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There is a growing interest in designing electrocatalysts for highly selective electroreduction of CO2 to deeply reduced products such as CH4. However, CO2-to-CH4 conversion remains a great challenge in controlling the multi-electron/proton transfer and the adsorption of key intermediates. In this work, a metallacycle-based porous crystal (1) was synthesized for selective CO2-to-CH4 electroconversion in aqueous solution. The single-crystal analysis results disclosed that the metallacycle module of 1 features open metal sites and could be self-adaptive to encapsulate guest molecules of different sizes in its cavity. These enable the metallacycle to function as a nano-reactor to mimic the enzymatic cavity that is surrounded by catalytically active sites and adaptively bind to diverse substrates and intermediates. Accordingly, 1 exhibits desirable CO2 capture capacity, and its porous framework further promotes CO2 diffusion to catalytic sites. The above merits bring about an excellent CH4 selectivity of 70% with a partial current density of 10.3 mA cm−2 in a H-type cell at −1.5 V (versus the reversible hydrogen electrode), while a CH4 selectivity up to 81% with a partial current density of 23 mA cm−2 in a flow cell. Mechanistic investigations suggested that the adaptive cavity and the synergistic effect of aromatic hydrogen atoms, via hydrogen-bonding interactions, are beneficial to stabilize the key intermediates of CO2-to-CH4 conversion. This work develops a novel platform to regulate the reactivity and selectivity of CO2 electroreduction reactions. [ABSTRACT FROM AUTHOR]

The Vondrak filter is a unique technique for smoothing data. The filter aims to achieve a balance between the fidelity and the smoothness of the filtered results. It can therefore preserve the original attributes of the observational data while, at the same time, smooth out the noise. We reformulate the 1-D Vondrak filter that has been widely used in data processing in fields such as astronomy and geophysics and then extend it into two dimensions. The method of conjugate gradients is used to solve the least squares optimization problem. The proposed 2-D filter is a powerful tool for enhancing the quality of various geoscience and remote sensing data such as satellite images. Various tests with simulated and real synthetic aperture radar interferograms show that the new filter is very effective in removing the noise. Index Terms--Least squares, synthetic aperture radar (SAR), Vondrak filter, 2-D filter.

Duchenne muscular dystrophy (DMD) is a lethal X-linked disorder associated with dystrophin deficiency that results in chronic inflammation and severe skeletal muscle degeneration. In DMD mouse models and patients, we [...]

Inflammation may underlie the metabolic disorders of insulin resistance and type 2 diabetes. I[kappa]B kinase [beta] (IKK-[beta], encoded by Ikbkb) is a central coordinator of inflammatory responses through activation of NF-[kappa]B. To understand the role of IKK-[beta] in insulin resistance, we used mice lacking this enzyme in hepatocytes (Ikbkb[sup.[DELTA]hep]) or myeloid cells (Ikbkb[sup.[DELTA]mye]). Ikbkb[sup.[DELTA]hep] mice retain liver insulin responsiveness, but develop insulin resistance in muscle and fat in response to high fat diet, obesity or aging. In contrast, Ikbkb[sup.[DELTA]mye] mice retain global insulin sensitivity and are protected from insulin resistance. Thus, IKK-[beta] acts locally in liver and systemically in myeloid cells, where NF-[kappa]B activation induces inflammatory mediators that cause insulin resistance. These findings demonstrate the importance of liver cell IKK-[beta] in hepatic insulin resistance and the central role of myeloid cells in development of systemic insulin resistance. We suggest that inhibition of IKK-[beta], especially in myeloid cells, may be used to treat insulin resistance., Author(s): Melek C Arkan [1]; Andrea L Hevener [2]; Florian R Greten [1]; Shin Maeda [1]; Zhi-Wei Li [1, 3]; Jeffrey M Long [4]; Anthony Wynshaw-Boris [4]; Giuseppe Poli [5]; [...]

Acute injury to the intestinal mucosa is a major dose-limiting complication of abdominal radiation therapy. We studied the role of the transcription factor NF-[kappa]B in protection against radiation-induced apoptosis in the intestinal epithelium in vivo. We use mice in which NF-[kappa]B signaling through I[kappa]B-kinase (IKK)-[beta] is selectively ablated in intestinal epithelial cells to show that failure to activate epithelial cell NF-[kappa]B in vivo results in a significant increase in radiation-induced epithelial cell apoptosis. Furthermore, bacterial lipopolysaccharide, which is normally a radioprotective agent, is radiosensitizing in IKK[beta]-deficient intestinal epithelial cells. Increased apoptosis in IKK[beta]-deficient intestinal epithelial cells was accompanied by increased expression and activation of the tumor suppressor p53 and decreased expression of antiapoptotic Bcl-2 family proteins. These results demonstrate the physiological importance of the NF-[kappa]B system in protection against radiation-induced death in the intestinal epithelium in vivo and identify IKK[beta] as a key molecular target for radioprotection in the intestine. Selective preactivation of NF-[kappa]B through IKK[beta] in intestinal epithelial cells could provide a therapeutic modality that allows higher doses of radiation to be tolerated during cancer radiotherapy.

We studied the role of NF-[kappa]B in acute inflammation caused by gut ischemia-reperfusion through selective ablation of I[kappa]B kinase (IKK)-[beta], the catalytic subunit of IKK that is essential for NF-[kappa]B activation. Ablation of IKK-[beta] in enterocytes prevented the systemic inflammatory response, which culminates in multiple organ dysfunction syndrome (MODS) that is normally triggered by gut ischemia-reperfusion. IKK-[beta] removal from enterocytes, however, also resulted in severe apoptotic damage to the reperfused intestinal mucosa. These results show the dual function of the NF-[kappa]B system, which is responsible for both tissue protection and systemic inflammation, and underscore the caution that should be exerted in using NF-[kappa]B and IKK inhibitors., Author(s): Lee-Wei Chen [1, 3]; Laurence Egan [2]; Zhi-Wei Li [1]; Florian R. Greten [1]; Martin F. Kagnoff [2]; Michael Karin (corresponding author) [1] NF-[kappa]B is a transcription factor that [...]

Research demonstrates that immunostimulatory effect of bacterial DNA and synthetic oligonucleotides stimulate innate immunity. Data point out that DNA-dependent protein kinase and IKKbeta produce cytokine during immunostimulation suggesting a possible link between DNA repair and innate immunity.

We previously have reported corpus callosum defects in transgenic mice expressing the [Beta]-amyloid precursor protein ([Beta]APP) with a deletion of exon 2 and at only 5% of normal levels. This finding indicates a possible involvement of [Beta]APP in the regulation or guidance of axon growth during neural development. To determine to what degree the [Beta]APP mutation interacts with genetic background alleles that predispose for forebrain commissure defects in some mouse lines, we have assessed the size of the forebrain commissures in a sample of 298 mice. Lines with mixed genetic background were compared with congenic lines obtained by backcrossing to the parental strains C57BL/6 and 129/SvEv. Mice bearing a null mutation of the [Beta]APP gene also were included in the analysis. We show that, independently of genetic background, both lack and underexpression of [Beta]APP are associated with reduced brain weight and reduced size of forebrain commissures, especially of the ventral hippocampal commissure. In addition, both mutations drastically increase the frequency and severity of callosal agenesis and hippocampal commissure defects in mouse lines with 129/SvEv or 129/Ola background.

Lithium–sulfur batteries (LSBs) have tremendous attractive interest for their high theoretical energy density, natural abundance, and environmental friendliness. However, the commercialization remains constrained by the shuttle effect and sluggish kinetics of polysulfides. Herein, a spraying/discharging strategy is employed to fabricate binder‐free ω‐Li3V2O5 (ω‐LVO) catalytic network with multi‐polarization centers by intercalating Li‐ions into tetrahedral V2O5 for addressing the mentioned issues. Li (0.51 eV) and V (0.57 eV), which have a strong positive electric potential, and O (−0.57 eV), which has a strong negative electric potential, exhibit high polarity that can capture polysulfides effectively. In addition, the amounts of the polarity sites would be significantly increased because the catalyst is composed of light elements. Therefore, the ω‐LVO octahedron can catalyze polysulfides to short‐chains sufficiently. The blue shift in synchronous ultraviolet‐visible spectra and ultra‐low Tafel plots of 34 and 20 mV dec−1 at two discharge plateaus demonstrate excellent kinetics behavior even with a low catalyst loading. Furthermore, the conductive networks facilitate electronic/ionic transmission and thereby boost their electrochemical performances. This work offers an efficacious method to promote kinetics behaviors and lessen the gap between theoretical specific capacities and future commercialization of LSBs. [ABSTRACT FROM AUTHOR]

Gene disruptions and deletions of up to 20 kb have been generated by homologous recombination with appropriate targeting vectors in murine embryonic stem (ES) cells. Because we could not obtain a deletion of about 200 kb in the mouse amyloid precursor protein gene by the classical technique, we employed strategies involving the insertion of loxP sites upstream and downstream of the region to be deleted by homologous recombination and elicited excision of the loxP-flanked region by introduction of a Cre expression vector into the ES cells. In the first approach, the loxP sequences were inserted in two successive steps and after each step, ES cell clones were isolated and characterized. Deletion of the loxP-flanked sequence was accomplished by introducing the cre gene in a third step. In the second approach, ES cells containing the upstream loxP cassette were electroporated simultaneously with the downstream loxP targeting vector and the Cre expression plasmid. ES cells were obtained that gave rise to chimeric mice capable of germ-line transmission of the deleted amyloid precursor protein allele.

Background: Ustekinumab (UST), a newly-used biologic targeting p40 subunit of IL12 and IL23 in China, exerts a confirmed therapeutic effect on the induction and maintenance therapies for refractory Crohn's disease (CD). Therapeutic drug monitoring based on trough and antibody concentration is of core importance when treating patients who lose response to UST. We aimed to analyze the UST exposure-response relationship in CD treatment in the real-world setting.Methods: We retrospectively enrolled patients with CD who received UST between March 1, 2020 and May 31, 2021, at the inflammatory bowel disease (IBD) center of the Sun Yat-Sun Affiliated Sixth Hospital. Baseline characteristic information, biomarker examination, clinical outcomes determined by the Crohn's disease activity index (CDAI), and endoscopic outcomes evaluated using a simple endoscopic score for Crohn's disease (SES-CD) at week 16/20 were collected. The optimal UST cut-off trough concentration was identified using receiver operating characteristic curve (ROC) analysis.Results: Nineteen eligible patients were included in the study, the mean age was 29.1 ± 9.1 years and the mean disease duration was 5.5 ± 4.7 years. At the initiation of the study, 89.5% of the patients had been exposed to prior biologics, 42.1% had previous CD-related surgeries, and 52.6% had perianal diseases. At week 16/20 after the UST initiation, clinical response, clinical remission, endoscopic response, and endoscopic remission were 89.5%, 84.2%, 42.2%, and 73.7%, respectively. The cut-off optimal trough concentration for UST was 1.12 μg/mL, as determined by the ROC with an area under the curve (AUC) of 0.78, sensitivity of 87.5%, and specificity of 72.7%. Patients with a UST trough concentration > 1.12 μg/mL had a significantly higher rate of endoscopic remission than those without (70.0% vs. 11.1%, P = 0.02).Conclusions: UST is an effective therapeutic option for refractory CD treatment. A UST trough concentration above 1.12 μg/mL was associated with endoscopic remission at week 16/20 after UST initiation. Trial registration This study was approved and retrospectively registered by the Ethics Committee of Sun Yat-Sen University (2021ZSLYEC-066, March 29, 2021) and the Clinical Trial Registry (NCT04923100, June 10, 2021). [ABSTRACT FROM AUTHOR]

Functional analysis of the mouse beta-amyloid precursor protein (beta-APP) gene by incorporating a cassette consisting of a putative transcription terminating sequence and a neomycin resistance gene into exon 2 reveals that the brain and other tissues in mice that are homozygous to the cassette incorporation contain beta-APP-specific RNA at a concentration 5- to 10-fold less than that in wild type protein. The levels of the shortened beta-APP-specific protein were low in the brain. The mice display damaged exploratory behavior and spatial learning characteristics with a high level of corpus callosum agenesis.