A Dual-Focus Workflow for Simultaneously Engineering High Activity and Thermal Stability in Methyl Parathion Hydrolase.

Industrial fermentation applications typically require enzymes that exhibit high stability and activity at high temperatures. However, efforts to simultaneously improve these properties are usually limited by a trade-off between stability and activity. This report describes a computational strategy to enhance both activity and thermal stability of the mesophilic organophosphate-degrading enzyme, methyl parathion hydrolase (MPH). To predict hotspot mutation sites, we assembled a library of features associated with the target properties for each residue and then prioritized candidate sites by hierarchical clustering. Subsequent in silico screening with multiple algorithms to simulate selective pressures yielded a subset of 23 candidate mutations. Iterative parallel screening of mutations that improved thermal stability and activity yielded, MPHase-m5b, which exhibited 13.3 °C higher Tm and 4.2 times higher catalytic activity than wild-type (WT) MPH over a wide temperature range. Systematic analysis of crystal structures, molecular dynamics (MD) simulations, and Quantum Mechanics/Molecular Mechanics (QM/MM) calculations revealed a wider entrance to the active site that increased substrate access with an extensive network of interactions outside the active site that reinforced αß/ßα sandwich architecture to improve thermal stability. This study thus provides an advanced, rational design framework to improve efficiency in engineering highly active, thermostable biocatalysts for industrial applications.

Targeted large fragment deletion in plants using paired crRNAs with type I CRISPR system.

The CRISPR-Cas systems have been widely used as genome editing tools, with type II and V systems typically introducing small indels, and type I system mediating long-range deletions. However, the precision of type I systems for large fragment deletion is still remained to be optimized. Here, we developed a compact Cascade-Cas3 Dvu I-C system with Cas11c for plant genome editing. The Dvu I-C system was efficient to introduce controllable large fragment deletion up to at least 20 kb using paired crRNAs. The paired-crRNAs design also improved the controllability of deletions for the type I-E system. Dvu I-C system was sensitive to spacer length and mismatch, which was benefit for target specificity. In addition, we showed that the Dvu I-C system was efficient for generating stable transgenic lines in maize and rice with the editing efficiency up to 86.67%. Overall, Dvu I-C system we developed here is powerful for achieving controllable large fragment deletions.

Global attention-enabled texture enhancement network for MR image reconstruction.

PURPOSE: Although recent convolutional neural network (CNN) methodologies have shown promising results in fast MR imaging, there is still a desire to explore how they can be used to learn the frequency characteristics of multicontrast images and reconstruct texture details. METHODS: A global attention-enabled texture enhancement network (GATE-Net) with a frequency-dependent feature extraction module (FDFEM) and convolution-based global attention module (GAM) is proposed to address the highly under-sampling MR image reconstruction problem. First, FDFEM enables GATE-Net to effectively extract high-frequency features from shareable information of multicontrast images to improve the texture details of reconstructed images. Second, GAM with less computation complexity has the receptive field of the entire image, which can fully explore useful shareable information of multi-contrast images and suppress less beneficial shareable information. RESULTS: The ablation studies are conducted to evaluate the effectiveness of the proposed FDFEM and GAM. Experimental results under various acceleration rates and datasets consistently demonstrate the superiority of GATE-Net, in terms of peak signal-to-noise ratio, structural similarity and normalized mean square error. CONCLUSION: A global attention-enabled texture enhancement network is proposed. it can be applied to multicontrast MR image reconstruction tasks with different acceleration rates and datasets and achieves superior performance in comparison with state-of-the-art methods.

Conicity-index predicts all-cause mortality in Chinese older people: a 10-year community follow-up.

BACKGROUND: Abdominal obesity (AO) has been regarded as the most dangerous type of obesity. The Conicity-index (C-index) had a high ability to discriminate underlying AO. The purpose of this study was to determine the ability of C-index to predict all-cause mortality among non-cancer Chinese older people. METHODS: The participants were residents of the Wanshou Road community in Beijing, China. Receiver operating curve (ROC) curves were used to determine the sensitivity and specificity of the best cut-off values for different anthropometric measures for predicting all-cause mortality. The area under the curve (AUC) of the ROC curves were calculated to compare the relative ability of various anthropometric measures to correctly identify older people in the community where all-cause mortality occurs. Included subjects were grouped according to C-index tertiles. The association between C-index and all-cause mortality was verified using Kaplan-Meier survival analysis and different Cox regression models. RESULTS: During a mean follow-up period of 9.87 years, 1821 subjects completed follow-up. The average age was 71.21 years, of which 59.4% were female. The ROC curve results showed that the AUC of the C-index in predicting all-cause mortality was 0.633. Kaplan-Meier survival curves showed a clear dose-response relationship between C-index and all-cause mortality. With the increase of C-index, the survival rate of the study population showed a significant downward trend (P < 0.05). Adjusted for age, gender, hip circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose (FBG), 2-h postprandial blood glucose (2hPG), glycosylated hemoglobin, high-density lipids protein (LDL), triglyceride, serum creatinine, serum uric acid, urine albumin-creatinine ratio (UACR), Mini-Mental State Examination (MMSE), smoking history, and drinking history, COX regression analysis showed that in the model adjusted for all covariates, the risk of all-cause mortality in tertile 3 was 1.505 times that in tertile 1, and the difference was statistically significant. CONCLUSIONS: The C-index is an independent risk factor for all-cause mortality in the non-cancer Chinese older people.

A Novel Gelatin-Based Sustained-Release Molluscicide for Control of the Invasive Agricultural Pest and Disease Vector Pomacea canaliculata.

Pomacea canaliculata, one of the 100 most destructive invasive species in the world, and it is an important intermediate host of Angiostrongylus cantonensis. The molluscicides in current use are an effective method for controlling snails. However, most molluscicides have no slow-release effect and are toxic to nontarget organisms. Thus, these molluscicides cannot be used on a large scale to effectively act on snails. In this study, gelatin, a safe and nontoxic substance, was combined with sustained-release molluscicide and was found to reduce the toxicity of niclosamide to nontarget organisms. We assessed the effects of gelatin and molluscicide in controlling P. canaliculata snails and eggs. The results demonstrated that the niclosamide retention time with 1.0% and 1.5% gelatin sustained-release agents reached 20 days. Additionally, the mortality rate of P. canaliculata and their eggs increased as the concentration of the niclosamide sustained-release agents increased. The adult mortality rate of P. canaliculata reached 50% after the snails were exposed to gelatin with 0.1 mg/L niclosamide for 48 h. The hatching rate of P. canaliculata was only 28.5% of the normal group after the treatment was applied. The sustained-release molluscicide at this concentration was less toxic to zebrafish, which means that this molluscicide can increase the safety of niclosamide to control P. canaliculata in aquatic environments. In this study, we explored the safety of using niclosamide sustained-release agents with gelatin against P. canaliculata. The results suggest that gelatin is an ideal sustained-release agent that can provide a foundation for subsequent improvements in control of P. canaliculata.

Suppression of Sox4 protects against myocardial ischemic injury by reduction of cardiac apoptosis in mice.

Sox4 participates in the progression of embryo development and regulation of apoptosis in tumors. However, the effect and mechanism of Sox4 in myocardial infarction (MI) remains unclear. Therefore, we aimed at examining the role and molecular mechanism of Sox4 in the process of cardiomyocytes apoptosis during MI. The expression of Sox4 were obviously increased both in MI mice and in neonatal mouse cardiomyocytes treated with H2 O2 . Overexpression of Sox4 promoted cardiomyocyte apoptosis with or without H2 O2 , whereas knocking down of Sox4 alleviated H2 O2 -induced apoptosis in cardiomyocytes. Furthermore, silencing Sox4 by AAV-9 carried short hairpin RNA targeting Sox4 (AAV-9-sh-Sox4) markedly decreased cardiac infarct area, imprfoved cardiac dysfunction, and reversed apoptosis in MI mice. Mechanistically, there is a potential Sox4-binding site in the promoter region of Bim, and forced expression of Sox4 significantly promoted Bim expression in cultured cardiomyocytes with or without H2 O2 , whereas knocking down of Sox4 inhibited the expression of Bim. Further studies showed that silencing Bim attenuated Sox4-induced apoptosis in cardiomyocytes, indicating that Sox4 promoted cardiomyocytes apoptosis through regulation of Bim expression, which can be used as a potential therapeutic target for MI.

Gamma-aminobutyric acid enhances tolerance to iron deficiency by stimulating auxin signaling in cucumber (Cucumis sativusL.).

Iron deficiency severely affects crop yield and quality. Gamma-aminobutyric acid (GABA) plays a vital role in plant responses to multifarious stresses. However, the role of GABA in Fe deficiency responses and the potential mechanisms remain largely unknown in cucumber. Here, we found that Fe deficiency raised the GABA levels in leaves and roots of cucumber. To probe the role of GABA in Fe deficiency, the seedlings were subjected to five levels of GABA concentrations (0, 5, 10, 20 and 40 mmol L-1) for 7 days under Fe deficiency. The results demonstrated that 20 mM GABA in alleviating the Fe deficiency-induced stress was the most effective. GABA pretreatment reduced the Fe deficiency-induced chlorosis and inhibition of photosynthesis and growth, and significantly enhanced the contents of iron in shoots and roots. Exogenous GABA significantly decreased the pH of nutrient solution and increased ferric-chelate reductase (FCR) activity induced by Fe deficiency and the transcript levels of Fe uptake-related genes HA1, FRO2 and IRT1 in roots. GABA also increased the content of auxin (IAA) and expression of auxin biosynthesis (YUC4), response (IAA1), and transport (PIN1) genes under Fe deficiency. Furthermore, exogenous the auxin transport inhibitor 1-naphthylphthalamic acid (NPA) application abolished the GABA-induced changes in Fe deficiency. In summary, we found that GABA improves tolerance to iron deficiency via an auxin-dependent mechanism in cucumber.

Searching for valuable differentially expressed miRNAs in postmenopausal osteoporosis by RNA sequencing.

AIM: Postmenopausal osteoporosis is a systemic and chronic bone disease in women. In order to understand the pathological mechanism of postmenopausal osteoporosis, we aimed to find the potential differentially expressed miRNAs in the disease. METHODS: Firstly, RNA sequencing was used to identify differentially expressed miRNAs, followed by the construction of the miRNA-target mRNA regulatory network. Then, Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes were used to analyze the biological function of target mRNAs. Finally, electronic validation of identified differentially expressed miRNAs and target mRNAs was performed. RESULTS: A total of 33 differentially expressed miRNAs (18 upregulated and 15 downregulated miRNAs) and 6820 miRNA-mRNA pairs were identified. Among which, seven miRNAs with high degree including hsa-miR-17-5p, hsa-miR-1-3p, hsa-miR-193b-3p, hsa-miR-125b-5p, hsa-miR-10b-5p, hsa-miR-100-5p and hsa-miR-30a-3p were obtained in the miRNA-mRNA regulatory network. TGF-beta was the most significantly enriched signaling pathway of target mRNAs. The electronic validation result of hsa-miR-1-3p, hsa-miR-193b-3p, hsa-miR-10b-5p, hsa-miR-100-5p, hsa-miR-133b, hsa-miR-708-5p, CRK, RAB5C, CCND1 and PCYOX1 was consisted with the RNA sequencing analysis. CONCLUSION: Dysfunctional miRNAs may play significant roles in postmenopausal osteoporosis.

OS1 functions in the allocation of nutrients between the endosperm and embryo in maize seeds.

Uncovering the genetic basis of seed development will provide useful tools for improving both crop yield and nutritional value. However, the genetic regulatory networks of maize (Zea mays) seed development remain largely unknown. The maize opaque endosperm and small germ 1 (os1) mutant has opaque endosperm and a small embryo. Here, we cloned OS1 and show that it encodes a putative transcription factor containing an RWP-RK domain. Transcriptional analysis indicated that OS1 expression is elevated in early endosperm development, especially in the basal endosperm transfer layer (BETL), conducting zone (CZ), and central starch endosperm (CSE) cells. RNA sequencing (RNA-Seq) analysis of the os1 mutant revealed sharp downregulation of certain genes in specific cell types, including ZmMRP-1 and Meg1 in BETL cells and a majority of zein- and starch-related genes in CSE cells. Using a haploid induction system, we show that wild-type endosperm could rescue the smaller size of os1 embryo, which suggests that nutrients are allocated by the wild-type endosperm. Therefore, our data imply that the network regulated by OS1 accomplishes a key step in nutrient allocation between endosperm and embryo within maize seeds. Identification of this network will help uncover the mechanisms regulating the nutritional balance between endosperm and embryo.

Identifying and engineering a critical amino acid residue to enhance the catalytic efficiency of Pseudomonas sp. methyl parathion hydrolase.

Methyl parathion hydrolase (MPH) that hydrolyzes a wide range of organophosphorus pesticides can be used to remediate land polluted by the pesticides. Here, the catalytic efficiency of methyl parathion hydrolase from Pseudomonas sp. (WBC-3) was enhanced by searching and engineering a critical site far away from the binding pocket. In the first round, a four-site mutant with a modest increased catalytic efficiency (3.2-fold kcat/Km value of the wild type) was obtained with random mutagenesis. By splitting and re-combining the four substitutions in the mutant, the critical site S277, was identified to show the most significant effects of improving binding affinity and catalytic efficiency. With further site-saturation mutagenesis focused on the residue S277, another two substitutions were discovered to have even more significant decrease in Km (40.2 and 47.6 µM) and increased in kcat/Km values (9.5- and 10.3-fold of the wild type) compared to the original four-site mutant (3.0- and 3.2-fold). In the three-dimensional structure, residue S277 is located at a hinge region of a loop, which could act as a "lid" at the substrate entering to the binding pocket. This suggests that substitutions of residue S277 could affect substrate binding via conformational change in substrate entrance region. This work provides a valuable protocol combining random mutagenesis, site-saturation mutagenesis, structural and bioinformatics analyses to obtain mutants with high catalytic efficiency from a screening library of a modest size (3200 strains).

Spatial and temporal patterns of microclimates at an urban forest edge and their management implications.

Fragmented forests generate a variety of forest edges, leading to microclimates in the edge zones that differ from those in the forest interior. Understanding microclimatic variation is an important consideration for managers because it helps when making decisions about how to restrict the extent of edge effects. Thus, our study attempted to characterize the changing microclimate features at an urban forest edge located on Mt. Gwanak, Seoul, South Korea. We examined edge effects on air temperature, relative humidity, soil temperature, soil moisture, and photosynthetically active radiation (PAR) during the hottest three consecutive days in August 2016. Results showed that each variable responded differently to the edge effects. This urban forest edge had an effect on temporal changes at a diurnal scale in all microclimate variables, except soil moisture. In addition, all variables except relative humidity were significantly influenced by the edge effect up to 15 m inward from the forest boundary. The relative humidity fluctuated the most and showed the deepest extent of the edge effect. Moreover, the edge widths calculated from the relative humidity and air temperature both peaked in the late afternoon (16:00 h). Our findings provide a reference for forest managers in designing urban forest zones and will contribute to the conservation of fragmented forests in urban areas.

Cell cycle arrest induced by inhibitors of epigenetic modifications in maize (Zea mays) seedling leaves: characterization of the process and possible mechanisms involved.

Epigenetic modifications play crucial roles in the regulation of chromatin architecture and are involved in cell cycle progression, including mitosis and meiosis. To explore the relationship between epigenetic modifications and the cell cycle, we treated maize (Zea mays) seedlings with six different epigenetic modification-related inhibitors and identified the postsynthetic phase (G2 ) arrest via flow cytometry analysis. Total H4K5ac levels were significantly increased and the distribution of H3S10ph signalling was obviously changed in mitosis under various treatments. Further statistics of the cells in different periods of mitosis confirmed that the cell cycle was arrested at preprophase. Concentrations of hydrogen peroxide were relatively higher in the treated plants and the antioxidant thiourea could negate the influence of the inhibitors. Moreover, all of the treated plants displayed negative results in the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) and γ-H2AX immunostaining assays after exposure for 3 d. Additionally, the expression level of topoisomerase genes in the treated plants was relatively lower than that in the untreated plants. These results suggest that these inhibitors of epigenetic modifications could cause preprophase arrest via reactive oxygen species formation inhibiting the expression of DNA topoisomerase genes, accompanied by changes in the H4K5ac and H3S10ph histone modifications.

Establishment of a novel method without sequence modification for developing NoV P particle-based chimeric vaccines.

The Norovirus (NoV) P particle (PP) is a subviral particle formed by 24 copies of the protruding (P) domain of the capsid protein. Each P domain has three surface loops that can be used for foreign antigen presentation. Hence, PPs have been demonstrated to be an excellent platform for vaccine development against many pathogens. However, current processes for preparing those chimeric PP vaccines vary and would change the original sequence of the PP. A detailed strategy also has not been reported for inserting a foreign antigen into all three loops. In order to develop a novel method for preparing distinct types of PP-based protein vaccines, we created two restriction enzyme sites (EagI and KpnI) in the P domain by site-directed mutagenesis without changing its original sequence. A synthesized gene with three copies of the Alzheimer's disease (AD) immunogen Aß1-6 was then incorporated in loop2 of the P domain. Additionally, a synthesized gene with one copy of Aß1-6 was inserted into each loop of the P domain. Furthermore, two recombinant proteins PP-3 copy-Aß1-6-loop2 and PP-1 copy-Aß1-6-loop123 were successfully purified without affecting PP formation. Particle size analysis and TEM observations demonstrated that the two chimeric P particles were still able to form 24-mer nanoparticles. Moreover, the two chimeric PP-based AD vaccines could both efficiently elicit strong immune responses in the mouse model. In conclusion, we have successfully established a novel method for preparing vaccines based on the NoV PP which would not affect PP sequence and function.

Comparison of chromatin epigenetic modification patterns among root meristem, elongation and maturation zones in maize (Zea mays L.).

Plant roots mainly consist of division, elongation and maturation regions. Histone modifications of chromatin play a vital role in plant cell growth and differentiation. However, there has been no systematic attempt to investigate the distribution patterns of histone modifications in the different plant root zones. In this study, histone H3 acetylation (H3K9ac), histone H4 acetylation (H4K5ac), and histone H3 methylation (H3K4me2, H3K4me3, H3K9me1, H3K9me2, and H3K27me2) levels and distribution patterns were examined in the root meristem, elongation and maturation zones of maize primary roots. Overall, the cells of the maturation zone displayed the highest level of multiple histone modifications. The lowest level of histone modification was detected in the root meristem. H3K9ac was enriched in the euchromatin and nucleoli of most nuclei from the elongation and maturation zones. The nucleoli of more than 60% of cells from all root regions were labeled by H4K5ac. In only a small proportion of cells (less than 7%), knobs showed H4K5ac signals. H3K4me2 and H3K4me3 were specifically detected in euchromatin. H3K9me1, H3K9me2 and H3K27me2 labeled heterochromatin and euchromatin in all the root tissues analyzed. Over 30% of elongation and maturation cells exhibited H3K9me1 signals around knobs, approximately 5% of maturation cells showed signals of H3K9me2 around knobs, and H3K27me2 was stained weakly in approximately 95% of maturation cells in knobs. Analysis of the genomic patterns of histone modifications across functionally distinct regions of maize roots reveals a root zone-specific chromatin distribution.

Pharmacokinetic study of Q808 in rhesus monkey using liquid chromatography-tandem mass spectrometry.

Background: Q808 is a novel antiepileptic agent currently in development. In this study, we established and validated a LC-MS/MS method for the quantification of Q808 in Rhesus monkey plasma. Furthermore, we applied this method to investigate the pharmacokinetics of Q808 in Rhesus monkeys. Methods: Samples containing diazepam as an internal standard (IS) were subjected to liquid-liquid extraction (LLE) and separated using a Zorbax Extend C18 column. The detection of Q808 and IS was performed using multiple reaction monitoring mode (MRM), specifically monitoring precursor-to-product ion transitions at m/z 297.9 to 213.9 and m/z 285.2 to 193.1 for Q808 and IS, respectively. For the pharmacokinetic study of Q808, a total of 30 healthy Rhesus monkeys (half male and half female) were administered single oral doses, single IV doses, or multiple oral doses of Q808. Blood samples were collected at predetermined time points for subsequent pharmacokinetic analysis. Results: The developed LC-MS/MS method exhibited linearity within the concentration range of 1.5-750 ng/mL with intra-day precision ≤8.3% and inter-day precision ≤14.6%. Additionally, accuracy was found to be ≤ 3.4%. In the pharmacokinetic study involving single oral doses of Q808 in Rhesus monkeys, Q808 was absorbed with a median time to peak plasma concentration ranging from 4.50-6.00 h and was eliminated with a terminal elimination half-life (t1/2) between 9.34-11.31 h. No definitive conclusion regarding linear pharmacokinetic characteristics could be drawn. The absolute bioavailability was determined as 20.95%, indicating limited systemic exposure after oral administration. Multiple dosing did not result in significant accumulation based on an accumulation factor Rac value of 1.31. Conclusion: We have successfully developed and validated a rapid yet sensitive LC-MS/MS method for quantifying levels of Q808 in rhesus monkey plasma for the first time. The determination method and pharmacokinetic characteristics of Q808 in rhesus monkey support the next steps in drug development.

Comprehensive analysis identifies long non-coding RNA RNASEH1-AS1 as a potential prognostic biomarker and oncogenic target in hepatocellular carcinoma.

RNASEH1-AS1, a long non-coding RNA (lncRNA) divergently transcribed from the antisense strand of its neighboring protein-coding gene ribonuclease H1 (RNASEH1), has recently been demonstrated to be involved in tumor progression. However, the association between RNASEH1-AS1 and hepatocellular carcinoma (HCC) remains unclear. In the present study, first, the expression of RNASEH1-AS1 in HCC and its correlation with clinicopathological features, prognosis, diagnosis, immune cell infiltration of HCC patients was inspected using relevant R packages based on The Cancer Genome Atlas (TCGA) data. RNASEH1-AS1 was found to be up-regulated in most cancer types, including HCC, and its overexpression was significantly associated with histologic grade and AFP level as well as poor prognosis, and was an independent risk factor affecting overall survival with good diagnostic and prognostic values for HCC. RNASEH1-AS1 was inversely associated with the infiltration of most immune cell types, including plasmacytoid dendritic cells (pDC), B cells and neutrophils. Second, a total of 1109 positively co-expressed genes (PCEGs) of RNASEH1-AS1 were screened out in HCC by correlation analysis in batches (|Spearman's r| >0.4 and adjusted P value <0.01). GO and KEGG enrichment analysis indicated that PCEGs of RNASEH1-AS1 were mainly related to RNA processing, ribosome biogenesis, transcription and histone acetylation. The top 10 hub genes (EIF4A3, WDR43, WDR12, DKC1, NAT10, UTP18, DDX18, BYSL, DDX10, PDCD11) were identified by constructing the protein-protein interaction (PPI) network, and they were all highly expressed in HCC and positively correlated with histological grade. Third, a risk model was constructed based on four RNASEH1-AS1-related hub genes (EIF4A3, WDR12, DKC1, and NAT10) with good prognostic predictive potential via univariate Cox and the least absolute selection operator (LASSO) regression analysis. Fourth, experimental validation revealed that RNASEH1-AS1 was significantly elevated in HCC tissues and several cell lines, and its knockdown could suppress the proliferation, migration, and invasion of HCC cells. Finally, mechanistic studies demonstrated that the stability of RNASEH1-AS1 could be regulated by DKC1 via their direct interaction. Taken together, RNASEH1-AS1 may serve as a potential prognostic and diagnostic biomarker and oncogenic lncRNA for HCC.

Significance of m6A in subtype identification, immunological evolution, and therapeutic sensitivity of RA.

N6-methyladenosine (m6A) is one kind of important epigenetic modification pattern which is extensively involved in immune regulation. The development and progression of autoimmune diseases are closely related to immune dysregulation. Considering that rheumatoid arthritis (RA) is a typical autoimmune disease, the m6A process might be one of the important regulatory mechanisms in the pathogenesis of RA. In this study, we identified five differentially expressed m6A regulators in normal and RA samples from the GEO database. With these five regulators, we constructed the nomogram, and it could accurately identify the risk of RA morbidity. Next, we identified 121 differentially expressed genes (DEGs) between normal and RA samples, of which 36 DEGs were co-expressed with these five m6A regulators. We noted that these DEGs were highly enriched in multiple immunoregulatory signaling pathways, such as cytokine-mediated immune cell chemotaxis, adhesion, and activation. To further characterize the heterogeneity of immunological features, we clustered the RA samples into two subtypes. The C2 subtype has higher infiltration levels of pro-inflammatory cells and activity of pro-inflammatory signaling pathways. Thus, the inflammatory response might be more vigorous in the C2 subtype. Next, we constructed the m6Asig system with the SVM machine learning algorithms and least absolute shrinkage and selection operator (LASSO) regression. The m6Asig could accurately distinguish the C1 and C2 subtypes, which indicated that the m6Asig could be a potential biomarker for the inflammatory activity of RA. Finally, by comparing the information from the CellMiner, TTD, and DrugBank databases, we determined 25 drugs. The targets of these drugs were positively correlated with m6Asig. To be clarified, the above findings were derived from bioinformatics and statistical analyses, and further experimental validation still requires. In summary, this study further revealed the m6A and immunoregulation mechanisms in RA pathogenesis. Also, the m6Asig could be a novel biomarker with potential applicability in the clinical management of RA.

Feasibility of anaerobic co-digestion of biodegradable plastics with food waste, investigation of microbial diversity and digestate phytotoxicity.

The effects of biodegradable plastics of different thicknesses (30 and 40 µm) and sizes (20 × 20, 2 × 2, and 1 × 1 mm) on anaerobic digestion of food waste and digestate phytotoxicity were investigated. Methane productions (38 days) for the groups with 20 × 20, 2 × 2, and 1 × 1 mm of 30 µm plastics were 92.46, 138.27, and 259.95 mL/gVSremoval, respectively which are nearly 58 % higher than the control group (58.86 mL/gVSremoval). Methane production in 40 µm plastics groups was lower than in 30 µm groups of equal size. All sizes of 30 µm plastics promoted substrate hydrolysis, acidification, and relative abundance of key hydrolytic bacteria and methanogens. Phytotoxicity tests results showed that seed root elongation was inhibited in groups with 40 µm plastics. In conclusion, 30 µm biodegradable plastics were more suitable for anaerobic digestion with food waste than 40 µm.

Preparation of catalyst for CO2 hydrogenation reaction based on the idea of element sharing and preliminary exploration of catalytic mechanism.

Under the background of the continuous rise of CO2 annual emissions, the development of CO2 capture and utilization technology is urgent. This study focuses on improving the catalytic capacity of the catalyst for CO2 hydrogenation, improving the efficiency of CO2 conversion to methanol, and converting H2 into chemical substances to avoid the danger of H2 storage. Based on the concept of element sharing, the ASMZ (Aluminum Shares Metal Zeolite catalysts) series catalyst was prepared by combining the CuO-ZnO-Al2O3 catalyst with the ZSM-5 zeolite using the amphoteric metal properties of the Al element. The basic structural properties of ASMZ catalysts were compared by XRD, FTIR, and BET characterization. Catalytic properties of samples were measured on a micro fixed-bed reactor. The catalytic mechanism of the catalyst was further analyzed by SEM, TEM, XPS, H2-TPR, and NH3-TPD. The results show that the ASMZ3 catalyst had the highest CO2 conversion rate (26.4%), the highest methanol selectivity (76.0%), and the lowest CO selectivity (15.3%) in this study. This is mainly due to the fact that the preparation method in this study promotes the exposure of effective weakly acidic sites and medium strength acidic sites (facilitating the hydrogenation of CO2 to methanol). At the same time, the close binding of Cu-ZnO-Al2O3 (CZA) and ZSM-5 zeolite also ensures the timely transfer of catalytic products and ensures the timely play of various catalytic active centers. The preparation method of the catalyst in this study also provides ideas for the preparation of other catalysts.

Emulsion-Based Multi-Phase Integrated Microbeads with Inner Multi-Interface Structure Enable Dual-Modal Imaging for Precision Endovascular Embolization.

Microsphere-based embolic agents have gained prominence in transarterial embolization (TAE) treatment, a critical minimally invasive therapy widely applied for a variety of diseases such as hypervascular tumors and acute bleeding. However, the development of microspheres with long-term, real-time, and repeated X-ray imaging as well as ultrasound imaging remains challenging. In this study, emulsion-based dual-modal imaging microbeads with a unique internal multi-interface structure is developed for TAE treatment. The embolic microbeads are fabricated from a solidified oil-in-water (O/W) emulsion composed of crosslinked CaAlg-based aqueous matrix and dispersed radiopaque iodinated oil (IO) droplets through a droplet-based microfluidic fabrication method. The CaAlg-IO microbeads exhibit superior X-ray imaging visibility due to the incorporation of exceptionally high iodine level up to 221 mgI mL-1, excellent ultrasound imaging capability attributed to the multi-interface structure of the O/W emulsion, great microcatheter deliverability thanks to their appropriate biomechanical properties and optimal microbead density, and extended drug release behavior owing to the biodegradation nature of the embolics. Such an embolic agent presents a promising emulsion-based platform to utilize multi-phased structures for improving endovascular embolization performance and assessment capabilities.