Single-cell genomic variation induced by mutational processes in cancer.

How cell-to-cell copy number alterations that underpin genomic instability1 in human cancers drive genomic and phenotypic variation, and consequently the evolution of cancer2, remains understudied. Here, by applying scaled single-cell whole-genome sequencing3 to wild-type, TP53-deficient and TP53-deficient;BRCA1-deficient or TP53-deficient;BRCA2-deficient mammary epithelial cells (13,818 genomes), and to primary triple-negative breast cancer (TNBC) and high-grade serous ovarian cancer (HGSC) cells (22,057 genomes), we identify three distinct 'foreground' mutational patterns that are defined by cell-to-cell structural variation. Cell- and clone-specific high-level amplifications, parallel haplotype-specific copy number alterations and copy number segment length variation (serrate structural variations) had measurable phenotypic and evolutionary consequences. In TNBC and HGSC, clone-specific high-level amplifications in known oncogenes were highly prevalent in tumours bearing fold-back inversions, relative to tumours with homologous recombination deficiency, and were associated with increased clone-to-clone phenotypic variation. Parallel haplotype-specific alterations were also commonly observed, leading to phylogenetic evolutionary diversity and clone-specific mono-allelic expression. Serrate variants were increased in tumours with fold-back inversions and were highly correlated with increased genomic diversity of cellular populations. Together, our findings show that cell-to-cell structural variation contributes to the origins of phenotypic and evolutionary diversity in TNBC and HGSC, and provide insight into the genomic and mutational states of individual cancer cells.

EGR1-mediated metabolic reprogramming to oxidative phosphorylation contributes to ibrutinib resistance in B-cell lymphoma.

The use of Bruton tyrosine kinase inhibitors, such as ibrutinib, to block B-cell receptor signaling has achieved a remarkable clinical response in several B-cell malignancies, including mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL). Acquired drug resistance, however, is significant and affects the long-term survival of these patients. Here, we demonstrate that the transcription factor early growth response gene 1 (EGR1) is involved in ibrutinib resistance. We found that EGR1 expression is elevated in ibrutinib-resistant activated B-cell-like subtype DLBCL and MCL cells and can be further upregulated upon ibrutinib treatment. Genetic and pharmacological analyses revealed that overexpressed EGR1 mediates ibrutinib resistance. Mechanistically, TCF4 and EGR1 self-regulation induce EGR1 overexpression that mediates metabolic reprogramming to oxidative phosphorylation (OXPHOS) through the transcriptional activation of PDP1, a phosphatase that dephosphorylates and activates the E1 component of the large pyruvate dehydrogenase complex. Therefore, EGR1-mediated PDP1 activation increases intracellular adenosine triphosphate production, leading to sufficient energy to enhance the proliferation and survival of ibrutinib-resistant lymphoma cells. Finally, we demonstrate that targeting OXPHOS with metformin or IM156, a newly developed OXPHOS inhibitor, inhibits the growth of ibrutinib-resistant lymphoma cells both in vitro and in a patient-derived xenograft mouse model. These findings suggest that targeting EGR1-mediated metabolic reprogramming to OXPHOS with metformin or IM156 provides a potential therapeutic strategy to overcome ibrutinib resistance in relapsed/refractory DLBCL or MCL.

Biomimetic Electrochemical Sensor Based on Single-Atom Nickel Laccase Nanoenzyme for Quercetin Detection.

Laccase, a member of the copper oxidase family, has been used as a green catalyst in the environmental and biochemical industries. However, laccase nanoenzymes are limited to materials with copper as the active site, and noncopper laccase nanoenzymes have been scarcely reported. In this study, inspired by the multiple copper active sites of natural laccase and the redox Cu2+/Cu+ electron transfer pathway, a novel nitrogen/nickel single-atom nanoenzyme (N/Ni SAE) with high laccase-like activity was prepared by inducing Ni and dopamine precipitation through a controllable water/ethanol interface reaction. Compared with that of laccase, the laccase activity simulated by N/Ni SAE exhibited excellent stability and reusability. The N/Ni SAE exhibited a higher efficiency toward the degradation of 2,4-dichlorophenol, hydroquinone, bisphenol A, and p-aminobenzene. In addition, a sensitive electrochemical biosensor was constructed by leveraging the laccase-like activity of N/Ni SAE; this sensor offered unique advantages in terms of catalytic activity, selectivity, stability, and repeatability. Its detection ranges for quercetin were 0.01-0.1 and 1.0-100 µM, and the detection limit was 3.4 nM. It was also successfully used for the quantitative detection of quercetin in fruit juices. Therefore, the single-atom biomimetic nanoenzymes prepared in this study promote the development of a new electrochemical strategy for the detection of various bioactive molecules and show great potential for practical applications.

Itaconate inhibits SYK through alkylation and suppresses inflammation against hvKP induced intestinal dysbiosis.

Hypervirulent Klebsiella pneumoniae (hvKP) is a highly lethal opportunistic pathogen that elicits more severe inflammatory responses compared to classical Klebsiella pneumoniae (cKP). In this study, we investigated the interaction between hvKP infection and the anti-inflammatory immune response gene 1 (IRG1)-itaconate axis. Firstly, we demonstrated the activation of the IRG1-itaconate axis induced by hvKP, with a dependency on SYK signaling rather than STING. Importantly, we discovered that exogenous supplementation of itaconate effectively inhibited excessive inflammation by directly inhibiting SYK kinase at the 593 site through alkylation. Furthermore, our study revealed that itaconate effectively suppressed the classical activation phenotype (M1 phenotype) and macrophage cell death induced by hvKP. In vivo experiments demonstrated that itaconate administration mitigated hvKP-induced disturbances in intestinal immunopathology and homeostasis, including the restoration of intestinal barrier integrity and alleviation of dysbiosis in the gut microbiota, ultimately preventing fatal injury. Overall, our study expands the current understanding of the IRG1-itaconate axis in hvKP infection, providing a promising foundation for the development of innovative therapeutic strategies utilizing itaconate for the treatment of hvKP infections.

Pyrene-Alkyne-Based Conjugated Porous Polymers with Skeleton Distortion-Mediated •O2- and 1O2 Generation for High-Selectivity Organic Photosynthesis.

Reactive oxygen species (ROS) play a crucial role in determining photocatalytic reaction pathways, intermediate species, and product selectivity. However, research on ROS regulation in polymer photocatalysts is still in its early stages. Herein, we successfully achieved series of modulations to the skeleton of Pyrene-alkyne-based (Tetraethynylpyrene (TEPY)) conjugated porous polymers (CPPs) by altering the linkers (1,4-dibromobenzene (BE), 4,4'-dibromobiphenyl (IP), and 3,3'-dibromobiphenyl (BP)). Experiments combined with theoretical calculations indicate that BE-TEPY exhibits a planar structure with minimal exciton binding energy, which favors exciton dissociation followed by charge transfer with adsorbed O2 to produce •O2-. Thus BE-TEPY shows optimal photocatalytic activity for phenylboronic acid oxidation and [3+2] cycloaddition. Conversely, the skeleton of BP-TEPY is significantly distorted. Its planar conjugation decreases, intersystem crossing (ISC) efficiency increases, which makes it more prone for resonance energy transfer to generate 1O2. Therefore, BP-TEPY displays best photocatalytic activity in [4+2] cycloaddition and thioanisole oxidation. Both above reactant conversion and its product selectivity exceed 99%. This work systematically reveals the intrinsic structure-activity relationship among the skeleton structure of CPPs, excitonic behavior, and selective generation of ROS, providing new insights for the rational design of highly efficient and selective CPPs photocatalysts.

Heteropoly Blue/Carbon Nanotubes Nanocomposites as High-Performance Photothermal Conversion Materials.

To realize the direct and full use of the widely distributed solar energy, developing novel materials with superb photothermal conversion capability is essential. Although heteropoly blue has intrinsic outstanding solar absorption and photothermal conversion properties, its spectral absorption in the infrared region is weak. Here, composites of heteropoly blue and carbon nanotubes (HPB/CNTs) are synthesized depending on electrostatic interactions by facile microwave sonication and freeze-drying. The doped CNTs can dramatically improve the spectral absorption performance of HPB ontology in the infrared region. As a result, the light absorption of the optimized HPB/CNTs (20 %) reaches more than 95 % in the range of 200-2400 nm, showing promising prospects as high-performance photothermal conversion material in the applications of solar desalination and wastewater treatment.

Development of a "turn off-on" whole-cell biosensor for sulforaphane detection based on the ultrasensitive activator HrpRS.

Sulforaphane (SFN), a defense secondary metabolite, can be used to predict the health status of plants and also has pharmacological effects, including anticancer, antioxidant, and anti-inflammatory properties. The detection of SFN is therefore of great significance for the prevention and treatment of diseases. In this study, a "turn off" whole-cell biosensor that can rapidly and robustly respond to the presence of SFN was constructed based on the orthogonal genetic components (hrpR, hrpS, and PhrpL ) of Pseudomonas syringae (PS). The final optimized biosensor, p114(30R-30S), was able to inhibit 91.7% of the fluorescence intensity in the presence of 100-µM SFN. Subsequently, a HrpRS-regulated OFF-ON genetic switch was designed by reconstituting a reverse σ70 promoter on the σ54 -PhrpL promoter sequence; this was coupled with dual-color reporter genes to construct a "turn off-on" whole-cell SFN biosensor. The PhrpLB variant increased the expression of green fluorescence a factor of 11.9 and reduced the expression of red fluorescence by 85.8% compared with the system in the absence of SFN. Thus, a robust switching of signal output from "turn off" to "turn on" was realized. In addition, the biosensor showed good linearity in the SFN concentration ranges of 0.1-10 µM (R2  = 0.99429) and 10-100 µM (R2  = 0.99465) and a detection limit of ~0.1 µM.

A robust electrochemical sensor based on N,S-FeNi3/C for simultaneous detection of hydroquinone and arbutin in cosmetics.

For practical analysis and simultaneous detection of arbutin (AR) and hydrochinone (HQ) in cosmetics, an electrochemical sensor has been designed based on nitrogen and sulfur co-doped Fe-Ni alloy (N,S-FeNi3/C) nanoparticles. The N,S-FeNi3/C has been prepared for the first time via hydrothermal synthesis and high-temperature carbonization. N,S-FeNi3/C not only improves the charge transfer to the surface, but also provides rich active sites and fast ion diffusion rates owing to the iron and nickel bimetallic materials. In addition, the d-band structure of transition metals (nickel and iron) introduced by the N and S atoms exhibits an electronic structure similar to that of noble metal catalysts, thus enhancing electrocatalytic activity and increasing conductivity. Additionally, the double doping of S and N atoms significantly increases the active sites of carbon atoms; thus, N-S-FeNi3/C exhibits excellent electrochemical catalytic activity for the oxidation of AR and HQ. Further, the N,S-FeNi3/C sensor is used for the simultaneous determination of HQ and AR by square-wave pulse voltammetry. Distinct oxidation peaks of HQ and AR are observed at potentials of +0.028 V and +0.352 V (vs. SCE). The electrical signal increases linearly in the HQ concentration ranges of 0.1-100 µM and 0.05-70 µM for the simultaneous determination of AR and HQ with a detection limit as low as 0.0476 and 0.0135 µM (S/N = 3), respectively. Thus, rapid and accurate detection of AR and HQ in spiked cosmetics is successfully achieved, with a recovery ranging from 96.4 to 104.2%, and the relative standard deviation is lower than 3.8-4.0%.

Rapidly Synthesized Single-Ion Conductive Hydrogel Electrolyte for High-Performance Quasi-Solid-State Zinc-ion Batteries.

Single-ion conductive electrolytes can largely eliminate electrode polarization, reduce the proportion of anion migration and inhibit side reactions in batteries. However, they usually suffer from insufficient ion conductivity due to the strong interaction between cations and cationic receptors. Here we report an ultrafast light-responsive covalent organic frameworks (COF) with sulfonic acid groups modification as the acrylamide polymerization initiator. Benefiting from the reduced electrostatic interaction between Zn2+ and sulfonic acid groups through solvation effects, the as-prepared COF-based hydrogel electrolyte (TCOF-S-Gel) receives an ion conductivity of up to 27.2 mS/cm and Zn2+ transference number of up to 0.89. In addition, sufficient hydrogen bonds endow the single-ion conductive TCOF-S-Gel electrolyte to have good water retention and superb mechanical properties. The assembled Zn||TCOF-S-Gel||MnO2 full zinc-ion battery exhibits high discharge capacity (248 mAh/g at 1C), excellent rate capability (90 mAh/g at 10C) and superior cycling performance. These enviable results enlist the instantaneously photocured TCOF-S-Gel electrolyte to be qualified to large-scaled flexible high-performance quasi-solid-state zinc-ion batteries.

Efficient Conversion of Biomass to Formic Acid Coupled with Low Energy Consumption Hydrogen Production from Water Electrolysis.

The development of a new electrolytic water hydrogen production coupling system is the key to realize efficient and low-cost hydrogen production and promote its practical application. Herein, a green and efficient electrocatalytic biomass to formic acid (FA) coupled hydrogen production system has been developed. In such a system, carbohydrates such as glucose are oxidized to FA using polyoxometalates (POMs) as the redox anolyte, while H2 is evolved continuously at the cathode. Among them, the yield of glucose to FA is as high as 62.5 %, and FA is the only liquid product. Furthermore, the system requires only 1.22 V to drive a current density of 50 mA cm-2 , and the Faraday efficiency of hydrogen production is close to 100 %. Its electrical consumption is only 2.9 kWh Nm-3 (H2 ), which is only 69 % of that of traditional electrolytic water. This work opens up a promising direction for low-cost hydrogen production coupled with efficient biomass conversion.

Efficient Electrochemical Detection of Hydrogen Peroxide Based on Silver-Centered Preyssler-Type Polyoxometalate Hybrids.

Four polyoxometalate (POM)-based organic-inorganic hybrid compounds, namely, (H2bimb)6H8[((Mn(H2O)3(µ-bimb))0.5(Mn(H2O)4)(Mn(H2O)5)0.5(AgP5W30O110))2]·29H2O (1), [(Cu(Hbimb)(H2O)2(µ-bimb)Cu(Hbimb)(H2O))(Cu(H2O)2(µ-bimb)Cu(H2O)3)((Cu(H2O)2)0.5(µ-bimb)(Cu(H2O)3)0.5)H2(AgP5W30O110)]·12.5H2O (2), (H2bimb)2H[(Zn(Hbimb)(H2O)4(Zn(Hbimb)(H2O)2)0.5)2(AgP5W30O110)]·12H2O (3), and (H2bimb)3H2[(Ag(H2O)2)0.5(Ag(Hbimb)Ag(Hbimb)(µ-bimb)Ag)(Ag(H2O)2)0.5(AgP5W30O110)]·7H2O (4) (bimb = 1,4-bis(1H-imidazol-1-yl)benzene), were hydrothermally synthesized using a silver-centered Preyssler-type POM K14[AgP5W30O110]·18H2O (abbreviated as K-{AgP5W30}) as a precursor. In 1-4, {AgP5W30} clusters integrating the merits of Ag+ and {P5W30} units are modified by different transition metal (TM)-organic fragments to extend the structures into three-dimensional frameworks. As nonenzymatic electrochemical sensor materials, 1-4 show good electrocatalytic activity, high sensitivity, and a low detection limit for detecting hydrogen peroxide (H2O2); 4 possesses the highest sensitivity of 195.47 µA·mM-1·cm-2 for H2O2 detection. Most importantly, the average level of H2O2 detection of these {AgP5W30}-based materials outperforms that of Na-centered Preyssler-type {NaP5W30} and most Keggin-type POM-based materials. The performances of such {AgP5W30} materials mainly stem from the unique advantage of high-negatively charged {AgP5W30} clusters together with the good synergistic effect between {AgP5W30} and TMs. This work expands on the research of high-efficiency POM-based nonenzymatic electrochemical H2O2 sensors using Ag-containing POMs with high negative charges, which is also of great theoretical and practical significance to carry out health monitoring and environmental analysis.

Visible-Light-Driven Oxidation of Amines to Imines in Air Catalyzed by Polyoxometalate-Tris(bipyridine)ruthenium Hybrid Compounds.

The development of visible-light photocatalysts for the selective oxidative coupling of amines to imines is an area of great interest. Herein, four hybrid compounds based on polyoxometalate anions and tris(bipyridine)ruthenium cations, Ru(bpy)3[M6O19] (M = Mo, W) 1-2, [Ru(bpy)3]2[Mo8O26] 3, [Ru(bpy)3]2[W10O32] 4, are prepared and characterized by X-ray diffraction (single-crystal and powder), elemental analysis, energy-dispersive X-ray spectroscopy (EDS) analysis, infrared (IR) spectroscopy, and solid diffuse reflective spectroscopy. Single-crystal structural analysis indicates that polyoxometalate anions and tris(bipyridine)ruthenium cations interact with each other through extensive hydrogen bonds in these compounds. These hybrid species with strong visible-light-harvesting abilities and suitable photocatalytic energy potentials show excellent photocatalytic activity and selectivity for the oxidation of amines to imines at room temperature in air as an oxidant. Among them, compound 1 with the [Mo6O19]2- anion has the highest catalytic activity, which can swiftly convert >99.0% of benzylamine into N-benzylidenebenzylamine with a selectivity of 98.0% in 25 min illumination by a 10 W 445 nm light-emitting diode (LED). Its turnover frequency reaches 392 h-1, which is not only better than the homogeneous catalyst [Ru(bpy)3]Cl2 but also much superior to those achieved over most of reported heterogeneous catalysts. Moreover, it shows a wide generality for various aromatic amines, accompanied by the advantages of good recyclability and stability. The photocatalytic oxidation mechanism of amines to the corresponding imines over polyoxometalate-based hybrid compounds was fully investigated.

Ratiometric electrochemical sensing platform based on N-doped MOF-derived CoNi/C for the determination of p-phenylenediamine in hair dyes.

A stable ratiometric electrochemical sensing platform is introduced for the determination of p-phenylenediamine (PPD). Specifically, the proposed sensing platform employs nitrogen-doped MOF pyrolysis-derived CoNi/C (N-CoNi/C) which was deployed as the sensing agent and methylene blue (MB) as the internal reference, and the MB combined with N-CoNi/C nanomaterials by a simple immersion adsorption process. Full characterization of N-CoNi/C was carried out with respect to morphology, composition, and electrochemical behavior, and the sensing performance of the ratiometric electrochemical sensing platform was evaluated. Complete separation of the oxidation peaks of PPD and MB was achieved using the MB/N-CoNi/C composite modified glassy carbon electrode (MB/N-CoNi/C/GCE) and their ratio signals were used for quantitative determination of PPD. The electrical signal was linearly related to the concentration of PPD in the concentration range 0.3-100 µM, with a fitted correlation coefficient of 0.9987 and a detection limit of 0.091 µM (S/N = 3). Additionally, the sensor has been successfully used for the determination of PPD in commercial hair dyes with a recovery rate of over 95%.

Signal on-off ratiometric electrochemical sensor coupled with a molecularly imprinted polymer for the detection of carbendazim.

A stable ratiometric electrochemical sensor is introduced for the selective detection of carbendazim (CBD). Specifically, the proposed sensor employs a Co@Mo2C bimetallic nanomaterial as the glassy carbon electrode substrate and a layer of molecularly imprinted polymer (MIP) was in situ fabricated on glassy carbon electrode by electropolymerization, with o-aminophenol as the functional monomer and CBD acting as template. A ratiometric MIP sensor was constructed by adding ferrocene (Fc) internal reference directly to the sample solution. The bimetallic nanomaterials provide a large loading platform for the MIP layer through synergistic effects, amplifying the signal. Excellent CBD binding selectivity is achieved by the templating effect of the three-dimensional (3D) MIP layer. The internal standard is added directly to the electrolyte solution to be tested, allowing the new type of ratiometric electrochemical sensor to avoid the cumbersome steps of other methods and reducing the difficulty and human error of the experimental procedure. Combining a ratiometric strategy with a 3D MIP structure realises the dual-signal detection of CBD. The optimised sensor showed an excellent linear relationship between 0.01 and 1 000 µM, with a correlation coefficient of 0.997 and a detection limit of 3.4 nM (S/N = 3).

Copper-Bridged Tetrakis(4-ethynylphenyl)ethene Aggregates with Photo-Regulated 1 O2 and O2 .- Generation for Selective Photocatalytic Aerobic Oxidation.

Active species regulation is a key scientific issue that essentially determines the selectivity and activity of a photocatalyst. Herein, CuI -bridged tetrakis(4-ethynylphenyl)ethene aggregates (T4 EPE-Cu) with photo-regulated 1 O2 and O2 .- generation were demonstrated for selective photocatalytic aerobic oxidation. In this system, transient photovoltage combined with the density functional theory calculations confirmed that Cu-alkynyl was the main oxygen activation site. The adsorbed O2 tends to produce O2 .- because of the potential well effect of Cu-alkynyl under high-energy light excitation. But under low-energy light, O2 tends to produce 1 O2 via resonance energy transfer with Cu-alkynyl. For α-terpinene oxidation, the ratios of 1 O2 products to O2 .- products can be controlled from 1.3 (380 nm) to 10.7 (600 nm). Furthermore, T4 EPE-Cu exhibited ultrahigh photocatalytic performance for Glaser coupling and benzylamine oxidation, with a conversion and selectivity of over 99 %.

Molecular Iron Oxide Clusters Boost the Oxygen Reduction Reaction of Platinum Electrocatalysts at Near-Neutral pH.

The oxygen reduction reaction (ORR) is a key energy conversion process, which is critical for the efficient operation of fuel cells and metal-air batteries. Here, we report the significant enhancement of the ORR-performance of commercial platinum-on-carbon electrocatalysts when operated in aqueous electrolyte solutions (pH 5.6), containing the polyoxoanion [Fe28 (µ3 -O)8 (L-(-)-tart)16 (CH3 COO)24 ]20- . Mechanistic studies provide initial insights into the performance-improving role of the iron oxide cluster during ORR. Technological deployment of the system is demonstrated by incorporation into a direct formate microfluidic fuel cell (DFMFC), where major performance increases are observed when compared with reference electrolytes. The study provides the first examples of iron oxide clusters in electrochemical energy conversion and storage.

A high sensitivity electrochemical sensor based on a dual-template molecularly imprinted polymer for simultaneous determination of clenbuterol hydrochloride and ractopamine.

A nitrogen-doped Fe-MOF shows a high specific surface area and excellent electrical conductivity after high temperature carbonization. A novel electrochemical sensor based on a N@Fe-MOF@C loaded dual-template molecularly imprinted polymer (DTMIP) modified glassy carbon electrode (GCE) was proposed for the rapid and ultra-sensitive simultaneous detection of clenbuterol hydrochloride (CLB) and ractopamine (RAC). N@Fe-MOF@C combined with a MIP significantly enhanced the electrical signal. Cyclic voltammetry (CV) was used to detect CLB and RAC. The electrochemical polymerization was conducted with O-phenylenediamine as the functional monomer and CLB and RAC as template molecules. The factors affecting the sensor response were optimized. Under the optimal experimental conditions, the CV current response showed a linear range of 10-12-8 × 10-9 M for both CLB and RAC, and the detection limit (LOD) for both CLB and RAC was 3.03 × 10-13 M (S/N = 3). This electrochemical sensing system has high sensitivity, selectivity, excellent reproducibility, repeatability and stability. The recoveries of the actual samples (97.4%-101.2%) and reasonable relative standard deviations (RSDs) (1.06%-3.17%) indicate the practicability of the sensor system. The system has high application value in the rapid detection of CLB and RAC in clenbuterol hydrochloride tablets, human urine and raw pork.

Electrochemical sensor based on N-doped carbon dots decorated with manganese oxide nanospheres for simultaneous detection of p-aminophenol and paracetamol.

Nitrogen doped carbon dots were synthesized using the hydrothermal reaction of cellulose and urea, and then carbonized in a N2 atmosphere at a high temperature to prepare N-doped carbon dots decorated with manganese oxide nanospheres (N-CMOS) formed using cetyltrimethylammonium bromide (CTAB) and MnO. The introduction of N-CMOS resulted in a large specific surface area, abundant pores, favourable conductivity and an excellent electrocatalytic performance. A glassy carbon electrode modified with N-CMOS was used for the simultaneous identification of paracetamol (AP) and p-aminophenol (PAP) utilising differential pulse voltammetry. Under optimum conditions, the electrical sensor showed a wide linear range of 0.1-100 µM for PAP and 0.1-80 µM for AP, with detection limits of 0.0456 and 0.0303 µM (S/N = 3), respectively. The sensitivities for detecting PAP and AP were calculated as 1.615 and 1.971 µA µM-1 cm-2, respectively. The sensitivity and limit of detection (LOD) meet the requirements of detection of drug impurity limits in tablets. In addition, the sensor has been successfully applied to detect PAP and AP in paracetamol tablets. The constructed sensor not only possesses a superior repeatability, reproducibility and stability, but a relatively wide linear range, and a superior detection limit and sensitivity.

Gene regulation and suppression of type I interferon signaling by STAT3 in diffuse large B cell lymphoma.

STAT3 is constitutively activated in many cancers and regulates gene expression to promote cancer cell survival, proliferation, invasion, and migration. In diffuse large B cell lymphoma (DLBCL), activation of STAT3 and its kinase JAK1 is caused by autocrine production of IL-6 and IL-10 in the activated B cell-like subtype (ABC). However, the gene regulatory mechanisms underlying the pathogenesis of this aggressive lymphoma by STAT3 are not well characterized. Here we performed genome-wide analysis and identified 2,251 STAT3 direct target genes, which involve B cell activation, survival, proliferation, differentiation, and migration. Whole-transcriptome profiling revealed that STAT3 acts as both a transcriptional activator and a suppressor, with a comparable number of up- and down-regulated genes. STAT3 regulates multiple oncogenic signaling pathways, including NF-κB, a cell-cycle checkpoint, PI3K/AKT/mTORC1, and STAT3 itself. In addition, STAT3 negatively regulates the lethal type I IFN signaling pathway by inhibiting expression of IRF7, IRF9, STAT1, and STAT2 Inhibition of STAT3 activity by ruxolitinib synergizes with the type I IFN inducer lenalidomide in growth inhibition of ABC DLBCL cells in vitro and in a xenograft mouse model. Therefore, this study provides a mechanistic rationale for clinical trials to evaluate ruxolitinib or a specific JAK1 inhibitor combined with lenalidomide in ABC DLBCL.

Precise Molecular-Level Modification of Nafion with Bismuth Oxide Clusters for High-performance Proton-Exchange Membranes.

Fabricating proton exchange membranes (PEMs) with high ionic conductivity and ideal mechanical robustness through regulation of the membrane microstructures achieved by molecular-level hybridization remains essential but challenging for the further development of high-performance PEM fuel cells. In this work, by precisely hybridizing nano-scaled bismuth oxide clusters into Nafion, we have fabricated the high-performance hybrid membrane, Nafion-Bi12 -3 %, which showed a proton conductivity of 386 mS cm-1 at 80 °C in aqueous solution with low methanol permeability, and conserved the ideal mechanical and chemical stabilities as PEMs. Moreover, molecular dynamics (MD) simulation was employed to clarify the structural properties and the assembly mechanisms of the hybrid membrane on the molecular level. The maximum current density and power density of Nafion-Bi12 -3 % for direct methanol fuel cells reached to 432.7 mA cm-2 and 110.2 mW cm-2 , respectively. This work provides new insights into the design of versatile functional polymer electrolyte membranes through polyoxometalate hybridization.