Interfacial Colloidal Self-Assembly for Functional Materials.

ConspectusSelf-assembly bridges nanoscale and microscale colloidal particles into macroscale functional materials. In particular, self-assembly processes occurring at the liquid/liquid or solid/liquid/air interfaces hold great promise in constructing large-scale two- or three-dimensional (2D or 3D) architectures. Interaction of colloidal particles in the assemblies leads to emergent collective properties not found in individual building blocks, offering a much larger parameter space to tune the material properties. Interfacial self-assembly methods are rapid, cost-effective, scalable, and compatible with existing fabrication technologies, thus promoting widespread interest in a broad range of research fields.Surface chemistry of nanoparticles plays a predominant role in driving the self-assembly of nanoparticles at water/oil interfaces. Amphiphilic nanoparticles coated with mixed polymer brushes or mussel-inspired polydopamine were demonstrated to self-assemble into closely packed thin films, enabling diverse applications from electrochemical sensors and catalysis to surface-enhanced optical properties. Interfacial assemblies of amphiphilic gold nanoparticles were integrated with graphene paper to obtain flexible electrodes in a modular approach. The robust, biocompatible electrodes with exceptional electrocatalytic activities showed excellent sensitivity and reproducibility in biosensing. Recyclable catalysts were prepared by transferring monolayer assemblies of polydopamine-coated nanocatalysts to both hydrophilic and hydrophobic substrates. The immobilized catalysts were easily recovered and recycled without loss of catalytic activity. Plasmonic nanoparticles were self-assembled into a plasmonic substrate for surface-enhanced Raman scattering, metal-enhanced fluorescence, and modulated fluorescence resonance energy transfer (FRET). Strong Raman enhancement was accomplished by rationally directing the Raman probes to the electromagnetic hotspots. Optimal enhancement of fluorescence and FRET was realized by precisely controlling the spacing between the metal surface and the fluorophores and tuning the surface plasmon resonance wavelength of the self-assembled substrate to match the optical properties of the fluorescent dye.At liquid/solid interfaces, infiltration-assisted (IFAST) colloidal self-assembly introduces liquid infiltration in the substrate as a new factor to control the degree of order of the colloidal assemblies. The strong infiltration flow leads to the formation of amorphous colloidal arrays that display noniridescent structural colors. This method is compatible with a broad range of colloidal particle inks, and any solid substrate that is permeable to dispersing liquids but particle-excluding is suitable for IFAST colloidal assembly. Therefore, the IFAST technology offers rapid, scalable fabrication of structural color patterns of diverse colloidal particles with full-spectrum coverage and unprecedented flexibility. Metal-organic framework particles with either spherical or polyhedral morphology were used as ink particles in the Mayer rod coating on wettability patterned photopapers, leading to amorphous photonic structures with vapor-responsive colors. Anticounterfeiting labels have also been developed based on the complex optical features encoded in the photonic structures.Interfacial colloidal self-assembly at the water/oil interface and IFAST assembly at the solid/liquid/air interface have proven to be versatile fabrication platforms to produce functional materials with well-defined properties for diverse applications. These platform technologies are promising in the manufacturing of value-added functional materials.

Genetic insights into the relationship between immune cell characteristics and ischemic stroke: A bidirectional Mendelian randomization study.

BACKGROUND AND PURPOSE: Ischemic stroke, a major contributor to global disability and mortality, is underpinned by intricate pathophysiological mechanisms, notably neuroinflammation and immune cell dynamics. Prior research has identified a nuanced and often paradoxical link between immune cell phenotypes and ischemic stroke susceptibility. The aim of this study was to elucidate the potential causal links between the median fluorescence intensity (MFI) and morphological parameters (MP) of 731 immune cell types and ischemic stroke risk. METHODS: By analyzing extensive genetic datasets, we conducted comprehensive Mendelian randomization (MR) analyses to discern the genetic correlations between diverse immune cell attributes (MFI and MP) and ischemic stroke risk. RESULTS: Our study identified key immune cell signatures linked to ischemic stroke risk. Both B cells and T cells, among other immune cell types, have a bidirectional influence on stroke risk. Notably, the regulatory T-cell phenotype demonstrates significant neuroprotective properties, with all odds ratio (OR) values and confidence intervals (CIs) being less than 1. Furthermore, CD39 phenotype immune cells, particularly CD39+ CD8+ T cells (inverse variance weighting [IVW] OR 0.92, 95% CI 0.87-0.97; p = 0.002) and CD39+ activated CD4 regulatory T cells (IVW OR 0.93, 95% CI 0.90-0.97; p < 0.001), show notable neuroprotection against ischemic stroke. CONCLUSION: This investigation provides new genetic insights into the interplay between various immune cells and ischemic stroke, underscoring the complex role of immune processes in stroke pathogenesis. These findings lay a foundation for future research, which may confirm and expand upon these links, potentially leading to innovative immune-targeted therapies for stroke prevention and management.

Exploring correlations between immune cell phenotypes and the risk of epilepsy: A bidirectional Mendelian randomization study.

BACKGROUND: Neuroinflammation plays an important pathophysiological role in epilepsy; however, the precise connection between immune cells and epilepsy remains unclear. This study used Mendelian randomization (MR) to analyze the causal relationship between 731 immune cell traits and epilepsy. METHODS: Based on data from a genome-wide association study (GWAS), a bidirectional two-sample MR analysis was conducted to investigate the potential influence of immune cell phenotypes on epilepsy. Five MR methods were used to analyze the results, with the inverse variance weighted (IVW) method as the primary method, and the results were corrected using the false discovery rate (FDR) method. Sensitivity analyses were performed to test for heterogeneity and horizontal pleiotropy. RESULTS: After correction for FDR, four immune traits remained significantly associated with epilepsy risk: CD25 expression on memory (OR = 1.04, 95 % CI = 1.02 âˆ¼ 1.06,P = 2.55 × 10-4), IgD+CD38dim (OR = 1.05, 95 % CI = 1.02 âˆ¼ 1.08, P = 4.73 × 10-4), CD24+CD27+ (OR = 1.04, 95 % CI = 1.02 âˆ¼ 1.06, P = 4.82 × 10-4), and IgD-CD38dim (OR = 1.04, 95 % CI = 1.02 âˆ¼ 1.06, P = 1.04 × 10-3) B cells. The risk of generalized epilepsy was significantly associated with two immune cell traits, whereas that of focal epilepsy was significantly associated with seven immune cell traits. Furthermore, immune cell phenotypes are not affected by genetically predicted epilepsy. CONCLUSION: This MR study affirms the causal connection between circulating immune cells and epilepsy, offering guidance for further understanding of the immune mechanisms that underlie epilepsy and the discovery of novel targets for therapy.

Design, synthesis and herbicidal activity of novel cyclohexanedione derivations containing pyrazole and pyridine groups as potential HPPD inhibitors.

4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27; HPPD) is one of the important target enzymes in the development of herbicides. To discover novel HPPD inhibitors with unique molecular, 39 cyclohexanedione derivations containing pyrazole and pyridine groups were designed and synthesized. The preliminary herbicidal activity test results showed that some compounds had obvious inhibitory effects on monocotyledon and dicotyledonous weeds. The herbicidal spectrums of the highly active compounds were further determined, and the compound G31 exhibited the best inhibitory rate over 90% against Plantago depressa Willd and Capsella bursa-pastoris at the dosages of 75.0 and 37.5 g ai/ha, which is comparable to the control herbicide mesotrione. Moreover, compound G31 showed excellent crop safety, with less than or equal to 10% injury rates to corn, sorghum, soybean and cotton at a dosage of 225 g ai/ha. Molecular docking and molecular dynamics simulation analysis revealed that the compound G31 could stably bind to Arabidopsis thaliana HPPD (AtHPPD). This study indicated that the compound G31 could be used as a lead molecular structure for the development of novel HPPD inhibitors, which provided an idea for the design of new herbicides with unique molecular scaffold.

[Analysis of rare mutations associated with Thalassemia and their hematological characteristics in Chenzhou region of Hunan Province].

OBJECTIVE: To explore the distribution and hematological characteristics of rare thalassemia-associated mutations in Chenzhou region of Hunan Province with an aim to provide a basis for genetic counseling and effective prevention. METHODS: A total of 37 370 individuals enrolled from January 2015 to December 2021 were screened by routine blood test and hemoglobin electrophoresis. The genotypes were determined with high-throughput sequencing. RESULTS: A total of 8 455 thalassemia mutations (including 185 rare ones) were detected, which had involved 27 mutational types. Rare type α-Thalassemia --THAI and CD31 (AGG>AAG) have the typical microcytic hypochromic hematological features, whilst SEA-HPFH, CD14 (CTG>-TG), CD37 (TGG>TAG), -90(C>T), Codon 15 (G>A), IVS-I-128 (T>G), CD86 (GCC>GC-) and Chinese Gγ+(Aγδß)0 had typical microcytic hypochromic and ß-thalassemia-associated hematological features of elevated HbA2 or HbF. In addition, the -50（G>A）heterozygotes of ß-thalassemia had normal or slightly decreased MCV and MCH without an increase in HbA2. CONCLUSION: Various forms of thalassemia-associated mutations have been identified in the Chenzhou region of Hunan Province. Above finding has facilitated development of preventive and control strategies for thalassemia as well as birth health programs.

Genome-wide association analysis of Fusarium crown rot resistance in Chinese wheat landraces.

KEY MESSAGE: A novel locus for Fusarium crown rot (FCR) resistance was identified on chromosome 1B at 641.36-645.13 Mb using GWAS and could averagely increase 39.66% of FCR resistance in a biparental population. Fusarium crown rot can cause considerable yield losses. Developing and growing resistance cultivars is one of the most effective approaches for controlling this disease. In this study, 361 Chinese wheat landraces were evaluated for FCR resistance, and 27 with the disease index lower than 30.00 showed potential in wheat breeding programs. Using a genome-wide association study approach, putative quantitative trait loci (QTL) for FCR resistance was identified. A total of 21 putative loci on chromosomes 1A, 1B, 2B, 2D, 3B, 3D, 4B, 5A, 5B, 7A, and 7B were significantly associated with FCR resistance. Among these, a major locus Qfcr.sicau.1B-4 was consistently identified among all the trials on chromosome 1B with the physical regions from 641.36 to 645.13 Mb. A polymorphism kompetitive allele-specific polymerase (KASP) marker was developed and used to validate its effect in an F2:3 population consisting of 136 lines. The results showed the presence of this resistance allele could explain up to 39.66% of phenotypic variance compared to its counterparts. In addition, quantitative real-time polymerase chain reaction showed that two candidate genes of Qfcr.sicau.1B-4 were differently expressed after inoculation. Our study provided useful information for improving FCR resistance in wheat.

Methyl eugenol protects the kidney from oxidative damage in mice by blocking the Nrf2 nuclear export signal through activation of the AMPK/GSK3ß axis.

Disrupted redox homeostasis contributes to renal ischemia-reperfusion (IR) injury. Abundant natural products can activate nuclear factor erythroid-2-related factor 2 (Nrf2), thereby providing therapeutic benefits. Methyl eugenol (ME), an analog of the phenolic compound eugenol, has the ability to induce Nrf2 activity. In this study, we investigated the protective effects of ME against renal oxidative damage in vivo and in vitro. An IR-induced acute kidney injury (AKI) model was established in mice. ME (20 mg·kg-1·d-1, i.p.) was administered to mice on 5 consecutive days before IR surgery. We showed that ME administration significantly attenuated renal destruction, improved the survival rate, reduced excessive oxidative stress and inhibited mitochondrial lesions in AKI mice. We further demonstrated that ME administration significantly enhanced Nrf2 activity and increased the expression of downstream antioxidative molecules. Similar results were observed in vitro in hypoxia/reoxygenation (HR)-exposed proximal tubule epithelial cells following pretreatment with ME (40 µmol·L-1). In both renal oxidative damage models, ME induced Nrf2 nuclear retention in tubular cells. Using specific inhibitors (CC and DIF-3) and molecular docking, we demonstrated that ME bound to the binding pocket of AMPK with high affinity and activated the AMPK/GSK3ß axis, which in turn blocked the Nrf2 nuclear export signal. In addition, ME alleviated the development of renal fibrosis induced by nonfatal IR, which is frequently encountered in the clinic. In conclusion, we demonstrate that ME modulates the AMPK/GSK3ß axis to regulate the cytoplasmic-nuclear translocation of Nrf2, resulting in Nrf2 nuclear retention and thereby enhancing antioxidant target gene transcription that protects the kidney from oxidative damage.

Sequence-dependent recruitment of SRSF1 and SRSF7 to intronless lncRNA NKILA promotes nuclear export via the TREX/TAP pathway.

The TREX-TAP pathway is vital for mRNA export. For spliced mRNA, the TREX complex is recruited during splicing; however, for intronless mRNA, recruitment is sequence dependent. However, the export of cytoplasmic long noncoding RNA (lncRNA) is poorly characterized. We report the identification of a cytoplasmic accumulation region (CAR-N) in the intronless lncRNA, NKILA. CAR-N removal led to strong nuclear retention of NKILA, and CAR-N insertion promoted the export of cDNA transcripts. In vitro RNP purification via CAR-N, mass spectrometry, and siRNA screening revealed that SRSF1 and SRSF7 were vital to NKILA export, and identified a cluster of SRSF1/7 binding sites within a 55 nucleotide sequence in CAR-N. Significant nuclear enrichment of NKILA was observed for NKILA lacking CAR-N or the cluster of binding sites in knock-in models. Depletion of TREX-TAP pathway components resulted in strong nuclear retention of NKILA. RNA and protein immunoprecipitation verified that SRSF1/7 were bound to NKILA and interacted with UAP56 and ALYREF. Moreover, NKILA lacking CAR-N was unable to inhibit breast cancer cell migration. We concluded that the binding of SRSF1/7 to clustered motifs in CAR-N facilitated TREX recruitment, promoting the export of NKILA, and confirmed the importance of NKILA localization to its function.

Identification and Genome-Wide Association Analysis for Fusarium Crown Rot Resistance in Wheat.

Fusarium crown rot (FCR) is a fungal disease and severely decreases wheat production worldwide. Tibetan semiwild wheat, Yunnan hulled wheat, Xinjiang rice wheat, and Sichuan white wheat are four subspecies landraces endemic to western China and have rich genetic diversity in response to biotic and abiotic stresses. Here, a natural population, including 209 wheat accessions of four subspecies, was evaluated for FCR resistance. he genome-wide association study was performed using the wheat 55K single-nucleotide polymorphisms (SNPs). The results showed that the disease index (DI) ranged from 16.88 to 85.00, while six accessions showed moderate to high resistance (DI ≤ 30). Genome-wide association analysis identified 10 stable loci for FCR resistance on chromosomes 1B, 2A (5), 5A, 7A, 7B, and 7D. Four major loci-Qfcr.sicau.2A-1, Qfcr.sicau.2A-3, Qfcr.sicau.5A, and Qfcr.sicau.7D-explained 6.01 to 14.48, 9.76 to 13.11, 8.19 to 10.29, and 5.76 to 12.21% phenotypic variation, respectively. Quantitative trait loci (QTL) pyramiding analysis of these four major loci revealed that accessions with four resistance haplotypes could significantly decrease FCR severity by 9.35 to 31.61% compared with those without or with one to three resistance haplotypes. One kompetitive allele-specific PCR (KASP) marker each was successfully developed for Qfcr.sicau.2A-1 and Qfcr.sicau.7D. The KASP marker of Qfcr.sicau.2A-1 was used to genotype in an F6 recombinant inbred line population. The result showed that the lines carrying the resistance allele reduced FCR severity by 17.78%, demonstrating the importance of Qfcr.sicau.2A-1 in resistance breeding programs. Our findings provide valuable QTL and breeder-friendly PCR-based markers for applications in FCR resistance breeding programs. Our study also proved that gene pyramiding of major loci could enhance FCR resistance.

Mapping Stripe Rust Resistance QTL in 'N2496', a Synthetic Hexaploid Wheat Derivative.

Stripe rust is a destructive disease that affects plant growth and substantially reduces wheat yields globally. An economically and environmentally friendly way to control this disease is to use resistant cultivars. 'N2496' is a synthetic hexaploid wheat derivative that exhibits high resistance and could serve as a source of resistance for breeding programs. We developed three recombinant inbred lines (RILs) populations by crossing 'N2496' with common wheat cultivars 'CN16', 'CM107', and 'MM37'. Stripe rust responses were evaluated in all three populations using a mixture of current predominant Chinese Puccinia striiformis f. sp. tritici races. A stripe rust resistance quantitative trait locus (QTL) in the 'N2496'/'CN16' RIL population was mapped on chromosome arm 6BL at 519.35 to 526.55 Mb using bulked segregant RNA sequencing. The population was genotyped using simple sequence repeats and kompetitive allele-specific polymerase (KASP) markers. The QTL QYr.sicau-6B was localized to a 1.19-cM interval flanked by markers KASP-TXK-10 and KASP-TXK-6. The genetic effect of QYr.sicau-6B was validated in the 'N2496' × 'CM107' and 'N2496' × 'MM37' RILs populations and explained up to 63.16% of the phenotypic variation. RNA sequencing and quantitative real-time polymerase chain reaction identified two differentially expressed candidate genes in the physical interval of QYr.sicau-6B.

[The value of non-invasive prenatal testing for the identification of numerical and structural chromosomal abnormalities and copy number variations in the fetuses].

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for the identification of numerical and structural chromosomal abnormalities and copy number variations (CNVs) in fetuses. METHODS: 46 197 pregnant women undergoing NIPT at the Prenatal Diagnosis Center of Chenzhou First People's Hospital from January 2018 to December 2021 were selected as the study subjects. Positive cases were subjected to chromosomal karyotyping and copy number variation sequencing (CNV-seq) following amniocentesis. RESULTS: Nearly 50% of common chromosomal aneuploidies were found in the elder pregnant women. Among these, sex chromosome aneuploidies were mainly found in pregnant women with advanced age as well as borderline risks by serological screening. Rare autosomal aneuploidies and CNVs were mainly found in those with borderline or high risks by serological screening. The positive predictive values (PPV) for fetal chromosomal abnormalities indicated by NIPT were as follows: T21 (92.37%, 109/118), T18 (53.85%, 14/26), sex chromosome aneuploidies (45.04%, 59/131), T13 (34.62%, 9/26), CNVs (29.17%, 14/48), and rare autosomal aneuploidies (2.60%, 2/77). CONCLUSION: NIPT has a high detection rate for T21, T18, T13 and sex chromosome aneuploidies. It can also detect rare autosomal aneuploidies and CNVs, including some rare structural abnormalities, though verification is required by analyzing amniotic fluid samples.

Fine mapping of the tiller inhibition gene TIN4 contributing to ideal plant architecture in common wheat.

KEY MESSAGE: A tiller inhibition gene, TIN4, was mapped to an approximately 311 kb genomic interval on chromosome arm 2DL of wheat. The tiller is one of the key components of plant morphological architecture and a central agronomic trait affecting spike number in wheat. Low tiller number has been proposed as a major component of crop ideotypes for high yield potential. In this study, we characterized the development of tillering in near-isogenic lines (NIL7A and NIL7B), indicating that the TIN4 gene inhibited the growth of tillering buds and negatively regulated tiller number. Low-tillering was controlled by a single gene (TIN4) located on chromosome 2DL by genetic analysis and bulked segregant RNA-seq analysis. A total of 17 new polymorphic markers were developed in this study, and 61 recombinants were identified in the secondary F2 population containing 4,266 individuals. TIN4 was finally mapped on a 0.35 cM interval, co-segregated with molecular marker M380, within a 311 kb genomic interval of the wheat cultivar Chinese Spring reference genome sequence that contained twelve predicted genes. Yield experiments showed that the yield of low-tillering lines was higher than that of high-tillering lines at a higher density. Overall, this study provides a foundation for the construction of a low-tillering ideotype for improving wheat yield and further cloning TIN4 by map-based cloning approach.

High-Performance RuOx Catalyst with Advanced Mesoporous Structure for Oxygen Evolution Reaction.

Polymer electrolyte membrane water electrolysis (PEMWE) is regarded as one of the most important cornerstone technologies in the upcoming hydrogen society. However, one of the major problems it encounters is its slow oxygen evolution kinetics, which necessitates the use of large amounts of precious metal catalysts to ensure a satisfactory reaction rate. Herein, we have prepared a series of RuOx with porous structures and ultrahigh Ru utilization toward the oxygen evolution reaction. All porous samples exhibit an enhanced catalytic performance compared with commercial RuOx. Particularly, for the RuOx-350 sample, the overpotential to reach 10 mA cm-2 is as low as 225 mV. It has obvious advantages among all reported pure RuO2-based catalysts. Here, a new strategy was raised to construct efficient RuO2 electrocatalysts with outstanding activity and stability for water electrolysis technology.

Caging Cationic Polymer Brush-Coated Plasmonic Nanostructures for Traceable Selective Antimicrobial Activities.

Cationic polymers are under intense research to achieve prominent antimicrobial activity. However, the cellular and in vivo toxicity caused by nonspecific electrostatic interaction has become a major challenge for their practical applications. Here, the development of a "caging" strategy based on the use of a block copolymer consisting of a stealth block and an anionic block that undergoes degradation in presence of enzymes secreted by selective bacterial pathogens of interest is reported. The results have shown that antimicrobial cationic polymer brushes-coated gold nanorods (AuNRs) can be caged by the block polymer of poly(ethylene glycol) and anionic, lipase-degradable block of ε-caprolactone and methacrylic acid copolymer to afford neutrally charged surfaces. The caged AuNRs are activated by lipase released by bacteria of interest to endow an excellent bactericidal effect but show minimal binding and toxicity against mammalian cells and nonspecific bacteria that do not produce lipase. In this design, AuNRs play multifunctional roles as the scaffolds for polymer brushes, photothermal transducers, and imaging probes for traceable delivery of the activation and delivery of bactericidal cationic polymer brushes. The caging strategy opens new opportunities for the safe delivery of antimicrobial materials for the treatment of bacterial infections.

Metabolic Labeling Mediated Targeting and Thermal Killing of Gram-Positive Bacteria by Self-Reporting Janus Magnetic Nanoparticles.

Nanoparticles have been widely used in detection and killing of bacteria; however, targeting bacteria is still challenging. Delicate design of nanoparticles is required for simultaneous targeting, detection, and therapeutic functions. Here the use of Au/MnFe2 O4 (Au/MFO) Janus nanoparticles to target Gram-positive bacteria via metabolic labeling is reported and realize integrated self-reporting and thermal killing of bacteria. In these nanoparticles, the Au component is functionalized with tetrazine to target trans-cyclooctene group anchored on bacterial cell wall by metabolic incorporation of d-amino acids, and the MFO part exhibits peroxidase activity, enabling self-reporting of bacteria before treatment. The spatial separation of targeting and reporting functions avoids the deterioration of catalytic activity after surface modification. Also important is that MFO facilitates magnetic separation and magnetic heating, leading to easy enrichment and magnetic thermal therapy of labeled bacteria. This method demonstrates that metabolic labeling with d-amino acids is a promising strategy to specifically target and kill Gram-positive bacteria.

Antibiofilm Activity of Gallium(III) Complexed Anionic Polymers in Combination with Antibiotics.

Pseudomonas aeruginosa (P. aeruginosa) is a life-threatening pathogen associated with multiantibiotic resistance, which is largely caused by its strong ability to form biofilms. Recent research has revealed that gallium (III) shows an activity against the biofilm of P. aeruginosa by interfering with Fe metabolism. The antibacterial activity of the combination of Ga3+ ion and antibiotic rifampicin (RMP) against P. aeruginosa PAO1 is investigated. An anionic polymer poly{{2-[(2-methylprop-2-enoyl)oxy]ethyl}phosphonic acid} (PDMPOH) is exploited to form complexes (GaPD) with Ga3+ . The GaPD complexes act as a carrier of Ga3+ and release Ga3+ via enzymatic degradation by bacterial lipases. GaPD is found to damage the outer membrane, leading to enhanced cellular uptake of RMP and Ga3+ due to increased outer membrane permeability, which inhibits the RNA polymerase and interferes with Fe metabolism. The antibiofilm activity and biocompatibility of the GaPD system offer a promising treatment option for P. aeruginosa biofilm-related infections.

XAB2 depletion induces intron retention in POLR2A to impair global transcription and promote cellular senescence.

XAB2 is a multi-functional protein participating processes including transcription, splicing, DNA repair and mRNA export. Here, we report POLR2A, the largest catalytic subunit of RNA polymerase II, as a major target gene down-regulated after XAB2 depletion. XAB2 depletion led to severe splicing defects of POLR2A with significant intron retention. Such defects resulted in substantial loss of POLR2A at RNA and protein levels, which further impaired global transcription. Treatment of splicing inhibitor madrasin induced similar reduction of POLR2A. Screen using TMT-based quantitative proteomics identified several proteins involved in mRNA surveillance including Dom34 with elevated expression. Inhibition of translation or depletion of Dom34 rescued the expression of POLR2A by stabilizing its mRNA. Immuno-precipitation further confirmed that XAB2 associated with spliceosome components important to POLR2A expression. Domain mapping revealed that TPR motifs 2-4 and 11 of XAB2 were critical for POLR2A expression by interacting with SNW1. Finally, we showed POLR2A mediated cell senescence caused by XAB2 deficiency. Depletion of XAB2 or POLR2A induced cell senescence by up-regulation of p53 and p21, re-expression of POLR2A after XAB2 depletion alleviated cellular senescence. These data together support that XAB2 serves as a guardian of POLR2A expression to ensure global gene expression and antagonize cell senescence.

Uplink Sparse Channel Estimation for Hybrid Millimeter Wave Massive MIMO Systems by UTAMP-SBL.

The compressive sensing (CS)-based sparse channel estimator is recognized as the most effective solution to the excessive pilot overhead in massive MIMO systems. However, due to the complex signal processing in the wireless communication systems, the measurement matrix in the CS-based channel estimation is sometimes "unfriendly" to the channel recovery. To overcome this problem, in this paper, the state-of-the-art sparse Bayesian learning using approximate message passing with unitary transformation (UTAMP-SBL), which is robust to various measurement matrices, is leveraged to address the multi-user uplink channel estimation for hybrid architecture millimeter wave massive MIMO systems. Specifically, the sparsity of channels in the angular domain is exploited to reduce the pilot overhead. Simulation results demonstrate that the UTAMP-SBL is able to achieve effective performance improvement than other competitors with low pilot overhead.

[Effect of methyl eugenol on hypoxia/reoxygenation injury of human renal tubular epithelial cells and its mechanism].

This study aimed to investigate the effect of methyl eugenol(ME) on hypoxia/reoxygenation(H/R)-induced injury of human renal tubular epithelial HK-2 cells and its mechanism. The viability of HK-2 cells cultured with different concentrations of ME and exposed to H/R was detected by cell counting kit-8(CCK-8) assay. The effect of ME on the morphology of HK-2 cells was observed under an inverted microscope. The content of intracellular reactive oxygen species in different groups was detected after 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA) fluorescence staining. Cell apoptosis was determined by flow cytometry. Changes in mitochondrial membrane potential were monitored by JC-1 dye. The concentrations of nuclear factor erythroid 2 related factor 2(Nrf2), heme oxygenase-1(HO-1), and nicotinamide adenine dinucleotide phosphatase oxidase 4(Nox4) were measured by Western blot, followed by the assay of Nrf2 concentration changes in cytoplasm and nucleus by confocal fluorescence staining. The results showed that when the concentration of ME was 0-40 µmol·L~(-1), the activity of HK-2 cells was not affected. Compared with the model group, ME enhanced the activity of HK-2 cells and the cell morphology was normal. As revealed by further experiments, ME inhibited the release of reactive oxygen species and the decline in mitochondrial membrane potential of HK-2 cells after H/R injury, promoted Nrf2/HO-1 expression and Nrf2 translocation to the nucleus, and down-regulated the expression of Nox4, thereby significantly reducing apoptosis. This protective effect of ME could be reversed by the specific Nrf2 inhibitor ML385. These findings have preliminarily proved that ME effectively protected HK-2 cells against H/R injury, which might be related to its promotion of Nrf2/HO-1 signaling pathway and inhibition of Nox4. Such exploration on the possible mechanism of ME in the treatment of renal ischemia-reperfusion injury(IRI) and protection of organ function from the perspective of antioxidant stress has provided reference for related research on the treatment of acute kidney injury with traditional Chinese medicine.

Multi-Model- and Soft-Transition-Based Height Soft Sensor for an Air Cushion Furnace.

The floating height of the strip in an air cushion furnace is a key parameter for the quality and efficiency of production. However, the high temperature and high pressure of the working environment prevents the floating height from being directly measured. Furthermore, the strip has multiple floating states in the whole operation process. It is thus difficult to employ a single model to accurately describe the floating height in different states. This paper presents a multi-model soft sensor to estimate the height based on state identification and the soft transition. First, floating states were divided using a partition method that combined adaptive k-nearest neighbors and principal component analysis theories. Based on the identified results, a hybrid model for the stable state, involving a double-random forest model for the vibration state and a soft-transition model, was created to predict the strip floating height. In the hybrid model for the stable state, a mechanistic model combined thick jet theory and the equilibrium equation of force to cope with the lower floating height. In addition, a novel soft-transition model based on data gravitation that further reflects the intrinsic process characteristic was developed for the transition state. The effectiveness of the proposed approach was validated using a self-developed air cushion furnace experimental platform. This study has important value for the process prediction and control of air cushion furnaces.