Search

Background: Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood‐based assay to aid in the diagnosis, detection and prognostic evaluation of HCC. Methods: A three‐phase multicentre study was conducted to screen, optimise and validate HCC‐specific differentially methylated regions (DMRs) using next‐generation sequencing and quantitative methylation‐specific PCR (qMSP). Results: Genome‐wide methylation profiling was conducted to identify DMRs distinguishing HCC tumours from peritumoural tissues and healthy plasmas. The twenty most effective DMRs were verified and incorporated into a multilocus qMSP assay (HepaAiQ). The HepaAiQ model was trained to separate 293 HCC patients (Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 224) from 266 controls including chronic hepatitis B (CHB) or liver cirrhosis (LC) (CHB/LC, 96), benign hepatic lesions (BHL, 23), and healthy controls (HC, 147). The model achieved an area under the curve (AUC) of 0.944 with a sensitivity of 86.0% in HCC and a specificity of 92.1% in controls. Blind validation of the HepaAiQ model in a cohort of 523 participants resulted in an AUC of 0.940 with a sensitivity of 84.4% in 205 HCC cases (BCLC stage 0/A, 167) and a specificity of 90.3% in 318 controls (CHB/LC, 100; BHL, 102; HC, 116). When evaluated in an independent test set, the HepaAiQ model exhibited a sensitivity of 70.8% in 65 HCC patients at BCLC stage 0/A and a specificity of 89.5% in 124 patients with CHB/LC. Moreover, HepaAiQ model was assessed in paired pre‐ and postoperative plasma samples from 103 HCC patients and correlated with 2‐year patient outcomes. Patients with high postoperative HepaAiQ score showed a higher recurrence risk (Hazard ratio, 3.33, p <.001). Conclusions: HepaAiQ, a noninvasive qMSP assay, was developed to accurately measure HCC‐specific DMRs and shows great potential for the diagnosis, detection and prognosis of HCC, benefiting at‐risk populations. [ABSTRACT FROM AUTHOR]

Aging exhibits several hallmarks in common with cancer, such as cellular senescence, dysbiosis, inflammation, genomic instability, and epigenetic changes. In recent decades, research into the role of cellular senescence on tumor progression has received widespread attention. While how senescence limits the course of cancer is well established, senescence has also been found to promote certain malignant phenotypes. The tumor‐promoting effect of senescence is mainly elicited by a senescence‐associated secretory phenotype, which facilitates the interaction of senescent tumor cells with their surroundings. Targeting senescent cells therefore offers a promising technique for cancer therapy. Drugs that pharmacologically restore the normal function of senescent cells or eliminate them would assist in reestablishing homeostasis of cell signaling. Here, we describe cell senescence, its occurrence, phenotype, and impact on tumor biology. A "one‐two‐punch" therapeutic strategy in which cancer cell senescence is first induced, followed by the use of senotherapeutics for eliminating the senescent cells is introduced. The advances in the application of senotherapeutics for targeting senescent cells to assist cancer treatment are outlined, with an emphasis on drug categories, and the strategies for their screening, design, and efficient targeting. This work will foster a thorough comprehension and encourage additional research within this field. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy is an important approach for lung cancer patients. The study was designed to evaluate the feasibility of the compound probiotic supplements in improving the quality of life for lung cancer patients undergoing chemotherapy. Methods: This randomized, double‐blind, placebo‐controlled trial enrolled chemotherapy‐naive patients with lung cancer who were scheduled to receive platinum‐based doublet chemotherapy. All eligible patients were randomly administered (1:1) compound probiotic supplements (group BP‐1) or placebo (group C) for two chemotherapy cycles. The EORTC QLQ C30 questionnaire scores were evaluated before the first, second, and third cycles of chemotherapy. The primary endpoint was the difference in the EROTC QLQ C30 questionnaire score between the two groups after two cycles of chemotherapy. Results: A total of 110 patients were recruited from March 2021 to January 2022. After undergoing two cycles of chemotherapy, group BP‐1 were significantly better in various dimensions of the overall quality of life, role function, nausea and vomiting, appetite loss, constipation, and diarrhea relative to group C (76.90 ± 18.31 vs. 58.89 ± 17.17; 93.33 ± 11.58 vs. 85.93 ± 15.06; 0.00 ± 0.00 vs. 27.04 ± 29.15; 6.67 ± 13.53 vs. 22.22 ± 18.80; 0.95 ± 5.63 vs. 28.15 ± 22.42; 2.86 ± 9.47 vs. 15.56 ± 16.82; p < 0.05, respectively). The incidence of nausea and vomiting, appetite loss, constipation, and diarrhea in group BP‐1 was significantly lower than in group C (0% vs. 71.43%, 16.67% vs. 57.14%, 2.38% vs. 63.27%, and 7.14% vs. 42.86%, respectively, p < 0.001). Conclusions: Compound probiotic supplements can improve the quality of life and relieve chemotherapy‐related gastrointestinal side effects for lung cancer patients receiving platinum‐based doublet chemotherapy. (Chinese Clinical Trial Registry: ChiCTR1800019269). [ABSTRACT FROM AUTHOR]

Objective: Temporal lobe epilepsy (TLE) is the most common pharmacoresistant epilepsy in adults. Here we profiled local neural function in TLE in vivo, building on prior evidence that has identified widespread structural alterations. Using resting‐state functional magnetic resonance imaging (rs‐fMRI), we mapped the whole‐brain intrinsic neural timescales (INT), which reflect temporal hierarchies of neural processing. Parallel analysis of structural and diffusion MRI data examined associations with TLE‐related structural compromise. Finally, we evaluated the clinical utility of INT. Methods: We studied 46 patients with TLE and 44 healthy controls from two independent sites, and mapped INT changes in patients relative to controls across hippocampal, subcortical, and neocortical regions. We examined region‐specific associations to structural alterations and explored the effects of age and epilepsy duration. Supervised machine learning assessed the utility of INT for identifying patients with TLE vs controls and left‐ vs right‐sided seizure onset. Results: Relative to controls, TLE showed marked INT reductions across multiple regions bilaterally, indexing faster changing resting activity, with strongest effects in the ipsilateral medial and lateral temporal regions, and bilateral sensorimotor cortices as well as thalamus and hippocampus. Findings were similar, albeit with reduced effect sizes, when correcting for structural alterations. INT reductions in TLE increased with advancing disease duration, yet findings differed from the aging effects seen in controls. INT‐derived classifiers discriminated patients vs controls (balanced accuracy, 5‐fold: 76% ± 2.65%; cross‐site, 72%–83%) and lateralized the focus in TLE (balanced accuracy, 5‐fold: 96% ± 2.10%; cross‐site, 95%–97%), with high accuracy and cross‐site generalizability. Findings were consistent across both acquisition sites and robust when controlling for motion and several methodological confounds. Significance: Our findings demonstrate atypical macroscale function in TLE in a topography that extends beyond mesiotemporal epicenters. INT measurements can assist in TLE diagnosis, seizure focus lateralization, and monitoring of disease progression, which emphasizes promising clinical utility. [ABSTRACT FROM AUTHOR]

This article investigates the stability analysis of discrete‐time neural networks with time‐varying delays by the utilization of quadratic delay information. First, three extended negative‐definiteness lemmas for matrix‐valued quadratic function with different matrices injection are established. Second, a novel delay‐product‐type Lyapunov functional with the asymmetric summation is developed to relax the positive‐definiteness of functional. Then, the proposed negative definite approaches are utilized in combination with some typical summation inequalities to realize the construction of linear matrix inequalities. Based on these improved technologies, two delay‐dependent stability criteria with less conservatism and fewer computational burdens are derived. Finally, several numerical examples are presented to show the validity and superiority of the proposed methods. [ABSTRACT FROM AUTHOR]

Background: Diabetic peripheral neuropathy (DPN) is a common neurological complication of diabetes mellitus without efficient interventions. Both lysine demethylase 5B (KDM5B) and sirtuin‐3 (SIRT3) have been found to regulate islet function and glucose homeostasis. KDM5B was predicted to bind to the SIRT3 promoter by bioinformatics. Here, we investigated whether KDM5B affected DPN development via modulating SIRT3. Methods: The db/db mice and high glucose‐stimulated Schwann cells (RSC96) were used as in vivo and in vitro models of DPN, respectively. Glucose level, glucose and insulin tolerance of mice were measured. Neurological function was evaluated by motor nerve conduction velocity (MNCV), tactile allodynia assay and thermal sensitivity assay. Adenosine triphosphate level, oxygen consumption rate, extracellular acidification rate, β‐oxidation rate, acetyl‐CoA level, acetylation levels and activities of long‐chain acyl CoA dehydrogenase (LCAD) and pyruvate dehydrogenase (PDH) were detected. Methyl thiazolyl tetrazolium assay was adopted to determine cell viability. Reactive oxygen species (ROS) production was detected by MitoSox staining. Western blotting for measuring target protein levels. Molecular mechanisms were investigated by co‐immunoprecipitine (Co‐IP), chromatin immunoprecipitation (ChIP) and luciferase reporter assay. Results: KDM5B was up‐regulated, while SIRT3 was down‐regulated in DPN models. SIRT3 overexpression or AMPK activation ameliorated mitochondrial metabolism dysfunction and ROS overproduction during DPN. KDM5B overexpression triggered mitochondrial metabolism disorder and oxidative stress via directly transcriptional inhibiting SIRT3 expression by demethylating H3K4me3 or indirectly repressing AMPK pathway‐regulated SIRT3 expression. Conclusion: KDM5B contributes to DPN via regulating SIRT3‐mediated mitochondrial glucose and lipid metabolism. KDM5B inhibition may be an effective intervention for DPN. [ABSTRACT FROM AUTHOR]

The mutual confinement of ceramics and metals in laminated composites tends to change the original properties of ceramics and metals. In this study, two kinds of laminated composites, Al2O3/Ti and Al2O3/Ti/Ni, were prepared. Three‐point bending experiments revealed that Al2O3/Ti underwent brittle fracture after elastic deformation. The fracture morphology analysis revealed that the Ti in Al2O3/Ti became brittle due to the formation of columnar crystals. The temperature gradient perpendicular to the direction of laminations during preparation was responsible for the formation of columnar crystals. The force–displacement curves of the Al2O3/Ti/Ni combine the properties of elastic deformation of ceramics and plastic deformation of metals. The reason why the Al2O3/Ti/Ni did not fracture completely in the bending experiments is that Ni maintained the toughness, and there is a good interfacial bond among Al2O3, Ti, and Ni. The indentation crack analysis revealed that cracks have long transverse propagation and short longitudinal propagation in both laminated composites. Finite element analysis revealed that this was due to compressive stress in the Al2O3 layer and tensile stress in the metal layer. This compressive stress consumes the crack energy in the longitudinal direction and stops the crack in the metal layer. The brittle to ductile gradient transition among Al2O3, Ti, and Ni, combined with the guidance of crack propagation direction by the interfacial layer, enhances the ability of Al2O3/Ti/Ni to resist damage. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to explore predictors and construct a nomogram for risk stratification in primary extragastric mucosa‐associated lymphoid tissue (MALT) lymphoma. Methods: Extragastric MALT lymphoma cases newly diagnosed between November 2010 and April 2020 were assessed to construct a progression‐free survival (PFS)‐related nomogram. We also performed external validation of the nomogram in an independent cohort. Results: We performed multivariate analyses of 174 patients from 3 hospitals who were included in the training cohort. Stage, hepatitis B virus surface antigen (HBsAg) status, and Ki67 expression were significantly associated with PFS. These three factors were used to construct a nomogram, which was shown to have a C‐index of 0.89. Two risk groups (low risk and high risk) were identified by the prognostic model. The 5‐year PFS was 98.9% for the low‐risk group and 69.3% for the high‐risk group (p < 0.001). The overall survival (OS) could also be effectively distinguished by the nomogram, resulting in an OS of 100% for the low‐risk group and 94.6% for the high‐risk group (p = 0.01). These results were validated and confirmed in an independent cohort with 165 patients from another three hospitals. The 5‐year PFS rates were 94.8% and 66.7% for the low‐risk and high‐risk groups, respectively (p < 0.001). The 5‐year OS rates were 97.9% and 88.4%, respectively (p = 0.016). Conclusion: The nomogram could well distinguish the prognosis of low‐ and high‐risk patients with extragastric MALT lymphoma and is thus recommended for clinical use. [ABSTRACT FROM AUTHOR]

Under the growing crisis of the coronavirus disease 2019 pandemic, the global medical system is facing the predicament of an acute shortage of medical‐grade oxygen (O2, ≥ 99.5% purity). Herein, an oxygen generation device is manufactured that relies on electrochemical technology. The performance of the electrochemical oxygen generator (EOG) is remarkably improved to a practically applicable level, achieving long‐term (>200 h), stable, and quick production (>1.5 L min−1) of high purity O2 (99.9%) at high energy efficiency (496 L kW−1 h−1), via simultaneous optimization for intrinsic electrochemical reaction mechanisms, electrocatalysts, and external cell structure. The EOG also presents powerful competitiveness in user experience, which finds expression in high portability (4.7 kg), nearly instant O2 production (<1 s), and a quiet working condition (<39 dB). The EOG shows great potential to substitute commercial pressure swing adsorption O2 generation devices, which may significantly impact the traditional oxygen production industry. [ABSTRACT FROM AUTHOR]

Recent studies emphasize the importance of 5‐HT2C receptor (5‐HT2CR) signaling in the regulation of energy homeostasis. The 5‐HT2CR is the only G‐protein‐coupled receptor known to undergo post‐transcriptional adenosine to inosine (A‐to‐I) editing by adenosine deaminase acting on RNA (ADAR). 5‐HT2CR has emerged as an important role in the modulation of pancreatic β cell functions. This study investigated mechanisms behind the effects of palmitic acid (PA) on insulin secretion in different overexpressed 5‐HT2CR edited isoforms in pancreatic MIN6 β cells. Results showed that the expressions of 5HT2CR and ADAR2 were upregulated in the pancreatic islets of mice fed with high‐fat diet (HFD) compared to control mice. PA treatment significantly induced the expressions of 5‐HT2CR and ADAR2 in pancreatic MIN6 β cells. PA treatment significantly induced the editing of 5‐HT2CR in pancreatic MIN6 β cells. There was no significant difference in cell viability between naïve cells and three overexpressed 5‐HT2CR edited isoforms in pancreatic MIN6 β cells. Overexpressed 5‐HT2CR edited isoforms showed reduced glucose‐stimulated insulin secretion (GSIS) compared with green fluorescent protein (GFP) expressed cells. Moreover, 5‐HT2CR edited isoforms displayed reduced endoplasmic reticulum (ER) calcium release and store‐operated calcium entry (SOCE) activation, probably through inhibition of stromal interaction molecule 1 trafficking under PA treatment. Altogether, our results show that PA‐mediated editing of 5‐HT2CR modulates GSIS through alteration of ER calcium release and SOCE activation in pancreatic MIN6 β cells. [ABSTRACT FROM AUTHOR]

Summary: Identifying genic male‐sterility (GMS) genes and elucidating their roles are important to unveil plant male reproduction and promote their application in crop breeding. However, compared with Arabidopsis and rice, relatively fewer maize GMS genes have been discovered and little is known about their regulatory pathways underlying anther and pollen development. Here, by sequencing and analysing anther transcriptomes at 11 developmental stages in maize B73, Zheng58 and M6007 inbred lines, 1100 transcription factor (TF) genes were identified to be stably differentially expressed among different developmental stages. Among them, 14 maize TF genes (9 types belonging to five TF families) were selected and performed CRISPR/Cas9‐mediated gene mutagenesis, and then, 12 genes in eight types, including ZmbHLH51, ZmbHLH122, ZmTGA9‐1/‐2/‐3, ZmTGA10, ZmMYB84, ZmMYB33‐1/‐2, ZmPHD11 and ZmLBD10/27, were identified as maize new GMS genes by using DNA sequencing, phenotypic and cytological analyses. Notably, ZmTGA9‐1/‐2/‐3 triple‐gene mutants and ZmMYB33‐1/‐2 double‐gene mutants displayed complete male sterility, but their double‐ or single‐gene mutants showed male fertility. Similarly, ZmLBD10/27 double‐gene mutant displayed partial male sterility with 32.18% of aborted pollen grains. In addition, ZmbHLH51 was transcriptionally activated by ZmbHLH122 and their proteins were physically interacted. Molecular markers co‐segregating with these GMS mutations were developed to facilitate their application in maize breeding. Finally, all 14‐type maize GMS TF genes identified here and reported previously were compared on functional conservation and diversification among maize, rice and Arabidopsis. These findings enrich GMS gene and mutant resources for deeply understanding the regulatory network underlying male fertility and for creating male‐sterility lines in maize. [ABSTRACT FROM AUTHOR]

Visual selective attention allows us to filter relevant inputs from irrelevant inputs during visual processing. In contrast to rich research exploring how the brain facilitates task‐relevant inputs, less is known about how the brain suppresses irrelevant inputs. In this study, we used transcranial magnetic stimulation (TMS) to investigate the causal role of the right dorsolateral prefrontal cortex (DLPFC), a crucial brain area for attentional control, in distractor suppression. Specifically, 10‐Hz repetitive TMS (rTMS) was applied to the right DLPFC and Vertex at the stimuli onset (stimuli‐onset TMS) or 500 ms prior to the stimuli onset (prestimuli TMS). In a variant of the Posner cueing task, participants were instructed to identify the shape of a white target while ignoring a white or colored distractor whose location was either cued in advance or uncued. As anticipated, either the location cue or the colored distractor led to faster responses. Notably, the location cueing effect was eliminated by stimuli‐onset TMS to the right DLPFC, but not by prestimuli TMS. Further analyses showed that stimuli‐onset TMS quickened responses to uncued trials, and this TMS effect was derived from the inhibition at the distractor in both visual fields. In addition, TMS over the right DLPFC had no specific effect on the colored distractor compared to the white one. Considered collectively, these findings indicate that the DLPFC plays a crucial role in visuospatial distractor suppression and acts upon stimuli presentation. Besides, it seems the DLPFC contributes more to location‐based distractor suppression than to color‐based one. [ABSTRACT FROM AUTHOR]

Rationale: The aim of this study was to analyze the metabolomics of lung with different host inflammation of acute respiratory distress syndrome (ARDS) for the identification of biomarkers for predicting severity under different inflammatory conditions. Methods: Cecal ligation and puncture (CLP) and lipopolysaccharide (LPS)‐intratracheal injection induced acute lung injury (ALI) were used. A mouse model was used to explore lung metabolomic biomarkers in ALI/ARDS. The splenectomy model was used as an auxiliary method to distinguish between hyper‐ and hypo‐inflammatory subtypes. Plasma, lung tissue and bronchoalveolar lavage fluid (BALF) samples were collected from mice after CLP/LPS. The severity of lung injury was evaluated. Expression of tumor necrosis factor‐α (TNF‐α) in mice serum and lung was tested by enzyme‐linked immunosorbent assay (ELISA) and polymer chain reaction (PCR). Polymorphonuclear cells in BALF were counted. The lung metabolites were detected by gas chromatography/mass spectrometry (GC/MS), and the metabolic pathways predicted using the KEGG database. Results: The LPS/CLP‐Splen group had more severe lung injury than the corresponding ALI group; that in the CLP‐Splen group was more serious than in the LPS‐Splen group. TNF‐α expression was significantly elevated in the serum and lung tissue after LPS or CLP, and higher in the LPS/CLP‐Splen group than in the corresponding ALI group. The level of TNF‐α in the CLP‐Splen group was elevated significantly over that in the LPS‐Splen group. Both these groups also showed significant neutrophil exudation within the lungs. During differential inflammation, more differential metabolites were detected in the lungs of the CLP group ALI mice than in the LPS group. A total of 41 compounds were detected in the lungs of the CLP and CLP‐Splen groups. Contrastingly, eight compounds were detected in the lungs of the LPS and LPS‐Splen groups. The LPS‐Splen and CLP‐Splen groups had significant neutrophil exudation in the lung. Random forest analysis of lung‐targeted metabolomics data indicated 4‐hydroxyphenylacetic acid, 1‐aminocyclopentanecarboxylic acid (ACPC), cis‐aconitic acid, and hydroxybenzoic acid as strong predictors of the hyper‐inflammatory subgroup in the CLP group. Furthermore, with splenectomy, 13 differential metabolic pathways between the CLP and LPS groups were revealed. Conclusions: Hyper‐inflammatory subgroups of ARDS have a greater inflammatory response and a more active lung metabolism. Combined with the host inflammation background, biomarkers from metabolomics could help evaluate the response severity of ARDS. [ABSTRACT FROM AUTHOR]

Introduction: Perampanel is a highly selective and noncompetitive α‐amino‐3 ‐hydroxy‐5‐methyl‐4‐isoxazole propionate receptor (AMPAR) antagonist, which has been used as an orally administered antiepileptic drug in more than 55 countries. Recently, perampanel was shown to exert neuroprotective effects in hemorrhagic and ischemic stroke models via regulating blood–brain barrier (BBB) function. Aim: Here, the protective effects of perampanel were investigated in an in vitro neurovascular unit (NVU) system established using a triple cell co‐culture model (neurons, astrocytes, and brain microvascular endothelial cells) and in an in vivo traumatic brain injury (TBI) model. Results: Neurons in the NVU system exhibit a more mature morphological phenotype compared with neurons cultured alone, and the co‐culture system mimicked an impermeable barrier in vitro. Perampanel protects the NVU system against traumatic and excitotoxic injury, as evidenced by reduced lactate dehydrogenase (LDH) release and apoptotic rate. Treatment with perampanel attenuated lipid peroxidation and expression of inflammatory cytokines. In addition, perampanel increased Sirt3 protein expression, enhanced the activities of mitochondrial enzyme IDH2 and SOD2, and preserved BBB function in vitro. Knockdown of Sirt3 using specific siRNA (Si‐Sirt3) partially reserved the effects of perampanel on neuronal injury and BBB function. Treatment with perampanel in vivo attenuated brain edema, preserved neurological function, inhibited apoptosis and microglia activation after TBI. Furthermore, perampanel increased the expression of Sirt3 and preserved BBB function after TBI. The effect of perampanel on BBB function and brain edema was abolished by knockdown of Sirt3 in vivo. Conclusion: Our results indicate that the noncompetitive AMPAR antagonist perampanel protects the NVU system and reduces brain damage after TBI via activating the Sirt3 cascades. [ABSTRACT FROM AUTHOR]

The tunable growth of metal–organic materials has implications for engineering particles and surfaces for diverse applications. Specifically, controlling the self‐assembly of metal–phenolic networks (MPNs), an emerging class of metal–organic materials, is challenging, as previous studies suggest that growth often terminates through kinetic trapping. Herein, kinetic strategies were used to temporally and spatially control MPN growth by promoting self‐correction of the coordinating building blocks through oxidation‐mediated MPN assembly. The formation and growth mechanisms were investigated and used to engineer films with microporous structures and continuous gradients. Moreover, reactive oxygen species generated by ultrasonication expedite oxidation and result in faster (ca. 30 times) film growth than that achieved by other MPN assembly methods. This study expands our understanding of metal–phenolic chemistry towards engineering metal–phenolic materials for various applications. [ABSTRACT FROM AUTHOR]

Nowadays UAV filming is getting popular, more and more stunning aerial videos appearing online. Nonetheless, making a good uncut aerial video with only one‐long‐shot for the large‐scale outdoor scenes is still quite challenging, no many eye‐catching pieces available yet. It requires users to have both consummate drone controlling skill and good perception of filming aesthetics. If totally manual, the user has to simultaneously adjust the drone position and the mounted camera orientation during the whole flyby while trying to keep all operation changes executed smoothly. Recent research has proposed a number of planning tools for automatic or semi‐automatic aerial videography, however, most requires rather complex user inputs and heavy computations. In this paper, we propose a user‐friendly system designed to simplify the input and automatically generate continuous camera moves to capture compelling aerial videos that users prefer to see without any post cutting or editing. Assume a rough 2.5D scene model that includes all the regions of interest are available, users are only required to casually draw a single sketch on the 2D map. Our system will analyze this rough sketch input, compute the corresponding quality views in 3D safe flying zone, and then create a globally optimal camera trajectory passing through regions of user interest via solving a combinatorial problem. At end, we optimize the drone flying speed locally to make the resulting aerial videos more visually pleasing. [ABSTRACT FROM AUTHOR]

Abstract: Interleukin (IL)‐33/ST2 pathway plays crucial roles in tumour growth and metastasis. The aim of this study was to investigate the association of two functional polymorphisms (IL‐33 rs7025417 and ST2 rs3821204) with osteosarcoma (OS) risk. The rs7025417 and rs3821204 were genotyped by Taqman assay. IL‐33mRNA and protein levels were measured by real‐time PCR or enzyme‐linked immunosorbent assay. The luciferase activity was measured by a dual luciferase reporter gene assay. The allele‐specific transcription factor binding for rs7025417 was examined by ChIP‐seq. The IL‐33 rs7025417 CC genotype was significantly associated with a decreased risk of OS (CC vs TT: OR = 0.59, 95% CI, 0.41‐0.85; recessive model: OR = 0.68, 95% CI, 0.49‐0.94; C vs T: OR = 0.76, 95% CI, 0.63‐0.91). Combined analysis showed that the IL‐33 rs7025417CT/CC‐ST2 rs3821204CG/CC and the IL‐33 rs7025417CT/CC‐ST2 rs3821204GG genotypes also had a decreased risk of OS. IL‐33mRNA and protein levels in OS patients were significantly higher than controls. Patients with the rs7025417 CC genotype exhibited lower levels of IL‐33 (P = .03). The rs7025417 C allele presented a lower transcriptional activity by disrupting the binding site to c‐Myb (P < .01). Moreover, the rs3821204 G/C influences the transcriptional activity and ST2mRNA expression by altering the binding site of miR‐202‐3p. These findings suggest that the rs7025417 and rs3821204 may have a combined effect to protect against the development of OS by decreasing the expression levels of IL‐33 or ST2. [ABSTRACT FROM AUTHOR]

Abstract: A novel composite membrane consisting of an interconnected MOF scaffold coated with cross‐linked poly(ethylene glycol) (PEG) has been developed. As a result of its unique structure, the membrane shows an exceptional 18‐fold permeability enhancement as compared to pristine PEG membranes, without compromising the selectivity. This performance is unattainable with current mixed‐matrix membranes (MMMs). Our optimized membrane has a permeability of 2700 Barrer with a CO2/N2 selectivity of 35, which surpasses the latest Robeson upper bound. [ABSTRACT FROM AUTHOR]

Abstract: Maintaining endoplasmic reticulum (ER) homeostasis is essential for the production of biomolecules. ER retrieval, i.e., the retrograde transport of compounds from the Golgi to the ER, is one of the pathways that ensures ER homeostasis. However, the mechanisms underlying the regulation of ER retrieval in plants remain largely unknown. Plant ERD2‐like proteins (ERD2s) were recently suggested to function as ER luminal protein receptors that mediate ER retrieval. Here, we demonstrate that heterotrimeric G protein signaling is involved in ERD2‐mediated ER retrieval. We show that ERD2s interact with the heterotrimeric G protein Gα and Gγ subunits at the Golgi. Silencing of Gα, Gβ, or Gγ increased the retention of ER luminal proteins. Furthermore, overexpression of Gα, Gβ, or Gγ caused ER luminal proteins to escape from the ER, as did the co‐silencing of ERD2a and ERD2b. These results suggest that G proteins interact with ER luminal protein receptors to regulate ER retrieval. [ABSTRACT FROM AUTHOR]

Summary: Although hundreds of genetic male sterility (GMS) mutants have been identified in maize, few are commercially used due to a lack of effective methods to produce large quantities of pure male‐sterile seeds. Here, we develop a multicontrol sterility (MCS) system based on the maize male sterility 7 (ms7) mutant and its wild‐type Zea mays Male sterility 7 (ZmMs7) gene via a transgenic strategy, leading to the utilization of GMS in hybrid seed production. ZmMs7 is isolated by a map‐based cloning approach and encodes a PHD‐finger transcription factor orthologous to rice PTC1 and Arabidopsis MS1. The MCS transgenic maintainer lines are developed based on the ms7‐6007 mutant transformed with MCS constructs containing the (i) ZmMs7 gene to restore fertility, (ii) α‐amylase gene ZmAA and/or (iii) DNA adenine methylase gene Dam to devitalize transgenic pollen, (iv) red fluorescence protein gene DsRed2 or mCherry to mark transgenic seeds and (v) herbicide‐resistant gene Bar for transgenic seed selection. Self‐pollination of the MCS transgenic maintainer line produces transgenic red fluorescent seeds and nontransgenic normal colour seeds at a 1:1 ratio. Among them, all the fluorescent seeds are male fertile, but the seeds with a normal colour are male sterile. Cross‐pollination of the transgenic plants to male‐sterile plants propagates male‐sterile seeds with high purity. Moreover, the transgene transmission rate through pollen of transgenic plants harbouring two pollen‐disrupted genes is lower than that containing one pollen‐disrupted gene. The MCS system has great potential to enhance the efficiency of maize male‐sterile line propagation and commercial hybrid seed production. [ABSTRACT FROM AUTHOR]

We report an advanced synthesis strategy, termed 'exchange method using acid-solvent synergy for metal-organic framework synthesis' (EASY-MOFs), which can generally be applied to pillar-layered MOFs to generate new structures. Superior to de novo synthesis, EASY-MOFs provides an alternative synthesis route with advantages of high product purity, structural versatility and controllability. In addition, high product yield is possible without the need for tedious optimization of the synthetic conditions, which is often the case for de novo synthesis. More importantly, novel structures that are not obtainable by direct synthesis or conventional ligand-exchange strategies can be achieved by EASY-MOFs. Based on our experimental observations, we attribute the unique advantages of EASY-MOFs to the nucleation rate control during the disassembly-exchange-reassembly process and the seeding effect of the parent crystals promoted by the acid. [ABSTRACT FROM AUTHOR]

Low-rate Denial of Service (LDoS) is a new type of TCP-targeted attacks, which attempt to deny bandwidth to TCP flows while sending at sufficiently low-average rate to elude detection of DoS defense system. Therefore, LDoS attacks are difficult to be detected by routers and counter-DoS mechanisms. In this paper, an approach of detecting LDoS attacks is proposed by using the technology of signal processing based on the model of spectral energy distribution probability. The proposed approach calculates variances between the incoming traffic of normal TCP and attack flows to a server by using packet sampling sequence within a certain period. The network traffic is converted from the time domain to the frequency domain forming a spectral signal, and the distribution probability of spectral energy is estimated based on spectrum characteristics of rectangular pulses. This approach explores that the energy of LDoS attacks is mostly distributed in the main lobe width while that of normal TCP traffic is just concentrated near zero in frequency domain. Both the spectral energy of normal TCP traffic and LDoS attacks distributed in main lobe are calculated, and an energy threshold is set as decision value based on statistical results according to energy distribution properties. The existence of LDoS attacks is determined and detected by comparing calculated variances with the preset decision threshold value. Tests on the detection performance of the proposed approach were performed in NS-2 simulation environment, and detection rate was obtained by Hypothesis test. Experiment results show that the proposed approach has higher detection accuracy and less computation consuming. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The hypersensitive response (HR), a form of programmed cell death (PCD), is a tightly regulated innate immune response in plants that is hypothesized to restrict pathogen growth and disease development. Although considerable efforts have been made to understand HR PCD, it remains unknown whether the retrograde pathway from the Golgi to the endoplasmic reticulum (ER) is involved. Here we provide direct genetic evidence that two Nicotiana benthamiana homologs, ERD2a and ERD2b, function as ER luminal protein receptors and participate in HR PCD. Virus-induced gene silencing (VIGS) of ERD2a and/or ERD2b caused escape of ER-resident proteins from the ER, and resulted in plants that were more sensitive to ER stress. Silencing of ERD2b delayed HR PCD induced by the non-host pathogens Xanthomonas oryzae pv. oryzae and Pseudomonas syringae pv. tomato DC3000. However, both silencing of ERD2a and co-silencing of ERD2a and ERD2b exacerbated HR PCD. Individual and combined suppression of ERD2a and ERD2b exaggerated R gene-mediated cell death. Nevertheless, silencing of ERD2a and/or ERD2b had no detectable effects on bacterial growth. Furthermore, VIGS of several putative ligands of ERD2a/2b, including the ER quality control (ERQC) component genes BiP, CRT3 and UGGT, had different effects on HR PCD induced by different pathogens. This indicates that immunity-related cell death pathways are separate with respect to the genetic requirements for these ERQC components. These results suggest that ERD2a and ERD2b function as ER luminal protein receptors to ensure ERQC and alleviate ER stress, thus affecting HR PCD during the plant innate immune response. [ABSTRACT FROM AUTHOR]

BACKGROUND: It has been reported that antidiabetic drugs affect the risk of cancer and the prognosis of patients with diabetes, but few studies have demonstrated the influence of different antidiabetic agents on outcomes after anticancer therapy among patients with cancer. The objective of this study was to evaluate the influence of the antidiabetic drugs metformin and insulin on the prognosis of patients with advanced nonsmall cell lung cancer (NSCLC) plus type 2 diabetes who received first-line chemotherapy. METHODS: Data on patients with NSCLC who had diabetes from 5 hospitals in China during January 2004 to March 2009 were reviewed retrospectively. Ninety-nine patients were included in the final analysis. The influence of metformin and insulin on chemotherapy response rates and survival in these patients was evaluated. RESULTS: Chemotherapy with metformin (Group A) produced superior results compared with insulin (Group B) and compared with drugs other than metformin and insulin (Group C) in terms of both progression-free survival (PFS) (8.4 months vs 4.7 months vs 6.4 months, respectively; P = .002) and overall survival (OS) (20.0 months vs 13.1 months vs 13.0 months, respectively; P = .007). Although no significant differences in the response rate (RR) were observed between these 3 groups, when groups B and C (ie, the nonmetformin group) were combined, there was a tendency for better disease control in Group A than that in nonmetformin group. No significant difference in survival was observed between chemotherapy with insulin (Group B) versus other drugs (Group C). CONCLUSIONS: The current data suggested that metformin may improve chemotherapy outcomes and survival for patients who have NSCLC with diabetes. Cancer 2011;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background and Purpose: Paeoniflorin (PF) has ameliorative effects on learning and memory impairment and cerebral ischaemia in rats and has protective effects against the degeneration of dopaminergic neurons in substantia nigra. The neuroprotective effects of PF are most probably derived from its anti-inflammatory property. Abnormally high levels of intercellular adhesion molecule-1 (ICAM-1) have been found to be associated with a wide range of inflammatory and immune responses. Here we studied whether PF regulates the levels of ICAM-1 elevated in LPS-activated differentiated human monocytic U937 cells and TNF-α-stimulated human umbilical vein endothelial cells (HUVECs).Experimental Approach: mRNA levels were evaluated by RT-PCR. Protein levels were evaluated by Western blot analysis. An immunofluorescence technique was used to estimate NF-κB translocation, and NF-κB binding to nuclear DNA was determined by EMSA.Key Results: PF inhibited ICAM-1 expression elevated in LPS-induced U937 cells and TNF-α-stimulated HUVECs. Although previous reports showed that PF's action is mediated by activating adenosine A₁ receptors, application of a selective adenosine A₁ receptor antagonist did not change the inhibitory effect of PF in our experiments. To elucidate the underlying mechanisms of the effect of PF, we studied its effect on signalling pathways upstream of ICAM-1 expression. PF suppressed the activation of the NF-κB pathway, which regulates the expression of ICAM-1. The TLR4 and MAPK pathways were shown not to be involved in the effects of PF in these cells.Conclusions and Implications: PF inhibits ICAM-1 expression in LPS-treated U937 cells and TNF-α-stimulated HUVECs by suppressing the activation of the NF-κB pathway. [ABSTRACT FROM AUTHOR]

The article focuses on a study regarding alcoholic liver disease (ALD) which is a progressive liver disease. It mentions the role of roles of Kupffer cells ((KCs) in the pathogenesis of alcoholic liver disease, and states that chronic ethanol (EtOH) feeding activate KCs through lipopolysaccharide (LPS)/Toll-like receptor 4 (TLR-4) signaling pathway. It also mentions that EtOH enhances the permeability of intestinal mucosa.

The extract yields obtained by three methods in different solvents from chilli were compared. The antioxidant activities of chilli extracts vs. butylated hydroxytoluene (BHT) was determined through the peroxide value (POV), the beta-carotene bleaching assay and the 2,2-diphenyl-1-picrylhydrazyl radical scavenging method. The results showed that the extract yields by three extract methods, namely, Soxhlet, ultrasonic wave and saturation, were 16.32%, 15.78% and 11.62%, respectively, when 85% ethanol acted as solvent. The extracting efficiency of solvent from high to low was 95% ethanol > ethyl acetate > anhydrous ethanol > distilled water. The total phenol content of chilli extracts from ultrasonic wave with 85% ethanol as solvent was 73.91 mg gallic acid equivalents (GAE) per gram extracts and the value of inhibitory capacity IC50 on free radical (DPPH) was 38.99 mg mL−1. The POV of chilli extracts was close to that of BHT. The ultrasonic wave was more helpful for the extraction of antioxidant substance from chilli than other methods. In addition, the composition of chilli extracts was analysed by gas chromatography-mass spectrum (GC-MS). [ABSTRACT FROM AUTHOR]

This paper describes the differences between alkyl polyglucosides (APG) of natural alcohol and oxo-alcohol. The same reaction rate was observed for the one-step synthesis of APG from branched alcohols and from linear alcohols. Biodegradation studies showed that the primary biodegradability value of natural C8–10APG was slightly higher than for oxo-C10–11APG, and there was no significant difference between oxo-C12–13APG and C12–14APG. The primary biodegradability value of oxo-C14–15APG was lower than the four APG already named. The goal of this study of the physicochemical properties of these APG of natural alcohol and oxo-alcohol was to evaluate their differences. Diversification of APG selection will help improve its physicochemical properties and expand its application fields. The results are that the wetting abilities of oxo-C10–11APG and oxo-C12–13APG are better than the natural alcohol C8–10APG and C12–14APG, whereas the foamabilities of oxo-C10–11APG and oxo-C12–13APG are worse than those for natural C8–10APG and C12–14APG. There are no real differences in surface tension and detergency between APG of natural alcohol and oxo-alcohol. [ABSTRACT FROM AUTHOR]

Two hetero‐bimetallic [Zn(II)2M(II)] (M = Ca and Sr) complexes [Zn2Ca(L)(OAc)2] (1) and [Zn2Sr(L)(OAc)2] (2) with a novel asymmetrical bis(salamo)‐type tetraoxime ligand (H5L) were designed and synthesized, and characterized by elemental analyses, FT‐IR spectra, UV–vis absorption spectra, Density Functional Theory (DFT) calculation, Hirshfeld surface analyses and X‐ray single crystal diffractions. Compared with the symmetric bis(salamo)‐type ligands, the ligand H5L and its [Zn(II)2M(II)] (M = Ca and Sr) asymmetrical bis(salamo)‐type complexes synthesized for the first time in this paper have more novel structures and better properties. The results of ultraviolet titration show that the coordination ratio of ligand, alkaline earth metal and transition metal is 1:1:2. Complexes 1 and 2 have good luminescent properties and obvious antimicrobial activities. [ABSTRACT FROM AUTHOR]

Achieving fast‐charging capabilities in Li‐ion batteries (LIBs)—charging 80% of the battery capacity within 15 minutes—while maintaining an acceptable cycle life remains challenging due to various polarizations occurring at elevated charge rates. Such a goal is more tough at subzero, as temperature reduction slows the kinetics process including electrolyte mass transport and electrode charge transfer, substantially increasing the risk of lithium plating. Herein, it is found that adding LiFSI to a LiPF6 carbonate‐based electrolyte alters the Li+ solvation structure, endowing the dual‐salt electrolyte with a higher Li+ diffusion coefficient and lower desolvation energy. Benefit from the smaller structural change and the formation of a robust, conductive solid electrolyte interphase, the 12Ah‐pouch cells based on LiNi0.52Co0.2Mn0.28O2 cathodes and graphite anodes demonstrate fast‐charging capabilities and stable cycling performance across a wide temperature range of −20 to 50 ℃: charging 89% and 93% of pouch cell capacity within 4 minutes at 25 and 50 ℃ and 82% within 15 minutes at −20 ℃, maintaining capacity retention of 94% after 2000 cycles at 8C at 0 ℃ and 89% after 350 cycles at −20 ℃ at 4C. This work might offer new insights into enhancing the fast‐charging capabilities of LIBs under extreme conditions. [ABSTRACT FROM AUTHOR]