the cells; however, which proteins have a strong emulsification ability was unclear. Furthermore, as many cell wall proteins are connected to β-1,3-glucan via the carbohydrate moiety of the glycosylphosphatidylinositol (GPI)-anchor, which remains when detached from the cell membrane, emulsification might be detected by inhibiting GPI-anchor synthesis. ObjectiveThis study aimed to confirm whether emulsification could be detected by inhibiting GPI-anchor synthesis and identifying emulsification proteins released by inhibiting the synthesis of GPI-anchor or β-1,3-glucan. MethodsC. albicans was cultured in a medium containing a GPI-anchor synthesis inhibitor, and the emulsification by the culture supernatant was evaluated. We identified cell wall proteins released from the cells upon inhibition of β-1,3-glucan or GPI-anchor synthesis by mass spectrometry, their recombinant proteins were prepared, and their emulsification efficacy was evaluated. ResultsIn GPI-anchor synthesis inhibition, a weak emulsification phenomenon was observed compared to the β-1,3-glucan synthesis inhibition. Phr2 protein was released from the cells upon GPI-anchor synthesis inhibition, and recombinant Phr2 showed a strong emulsification activity. Phr2 and Fba1 proteins were released upon β-1,3-glucan synthesis inhibition, and recombinant Fba1 showed a strong emulsification activity. ConclusionsWe concluded that the emulsion phenomenon could be used to screen β-1,3-glucan and GPI-anchor synthesis inhibitors. Also, the two kinds of inhibitors could be distinguished by differences in the growth recovery by osmotic support and strength of emulsification. In addition, we identified the proteins involved in emulsification.

Research on chemical resistance characteristics of water-immersed coal with different metamorphic degrees

In order to reduce the risk of spontaneous combustion of coal left after long-term flooding in the goaf of the mine, in this paper, the inhibitory properties of different inhibitors on two kinds of water-immersed coals with different metamorphic degrees were studied in depth. The experiment selected Pingzhuang brown coal and Shaqu coking coal as research objects. The raw coal and water-immersed coal samples were compared and analyzed by thermogravimetric experiment method and Fourier transform infrared spectroscopy experiment method. The study showed that the activation temperature of brown coal and coking coal decreased by 7.91 and 2.25 °C respectively, and the activation energy decreased by 43.18 kJ/mol and 20.58 kJ/mol respectively. The natural tendency of coal was enhanced after water immersion, and water immersion had a greater impact on low-metamorphic brown coal. After adding four kinds of inhibitors, MgCl2, TEMPO, TPPI and PA to the two water-immersed coals, it was found that TPPI could significantly reduce the heat release rate of water-immersed brown coal, and the reduction value was 10.49 W/mg. The dry cracking temperature of water-immersed brown coal increased by 11.75 °C, and PA greatly increased the combustion activation energy of water-immersed coking coal by 25.77 kJ/mol. Meanwhile, it was found from the microscopic active groups that TTPI increased the content of water-immersed brown coal ether bonds by 4.84%. The absorption peak intensity of oxygen-containing functional groups such as C=O was significantly weakened. Similarly, PA also produced a large number of stable ethers in water-immersed coking coal, whose content increased by 5.21%, and the hydroxyl content decreased most significantly. The decomposition of TPPI into phosphoric acid after heating can inhibit the growth of active groups such as a large number of oxygen-containing functional groups in the water-immersed brown coal, thereby reducing the risk of spontaneous combustion. As a metal chelator, PA can reduce the catalytic effect of metal ions in water-immersed coking coal with fewer active groups, and inhibit coal spontaneous combustion by generating stable metal complexes to increase activation energy. This indicated that TTPI had the best inhibitory effect on water-immersed brown coal, while PA was more suitable for water-immersed coking coal.

Simazine Enhances Dark Fermentative H2 Production by Unicellular Halotolerant Cyanobacterium Aphanothece halophytica.

The halotolerant cyanobacterium Aphanothece halophytica is a potential H2 producer that induces H2 evolution under nitrogen deprivation. H2 is mainly produced via the catabolism of stored glycogen under dark anaerobic condition. H2 evolution is catalyzed by O2-sensitive bidirectional hydrogenase. The aim of this study was to improve H2 production by A. halophytica using various kinds of inhibitors. Among all types of inhibitors, simazine efficiently promoted the highest H2 production under dark conditions. High simazine concentration and long-term incubation resulted in a decrease in cell and chlorophyll concentrations. The optimal simazine concentration for H2 production by A. halophytica was 25 µM. Simazine inhibited photosynthetic O2 evolution but promoted dark respiration, resulting in a decrease in O2 level. Hence, the bidirectional hydrogenase activity and H2 production was increased. A. halophytica showed the highest H2 production rate at 58.88 ± 0.22 µmol H2 g−1 dry weight h−1 and H2 accumulation at 356.21 ± 6.04 μmol H2 g−1 dry weight after treatment with 25 µM simazine under dark anaerobic condition for 2 and 24 h, respectively. This study demonstrates the potential of simazine for the enhancement of dark fermentative H2 production by A. halophytica.

A Quantitative Assay for Ca2+ Uptake through Normal and Pathological Hemichannels.

Connexin (Cx) hemichannels (HCs) are large pore hexameric structures that allow the exchange of ions, metabolites and a variety of other molecules between the cell cytoplasm and extracellular milieu. HC inhibitors are attracting growing interest as drug candidates because deregulated fluxes through HCs have been implicated in a plethora of genetic conditions and other diseases. HC activity has been mainly investigated by electrophysiological methods and/or using HC-permeable dye uptake measurements. Here, we present an all-optical assay based on fluorometric measurements of ionized calcium (Ca2+) uptake with a Ca2+-selective genetically encoded indicator (GCaMP6s) that permits the optical tracking of cytosolic Ca2+ concentration ([Ca2+]cyt) changes with high sensitivity. We exemplify use of the assay in stable pools of HaCaT cells overexpressing human Cx26, Cx46, or the pathological mutant Cx26G45E, under control of a tetracycline (Tet) responsive element (TRE) promoter (Tet-on). We demonstrate the usefulness of the assay for the characterization of new monoclonal antibodies (mAbs) targeting the extracellular domain of the HCs. Although we developed the assay on a spinning disk confocal fluorescence microscope, the same methodology can be extended seamlessly to high-throughput high-content platforms to screen other kinds of inhibitors and/or to probe HCs expressed in primary cells and microtissues.

Abstract 357: Characterization of KRas pathway inhibitors in 2D and 3D screening formats

Abstract The KRas/Raf/MEK signalling axis has been identified to play a critical role in the formation of cancer, resulting in several investigational new drugs targeting this pathway. Identification of appropriate drugs is hampered, however, by the assumption that a three-dimensional setting may be required to observe significant inhibitory effects, possibly due to alternate gene expression and protein activity in such a “closer-to-physiology” setting. In order to explore that topic, in the current study we have made use of our 140 cell lines (CL)-2D proliferation panel (3 days incubation) and our 100CL-3D soft agar panel (> 7 days incubation). On these platforms, we have compared inhibitors targeting the KRas/Raf/MEK pathway via either KRas:SOS interaction (e.g. BI3406), the KRas mutation at G12C (e.g. AMG510), or Raf-kinase (e.g. AZ628) and MEK1/2-kinase activity (e.g. AZD6244). It showed that especially the Raf- and MEK kinase inhibitors exhibited significantly enhanced potency in the 3D soft agar setting in the majority of the cell lines tested. The other inhibitors also showed an increased potency under soft agar conditions, however, on clearly fewer cell lines and usually not as strongly. For all kinds of inhibitors tested, the most significant changes in potency were associated with enhanced efficacy as observed by stronger cell death induction. Differences may be attributable to three-dimensional growth, but also to the elongated duration of the soft agar assay. For selected conditions, we addressed this topic by analyzing the inhibitor impact on 3D spheroid growth after shorter incubation times. Our results show that 3D growth analysis either in the soft agar or spheroid setting clearly supports the development of KRas/Raf/MEK pathway inhibitors. Citation Format: Katharina Schaich, Daniel Feger, Oliver Siedentopf, Sarah Ulrich, Jan Erik Ehlert. Characterization of KRas pathway inhibitors in 2D and 3D screening formats [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 357.

Design, synthesis, and mechanism study of dimerized phenylalanine derivatives as novel HIV-1 capsid inhibitors

HIV-1 capsid (CA) plays indispensable and multiple roles in the life cycle of HIV-1, become an attractive target in antiviral therapy. Herein, we report the design, synthesis, and mechanism study of a novel series of dimerized phenylalanine derivatives as HIV-1 capsid inhibitors using 2-piperazineone or 2,5-piperazinedione as a linker. The structure-activity relationship (SAR) indicated that dimerized phenylalanines were more potent than monomers of the same chemotype. Further, the inclusion of fluorine substituted phenylalanine and methoxyl substituted aniline was found to be beneficial for antiviral activity. From the synthesized series, Q-c4 was found to be the most potent compound with an EC50 value of 0.57 μM, comparable to PF74. Interestingly, Q-c4 demonstrated a slightly higher affinity to the CA monomer than the CA hexamer, commensurate with its more significant effect in the late-stage of the HIV-1 lifecycle. Competitive SPR experiments with peptides from CPSF6 and NUP153 revealed that Q-c4 binds to the interprotomer pocket of hexameric CA as designed. Single-round infection assays showed that Q-c4 interferes with the HIV-1 life cycle in a dual-stage manner, affecting both pre-and post-integration. Stability assays in human plasma and human liver microsomes indicated that although Q-c4 has improved stability over PF74, this kind of inhibitor still requires further optimization. And the results of the online molinspiration software predicted that Q-c4 has desirable physicochemical properties but some properties still have some violation from the Lipinski rule of five. Overall, the dimerized phenylalanines are promising novel platforms for developing future HIV-1 CA inhibitors with considerable potential for optimization.

Research Advances in the Mechanisms of BRD4 and Its Inhibitors in Hematologic Malignancies--Review

Bromodomain-containing protein 4 (BRD4) is one of the most important members in the bromodomain and extra terminal domain(BET) family, it plays an important role in cellular physiology in human body, such as cell cycles, cell proliferation, and immune response. Recent studies have shown that BRD4 is associated with occurrence and development of acute myeloblastic leukemia, multiple myeloma and lymphoma. The mechanisms of BRD4 in hematologic malignancies including the regulation of c-Myc expression, and participation of the composition of super-enhancer, etc. At present, many kinds of inhibitors have been developed to target inhibit BRD4 for therapy in hematologic malignancies, and some of BRD4 inhibitors have entered phase Ⅱ clinical trials, which suggested that BRD4 inhibitors are expected to become new therapeutic agents for hematologic malignancies. In this review, the research advance of BRD4 and BRD4 inhibitors in hematologic malignancies was summarized briefly.

Novel super‐absorbent polymer‐grafted tea polyphenol composite inhibitor for the prevention of coal spontaneous combustion

SummaryAiming at the problems that the existing coal spontaneous combustion physical inhibitor has the disadvantages of short retarding time and low blocking efficiency, the novel super‐absorbent polymer‐grafted tea polyphenol composite inhibitor is prepared based on analyzing the advantages and disadvantages of various kinds of inhibitors. The orthogonal test was carried out with the water‐absorbent as the assessment index, and the optimum formulation of the composite inhibitor was obtained: the degree of neutralization was 90%, the amount of initiator was KPS (Potassium peroxydisulfate)/AA (Acroleic acid) = 1.2%, and the amount of cross‐linking agent was MBA (N,N' Methylene diene amide)/AA = 0.4%. The experimental results show that the temperature of the cross‐point of the coal sample treated by obtained composite inhibitor increased by 18°C compared with the raw coal, and the crossing point temperature delayed by 37 minutes, the activation energy increased by 38.552 kJ/mol. The further mechanism analysis shows that the inhibitor has good water‐retaining and water‐absorbing property. The function of cooling by absorbing heat, covering coal and insulating oxygen, and also inhibiting the oxidation activity of the coal molecule can effectively inhibit the spontaneous combustion of the coal.

Biological properties of almond proteins produced by aqueous and enzyme-assisted aqueous extraction processes from almond cake

The almond cake is a protein-rich residue generated by the mechanical expression of the almond oil. The effects of the aqueous (AEP) and enzyme-assisted aqueous extraction processes (EAEP) on the biological properties of the almond cake protein were evaluated. Total phenolic content (TPC), antioxidant capacity, inhibitory effects against crucial enzymes related to metabolic syndrome, antimicrobial potential, and in vitro protein digestibility profile were assessed. EAEP provided the best results for antioxidant capacity by both ORAC (397.2 µmol TE per g) and ABTS (650.5 µmol TE per g) methods and also showed a high (~ 98%) potential for α-glucosidase inhibition. The AEP resulted in protein extracts with the highest lipase inhibition (~ 70%) in a dose-dependent way. Enzymatic kinetic analyses revealed that EAEP generated uncompetitive inhibitors against α-glucosidase, while EAEP, AEP, and HEX-AEP (used as control) generated the same kind of inhibitors against lipase. No protein extract was effective against any of the bacteria strains tested at antimicrobial assays. An in silico theoretical hydrolysis of amandin subunits corroborated with the results found for antioxidant capacity, enzyme inhibitory experiments, and antimicrobial activity. Digestibility results indicated that the digestive proteases used were efficient in hydrolyzing almond proteins, regardless of the extraction applied and that HEX-AEP presented the highest digestibility (85%). In summary, EAEP and AEP skim proteins have the potential to be used as a nutraceutical ingredient. The biological properties observed in these extracts could help mitigate the development of metabolic syndrome where EAEP and AEP skim proteins could be potentially used as a prophylactic therapy for diabetes and obesity, respectively.

Corrosion inhibitor behavior in typical car radiators

A minor breakdown of the cooling system will cause engine overheating. One of the factors causing the engine overheating is the crust on radiator of cooling system. Based on the problem, therefore, corrosion on the cooling system, especially radiator, should be controlled. There are some methods in controlling the corrosion; one of them is the inhibitor treatment. The research aims to know the corrosion mechanism, the corrosion type, and the kind of inhibitor that produces the lowest corrosion rate. The tool used to measure the chemical composition of the radiator is spectrometer, while microscope optic is used to know the radiator corrosion type. The corrosion rate testing is used three electrode cells according to tafel extrapolation method. The results of the test of the nitric acid inhibitor treatment with the addition of various methods showed that the most optimal result is on the addition of nitric acid inhibitor by 5%. It is proven by the decrease of corrosion rate from 0.002207 mmpy to 0.0171 mmpy.

Feasibility Studies on the Effect of Natural Plant Compounds on Sludge Characteristics in a Batch-Type Aerobic Reactor and N-butyryl-L Homoserine Lactone

Quorum quenching using different kinds of inhibitors is a new subject of research that is used for biofilm prevention in wastewater treatment membrane systems. In this study, three natural compounds, namely tea, coffee and vanillin, were tested in order to evaluate their possible effects on wastewater sludge characteristics in a batch type aerobic reactor. The parameters evaluated included the soluble microbial products (total soluble microbial products, protein and carbohydrate fraction of soluble microbial products), extracellular polymeric substance concentrations (total extrapolymeric substances, protein and carbohydrate fraction of the extrapolymeric substances), floc size, zeta potential, sludge volume index and capillary suction time. The effects of these plant based compounds upon the quorum sensing N-butyryl-L-homoserine lactone signal were also investigated using gas chromatography – mass spectrometry (GC-MS) under optimized conditions. The results indicated different effects for each natural compound upon the sludge characteristics. The role of these natural compounds as quorum quenchers in the batch-type aerobic reactor was inconclusive due to their effects on extraction outputs. Understanding the effect of quorum quenchers on sludge characteristics is important and recent studies have been aimed at preventing biofilm formation in membrane bioreactors.

Study on Crack Initiation and Propagation of New Corrosion Inhibitor during Stress Corrosion of Aluminum Alloy

In this paper, a novel method combining electrochemical impedance spectroscopy (EIS) and phase shift was used to systematically study the effect of corrosion inhibitor (sodium succinate, sodium dodecyl benzene sulfonate, and new corrosion inhibitor, namely, bis [2-amino-3-(dodecyl dimethyl quaternary ammonium) propyl]-propylamine dichloro) on crack initiation and propagation of aluminum alloy during the slow strain rate tensile process. Using a variety of characterization methods to verify the feasibility of using the new method for in-situ prediction, Kramers–Kronig transformations have been used to validate the experimental data obtained with the EIS measurements. The corrosion inhibition mechanism of these three kinds of inhibitors in the SSRT process was analyzed.

Response of Isovalerate-Degrading Methanogenic Microbial Community to Inhibitors.

Isovalerate is one of the key intermediates during anaerobic digestion treating protein-containing waste/wastewater. Investigating the effect of different kinds of inhibitors on isovalerate-degrading microbial community is necessary to develop measures for improving the effectiveness of the treatment plants. In the present study, dynamic changes in the isovalerate-degrading microbial community in presence of inhibitors (ammonium, sulfide, mixed ammonium and sulfide, and chlortetracycline (CTC)) were investigated using high-throughput sequencing of 16S rRNA gene. Our observations showed that the isovalerate-degrading microbial community responded differently to different inhibitors and that the isovalerate degradation and gas production were strongly repressed by each inhibitor. We found that sulfide inhibited both isovalerate oxidation followed by methanogenesis, while ammonium, mixed ammonium and sulfide, and CTC mainly inhibited isovalerate oxidation. Genera classified into Proteobacteria and Chloroflexi were less sensitive to inhibitors. The two dominant genera, which are potential syntrophic isovalerate oxidizers, exhibited different responses to inhibitors that the unclassified_Peptococcaceae_3 was more sensitive to inhibitors than the unclassified_Syntrophaceae. Upon comparison to acetoclastic methanogen Methanosaeta, hydrogenotrophic methanogens Methanoculleus and Methanobacterium were less sensitive to inhibitors.

Corrosion Inhibitors as Building Evidence for Mild Steel: A Review

Mild steel is the most common type of metal used in large industries due to its acceptable material properties and low cost. However, a growing concern of its use has been limited as a result of its low resistance to corrosion especially in acidic and alkaline environments. The use of corrosion inhibitors has been encouraged by various researchers as a means slow down the corrosion rate and thus reduce monetary losses to industrial vessels, surfaces and equipment. This paper presents the types of inhibitors employed by different researchers on various mediums. It also seek to consider the limitation processes caused by some factors such as temperature of the media and concentration of the inhibitors and the media. Although the use of green inhibitors has been greatly encouraged due to its low cost but the combination of it with other kinds of inhibitors can prove to boost its effectiveness in corrosion inhibition process. Other organic materials such as animal discharge, and biomaterial should also be considered in future research works. These will further provide more literature to corrosion inhibition of mild steel which in essence promotes the life span of the metal.

Response to inhibitory conditions of acetate-degrading methanogenic microbial community

Investigating the effects of different kinds of inhibitors on the activity and structure of acetate-degrading microbial community involved in methane fermentation is critically important for developing countermeasures to make the fermentation process stable under different inhibitory conditions. In the present study, a mesophilic chemostat fed with acetate as the sole carbon source was constructed. Microbial community analysis based on high-throughput sequencing of 16S rRNA revealed that Methanothrix was the dominant methanogen and a variety of bacteria including acetate-oxidizing bacteria such as Tepidanaerobacter, Mesotoga, Geovibrio, and Geobacter were found. The activity and dynamic changes of the acetate-degrading microbial community under different inhibitory conditions were investigated. Addition of 600mgL-1 ammonium and 150mgL-1 sulfide reduced nearly half of the biogas production. The response of microbial community to sulfide inhibition was quicker than ammonium but the structure could recover in a short time. Addition of 8mgL-1 chlortetracycline (CTC) and 160mgL-1 enrofloxacin (EFX) exhibited a similar inhibitory effect on biogas production, with approximately 35% reduction. Compared to ammonium and sulfide, antibiotics showed stronger selective inhibition on some bacterial species. The genera related to acetate-oxidizing and sulfate-reducing bacteria showed stronger tolerance to CTC, which may be due to their low growth rates. Network analysis suggested that some genera which had close phylogenic relationship and similar functions showed constant positive correlation under different inhibitory conditions.

STAT3 operates as a novel transcription factor that regulates NEDD4 in Keloid

Keloid, marked by excessive deposition of extracellular matrix components, usually occurs after cutaneous trauma. The molecular mechanism involved in the etiology of keloid remains largely unknown in spite of extensive studies presented on the mechanism of Keloid. NEDD4 has come to be recognized as a potential mediator implicated in inflammation and keloid that could chronically develop. Despite this, the working mechanism of NEDD4 involved in keloid remains unclear. In our present report, STAT3 was identified as a novel transcriptional factor that can diametrically regulate the transcription of NEDD4 and the translation that ensues. The regulation by STAT3 over NEDD4 can be abolished as long as the p-STAT3 was inactivated in the presence of Niclosamide, a kind of inhibitors that work specifically on STAT3 signaling pathway. In turn, silencing of NEDD4 was also shown to be able to down-regulate the expression of p-STAT3. No direct protein-protein interactions between STAT3 and NEDD4 can be identified in our setting. The data we provided herein enrich the knowledge regarding the molecular mechanism of NEDD4 involved in the pathogenesis of keloid, defining a new regulatory role for STAT3 in keloid.

Bioactive constituents study of Pugionium cornutum L. Gaertn on intestinal motility

Thirty-one compounds were obtained and identified from the dried roots of Mongolian medicinal and edible plant, Pugionium cornutum L. Gaertn. Eight of them were new ones, and named as pugcornols A (1), B (2), C (3), and D (4), pugcornosides A (5), B (6), C (7), and D (8), respectively. Among them, 1–4 were rare naturally occurring thiohydantoin derivatives. Meanwhile, all the isolates were determined for their activities on isolated mice jejunum contraction, and ten of them increased height of the spontaneous contractions. Moreover, we partly clarified the mechanism of 5-(methylsulfinyl)-pentanenitrile (9), a characteristic compound in P. cornutum by using different kinds of inhibitor.