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Abstract Diffuse large B-cell lymphoma (DLBCL), an invasive lymphoma with substantial heterogeneity, can be mainly categorised into germinal centre B-cell-like (GCB) and non-GCB subtypes. DLBCL cells are highly susceptible to ferroptosis, which offers an effective avenue for treating recurrent and refractory DLBCL. Moreover, various heat shock proteins are involved in regulating the sensitivity of tumour cells to ferroptosis. Among these proteins, tailless complex polypeptide 1 (TCP1), a subunit of chaperonin-containing T-complex protein-1 (CCT), plays a role in tumour proliferation and survival. Therefore, we explored the role of TCP1 in different DLBCL subtypes, the sensitivity of GCB and non-GCB subtypes to the ferroptosis inducer RAS-selective lethal small molecule 3 (RSL3), and the underlying molecular mechanism. In GCB cells, TCP1 promoted RSL3-induced ferroptosis. Notably, TCP1 could bind with acyl-CoA synthetase long-chain family member 4 (ACSL4), a key enzyme regulating lipid composition and facilitating ferroptosis, to reduce its ubiquitination and degradation. This interaction activated the ACSL4/LPCAT3 signalling pathway and promoted ferroptosis in the GCB subtype. However, in the non-GCB subtype, TCP1 did not act as a positive regulator but served as a predictor of an unfavourable prognosis in patients with non-GCB. In conclusion, our results suggest that in DLBCL, high TCP1 expression enhances the sensitivity of GCB tumour cells to ferroptosis and serves as a marker of poor prognosis in patients with non-GCB DLBCL.

Abstract Exonucleases serve as efficient tools for signal processing and play an important role in biochemical reactions. Here, we identify the mechanism of cooperative exonuclease hydrolysis, offering a method to regulate the cooperative hydrolysis driven by exonucleases through the modulation of the number of bases in gap region. A signal transmission strategy capable of producing amplified orthogonal DNA signal is proposed to resolve the polarity of signals and byproducts, which provides a solution to overcome the signal attenuation. The gap-regulated mechanism combined with DNA strand displacement (DSD) reduces the unpredictable secondary structures, allowing for the coexistence of similar structures in hierarchical molecular networks. For the application of the strategy, a molecular computing model is constructed to solve the maximum weight clique problems (MWCP). This work enhances for our knowledge of these important enzymes and promises application prospects in molecular computing, signal detection, and nanomachines.

As a typical tight sandstone gas reservoir in the Ordos Basin, the second member of the Shanxi Formation in the XQ gas field in the Ordos Basin has had rich gas reservoirs and good development effects in the past. On the basis of previous studies, this paper brings new understanding to the sedimentary model of this area. Nine kinds of single lithofacies and seven kinds of lithofacies combinations are determined. Braided fluvial fan deposits in distributive fluvial systems likely developed in this area. The study area is part of the middle subfacies of this sedimentary facies, and five kinds of sedimentary microfacies environments developed. Finally, establishing sedimentary model based on sedimentary characteristics. The braided fluvial fan sedimentary model based on DFS is of great significance for deepening the understanding of terrestrial sedimentary systems and providing guidance for the exploration and development of oil and gas bearing basins.

Abstract Patients with inflammatory bowel disease (IBD) always suffer from severe abdominal pain and appear to be at high risk for colorectal cancer. Recently, the co-delivery of targeted drugs and gut microbiota has developed into an attractive strategy. A new strategy using gut microbiota fermentation to overcome the interspace diffuse resistance from the mucus layer to control drug release in inflammatory bowel sites (IBS sites) has not yet been available. Here, we designed an alginate hydrogel microsphere encapsulating bifidobacterium (Bac) and drug-modified nanoscale dietary fibers (NDFs). The hydrogel microsphere is responsible for protecting drugs from acidic and multi-enzymatic environments and delivering drugs to the colorectum. Subsequently, the fermentation of Bac by digesting NDFs and proteins as carbon and nitrogen sources can promote drug release and play a probiotic role in the gut microbiota. In vitro evidence indicated that small-sized NDF (NDF-1) could significantly promote short-chain fatty acid (SCFA) expression. Notably, NDF-1 hydrogel microspheres showed a boost release of 5-ASA in the IBS sites, resulting in the amelioration of gut inflammation and remodeling of gut microbiota in chronic colitis mice. This study developed a controlled release system based on microbial fermentation for the treatment of IBD.

ABSTRACTObjective To analyze the effect of granulocyte colony-stimulating factor (G-CSF) on outcomes in patients with acute myeloid leukemia (AML).Methods A total of 526 patients with AML in the Haematology Department were enrolled. They were divided into a G-CSF treatment group and a no G-CSF group according to whether G-CSF was administered in the induction chemotherapy period, with 355 cases in the G-CSF group and 171 cases in the no G-CSF group. Cox regression analysis and Kaplan-Meier curve analysis were used to analyze the effect of G-CSF on the first complete remission (CR1) phase and overall survival (OS). In addition, further analysis was performed based on an initial white blood cell count of 50 * 10^9/L.Results The application of G-CSF significantly shortened the CR1 phase and OS in patients with high leukocytes.Conclusions G/GM-CSF should be used with caution in patients with AML, especially those with high leukocytes.

Underwater object detection plays an essential role in ocean exploration, and the increasing amount of underwater object image data makes the study of advanced underwater object detection algorithms of great practical significance. However, there are problems with colour offset, low contrast, and target blur in underwater image data. An underwater object detection algorithm based on Faster R-CNN is proposed to solve these problems. First, the Swin Transformer is used as the backbone network of the algorithm. Second, by adding the path aggregation network, the deep feature map and the shallow feature map are superimposed and fused. Third, online hard example mining, makes the training process more efficient. Fourth, the ROI pooling is improved to ROI align, eliminating the two quantization errors of ROI pooling and improving the detection performance. Compared with other algorithms, the proposed algorithm’s based on improved Faster-RCNN on URPC2018 dataset is improved to 80.54%, and basically solve the problem of missed detection and false detection of objects of different sizes in a complex environment.

The five recognized zoonotic foodborne pathogens, namely, Listeria monocytogenes, Staphylococcus aureus, Streptococcus suis, Salmonella enterica and Escherichia coli O157:H7, pose a major threat to global health and social–economic development. These pathogenic bacteria can cause human and animal diseases through foodborne transmission and environmental contamination. Rapid and sensitive detection for pathogens is particularly important for the effective prevention of zoonotic infections. In this study, rapid and visual europium nanoparticle (EuNP)-based lateral flow strip biosensors (LFSBs) combined with recombinase polymerase amplification (RPA) were developed for the simultaneous quantitative detection of five foodborne pathogenic bacteria. Multiple T lines were designed in a single test strip for increasing the detection throughput. After optimizing the key parameters, the single-tube amplified reaction was completed within 15 min at 37 °C. The fluorescent strip reader recorded the intensity signals from the lateral flow strip and converted the data into a T/C value for quantification measurement. The sensitivity of the quintuple RPA-EuNP-LFSBs reached a level of 101 CFU/mL. It also exhibited good specificity and there was no cross-reaction with 20 non-target pathogens. In artificial contamination experiments, the recovery rate of the quintuple RPA-EuNP-LFSBs was 90.6–101.6%, and the results were consistent with those of the culture method. In summary, the ultrasensitive bacterial LFSBs described in this study have the potential for widespread application in resource-poor areas. The study also provides insights in respect to multiple detection in the field.

The Central Uplift in the Songliao Basin is a large consequent buried-hill structural belt between the east and west faulted zones. Some hydrocarbon-rich sags (e.g. Xujiaweizi and Changling), occur at both sides of the uplifted zone. The Central Uplift, which indicates richness in hydrocarbon resources, is a long-term hydrocarbon migration destination with favorable conditions for hydrocarbon accumulation. Drilling two risk-taking exploratory wells, LT2 and LP1, have been demonstrated by the recent breakthrough in hydrocarbon discoveries. In conformity with uplift-sag contacts and migration pathways, the researchers establish six accumulation models, namely dual consequent faults, dual antithetic faults, consequent-antithetic faults, consequent fault-consequent overlap, antithetic fault-consequent overlap, and dual consequent overlaps, and five carrier systems which include the fault-fracture network, sandy conglomerate-fault-fracture network, fault-unconformity-fracture network, sandy conglomerate-unconformity-fracture network, and sandy conglomerate-fault-fracture network-unconformity. The team divides the Central Uplift accumulation process into four stages, including fold basement denudation and leveling off, coupled weathering, and leaching in the faulted and uplifted zones, hydrocarbon accumulation with sealed overburden, and sustained hydrocarbon preservation in the Central Uplift. Based on an analogous study of hydrocarbon accumulation in the Central Uplift, they conclude that the salients between hydrocarbon-rich sags occurring in the fault subsidence period are similar in accumulation conditions to the Central Uplift. The buried hills and their internal configuration at the salients should be the focus of exploration since they are the strategic successors of hydrocarbon exploration in the Songliao Basin due to their excellent exploration potential.

BackgroundMultiple myeloma (MM) remains an incurable malignant tumor of plasma cells. Increasing evidence has reported that hypoxia and immune status contribute to the progression of MM. In this research, the prognostic value of the hypoxia–immune-related gene SLC19A1 in MM was evaluated by bioinformatics analysis.MethodRNA-sequencing (RNA-seq) data along with clinical information on MM were downloaded from the Gene Expression Omnibus (GEO) database. Consistent clustering analysis and ESTIMATE algorithms were performed to establish the MM sample subgroups related to hypoxia and immune status, respectively, based on the GSE24080 dataset. The differentially expressed analysis was performed to identify the hypoxia–immune-related genes. Subsequently, a hypoxia–immune-gene risk signature for MM patients was constructed by univariate and multivariate Cox regression analyses, which was also verified in the GSE4581 dataset. Furthermore, the mRNA expression of SLC19A1 was determined using qRT-PCR in 19 MM patients, and the correlations between the genetic expression of SLC19A1 and clinical features were further analyzed.ResultA total of 47 genes were identified as hypoxia–immune-related genes for MM. Among these genes, SLC19A1 was screened to construct a risk score model that had better predictive power for MM. The constructed prognostic signature based on SLC19A1 was verified in the GSE4581 dataset. All independent prognostic factors (age, β2-microglobulin, LDH, albumin, MRI, and gene risk score) were used to develop a nomogram that showed a better performance for predicting the survival probability of MM patients for 1–5 years. Furthermore, SLC19A1 was highly expressed in newly diagnosed and relapsed MM patients, and high expression of SLC19A1 is correlated with higher bone marrow aspiration plasma cells and β2-microglobulin levels in MM patients.ConclusionIn conclusion, our results suggest that SLC19A1 is aberrantly expressed in MM and highly expressed SLC19A1 might be a biomarker correlated with inferior prognosis. More importantly, we identified SLC19A1 as a hypoxia–immune-related gene in MM. Future functional and mechanistic studies will further clarify the roles of SLC19A1 in MM.

Abstract Background Disruption of microbiota balance may result in severe diseases in animals and phytotoxicity in plants. While substantial concerns have been raised on engineered nanomaterial (ENM) induced hazard effects (e.g., lung inflammation), exploration of the impacts of ENMs on microbiota balance holds great implications. Results This study found that rare earth oxide nanoparticles (REOs) among 19 ENMs showed severe toxicity in Gram-negative (G−) bacteria, but negligible effects in Gram-positive (G+) bacteria. This distinct cytotoxicity was disclosed to associate with the different molecular initiating events of REOs in G− and G+ strains. La2O3 as a representative REOs was demonstrated to transform into LaPO4 on G− cell membranes and induce 8.3% dephosphorylation of phospholipids. Molecular dynamics simulations revealed the dephosphorylation induced more than 2-fold increments of phospholipid diffusion constant and an unordered configuration in membranes, eliciting the increments of membrane fluidity and permeability. Notably, the ratios of G−/G+ reduced from 1.56 to 1.10 in bronchoalveolar lavage fluid from the mice with La2O3 exposure. Finally, we demonstrated that both IL-6 and neutrophil cells showed strong correlations with G−/G+ ratios, evidenced by their correlation coefficients with 0.83 and 0.92, respectively. Conclusions This study deciphered the distinct toxic mechanisms of La2O3 as a representative REO in G− and G+ bacteria and disclosed that La2O3-induced membrane damages of G− cells cumulated into pulmonary microbiota imbalance exhibiting synergistic pulmonary toxicity. Overall, these findings offered new insights to understand the hazard effects induced by REOs.

Abstract Background Encephalomyocarditis virus, member of Cardiovirus genus within Picornaviridae family, is an important pathogen that infects different domestic and wild animals. However, the molecular mechanism of its entry remains unclear. In this study, we investigated the mechanism of EMCV infectivity in relation to endocytic pathway using BHK-21 cells. Methods The function of numerous cellular key factors implicated in the various endocytic mechanisms were systematically explored using chemical inhibitors. Furthermore, RNA interference (RNAi) as well as the overexpression of dominant protein combined to virus infectivity assays, and confocal microscopy was used to examine EMCV infection in details. Results The results indicated that the EMCV entry into BHK-21 cells depends on caveolin, dynamin, and actin but not clathrin nor macropinocytosis pathways. The effects of overexpression and knockdown of caveolin-1, one components of the caveolae, was examined on EMCV infection. The results showed that EMCV infection was positive correlation with caveolin-1 expression. Confocal microscopy analysis and internalization assay showed that caveolin-1 is required at the early stage of EMCV infection. Conclusions Caveolin-1, dynamin, and actin-dependent endocytosis pathways are necessary for EMCV infection in vitro.

Drug abuse is becoming increasingly dangerous nowadays. Morphine (MOP), methamphetamine (MET) and ketamine (KET) are the most commonly abused drugs. The abuse of these drugs without supervision can cause serious harm to the human body and also endanger public safety. Developing a rapid and accurate method to screen drug suspects and thus control these drugs is essential to public safety. This paper presents a method for the simultaneous quantitative detection of these three drugs in hair by a europium nanoparticles-based fluorescence immunochromatographic assay (EuNPs−FIA). In our study, the test area of the nitrocellulose membrane was composed of three equally spaced detection lines and a quality control line. The test strip realized the quantitative analysis of the samples by detecting the fluorescence brightness of the europium nanoparticles captured on the test line within 15 min. For the triple test strip, the limits of detection of MOP, KET and MET were 0.219, 0.079 and 0.329 ng/mL, respectively. At the same time, it also showed strong specificity. The strip was stable and could be stored at room temperature for up to one year, and the average recovery rate was 85.98–115.92%. In addition, the EuNPs−FIA was validated by high-performance liquid chromatography (HPLC) analysis, and a satisfactory consistency was obtained. Compared to the current immunochromatographic methods used for detecting abused drugs in hair, this method not only increased the number of detection targets, but also ensured sensitivity, improving detection efficiency to a certain extent. The approach can also be used as an alternative to chromatography. It provides a rapid and accurate screening method for the detection of abused drugs in hair and has great application prospects in regard to public safety.

Legionella, a waterborne pathogen, is the main cause of Legionnaires’ disease. Therefore, timely and accurate detection and differentiation of Legionella pneumophila and non-Legionella pneumophila species is crucial. In this study, we develop an easy and rapid recombinase polymerase amplification assay combined with EuNPs-based lateral flow immunochromatography (EuNPs-LFIC-RPA) to specifically distinguish Legionella pneumophila and non-Legionella pneumophila. We designed primers based on the mip gene of Legionella pneumophila and the 5S rRNA gene of non-Legionella pneumophila. The recombinase polymerase amplification reaction could go to completion in 10 min at 37°C, and the amplification products could be detected within 5 min with EuNPs-LFIC strips. Using a florescent test strip reader, the quantitative results were achieved by reading the colored signal intensities on the strips. The sensitivity was 1.6 × 101 CFU/ml, and a linear standard linear curve plotted from the test strip reader had a correlation coefficient for the determination of Legionella pneumophila (R2 = 0.9516). Completed concordance for the presence or absence of Legionella pneumophila by EuNPs-LFIC-RPA and qPCR was 97.32% (κ = 0.79, 95% CI), according to an analysis of practical water samples (n = 112). In short, this work shows the feasibility of EuNPs-LFIC-RPA for efficient and rapid monitoring of Legionella pneumophila and non-Legionella pneumophila in water samples.

It is unclear whether 2D metal dichalcogenides (TMD) alone can cause ferroptotic cell death. Here, the authors show TMD nanosheets induced ferroptosis in mammalian cell lines and in a mouse model after aspiration of TMD materials into lungs, causing ferroptotic cell death.

Pseudorabies virus is a typical swine alphaherpesvirus, which can cause obvious neurological disorders and reproductive failure in pigs. It is capable of evading host antiviral immune response. However, the mechanism by which many PRV proteins assist the virus to evade innate immunity is not fully understood. This study identified PRV US3 protein as a crucial antagonistic viral factor that represses interferon beta (IFN-β) expression. A in-depth study showed that US3 protein restricted type I IFN production by targeting interferon regulatory factor 3 (IRF3), a key molecule required for type I IFN induction. Additionally, US3 protein interacted with IRF3, degraded its protein expression to block the phosphorylation of IRF3. These findings suggested a novel strategy utilized by PRV to inhibit IFN-β production and escape the host innate immunity.

Abstract: The geologic structure of deep formations, basic geologic pattern of fault depressions, geologic conditions of Lower Cretaceous Shahezi Formation tight gas reservoir, and the exploration direction in the next step in the Songliao Basin are examined based on a comprehensive and comparative analysis of the outcrop, drilling, seismic and geochemical data. Systematic comparison analysis shows that the geologic structure of deep formations in the basin is characterized by a double-layer structure with fault depression in the lower layer and depression in the upper layer. In the deep fault depression (DFD) stage, fault depressions bounded by faults or onlaps and uplifts, developed independently. The faults related to the formation and evolution of the fault depressions can be divided into regional discordogenic fault, basement depression controlling fault, and secondary fault inside depression, and their actions in the evolution of the fault depression groups are presented in the paper. Based on analysis of regional tectonics and basin evolution features, three exploration fields, tight conglomerate gas, volcanic rocks and basement buried hills are pointed out, and it is concluded the tight conglomerate gas in the Shahezi Formation is currently a new strategic field with the most promising exploration prospect. Based on comprehensive analysis of basic oil geologic features of Shahezi Formation, it is proposed that conglomerate is the main category of clastic reservoir in Shahezi Fromation, and parent rock composition, sedimentary structure and facies, and diagenesis are the main factors affecting the distribution of conglomerate reservoirs. Furthermore, the gas reservoirs in Shahezi Formation, all source and reservoir in one, include two types, lithologic and structural types. Favorable sedimentary facies belts in the gentle slope and steep slope control the distribution of the reservoirs, formation of lithologic traps and gas reservoir scale; while secondary faults inside fault depressions control the formation of structural traps and enrichment of natural gas. Finally, seven fault depressions in Shahezi Formation with the most promising prospect of tight gas have been sorted out through comprehensive evaluation. Key words: Songliao Basin, deep geologic structure, Cretaceous, Shahezi Formation, tight conglomerate gas, exploration prospect

Active electrocatalysts are the key to water splitting for hydrogen production through the electrolysis. In this paper, 50 nm silver nanoplates were used as templates for synthesis of Au–Ag island-shaped nanoplates by controlling the surface chemistry. The guiding mechanism of polyvinylpyrrolidone (PVP, Mw = 40 000) to Au–Ag island-shaped nanoplates crystal was also further investigated. It is found that the surface energy of Ag nanoplates between (100) and (111) crystal planes can be regulated by varying the amount of PVP in the system. Then a uniform Au-Ag triangular island nanostructure was obtained. Compared with the Ag nanoplates catalysts, the Au–Ag island nanoplates catalysts show the superior catalytic performances in hydrogen evolution electrocatalysis (HER). These results demonstrate a new surface chemistry modification by PVP and a galvanic displacement reaction for designing the active electrocatalysts. More importantly, the Au–Ag island-shaped nanoplates show an unconventional growth mode of preserving the original Ag nano-triangular crystal structure. The enhanced performance in electrocatalysis can be mainly attributed to Au–Ag alloy structure, which allows the appearance of synergistic effects. The present work demonstrates the crucial roles of surface chemistry in catalysts synthesis, which may guide the design of active bimetallic catalysts.

Small molecules that can specifically bind to a DNA abasic site (AP site) have received much attention due to their importance in DNA lesion identification, drug discovery, and sensor design. Herein, the AP site binding behavior of sanguinarine (SG), a natural alkaloid, was investigated. In aqueous solution, SG has a short-wavelength alkanolamine emission band and a long-wavelength iminium emission band. At pH 8.3, SG experiences a fluorescence quenching for both bands upon binding to fully matched DNAs without the AP site, while the presence of the AP site induces a strong SG binding and the observed fluorescence enhancement for the iminium band are highly dependent on the nucleobases flanking the AP site, while the alkanolamine band is always quenched. The bases opposite the AP site also exert some modifications on the SG's emission behavior. It was found that the observed quenching for DNAs with Gs and Cs flanking the AP site is most likely caused by electron transfer between the AP site-bound excited-state SG and the nearby Gs. However, the flanking As and Ts that are not easily oxidized favor the enhanced emission. This AP site-selective enhancement of SG fluorescence accompanies a band conversion in the dominate emission from the alkanolamine to iminium band thus with a large emission shift of about 170 nm. Absorption spectra, steady-state and transient-state fluorescence, DNA melting, and electrolyte experiments confirm that the AP site binding of SG occurs and the stacking interaction with the nearby base pairs is likely to prevent the converted SG iminium form from contacting with water that is thus emissive when the AP site neighbors are bases other than guanines. We expect that this fluorophore would be developed as a promising AP site binder having a large emission shift.

As a typical tight sandstone gas reservoir in the Ordos Basin, the second member of the Shanxi Formation in the XQ gas field in the Ordos Basin has had rich gas reservoirs and good development effects in the past. On the basis of previous studies, this paper brings new understanding to the sedimentary model of this area. Nine kinds of single lithofacies and seven kinds of lithofacies combinations are determined. Braided fluvial fan deposits in distributive fluvial systems likely developed in this area. The study area is part of the middle subfacies of this sedimentary facies, and five kinds of sedimentary microfacies environments developed. Finally, establishing sedimentary model based on sedimentary characteristics. The braided fluvial fan sedimentary model based on DFS is of great significance for deepening the understanding of terrestrial sedimentary systems and providing guidance for the exploration and development of oil and gas bearing basins. [ABSTRACT FROM AUTHOR]

Photoreceptor connecting cilium (CC) is structurally analogous to the transition zone (TZ) of primary cilia and gates the molecular trafficking between the inner and the outer segment (OS). Retinal dystrophies with underlying CC defects are manifested in a broad array of syndromic conditions known as ciliopathies as well as nonsyndromic retinal degenerations. Despite extensive studies, many questions remain in the mechanism of protein trafficking across the photoreceptor CC. Here, we genetically inactivated mouse Tmem138, a gene encoding a putative transmembrane protein localized to the ciliary TZ and linked to ciliopathies. Germline deletion of Tmem138 abolished OS morphogenesis, followed by rapid photoreceptor degeneration. Tmem138 was found localized to the photoreceptor CC and was required for localization of Ahi1 to the distal subdomain of the CC. Among the examined set of OS proteins, rhodopsin was mislocalized throughout the mutant cell body prior to OS morphogenesis. Ablation of Tmem138 in mature rods recapitulated the molecular changes in the germline mutants, causing failure of disc renewal and disintegration of the OS. Furthermore, Tmem138 interacts reciprocally with rhodopsin and a related protein Tmem231, and the ciliary localization of the latter was also altered in the mutant photoreceptors. Taken together, these results suggest a crucial role of Tmem138 in the functional organization of the CC, which is essential for rhodopsin localization and OS biogenesis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although substantial concerns about the inflammatory effects of engineered nanomaterial (ENM) have been raised, experimentally assessing toxicity of various ENMs is challenging and time-consuming. Alternatively, quantitative structure–activity relationship (QSAR) models have been employed to assess nanosafety. However, no previous attempt has been made to predict the inflammatory potential of ENMs. OBJECTIVES: By employing metal oxide nanoparticles (MeONPs) as a model ENM, we aimed to develop QSAR models for prediction of the inflammatory potential by their physicochemical properties. METHODS: We built a comprehensive data set of 30 MeONPs to screen a proinflammatory cytokine interleukin (IL)-1 beta (IL-1ß) release in THP-1 cell line. The in vitro hazard ranking was validated in mouse lungs by oropharyngeal instillation of six randomly selected MeONPs. We established QSAR models for prediction of MeONP-induced inflammatory potential via machine learning. The models were further validated against seven new MeONPs. Density functional theory (DFT) computations were exploited to decipher the key mechanisms driving inflammatory responses of MeONPs. RESULTS: Seventeen out of 30 MeONPs induced excess IL-1ß production in THP-1 cells. In vivo disease outcomes were highly relevant to the in vitro data. QSAR models were developed for inflammatory potential, with predictive accuracy (ACC) exceeding 90%. The models were further validated experimentally against seven independent MeONPs (ACC = 86%). DFT computations and experimental results further revealed the underlying mechanisms: MeONPs with metal electronegativity lower than 1.55 and positive ?-potential were more likely to cause lysosomal damage and inflammation. CONCLUSIONS: IL-1ß released in THP-1 cells can be an index to rank the inflammatory potential of MeONPs. QSAR models based on IL-1ß were able to predict the inflammatory potential of MeONPs. Our approach overcame the challenge of time- and labor-consuming biological experiments and allowed for computational assessment of MeONP inflammatory potential by characterization of their physicochemical properties. [ABSTRACT FROM AUTHOR]

Fresh Rehmanniae Radix, as well as its processed products, are widely used in the clinical practice of traditional Chinese medicine. It is mainly available in four forms: fresh Rehmanniae Radix, raw Rehmanniae Radix, prepared Rehmanniae Radix, and nine-steamed, nine-dried Rehmanniae Radix. Pharmacological studies have shown that all Rehmanniae Radix forms contain iridoid glycosides and sugar compounds with various effects, including hypoglycemic, anti-inflammatory, neuroprotective, immunological enhancement, and bone marrow hematopoiesis-promoting activities. Differences in the efficacy among these Rehmanniae Radix forms and their processed products have been attributed to variations in their chemical compositions, particularly in iridoid glycosides and sugar compounds; however, the specific compositional differences in glycosides and sugars among the four forms of Rehmanniae Radix have not been clarified. Therefore, this study aims to qualitatively characterize the iridoid glycosides and sugar compounds in fresh Rehmanniae Radix, raw Rehmanniae Radix, prepared Rehmanniae Radix, and nine-steamed, nine-dried Rehmanniae Radix.

The anion binding behavior of the Mg(Mn) site in cytochrome c oxidase from Rhodobacter sphaeroide is examined to understand its role in proton pumping at Mg(Mn) center when [Cu.sub.A] is oxidized. The results for the aqueous ligands of Mn(II) probed with deuterium, cyanide, and azide under reduced and oxidized conditions showed that cyanide binds to the Mn(II) ion of the [Cu.sub.A]-Mg(Mn) site when [Cu.sub.A] is reduced but not when [Cu.sub.A] is oxidized.

The serine 44 residue in Rhodobacter sphaeroides eukaryotic cytochrome c oxidase (Rs CcO) was mutated to a glycine to create a bovine-like mutant form, S44G, to test the possible effect of hydrogen bonding on the histidine ligand of heme a. The hydrogen-bonding partner of the histidine ligand of heme a is found to be determinant of the EPR spectral differences between bovine and bacterial CcO and the heme a redox potential could be altered by a nearby carboxyl group whose protonation leads to a proton-coupled electron transfer process.

O-GlcNAcylation and phosphorylation are two posttranslational modifications that antagonistically regulate protein function. However, the regulation of and the cross talk between these two protein modifications are poorly understood in plants. Here we investigated the role of O-GlcNAcylation during vernalization, a process whereby prolonged cold exposure promotes flowering in winter wheat (Triticum aestivum), and analyzed the dynamic profile of O-GlcNAcylated and phosphorylated proteins in response to vernalization. Altering O-GlcNAc signaling by chemical inhibitors affected the vernalization response, modifying the expression of VRN genes and subsequently affecting flowering transition. Over a vernalization time-course, O-GlcNAcylated and phosphorylated peptides were enriched from winter wheat plumules by Lectin weak affinity chromatography and iTRAQ-TiO2, respectively. Subsequent mass spectrometry and gene ontology term enrichment analysis identified 168 O-GlcNAcylated proteins that are mainly involved in responses to abiotic stimulus and hormones, metabolic processing, and gene expression; and 124 differentially expressed phosphorylated proteins that participate in translation, transcription, and metabolic processing. Of note, 31 vernalization-associated proteins were identified that carried both phosphorylation and O-GlcNAcylation modifications, of which the majority (97%) exhibited the coexisting module and the remainder exhibited the potential competitive module. Among these, TaGRP2 was decorated with dynamic O-GlcNAcylation (S87) and phosphorylation (S152) modifications, and the mutation of S87 and S152 affected the binding of TaGRP2 to the RIP3 motif of TaVRN1 in vitro. Our data suggest that a dynamic network of O-GlcNAcylation and phosphorylation at key pathway nodes regulate the vernalization response and mediate flowering in wheat. [ABSTRACT FROM AUTHOR]

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Photodynamic therapy (PDT) has emerged as a powerful tumor treatment tool due to its advantages including minimal invasiveness, high selectivity and thus dampened side effects. On the other side, the efficacy of PDT is severely frustrated by the limited oxygen level in tumors, thus promoting its combination with other therapies, particularly photothermal therapy (PTT) for bolstered tumor treatment outcomes. Meanwhile, nanomedicines that could respond to various stimuli in the tumor microenvironment (TME) provide tremendous benefits for combined phototherapy with efficient hypoxia relief, tailorable drug release and activation, improved cellular uptake and intratumoral penetration of nanocarriers, etc. In this review, we will introduce the merits of combining PTT with PDT, summarize the recent important progress of combined phototherapies and their combinations with the dominant tumor treatment regimen, chemotherapy based on smart nanomedicines sensitive to various TME stimuli with a focus on their sophisticated designs, and discuss the challenges and future developments of nanomedicine-mediated combined phototherapies.

Lectins selectively recognize sugars or glycans for defense in living cells, but less is known about their roles in the development process and the functional network with other factors. Here, we show that Arabidopsis (Arabidopsis thaliana) JACALIN-LECTIN LIKE1 (AtJAC1) functions in flowering time control. Loss of function of AtJAC1 leads to precocious flowering, whereas overexpression of AtJAC1 causes delayed flowering. AtJAC1 influences flowering through regulation of the key flowering repressor gene FLOWERING LOCUS C (FLC). Genetic analysis revealed that AtJAC1's function is mostly dependent on GLYCINE-RICH RNA-BINDING PROTEIN7 (GRP7), an upstream regulator of FLC. Biochemical and cell biological data indicated that AtJAC1 interacted physically with GRP7 specifically in the cytoplasm. AtJAC1 influences the nucleocytoplasmic distribution of GRP7, with predominant nuclear localization of GRP7 when AtJAC1 function is lost but retention of GRP7 in the cytoplasm when AtJAC1 is overexpressed. A temporal inducible assay suggested that AtJAC1's regulation of flowering could be compromised by the nuclear accumulation of GRP7. In addition, GRP7 binds to the antisense precursor messenger RNA of FLC through a conserved RNA motif. Loss of GRP7 function leads to the elevation of total FLC antisense transcripts and reduced proximal-distal polyadenylation ratio, as well as histone methylation changes in the FLC gene body region and increased total functional sense FLC transcript. Attenuating the direct binding of GRP7 with competing artificial RNAs leads to changes of FLC antisense precursor messenger RNA processing and flowering transition. Taken together, our study indicates that AtJAC1 coordinates with GRP7 in shaping plant development through the regulation of RNA processing in Arabidopsis. [ABSTRACT FROM AUTHOR]

Inflorescence and spikelet development determine grain yields in cereals. Although multiple genes are known to be involved in the regulation of floral organogenesis, the underlying molecular network remains unclear in cereals. Here, we report that the rice (Oryza sativa) microRNA396d (OsmiR396d) and its Os Growth Regulating Factor (OsGRF) targets, together with Os Growth Regulating Factor-Interacting Factor1 (OsGIF1), are involved in the regulation of floral organ development through the rice JMJD2 family jmjC gene 706 (OsJMJ706) and crinkly4 receptor-like kinase (OsCR4). Transgenic knockdown lines of OsGRF6, a predicted target of OsmiR396d, and overexpression lines of OsmiR396d showed similar defects in floral organ development, including open husks, long sterile lemmas, and altered floral organ morphology. These defects were almost completely rescued by overexpression of OsGRF6. OsGRF6 and its ortholog OsGRF10 were the most highly expressed OsGRF family members in young inflorescences, and the grf6/grf10 double mutant displayed abnormal florets. OsGRF6/OsGRF10 localized to the nucleus, and electrophoretic mobility shift assays revealed that both OsGRF6 and OsGRF10 bind the GA response element in the promoters of OsJMJ706 and OsCR4, which were reported to participate in the regulation of floral organ development. In addition, OsGRF6 and OsGRF10 could transactivate OsJM]706 and OsCR4, an activity that was enhanced in the presence of OsGIF1, which can bind both OsGRF6 and OsGRF10. Together, our results suggest that OsmiR396d regulates the expression of OsGRF genes, which function with OsGIF1 in floret development through targeting of JMJ706 and OsCR4. This work thus reveals a microRNA-mediated regulation module for controlling spikelet development in rice. [ABSTRACT FROM AUTHOR]

Double-stranded DNAs (ds-DNAs) have been identified as efficient templates favoring the formation of fluorescent copper nanoparticles (Cu NPs). Herein, we have tried to synthesize fluorescent Cu NPs using single-stranded DNAs (ss-DNAs) as templates and to identify the critical DNA sequences. By comparing the results using homopolymer DNAs, hairpin DNAs, and pristine ss-DNAs as templates, we found that DNA thymine base plays a dominant role in producing red-emissive fluorescent Cu NPs on ss-DNA templates. The thymine-dependent growth of the fluorescent Cu NPs is confirmed by Hg2+ mediated T-T base pair in comparison with the other non-specific metal ions, which could be developed into a practical sensor for turn-on fluorescence detection of Hg2+ with a high selectivity. The mechanism is briefly discussed according the DNA sequence-dependent formation of fluorescent Cu NPs. This work demonstrates the sequence role in producing fluorescent Cu NPs that could serve as promising fluorescent nanoprobes in biosensing and DNA-hosted Cu nanomaterials. [ABSTRACT FROM AUTHOR]

Various DNAs were employed as hosts to investigate the sequence-dependent formation of fluorescent Au nanoclusters (Au NCs) in aqueous solution. By comparison among hairpin DNAs (HP-DNAs) with a pristine stem segment and varied loop sequences, we found that the emission behavior of the HP-DNA-hosted Au NCs is dependent on the loop sequences. The most efficient host to produce fluorescent Au NCs is the cytosine loop. However, relative to the cytosine and guanine loops, the loop composed of thymine as well as adenine produces Au NCs with a much weaker emission. Additionally, the emission behavior of Au NCs hosted by the single-stranded DNAs (ss-DNAs) with an identical base composition to the corresponding HP-DNAs still exhibits a cytosine-rich dependence. The fully matched DNAs seem to be less efficient than the corresponding loop and ss-DNA structures. Furthermore, the emission properties of HP-DNA-hosted Au NCs can be modulated by the loop length. The sequence-dependent formation of fluorescent Au NCs is believed to be caused by differences in binding nucleophilicity of the DNA heterocyclic nitrogen and exocyclic keto groups to the hydrolyzed Au(III) species. This work demonstrates the role of sequence in producing Au NCs that could serve as promising fluorescent nanoprobes in biosensing and DNA-hosted Au nanomaterials. [ABSTRACT FROM AUTHOR]

Aim. To investigate clinical significance of runt-related transcription factor (RUNX)-2 in epithelial ovarian cancer (EOC). Methods. RUNX2 protein expression and its subcellular localization were detected by immunohistochemistry in 116 patients with EOC. Results. RUNX2 protein was predominantly expressed in cell nucleus of EOC tissues. The expression level of RUNX2 in EOC tissues was significantly higher than that in normal ovarian tissues (P < 0.001). In addition, the nuclear labeling index (LI) of RUNX2 in tumor cells was significantly associated with the advanced clinical stage of EOC tissues (P = 0.001). Moreover, EOC patients with high RUNX2 LI had significantly shorter overall (P < 0.001) and progression-free (P = 0.002) survival than those with low RUNX2 LI. Especially, subgroup analysis revealed that EOC patients with high clinical stages (III ∼IV) in high RUNX2 expression group demonstrated a significantly worse clinical outcome than those in low RUNX2 expression group, but patients with low clinical stages (I ∼II) had no significantly different prognosis between high and low RUNX2 expression groups. Conclusions. Our data suggest for the first time that RUNX2 overexpression is associated with advanced tumor progression and poor clinical outcome of EOC patients. RUNX2 might be a novel prognostic marker of EOC. [ABSTRACT FROM AUTHOR]

DNA single-nucleotide polymorphism (SNP) detection has attracted much attention due to mutation-related diseases. Various fluorescence methods for SNP detection have been proposed and many are already in use. However, fluorescence enhancement for signal-on SNP identification without label modification still remains a challenge. Here, we find that the abasic site (AP site) in a DNA duplex can be developed as a binding pocket favorable for the occurrence of the excited-state intramolecular proton transfer (ESIPT) of a 3-hydroxyflavone, fisetin, which is used as a proof of concept for effective SNP identification. Fisetin binding at the AP site is highly selective for target thymine or cytosine facing the AP site by observation of a drastic increase in the ESIPT emission band. In addition, the target recognition selectivity based on this ESIPT process is not affected by flanking bases of the AP site. The binding selectivity of fisetin at the AP site is also confirmed by measurements of fluorescence resonance energy transfer, emission lifetime and DNA melting. The fluorescent signal-on sensing for SNP based on this fluorophore is substantially advantageous over the previously used fluorophores such as the AP site-specific signal-off organic ligands with a similar fluorescing mechanism before and after binding to DNA with hydrogen bonding interaction. We expect that this approach will be employed to develop a practical SNP detection method by locating an AP site toward a target and employing an ESIPT probe as readout. [ABSTRACT FROM AUTHOR]

Radix Rehmanniae (RR) is a kind of herb which is widely used in the clinical and food processing industry. There are four forms of RR used in traditional Chinese medicine practice, which include fresh RR (FRR), raw RR (RRR), processed RR (PRR), and another processed RR (APRR), in which the APRR was processed by nine cycles of repeated steaming and drying. There are a large number of saccharides in RR. However, the differences in content were shown by different processing methods. In this study, an effective method using high-performance liquid chromatography (HPLC) and high-performance liquid chromatography-mass spectrometry (LC-MS) coupled with multivariate statistical analysis to rapidly distinguish different RR samples and validate the proposed chemical conversion mechanism. The datasets of the content of saccharides were subjected to principal component analysis (PCA) and one-way analysis of variance. The results showed that there different changes occurred in the contents of saccharides corresponding to the different processing methods, in which the contents of monosaccharides—namely arabinose, glucose, mannose, and galactose—had an increasing trend or remained relatively stable. However, the contents of fructose and oligosaccharides, including manninotriose, melibiose, sucrose, and raffinose, first increased and then reduced, or gradually decreased, yet the content of stachyose gradually decreased. The MSn data indicated that manninotriose, melibiose, and some monosaccharides were produced by the hydrolysis of oligosaccharides. In addition, the fragmentation pathways of 1-phenyl-3-methyl-5-pyrazolone (PMP) derivatization of monosaccharides were also found that its glycosidic bond was first broken and subsequently its inside ring broke, and the characteristic fragment ions were produced at m/z 511.22, 493.20, 373.16, and 175.08 in the PMP derivatization of monosaccharides. In conclusion, this study illustrates the change and chemical conversion mechanism of saccharides by processing in RR samples which might play a key role in further application of RR.

The frequency and time resolved conductivity in a photoexcited large-area monolayer tungsten disulfide (WS2) have been simultaneously determined by using time-resolved terahertz spectroscopy. We use the Drude–Smith model to successfully reproduce the transient photoconductivity spectra, which demonstrate that localized free carriers, not bounded excitons, are responsible for the THz transport. Upon the optical excitation with 400 nm and 530 nm wavelength, the relaxation dynamics of the free carriers include fast and slow decay components with time constants approximately smaller than 1 ps and between 5–7 ps, respectively. The former sub-picosecond decay is attributed to the charge carrier loss induced by the exciton formation, while both the Auger recombination and the surface trapping can contribute to the slow relaxation. [ABSTRACT FROM AUTHOR]