CLK2 mediates IκBα-independent early termination of NF-κB activation by inducing cytoplasmic redistribution and degradation.

Activation of the NF-κB pathway is strictly regulated to prevent excessive inflammatory and immune responses. In a well-known negative feedback model, IκBα-dependent NF-κB termination is a delayed response pattern in the later stage of activation, and the mechanisms mediating the rapid termination of active NF-κB remain unclear. Here, we showed IκBα-independent rapid termination of nuclear NF-κB mediated by CLK2, which negatively regulated active NF-κB by phosphorylating the RelA/p65 subunit of NF-κB at Ser180 in the nucleus to limit its transcriptional activation through degradation and nuclear export. Depletion of CLK2 increased the production of inflammatory cytokines, reduced viral replication and increased the survival of the mice. Mechanistically, CLK2 phosphorylated RelA/p65 at Ser180 in the nucleus, leading to ubiquitin‒proteasome-mediated degradation and cytoplasmic redistribution. Importantly, a CLK2 inhibitor promoted cytokine production, reduced viral replication, and accelerated murine psoriasis. This study revealed an IκBα-independent mechanism of early-stage termination of NF-κB in which phosphorylated Ser180 RelA/p65 turned off posttranslational modifications associated with transcriptional activation, ultimately resulting in the degradation and nuclear export of RelA/p65 to inhibit excessive inflammatory activation. Our findings showed that the phosphorylation of RelA/p65 at Ser180 in the nucleus inhibits early-stage NF-κB activation, thereby mediating the negative regulation of NF-κB.

Nanoarchitectonics of Bimetallic Cu-/Co-Doped Nitrogen-Carbon Nanozyme-Functionalized Hydrogel with NIR-Responsive Phototherapy for Synergistic Mitigation of Drug-Resistant Bacterial Infections.

Superbug infections and transmission have become major challenges in the contemporary medical field. The development of novel antibacterial strategies to efficiently treat bacterial infections and conquer the problem of antimicrobial resistance (AMR) is extremely important. In this paper, a bimetallic CuCo-doped nitrogen-carbon nanozyme-functionalized hydrogel (CuCo/NC-HG) has been successfully constructed. It exhibits photoresponsive-enhanced enzymatic effects under near-infrared (NIR) irradiation (808 nm) with strong peroxidase (POD)-like and oxidase (OXD)-like activities. Upon NIR irradiation, CuCo/NC-HG possesses photodynamic activity for producing singlet oxygen(1O2), and it also has a high photothermal conversion effect, which not only facilitates the elimination of bacteria but also improves the efficiency of reactive oxygen species (ROS) production and accelerates the consumption of GSH. CuCo/NC-HG shows a lower hemolytic rate and better cytocompatibility than CuCo/NC and possesses a positive charge and macroporous skeleton for restricting negatively charged bacteria in the range of ROS destruction, strengthening the antibacterial efficiency. Comparatively, CuCo/NC and CuCo/NC-HG have stronger bactericidal ability against methicillin-resistant Staphylococcus aureus (MRSA) and ampicillin-resistant Escherichia coli (AmprE. coli) through destroying the cell membranes with a negligible occurrence of AMR. More importantly, CuCo/NC-HG plus NIR irradiation can exhibit satisfactory bactericidal performance in the absence of H2O2, avoiding the toxicity from high-concentration H2O2. In vivo evaluation has been conducted using a mouse wound infection model and histological analyses, and the results show that CuCo/NC-HG upon NIR irradiation can efficiently suppress bacterial infections and promote wound healing, without causing inflammation and tissue adhesions.

Anchoring Ultrafine ß-Mo2C Clusters Inside Porous Co-NC Using MOFs for Electric-Powered Coproduction of Valuable Chemicals.

Electroredox of organics provides a promising and green approach to producing value-added chemicals. However, it remains a grand challenge to achieve high selectivity of desired products simultaneously at two electrodes, especially for non-isoelectronic transfer reactions. Here a porous heterostructure of Mo2C@Co-NC is successfully fabricated, where subnanometre ß-Mo2C clusters (<1 nm, ≈10 wt%) are confined inside porous Co, N-doped carbon using metalorganic frameworks. It is found that Co species not only promote the formation of ß-Mo2C but also can prevent it from oxidation by constructing the heterojunctions. As noted, the heterostructure achieves >96% yield and 92% Faradaic efficiency (FE) for aldehydes in anodic alcohol oxidation, as well as >99.9% yield and 96% FE for amines in cathodal nitrocompounds reduction in 1.0 M KOH. Precise control of the reaction kinetics of two half-reactions by the electronic interaction between ß-Mo2C and Co is a crucial adjective. Density functional theory (DFT) gives in-depth mechanistic insight into the high aldehyde selectivity. The work guides authors to reveal the electrooxidation nature of Mo2C at a subnanometer level. It is anticipated that the strategy will provide new insights into the design of highly effective bifunctional electrocatalysts for the coproduction of more complex fine chemicals.

An Introduced RNA-Only Approach for Plasmid Curing via the CRISPR-Cpf1 System in Saccharomyces cerevisiae.

The CRISPR-Cas system has been widely used for genome editing due to its convenience, simplicity and flexibility. Using a plasmid-carrying Cas protein and crRNA or sgRNA expression cassettes is an efficient strategy in the CRISPR-Cas genome editing system. However, the plasmid remains in the cells after genome editing. Development of general plasmid-curing strategies is necessary. Based on our previous CRISPR-Cpf1 genome-editing system in Saccharomyces cerevisiae, the crRNA, designed for the replication origin of the CRISPR-Cpf1 plasmid, and the ssDNA, as a template for homologous recombination, were introduced for plasmid curing. The efficiency of the plasmid curing was 96 ± 4%. In addition, we further simplified the plasmid curing system by transforming only one crRNA into S. cerevisiae, and the curing efficiency was about 70%. In summary, we have developed a CRISPR-mediated plasmid-curing system. The RNA-only plasmid curing system is fast and easy. This plasmid curing strategy can be applied in broad hosts by designing crRNA specific for the replication origin of the plasmid. The plasmid curing system via CRISPR-Cas editing technology can be applied to produce traceless products without foreign genes and to perform iterative processes in multiple rounds of genome editing.

Cu2+@metal-organic framework-derived amphiphilic sandwich catalysts for enhanced hydrogenation selectivity of ketenes at the oil-water interface.

Selective catalysis has always been an essential process for manufacturing various fine chemicals, such as food additives, pharmaceuticals and perfumes. Practically, pure target products are difficult to obtain even after complex purification procedures during industrial production. The development of a cost-effective, highly chemoselective and long-life catalyst may be an attractive solution, but such a catalyst is elusive. Herein, a novel class of amphiphilic N-doped carbon (NC), featuring graphitic carbon (GC) and highly dispersed Cu@Co NPs, was fabricated via simple calcination of a Cu2+-doped bimetallic metal-organic framework (MOF) precusor directly. Compared with monometallic Co@GC/NC, the side reaction of CO bond hydrogenation is obviously restrained, and thus, pure target product can be systematically obtained by Cu@Co@GC/NC, highlighting the high selectivity of Cu. More importantly, an amphiphilic characteristic in Cu@Co@GC/NC is a significant knob to integrate organic substrates with water very well. This amphiphilic material shows great potential as a field-deployable pathway for dispersible metal catalysts in organic systems.

A New Species of Free-living Marine Nematode (Ptycholaimellus: Chromadoridae: Chromadorida: Nematoda) from Mangrove Wetlands in China.

This study presents a new species of free-living marine nematode, Ptycholaimellus luoyang sp. nov., from mangrove wetlands in China. The identification was confirmed by analyzing morphological characteristics and three genes: COI, 18S rDNA, and 28S rDNA. This species is distinguished from allied species by its short cephalic setae, cylindrical pharynx with anterior swelling, sclerotized transverse ridges occurring near the dorsal tooth, rod-like gubernaculum and proximal, arch-like, slightly waved, middle curved, and distally pointed spicules. The Bayesian topology was regarded as morphological evidence of P. luoyang sp. nov. being a distinct species. Interspecific and intrageneric thresholds of the K2P distance divergence have been presented here for the first time.

SYNGR2 serves as a prognostic biomarker and correlates with immune infiltrates in esophageal squamous cell carcinoma.

BACKGROUND: Synaptogyrin-2 (SYNGR2) plays an important role in regulating membrane traffic in non-neuronal cells. However, the role of SYNGR2 in esophageal squamous cell carcinoma (ESCC) remains unclear. METHODS: All original data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and integrated via R 3.5.3. SYNGR2 expression was explored in the TCGA and GEO databases. The correlations between SYNGR2 and cancer immune characteristics were analyzed via the TIMER and TISIDB databases. RESULTS: In general, SYNGR2 was predominantly overexpressed and had reference values in the diagnosis and prognostic estimation of ESCC. Upregulated SYNGR2 was associated with poorer overall survival, disease-specific survival and T stage in ESCC. Mechanistically, we identified hub genes that included a total of 38 SYNGR2-related genes, which were tightly associated with the protein polyubiquitination pathway in ESCC patients. SYNGR2 expression was negatively related to the infiltrating levels of T helper cells. SYNGR2 methylation was positively correlated with the expression of chemokines (CCL2 and CXCL12), chemokine receptors (CCR1 and CCR2), immunoinhibitors (CXCL12 and TNFRSF4) and immunostimulators (CSF1R and PDCD1LG2) in ESCC. CONCLUSION: SYNGR2 may be used as a biomarker for determining prognosis and immune infiltration in ESCC.

Encapsulating Copper Nanocrystals into Metal-Organic Frameworks for Cascade Reactions by Photothermal Catalysis.

Composite materials with multifunctional properties usually possess synergetic effects in catalysis toward cascade reactions. In this work, a facile strategy to the encapsulation of octahedral Cu2 O nanocrystals (NCs) by metal-organic frameworks (MOFs) is reported, and an oriented growth of MOF enclosures (namely, HKUST-1) around Cu2 O NCs with desired feedstock ratio is achieved. The strategy defines the parameter range that precisely controls the etching rate of metal oxide and the MOF crystallization rate. Finally, the Cu@HKUST-1 composites with uniform morphology and controlled MOF thickness have been successfully fabricated after the reduction of Cu2 O to Cu NCs in HKUST-1. The integration of Cu NCs properties with MOF advantages helps to create a multifunctional catalyst, which exhibits cooperative catalytic activity and improved recyclability toward the one-pot cascade reactions under mild conditions involving visible-light irradiation. The superior performance can be attributed to the plasmonic photothermal effect of Cu NCs, while HKUST-1 shell provides Lewis acid sites, substrates and H2 enrichment, and stabilizes the Cu cores.

Photocatalytic cascade reactions and dye degradation over CdS-metal-organic framework hybrids.

Two bifunctional CdS-MOF composites have been designed and fabricated. The hybrids exhibited synergistic photocatalytic performance toward two cascade reactions under visible light integrating photooxidation activity of CdS and Lewis acids/bases of the MOF. The composite further promoted the photodegradation of dyes benefiting from effective electron transfer between the MOF and CdS.

Novel CoNi-metal-organic framework crystal-derived CoNi@C: synthesis and effective cascade catalysis.

Evaluating the catalytic influence of metal sites on derivates obtained from the calcination of metal-organic frameworks (MOFs) is very important for the rational construction of novel MOFs. Based on this catalytic functional guidance, two new Co-MOF and CoNi-MOF crystals were designed and synthesized, and further pyrolyzed to obtain corresponding porous carbon-based catalysts. Interestingly, the derivates exhibited better catalytic performance toward the tandem reaction of dehydrogenation of NH3BH3 and subsequent hydrogenation reduction of nitro/olefin compounds than those of the CoNi-ZIF (a star MOF)-derived CoNi@carbon and most metal catalysts. Significantly, the CoNi@C maintained excellent activity, even after 30 cycles, demonstrating its great longevity and durability, which are especially important for the practical application of metal catalysts in industrial catalysis.

Nosocomial cross-infection of hypervirulent Listeria monocytogenes sequence type 87 in China.

BACKGROUND: To investigate the epidemiological and phenotypic characteristics and molecular relatedness of L. monocytogenes, which were cultured from the blood and cerebrospinal fluid (CSF) samples isolated from two neonates. METHODS: In the present case study, two infected neonates were interviewed and epidemiological investigation performed. The phenotypic characteristics and molecular relatedness of L. monocytogenes was characterized by serotyping, pulsed-field gel electrophoresis and whole-genome sequencing (WGS). RESULTS: The field investigation found that the two neonates were born in the same hospital (Hospital B) and admitted to the neonatal department through different channels within half an hour by different nurses, where they were weighed and placed in different but adjacent incubators. Then they were cared for by the same group of nurses that evening. It is worth noting that there was no record of sanitation of the neonatal incubator of neonate-1. The serotype of the two isolated L. monocytogenes were 1/2b, with an indistinguishable pulsotypes and were sequence type (ST) 87. WGS showed that there were no core SNP differences identified. In order to explore the genomic traits associated with L. monocytogenes virulence genes, we identified the Listeria pathogenicity island 4 and found that the genome was devoid of any stress islands. There are no positive results from the environmental samples. Considering the genomic data together with epidemiological evidence and clinical symptoms, insufficient surface cleaning along with the nursing staff caring for these neonates was considered as cross-infection factors. CONCLUSIONS: To our knowledge, this is the first report of a nosocomial cross-infection of L. monocytogenes ST87 between two neonates, which carries the recently identified gene cluster expressing the cellobiose-family phosphotransferase system (PTS-LIPI-4) between two neonates. The test results of environmental samples in the hospital indicate that strict sterilization and patient isolation measures cannot be emphasized enough in neonatal nursing.

Location determination of metal nanoparticles relative to a metal-organic framework.

Metal nanoparticles (NPs) stabilized by metal-organic frameworks (MOFs) have been intensively studied in recent decades, while investigations on the location of guest metal NPs relative to host MOF particles remain challenging and very rare. In this work, we have developed several characterization techniques, including high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) tomography, hyperpolarized 129Xe NMR spectroscopy and positron annihilation spectroscopy (PAS), which are able to determine the specific location of metal NPs relative to the MOF particle. The fine PdCu NPs confined inside MIL-101 exhibit excellent catalytic activity, absolute selectivity and satisfied recyclability in the aerobic oxidation of benzyl alcohol in pure water. As far as we know, the determination for the location of metal NPs relative to MOF particles and pore structure information of metal NPs/MOF composites by 129Xe NMR and PAS techniques has not yet been reported.

Three-Shell Cu@Co@Ni Nanoparticles Stabilized with a Metal-Organic Framework for Enhanced Tandem Catalysis.

Transition-metal catalysts, particularly featuring a triple-layered core-shell structure, are very promising for practical application; however, reports on their synthesis and catalytic application for a cascade reaction were very rare. In this work, tiny Cu@Co@Ni core-shell nanoparticles (∼3.3 nm) containing Cu core, Co middle shell, and Ni outer shell stabilized by metal-organic framework (MOF) were successfully synthesized to give a quadruple-layered Cu@Co@Ni/MOF at moderate conditions. The catalyst exhibited superior catalytic performance toward the in situ hydrogenation of nitroarenes using the H2 generated from the hydrolysis of ammonia borane (NH3BH3) under mild conditions. Interestingly, the Cu@Co@Ni/MOF also showed excellent catalytic activity toward CO oxidation reaction, which outperforms those of noble-metal catalysts. To our knowledge, this is the first report on transition-metal nanoparticles with a three-layered core-shell structure stabilized by MOF as a cooperative catalyst for cascade reaction and CO oxidation.

The risk of glaucoma and serotonergic antidepressants: A systematic review and meta-analysis.

BACKGROUND: The aim of current study was to conduct a systematic review and meta-analysis to explore the relationship between antidepressant use and glaucoma. METHODS: Eight major electronic databases were searched from inception until March 19th, 2018 to obtain relevant studies that evaluated associations of antidepressants [including selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs)] treatment and the risk of primary open-angle glaucoma (POAG) or primary angle-closure glaucoma (PACG) as well as intraocular pressure (IOP), and related anterior chamber parameters compared to participants not exposed to antidepressant treatment. A random-effects meta-analysis was conducted. RESULTS: Six case-control studies and one cohort study were eligible (N = 801,754). The use of SSRIs was not associated with a higher risk of glaucoma (k = 7, pooled adjusted odds ratio (pAOR) = 0.956, 95% confidence interval (CI) = 0.807 to 1.133, p = 0.604). In addition, IOP was lower in participants exposed to antidepressants (SSRIs and SNRIs) (k = 4, Hedges' g = -0.519, 95% CI = -0.743 to -0.296, p < 0.001). Finally, pupillary diameter was higher in participants exposed to antidepressant treatment (k = 4, Hedges' g = 0.681, 95% CI = 0.462 to 0.900, p < 0.001). LIMITATIONS: High heterogeneity of included studies limit the establishment of causal inferences. CONCLUSIONS: This meta-analysis indicates that a putative association between the use of SSRIs and a higher risk of glaucoma remains to be proven. However, antidepressant drug treatment may be associated with significantly lower IOP and higher pupillary diameter. The mechanisms underpinning these associations deserve further investigation.

Low-cost CuNi@MIL-101 as an excellent catalyst toward cascade reaction: integration of ammonia borane dehydrogenation with nitroarene hydrogenation.

Bimetallic CuNi nanoparticles (NPs) with low cost were rationally confined inside MIL-101 to give CuNi@MIL-101, which exhibits high efficiency and excellent recyclability toward the hydrogenation of nitroarenes under mild conditions on coupling with ammonia borane dehydrogenation. This is the first report on MOF-stabilized base metal NPs for cascade reactions.

Characterization of the Salmonella enterica Serotype Isangi Isolated from Patients for the First Time in China.

No studies have reported the isolation of serotype Salmonella Isangi from cases of salmonellosis in mainland China. We investigated an outbreak of foodborne disease with salmonella and collected the samples from the patients and surplus foods. Salmonella strains were isolated and the serotype was identified according to the Kauffmann-White scheme. The relatedness of the isolates was determined using pulsed-field gel electrophoresis (PFGE) and whole genome sequencing (WGS). Antimicrobial susceptibility was conducted by the broth microdilution method. There were 74 diners in the case, 33 of which got ill, with an attack rate of 44.6% (33/74). A total of 24 samples were collected from the outbreak cases, six Salmonella Isangi strains were isolated and susceptible to all tested drugs. PFGE and WGS analysis suggested that the pathogen dissemination through a single or limited vector(s), the steamed fish and mixed food (fry spicy chicken, braised pork ribs, and goose leg), may be the source of infection or be cross-contaminated. We first report the characteristics of an outbreak and molecular strain relatedness of Salmonella Isangi in mainland China.

Singlet Oxygen-Engaged Selective Photo-Oxidation over Pt Nanocrystals/Porphyrinic MOF: The Roles of Photothermal Effect and Pt Electronic State.

The selectivity control toward aldehyde in the aromatic alcohol oxidation remains a grand challenge using molecular oxygen under mild conditions. In this work, we designed and synthesized Pt/PCN-224(M) composites by integration of Pt nanocrystals and porphyrinic metal-organic frameworks (MOFs), PCN-224(M). The composites exhibit excellent catalytic performance in the photo-oxidation of aromatic alcohols by 1 atm O2 at ambient temperature, based on a synergetic photothermal effect and singlet oxygen production. Additionally, in opposition to the function of the Schottky junction, injection of hot electrons from plasmonic Pt into PCN-224(M) would lower the electron density of the Pt surface, which thus is tailorable for the optimized catalytic performance via the competition between the Schottky junction and the plasmonic effect by altering the light intensity. To the best of our knowledge, this is not only an unprecedented report on singlet oxygen-engaged selective oxidation of aromatic alcohols to aldehydes but also the first report on photothermal effect of MOFs.

Prevalence of Foodborne Pathogens in Cooked Meat and Seafood from 2010 to 2013 in Shandong Province, China.

BACKGROUND: Current food safety issues are deleteriously reshaping the lifestyle of the population in the developing world. The globalization of food supply impacts patterns of foodborne disease outbreaks worldwide, and consumers are having increased concern about microbiological food safety. METHODS: A total of 2305 samples including sauced meat, sausage, smoked meat, shrimp, sashimi and shellfish were collected from different farmer's markets and supermarkets. The prevalence of selected foodborne pathogens was evaluated in cooked meat and seafood from 2010 to 2013 in Shandong Province, China. RESULTS: The average contamination rate was 6.39% (93.1456) for the selected pathogens in cooked meat and 16.84% (143.849) for V. parahaemolyticus in seafood. For the selected pathogens, 0.55%, 1.03%, 1.17%, 3.64% and 16.84% samples were contaminated with E.coli O157: H7, Salmonella spp., L. monocytogenes, S. aureus and VP, respectively. There was a significant (P<0.05) difference in the contamination rate between the farmer's markets and supermarkets. CONCLUSION: The contamination was decreasing in cooked meat and maintaining a relatively high level in seafood from 2010 to 2013. E. coli O157: H7, S. aureus, L. monocytogenes and Salmonella spp. existed at a relatively low rate in retail foods. For VP, the contamination rate has been maintained at a relatively high level in Shandong Province in China. Moreover, cooked meat and seafood obtained from farmer's markets are more susceptible to be contaminated compared to those from supermarkets.

Three new and two known free-living marine nematode species of the family Ironidae from the East China Sea.

Three new and two known species of free-living marine nematodes of the family Ironidae from the East China Sea are described and illustrated. Conilia sinensis sp. nov. is identified by the relatively large body size (1883-2399 µm); the well developed lips; the number, shape and length of spicule (single and striated, length 87-100 µm as arc); the shape of telamon; the number of supplements (1). Pheronous donghaiensis sp. nov. is characterized by its sharp tail point; caudal gland absent; buccal cavity armed with four big solid teeth and rows of minute denticles; spicules stout, with central septum at proximal end, male caudal region with two rows of small conical subventral papillae. Trissonchulus latispiculum sp. nov. can be distinguished by its head not set off from remaining body, tail short and blunt, buccal cavity with minute denticles, spinneret opening slightly ventrally, spicule broad and alate with central septum and head on proximal end. Trissonchulus benepapillosus (Schulz, 1935) and Trissonchulus oceanus Cobb 1920 which are first reported from China, are redescribed in detail with emphasis on new or hitherto poorly described morphological features. Types are deposited in the Institute of Oceanology, Chinese Academy of Sciences.