Deacetylase Sirtuin 1 mitigates type I IFN- and type II IFN-induced signaling and antiviral immunity.

Type I and type II IFNs are important immune modulators in both innate and adaptive immunity. They transmit signaling by activating JAK-STAT pathways. Sirtuin 1 (SIRT1), a class III NAD+-dependent deacetylase, has multiple functions in a variety of physiological processes. Here, we characterized the novel functions of SIRT1 in the regulation of type I and type II IFN-induced signaling. Overexpression of SIRT1 inhibited type I and type II IFN-induced interferon-stimulated response element activation. In contrast, knockout of SIRT1 promoted type I and type II IFN-induced expression of ISGs and inhibited viral replication. Treatment with SIRT1 inhibitor EX527 had similar positive effects. SIRT1 physically associated with STAT1 or STAT3, and this interaction was enhanced by IFN stimulation or viral infection. By deacetylating STAT1 at K673 and STAT3 at K679/K685/K707/K709, SIRT1 downregulated the phosphorylation of STAT1 (Y701) and STAT3 (Y705). Sirt1+/- primary peritoneal macrophages and Sirt1+/- mice exhibited enhanced IFN-induced signaling and antiviral activity. Thus, SIRT1 is a novel negative regulator of type I and type II IFN-induced signaling through its deacetylase activity.IMPORTANCESIRT1 has been reported in the precise regulation of antiviral (RNA and DNA) immunity. However, its functions in type I and type II IFN-induced signaling are still unclear. In this study, we deciphered the important functions of SIRT1 in both type I and type II IFN-induced JAK-STAT signaling and explored the potential acting mechanisms. It is helpful for understanding the regulatory roles of SIRT1 at different levels of IFN signaling. It also consolidates the notion that SIRT1 is an important target for intervention in viral infection, inflammatory diseases, or even interferon-related therapies.

Theoretical Insights into the Mechanism and Origin of Solvent-Dependent Selectivity in the Cyclization of Propargyl Alcohols for the Divergent Synthesis of N-Heterocycles.

This study elucidates the mechanisms and principles governing chemoselectivity in synthesizing two distinct N-heterocycles, benzimidazole thiazine and benzothiazole imidazole, through BF3•OEt2-catalyzed cyclization reactions of propargyl alcohols with benzimidazole thiols. Employing density functional theory calculations, we highlight the crucial role of fluorine source in influencing chemoselectivity. In DCM, BF3, as the catalytic center, coordinates with propargyl alcohol's hydroxyl group to form a precursor. Conversely, in DMF, [BF2•DMF]+, formed from DMF and BF3•OEt2, acts as the catalytic center, activating the propargyl alcohol's hydroxyl group. The mechanisms in both solvents involve sequential steps: B-O bond formation, C-O bond cleavage, S-C bond formation, hydrogen atom transfer (HAT), cyclization, and deprotonation. A notable difference is the HAT process: in DCM, it follows a 1,5-HAT process, while in DMF, BF4- formation from DMF and BF3•OEt2 provides a fluorine source and introduces steric hindrance, favoring a 1,6-HAT process and leading to unique chemoselectivity. This pioneering research showcases the impact of DMF on cyclization reactions, offering valuable insights for comprehending and designing reactions driven by fluorine sources. Crucially, our results propose an innovative reaction mechanism featuring lower potential energy surfaces, enhancing our understanding of the intricate interplay among reactants, catalysts, and solvents.

Structural identification and combination mechanism of iron (II)-chelating Atlantic salmon (Salmo salar L.) skin active peptides.

In order to utilize salmon skin for high value, and investigate the structural identification and combination mechanism of iron (II)-chelating peptides systemically, Atlantic salmon (Salmo salar L.) skin, a by-product of Atlantic salmon processing, was treated by two-step enzymatic hydrolysis to obtain salmon skin active peptides (SSAP). Then they reacted with iron (II) to obtain iron (II)-chelating salmon skin active peptides (SSAP-Fe) with a high iron (II) chelating ability of 98.84%. The results of Fourier transform infrared spectroscopy (FTIR), circular dichroism (CD) spectroscopy, 8-anilino-1-naphthalenesulfonic acid ammonium salt hydrate (ANS) combined fluorescence measurement, isothermal titration calorimetry (ITC) and full wavelength ultraviolet (UV) scanning showed that the structural characteristics of SSAP changed before and after chelating iron (II). Reverse phase high performance liquid chromatography (RP-HPLC) and mass spectrometry were used to identify and quantify the peptides in SSAP-Fe. Four peptide sequences (STEGGG, GIIKYGDDFMH, PGQPGIGYDGPAGPPGPPGPPGAP and QNQRESWTTCRSQSSLPDG) were identified. The content of PGQPGIGYDGPAGPPGPPGPPGAP was the highest, at 25.17 µg/mg. The pharmacokinetic and pharmacodynamic properties of these four peptides were also investigated, and the results indicated that they have satisfactory predicted ADMET properties. Molecular docking technology was used to analyze the binding sites between iron (II) and SSAP, and it was found that PGQPGIGYDGPAGPPGPPGPPGAP had the lowest predicted binding energy with iron (II) and the most stable predicted binding energy with iron (II). This results showed that the stability of SSAP-Fe were closely related to the number of covalent bonds and the types of amino acids. This study revealed the structure and combination mechanism of SSAP-Fe, and indicated that SSAP-Fe prepared by chelation may be used as a Fe supplement that can be applied in functional foods or ingredients.

Discriminatory Gate-Opening Effect in a Flexible Metal-Organic Framework for Inverse CO2 /C2 H2 Separation.

Considering the significant application of acetylene (C2 H2 ) in the manufacturing and petrochemical industries, the selective capture of impurity carbon dioxide (CO2 ) is a crucial task and an enduring challenge. Here, a flexible metal-organic framework (Zn-DPNA) accompanied by a conformation change of the Me2 NH2 + ions in the framework is reported. The solvate-free framework provides a stepped adsorption isotherm and large hysteresis for C2 H2 , but type-I adsorption for CO2 . Owing to their uptakes difference before gate-opening pressure, Zn-DPNA demonstrated favorable inverse CO2 /C2 H2 separation. According to molecular simulation, the higher adsorption enthalpy of CO2 (43.1 kJ mol-1 ) is due to strong electrostatic interactions with Me2 NH2 + ions, which lock the hydrogen-bond network and narrow pores. Furthermore, the density contours and electrostatic potential verifies the middle of the cage in the large pore favors C2 H2 and repels CO2 , leading to the expansion of the narrow pore and further diffusion of C2 H2 . These results provide a new strategy that optimizes the desired dynamic behavior for one-step purification of C2 H2 .

Porous MOF Featuring 2D Intersecting Channels Based on a Pentanuclear Mn5(COO)10CO3 Cluster with Upgrading of Pipeline Natural Gas.

Natural gas plays a crucial role in daily and industrial production, but the impurities contained in natural gas limit its further use. It is very important to develop adsorbents that can separate CH4 from multicomponent mixtures, but there are still many challenges and problems. Herein, a novel porous MOF {[Mn5(pbdia)2(CO3)(H2O)2] ↔ 5H2O ↔ 2DMF}n (pbdia = 2,2'-(5-carboxy-1,3-phenylene)bis(oxy) diterephthalic acid) was successfully synthesized based on a flexible pentacarboxylic acid ligand and a unique pentanuclear Mn5(COO)10CO3 cluster. The MOF reveals a 3D porous structure with 2D intersecting channels, which shows high C3H8, C2H6, and CO2 adsorption capacities and affinities over CH4. Moreover, the ideal adsorption solution theory selectivities of C3H8/CH4, C2H6/CH4, and CO2/CH4 can reach 263.0, 27.0, and 7.7, respectively, suggesting a potential for removing the low content of C3H8, C2H6, and CO2 from pipeline natural gas, which was further confirmed by breakthrough curves and GCMC simulations.

Effect of Macromolecular Structure on Phase Separation Regime in 3D Printed Materials.

In this study, the fabrication of 3D-printed polymer materials with controlled phase separation using polymerization induced microphase separation (PIMS) via photoinduced 3D printing is demonstrated. While many parameters affecting the nanostructuration in PIMS processes are extensively investigated, the influence of the chain transfer agent (CTA) end group, i.e., Z-group, of macromolecular chain transfer agent (macroCTA) remains unclear as previous research has exclusively employed trithiocarbonate as the CTA end group. Herein, the effect of macroCTAs containing four different Z-groups on the formation of nanostructure of 3D printed materials is explored. The results show that the different Z-groups lead to distinct network formation and phase separation behaviors between the resins, influencing both the 3D printing process and the resulting material properties. Specifically, less reactive macroCTAs toward acrylic radical addition, such as O-alkyl xanthate and N-alkyl-N-aryl dithiocarbamate, result in translucent and brittle materials with macrophase separation morphology. In contrast, more reactive macroCTAs such as S-alkyl trithiocarbonate and 4-chloro-3,5-dimethylpyrazo dithiocarbamate produce transparent and rigid materials with nano-scale morphology. Findings of this study provide a novel approach to manipulate the nanostructure and properties of 3D printed PIMS materials, which can have important implications for materials science and engineering.

Removable partial prosthesis combined with swallowing training is an efficient clinical solution for oral cancer post-operation patients with palatal defect and dysphagia: a prospective study.

OBJECTIVE: Dysphagia is one of the major complications of oral cancer patients, and is disturbing thousands of patients worldwide. Our study aim to evaluate the clinical efficacy of prosthesis combined with swallowing training on palatal defect and dysphagia in post-operative oral cancer patients. MATERIALS AND METHODS: Sixteen oral cancer patients with palatal defect and dysphagia post-operation were treated with removable prosthesis and individualized swallowing function training. Swallowing function of patients before and after treatment was analyzed and compared by videofluoroscopic swallowing examination. The severity of depression and life quality were evaluated by Depression Scale (SDS) and Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) scores, respectively. RESULTS: Oral transit time (OTT) significantly shortened after treatment (P < 0.01), and Penetration-Aspiration Scale (PAS) scores was significantly higher after treatment (P < 0.001). Different consistency bolus showed different risk of aspiration. Thickened liquids were related to lower PAS scores (P < 0.001). SDS standard score was significantly lower after treatment (P < 0.05). The total score of FACT-H&N after treatment was significantly higher (P < 0.05). No patients came back for regressed swallowing function during the follow-up period (17.06 ± 2.376 months). CONCLUSION: Removable prosthesis and swallowing training can significantly improve swallowing function, reduce depression degree, and improve quality of life (QOL). CLINICAL RELEVANCE: Removable prosthesis combined with swallowing training is a cheap and effective method to improve QOL in patients with palate defect and dysphagia after oral cancer.

Engineering a Series of Isoreticular Pillared Layer Ultramicroporous MOFs for Gas and Vapor Uptake.

The accurate design and systematic engineering of MOFs is a large challenge due to the randomness of the synthesis process. Isoreticular chemistry provides a powerful approach for the regulation of pore environment in a more predictable and precise way to systematically control gas/vapor adsorption performances. Herein, utilizing an effective strategy of altering the "pillared" motifs of pillared layer structures, three isoreticular ultramicroporous MOFs were successfully constructed. Combined with the reported parent MOFs and two other recorded isoreticular MOFs modified with -NH2 and -CH3, gas and vapor uptake performances of this family of isoreticular pillared layer MOFs were systematically explored.

IL-17 Facilitates VCAM-1 Production and Monocyte Adhesion in Osteoarthritis Synovial Fibroblasts by Suppressing miR-5701 Synthesis.

Osteoarthritis (OA) is characterized by the infiltration and adhesion of monocytes into the inflamed joint synovium. Interleukin (IL)-17 is a critical inflammatory mediator that participates in the progression of OA, although the mechanisms linking IL-17 and monocyte infiltration are not well understood. Our analysis of synovial tissue samples retrieved from the Gene Expression Omnibus (GEO) dataset exhibited higher monocyte marker (CD11b) and vascular cell adhesion molecule 1 (VCAM-1) levels in OA samples than in normal, healthy samples. The stimulation of human OA synovial fibroblasts (OASFs) with IL-17 increased VCAM-1 production and subsequently enhanced monocyte adhesion. IL-17 affected VCAM-1-dependent monocyte adhesion by reducing miR-5701 expression through the protein kinase C (PKC)-α and c-Jun N-terminal kinase (JNK) signaling cascades. Our findings improve our understanding about the effect of IL-17 on OA progression and, in particular, VCAM-1 production and monocyte adhesion, which may help with the design of more effective OA treatments.

Cutpoints for Muscle Mass and Strength Derived from Weakness or Mobility Impairment and Compared with Other Diagnostic Criteria in Community-Dwelling Elderly People.

We identified the strength cutpoints concerning mobility impairment, then identified the muscle mass cutpoints concerning weakness, and compared the results with other diagnostic criteria to develop the clinical diagnostic criteria associated with functional impairment. In 7583 elderly people, classification and regression tree (CART) and receiver operating characteristic curve (ROC) analyses were used for determining cutpoints for handgrip strength (HGS) and appendicular lean mass (ALM) indices associated with slowness or weakness. Logistic regressions were then used to quantify the strength of the association between muscle mass (or strength) categories and weakness (or slowness). The CART second cutpoints of muscle mass and strength indices were lower than those specified by the ROC method and were between those cutpoints determined by the 20th and Mean-2SD methods. After adjusting for covariates, the associations remained significant in handgrip strength categories defined by the CART and ROC cutpoints and HGS/BMI categories defined by the CART, ROC, and 20th cutpoints in men and women (P < 0.05), ALM, ALM/Ht2 categories defined by all four cutpoints (P < 0.05) and ALM/BMI categories defined by CART and ROC cutpoints in men (P < 0.05), and ALM and ALM/Ht2 categories defined by the CART cutpoints in women (P < 0.05). Our approaches resulted in a definition of weak strength as handgrip strength or HGS/BMI less than 26.55 kg or 1.114 in men and less than 16.45 kg or 0.697 in women and then defined ALM, ALM/Ht2, or ALM/BMI less than 18.92 kg, 7.08 kg/m2, or 0.795 in men and less than 15.04 kg, 5.99 kg/m2, or 0.517 in women as low lean mass.

[Microassay of High-Risk Human Papillomavirus Genotype Based on R6G-ddATP/SNaPshot-Gel Fluorescence Method].

OBJECTIVE: R6G-ddATP was used as a dideoxy fluorescence substrate to establish the single base end extension (SNaPShot)-gel fluorescence method for the rapid detection of the genotypes of three high-risk human papillomaviruses (HR-HPV) ( HPV18, HPV33 and HPV35) genotypes. METHODS: HPV quality control products were used as as samples, and R6G-ddATP dideoxy fluorescence reagent was used as substrate. Firstly, HPV was amplified by using universal primers to obtain the first round of amplified products, which were purified and used as templates for subsequent SNaPShot reactions. Then, specific one-step extension primers were used to perform SNaPShot reaction to generate R6G-fluorescence-labeled DNA extension products. The product was subjected to agarose gel electrophoresis, the results of which were observed under a Gel Imager, and the HPV genotyping was done with different one-step extension primers. Each sample was tested three times and the results were compared with DNA sequencing results. RESULTS: The preferred annealing temperature for SNaPShot reaction is 55 ℃. Three HPV genotypes were examined by R6G-ddATP/SNaPShot gel fluorescence assay under optimal conditions, and the results were consistent with DNA sequencing results. CONCLUSION: The R6G-ddATP/SNaPShot-gel fluorescence method for the micro-detection methods of three HR-HPV genotypes was successfully established and can be used for rapid detection of HPV genotypes.

Chromatin 3D structure reconstruction with consideration of adjacency relationship among genomic loci.

BACKGROUND: Chromatin 3D conformation plays important roles in regulating gene or protein functions. High-throughout chromosome conformation capture (3C)-based technologies, such as Hi-C, have been exploited to acquire the contact frequencies among genomic loci at genome-scale. Various computational tools have been proposed to recover the underlying chromatin 3D structures from in situ Hi-C contact map data. As connected residuals in a polymer, neighboring genomic loci have intrinsic mutual dependencies in building a 3D conformation. However, current methods seldom take this feature into account. RESULTS: We present a method called ShNeigh, which combines the classical MDS technique with local dependence of neighboring loci modeled by a Gaussian formula, to infer the best 3D structure from noisy and incomplete contact frequency matrices. We validated ShNeigh by comparing it to two typical distance-based algorithms, ShRec3D and ChromSDE. The comparison results on simulated Hi-C dataset showed that, while keeping the high-speed nature of classical MDS, ShNeigh can recover the true structure better than ShRec3D and ChromSDE. Meanwhile, ShNeigh is more robust to data noise. On the publicly available human GM06990 Hi-C data, we demonstrated that the structures reconstructed by ShNeigh are more reproducible between different restriction enzymes than by ShRec3D and ChromSDE, especially at high resolutions manifested by sparse contact maps, which means ShNeigh is more robust to signal coverage. CONCLUSIONS: Our method can recover stable structures in high noise and sparse signal settings. It can also reconstruct similar structures from Hi-C data obtained using different restriction enzymes. Therefore, our method provides a new direction for enhancing the reconstruction quality of chromatin 3D structures.

Long noncoding RNA MEG3 silencing protects against hypoxia-induced pheochromocytoma-12 cell injury through inhibition of TIMP2 promoter methylation.

Hypoxia is a common pathological process caused by insufficient oxygen. Long noncoding RNAs (lncRNAs) have been proven to participate in this pathology. Hypoxia is reported to significantly reduce the secretion of tissue inhibitor of metalloproteinase 2 (TIMP2) and TIMP2 induces pheochromocytoma-12 (PC12) cell cycle arrest. Thus, our study aimed to explore the mechanism by which lncRNA maternally expressed gene 3 (MEG3) was implicated in hypoxia-induced PC12 cell injury through TIMP2 promoter methylation. To elucidate the potential biological significance of MEG3 and the regulatory mechanism between MEG3 and TIMP2, a hypoxia-induced PC12 cell injury model was generated. The hypoxia-exposed cells were subjected to a series of overexpression plasmids and short hairpin RNAs, followed by the measurement of levels of MEG3, TIMP2, lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS), Bcl-2-associated X protein, B-cell lymphoma-2, and caspase-3, as well as the changes in MMP, cell proliferation, apoptosis, and cell cycle progression. On the basis of the findings, MEG3 was upregulated in hypoxia-injured PC12 cells. MEG3 recruited methylation proteins DNMT3a, DNMT3b, and MBD1 and accelerated TIMP2 promoter methylation, which in turn inhibited its expression. Moreover, PC12 cells following MEG3 silencing and TIMP2 overexpression exhibited significantly decreased levels of LDH, MDA, and ROS along with cell apoptosis, yet increased SOD and MMP levels, as well as cell cycle entry to the S phase and cell proliferation. In conclusion, MEG3 silencing suppresses hypoxia-induced PC12 cell injury by inhibiting TIMP2 promoter methylation. This study may provide novel therapeutic targets for hypoxia-induced injury.

One-step generation of composite soybean plants with transgenic roots by Agrobacterium rhizogenes-mediated transformation.

BACKGROUND: Agrobacterium rhizogenes-mediated (ARM) transformation is a highly efficient technique for generating composite plants composed of transgenic roots and wild-type shoot, providing a powerful tool for studying root biology. The ARM transformation has been established in many plant species, including soybean. However, traditional transformation of soybean, transformation efficiency is low. Additionally, the hairy roots were induced in a medium, and then the generated composite plants were transplanted into another medium for growth. This two-step operation is not only time-consuming, but aggravates contamination risk in the study of plant-microbe interactions. RESULTS: Here, we report a one-step ARM transformation method with higher transformation efficiency for generating composite soybean plants. Both the induction of hairy roots and continuous growth of the composite plants were conducted in a single growth medium. The primary root of a 7-day-old seedling was decapitated with a slanted cut, the residual hypocotyl (maintained 0.7-1 cm apical portion) was inoculated with A. rhizogenes harboring the gene construct of interest. Subsequently, the infected seedling was planted into a pot with wet sterile vermiculite. Almost 100% of the infected seedlings could produce transgenic positive roots 16 days post-inoculation in 7 tested genotypes. Importantly, the transgenic hairy roots in each composite plant are about three times more than those of the traditional ARM transformation, indicating that the one-step method is simpler in operation and higher efficiency in transformation. The reliability of the one-step method was verified by CRISPR/Cas9 system to knockout the soybean Rfg1, which restricts nodulation in Williams 82 (Nod-) by Sinorhizobium fredii USDA193. Furthermore, we applied this method to analyze the function of Arabidopsis YAO promoter in soybean. The activity of YAO promoter was detected in whole roots and stronger in the root tips. We also extended the protocol to tomato. CONCLUSIONS: We established a one-step ARM transformation method, which is more convenient in operation and higher efficiency (almost 100%) in transformation for generating composite soybean plants. This method has been validated in promoter functional analysis and rhizobia-legume interactions. We anticipate a broad application of this method to analyze root-related events in tomato and other plant species besides soybean.

2,3,5,4'-tetrahydoxystilbene-2-O-ß-D-glucoside eliminates staurosporine-induced cytotoxicity by restoring BDNF-TrkB/Akt signaling axis.

2,3,5,4'-Tetrahydroxystilbene-2-O-ß-d-glucoside (THSG) is the major active ingredient in Plygonum multiflorum that displays a great deal of health-benefits including anti-oxidation, anti-hyperlipidemia, anti-cancer, anti-inflammation and neuroprotection. However, it is unclear whether THSG exerts neuroprotective functions by regulating neurotrophic factors and their associated signaling pathways. In this study, hippocampal neurons were challenged with staurosporine (STS) to establish a neural damage model. We found that STS-induced cytotoxicity introduced significant morphological collapse and initiating cell apoptosis, along with the down regulation of BDNF and TrkB/Akt signaling axis. In contrast, neurons pretreated with THSG showed resistance to STS-induced toxicity and maintained cell survival. THSG rescued STS induced dysfunctions of BDNF and its associated TrkB/Akt signaling, and restored the expression of Bcl-2 and Caspase-3. However, inhibition of TrkB activity by K252a or Akt signaling by LY294002 abolished the neuroprotective effects of THSG. Therefore, BDNF and TrkB/Akt signaling axis is a promise target for THSG mediated neuroprotective functions.

USP7-TRIM27 axis negatively modulates antiviral type I IFN signaling.

Ubiquitination and deubiquitination are important post-translational regulatory mechanisms responsible for fine tuning the antiviral signaling. In this study, we identified a deubiquitinase, the ubiquitin-specific peptidase 7/herpes virus associated ubiquitin-specific protease (USP7/HAUSP) as an important negative modulator of virus-induced signaling. Overexpression of USP7 suppressed Sendai virus and polyinosinic-polycytidylic acid and poly(deoxyadenylic-deoxythymidylic)-induced ISRE and IFN-ß activation, and enhanced virus replication. Knockdown or knockout of endogenous USP7 expression had the opposite effect. Coimmunoprecipitation assays showed that USP7 physically interacted with tripartite motif (TRIM)27. This interaction was enhanced after SeV infection. In addition, TNF receptor-associated factor family member-associated NF-kappa-B-binding kinase (TBK)-1 was pulled down in the TRIM27-USP7 complex. Overexpression of USP7 promoted the ubiquitination and degradation of TBK1 through promoting the stability of TRIM27. Knockout of endogenous USP7 led to enhanced TRIM27 degradation and reduced TBK1 ubiquitination and degradation, resulting in enhanced type I IFN signaling. Our findings suggest that USP7 acts as a negative regulator in antiviral signaling by stabilizing TRIM27 and promoting the degradation of TBK1.-Cai, J., Chen, H.-Y., Peng, S.-J., Meng, J.-L., Wang, Y., Zhou, Y., Qian, X.-P., Sun, X.-Y., Pang, X.-W., Zhang, Y., Zhang, J. USP7-TRIM27 axis negatively modulates antiviral type I IFN signaling.

Degradation of high-concentration simulated organic wastewater by DBD plasma.

In this study, a high-concentration simulated organic wastewater, made by dissolving methyl violet in water, was degraded using dielectric barrier discharge (DBD) plasma generated in air and O2 respectively. The decoloration rate and chemical oxygen demand (COD) of wastewater were evaluated during plasma treatments with the initial concentration of methyl violet of 300 mg L-1. Results showed that the highest decoloration rate of around 100% within 10 min and the highest COD decrease of 33% within 60 min could be achieved with the O2 plasma treatment at the discharge voltage of 10 kV, while air plasma treatment showed lower efficiency in decolorizing the methyl violet solution and lower COD decrease (24%) after 60 min treatment. UV-Vis spectroscopy and chemical analysis of generated by-products during the plasma-enabled degradation process revealed that the methyl violet molecules could be completely decomposed into some refractory organics in the solution. Based on the experimental results and literature review, a pathway of methyl violet degradation attributed to energetic electrons and highly reactive species generated by DBD was proposed.

Recirculating Th2 cells induce severe thymic dysfunction via IL-4/STAT6 signaling pathway.

Thymic involution happened early in life, but a certain ratio of activated CD4+ T cells will persistently recirculate into the thymus from the periphery and it have been suggested to be able to inhibit the development of embryonic thymocytes. Our present study was aimed to elucidate the specific mechanism how activated CD4+ T cells could influence upon developing thymocytes by using fetal thymic organ culture (FTOC) and kidney capsule transplantation. Our results demonstrated that Th2 cells were found to play a fundamental role in the inhibition of embryonic thymocyte development since a very low concentration of Th2 cells could obviously reduce the total number of thymocytes. And this effect was not tenable in other Th cell type. Notably, IL-4, the major cytokine secreted by Th2 cells, was suggested the key factor playing the inhibition role. In addition to reduced cell population, the proportion of double positive (DP) T cells was also heavily decreased. Furthermore, we demonstrated that it was the downstream effector signal transducer and activator of transcription 6 (STAT6) of IL-4 partially manipulate this inhibition. Together, these findings reveal a novel influence of Th2 cells re-entering the thymus on thymic involution.

Direct Evidence: Enhanced C2H6 and C2H4 Adsorption and Separation Performances by Introducing Open Nitrogen-Donor Sites in a MOF.

To comparably analyze the influence of a porous environment on the gas adsorption in MOFs, based on an imidazole-decorated MOF, {[Zn(imtp)]·DMA·1.5H2O} n (1-im, H2imtp = 2-(imidazol-1-yl) terephthalic acid), an analogue MOF, {[Zn(tztp)]·DMA} n (1-tz, H2tztp = 2-(1 H-1,2,4-triazol-1-yl) terephthalic acid) has been synthesized by replacing imidazole with triazole motifs. The two MOFs are isostructural frameworks containing 1D channels; however, they possess different porous wall environments. The open nitrogen-decorated channels in 1-tz lead to significantly enhanced C2H6 (76.5 cm3 g-1) and C2H4 (73.1 cm3 g-1) uptakes at 298 K and 1 atm, which are 5 times of the adsorption amounts of C2H6 and C2H4 in 1-im that is the absence of exposed N atoms in the channels. Furthermore, the activated 1-tz also reveals higher adsorption selectivities for C2H6 and C2H4 over CH4. The different sorption properties were further uncovered by theoretical simulations.

Nicotinic Acetylcholine Receptor Alpha7 Subunit Mediates Vagus Nerve Stimulation-Induced Neuroprotection in Acute Permanent Cerebral Ischemia by a7nAchR/JAK2 Pathway.

BACKGROUND The role of nicotinic acetylcholine receptor alpha7 subunit (a7nAchR) in the treatment of acute cerebral ischemia by VNS has not been thoroughly clarified to date. Therefore, this study aimed to investigate the specific role of a7nAchR and explore whether this process is involved in the mechanisms of VNS-induced neuroprotection in rats undergoing permanent middle cerebral artery occlusion (PMCAO) surgery. MATERIAL AND METHODS Rats received a7nAChR antagonist (A) or antagonist placebo injection for control (AC), followed by PMCAO and VNS treatment, whereas the a7nAChR agonist (P) was utilized singly without VNS treatment but only with PMCAO pretreatment. The rats were randomly divided into 6 groups: sham PMCAO, PMCAO, PMCAO+VNS, PMCAO+VNS+A, PMCAO+VNS+AC, and PMCAO+P. Neurological function and cerebral infarct volume were measured to evaluate the level of brain injury at 24 h after PMCAO or PMCAO-sham. Moreover, the related proteins levels of a7nAChR, p-JAK2, and p-STAT3 in the ischemic penumbra were assessed by Western blot analysis. RESULTS Rats pretreated with VNS had significantly improved neurological function and reduced cerebral infarct volume after PMCAO injury (p<0.05). In addition, VNS enhanced the levels of a7nAchR, p-JAK2, and p-STAT3 in the ischemic penumbra (p<0.05). However, inhibition of a7nAchR not only attenuated the beneficial neuroprotective effects induced by VNS, but also decreased levels of p-JAK2 and p-STAT3. Strikingly, pharmacological activation of a7nAchR can partially substitute for VNS-induced beneficial neurological protection. CONCLUSIONS These results suggest that a7nAchR is a pivotal mediator of VNS-induced neuroprotective effects on PMCAO injury, which may be related to suppressed inflammation via activation of the a7nAchR/JAK2 anti-inflammatory pathway.