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Mitosis and spindle assembly require the microtubule-associated protein Xenopus kinesin-like protein 2 (TPX2). Although TPX2 is highly expressed in several malignant tumor forms, little is known about its role in cancer. In this study, we performed the gene set enrichment analysis of TPX2 in 33 types of cancers and an extensive pan-cancer bioinformatic analysis using prognosis, tumor mutational burdens, microsatellite instability, tumor microenvironment, and immune cell infiltration data. According to the differential expression study, TPX2 was found to be overexpressed across all studied cancer types. Based on the survival analysis, increased TPX2 expression was associated with a poor prognosis for most cancers. The TPX2 expression level was confirmed to correlate with the clinical stage, microsatellite instability, and tumor mutational burden across all cancer types. Furthermore, TPX2 expression has been linked to tumor microenvironments and immune cell infiltration, particularly in bladder urothelial carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, stomach adenocarcinoma, and uterine corpus endometrial carcinoma. Finally, the gene set enrichment analysis implicated TPX2 in the regulation of aminoacyl tRNA biosynthesis, which is the most important tumor cell cycle signaling pathway. This comprehensive pan-cancer analysis shows that TPX2 is a prognostic molecular biomarker for most cancers and suggests its potential as an effective therapeutic target for the treatment of these diseases.

Drought causes significant losses in vegetation net primary productivity (NPP). However, the lack of real-time, large-scale NPP data poses challenges in analyzing the relationship between drought and NPP. Solar-induced chlorophyll fluorescence (SIF) offers a real-time approach to monitoring drought-induced NPP dynamics. Using two drought events in the Huang–Huai–Hai Plain from 2010 to 2020 as examples, we propose a new SIF/NPP ratio index to quantify and evaluate SIF’s capability in monitoring drought-induced NPP dynamics. The findings reveal distinct seasonal changes in the SIF/NPP ratio across different drought events, intensities, and time scales. SIF demonstrates high sensitivity to commonly used vegetation greenness parameters for NPP estimation (R2 > 0.8, p < 0.01 for SIF vs NDVI and SIF vs LAI), as well as moderate sensitivity to land surface temperature (LST) and a fraction of absorbed photosynthetically active radiation (FAPAR) (R2 > 0.5, p < 0.01 for SIF vs FAPAR and R2 > 0.6, p < 0.01 for SIF vs LST). However, SIF shows limited sensitivity to precipitation (PRE). Our study suggests that SIF has potential for monitoring drought-induced NPP dynamics, offering a new approach for real-time monitoring and enhancing understanding of the drought–vegetation productivity relationship.

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Recently, microRNAs (miRNA), small noncoding RNAs, have taken center stage in the field of human molecular oncology. However, their roles in tumor biology remain largely unknown. According to the assumption that miRNAs implicated in a specific tumor phenotype will show aberrant regulation of their target genes, we introduce an approach based on the miRNA target–dysregulated network (MTDN) to prioritize novel disease miRNAs. Target genes have predicted binding sites for any miRNA. The MTDN is constructed by combining computational target prediction with miRNA and mRNA expression profiles in tumor and nontumor tissues. Application of the proposed method to prostate cancer reveals that known prostate cancer miRNAs are characterized by a greater number of dysregulations and coregulators and the tendency to coregulate with each other and that they share a higher proportion of targets with other prostate cancer miRNAs. Support vector machine classifier, based on these features and changes in miRNA expression, is constructed and gives an average overall prediction accuracy of 0.8872 in cross-validation tests. The classifier is then applied to miRNAs in the MTDN. Functions enriched by dysregulated targets of novel predicted miRNAs are closely associated with oncogenesis. In addition, predicted cancer miRNAs within families or from different families show combinatorial dysregulation of target genes, as revealed by analysis of the MTDN modular organization. Finally, 3 miRNA target regulations are verified to hold in prostate cancer cells by transfection assays. These results show that the network-centric method could prioritize novel disease miRNAs and model how oncogenic lesions are mediated by miRNAs, providing important insights into tumorigenesis. Mol Cancer Ther; 10(10); 1857–66. ©2011 AACR.

Aim: This study aimed to develop a predictive model for patients with duodenal carcinoma. Methods: Duodenal carcinoma patients from the Surveillance, Epidemiology, and End Results database (2010–2015) and the First Affiliated Hospital of Nanchang University (2010–2021) were enrolled. A nomogram was constructed according to least absolute shrinkage and selection operator regression analysis, the Akaike information criterion approach and Cox regression analysis. Results: Five independent prognostic factors were significantly associated with the prognosis of the duodenal carcinoma patients. A nomogram was constructed with a C-index in the training and validation cohorts of 0.671 (95% CI: 0.578–0.716) and 0.662 (95% CI: 0.529–0.773), respectively. Conclusion: The established nomogram model provided visualization of the risk of each prognostic factor.

Gamma synuclein (SNCG) is a neuronal protein that is also aberrantly overexpressed in various types of human cancer. SNCG overexpression promotes cancer invasion and metastasis. However, the mechanisms that drive cancer metastasis upon SNCG expression remain elusive. Elucidation of the mechanisms underlying the promotion of cancer metastasis by SNCG may help discover therapeutic avenues for SNCG-overexpressed cancer. Here, we show that SNCG promotes transforming growth factor-β (TGF-β)-induced p38 mitogen-activated protein kinase (MAPK) phosphorylation. Mechanistically, SNCG promotes p38MAPK phosphorylation by interacting with the MAPK kinase 3/6 (MKK3/6) and prevents their degradation. SNCG knockdown leads to a decrease in TGF-β-induced phosphorylation of MKK3/6; and abrogates the induction of matrix metalloproteinase (MMP)-9 expression by TGF-β and its target gene Twist1. Furthermore, p38MAPK inhibition abrogates the promotion of MMP-9 expression and cancer cell invasion by SNCG. Both p38MAPK and MMP inhibitors can suppress the promotion of cancer cell invasion by SNCG. Finally, overexpression of SNCG in liver cancer cells promotes lung metastasis, which can be suppressed by the p38MAPK inhibitor. Together, our data uncover a previously unknown role of SNCG in promoting TGF-β-MKK3/6-p38MAPK signaling. This study highlights the critical role of p38MAPK in the promotion of cancer metastasis by SNCG, and indicates that p38MAPK inhibitor may serve as a potential therapeutic for SNCG-overexpressed cancer.

With the ever-growing development of information technology, the education sector has adopted advanced technologies to improve this field. Different procedures based on human-computer interaction (HCI) can be applied to the efficient interaction between humans and computers to enhance the productivity of computers in various fields, especially in education. Active learning is one of the major technological fields that improves the usability of active learning. With the implementation of HCI approaches such as project-based learning (PBL), active learning classrooms (ALCs), and multi-user virtual environments (MUVE), students’ learning capabilities and teachers’ teaching skills are improved and education becomes more effective. After studying different applications of HCI in active learning, the study proposed to extract common features and select the most efficient ones from them. For the evaluation process, we presented two techniques named Criteria Importance Through Inter Correlation (CRITIC) and Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) in order to select the most effective HCI approach among various options. We choose nine criteria along with ten alternatives and rank them based on their performance scores. For assigning weights to criteria, we utilized the CRITIC strategy, while the TOPSIS technique is applied for ranking the alternatives. In the proposed study, it is identified that the alternative with the highest performance score is kept in first place, while the alternative with the worst performance score is kept at the bottom. The study concluded that the efficient and effective approach was selected among various options, and it can be employed as a suggestion for decision-related issues and future directions.

The chemical epigenetic modifier 5-azacitidine (5-Aza C), a DNA methyltransferase inhibitor, was used to manipulate the endophytic fungus Penicillium sp. KMU18029. From its rice fermentation extract, a new polyketone compound (3S,4R)-3,4,8-trihydroxy-6-methyl-3,4-dihydronaphthalen-1(2H)-one (1), along with 13 known compounds, 3,4,8-trihydroxy-6-(hydroxymethyl)-3,4-dihydronaphthalen-1(2H)-one (2), decaturin B (3), 15-hydroxydecaturin A (4), oxalicine A (5), pileotin A (6), pyrandecarurin A (7), decaturenol A (8), decaturenoid (9), penisarins A (10), oxaline (11), (4E,8E)-N-D-2'-hydroxyocta-decanoyl-1-O-β-D-glycopy-ranosyl-9-methyl-4,8-sphingadienine (12), ergosterol (13) and stigma-5-en-3-O-β-glucoside (14), were separated. Among the known compounds, 2, 7, 12 and 14 were not found in our previous research on this strain. The structure of the new compound was identified by spectroscopic techniques such as HR-ESIMS, 1D NMR, 2D NMR and CD. Furthermore, all the isolated compounds were tested for their antimicrobial activities, and only compounds 1, 2 and 11 showed weak activities against S. aureus, with MICs of 128 μg/mL.

The C-terminal of G protein-coupled receptors is now recognized as being important for G protein activation and signaling function. To detect the role of C-terminal tail in receptor activation, we used the α1b-AR, which has a long C-terminal of 164 amino acids. We constructed the intramolecular FRET sensors, in which the C-terminal was truncated to 10 (∆C-10), 20 (∆C-20), 30 (∆C-30), 50 (∆C-50), 70 (∆C-70), or 90 (∆C-90). The truncated mutants of ∆C-10, ∆C-20, or ∆C-30 cannot induce FRET signal changes and downstream ERK1/2 phosphorylation. However, the truncated mutants of ∆C-50, ∆C-70, or ∆C-90 induce significant FRET signal changes and downstream ERK1/2 phosphorylation, especially ∆C-90. This is particularly true in the case of the ∆C-90, ∆C-70, or ∆C-50 which retained the potential phosphorylation sites (Ser401, Ser404, Ser408, or Ser410). The ∆C-90 showed an increase in agonist-induced FRET signal changes and ERK1/2 phosphorylation in PKC- or endocytosis-dependent and EGFR-, src-, or β-arrestin2-independent.

IL-12 is a pleiotropic cytokine that potently stimulates anti-tumor cytotoxic T and NK cell mediated immunity. Recombinant IL-12 reduces tumor growth in multiple mouse models, but its therapeutic application has been limited by severe toxicities. Protease dependent activation of therapeutics with high on-target, off-tumor toxicities may be used to localize activity to the tumor but achieving sufficient exposure of the activated therapeutic in the tumor microenvironment remains a challenge. We have previously shown our design strategy for masked, protease activated IL-12Fc that included optimization of blocking modules, fusion geometry, and linker design. Here we have further expanded our mechanistic evaluations by combining masked, protease activated IL-12Fc with attenuated potency engineering, and selected a lead candidate (ZW270) based on anti-tumor activity and non-human primate (NHP) tolerability. The relative activity of masked and unmasked IL-12Fc variants comprising wild type (wt) or attenuated (att) IL-12 potency was evaluated in CD8 T cell activity assays. The wt IL-12Fc displayed comparable potency to recombinant IL-12 and up to 100x reduced potency when masked. Introduction of attenuating mutations to the p40 subunit reduced the potency of the IL-12Fc by up to 20x and addition of the protease cleavable mask further reduced the potency to up to 5000x compared to wt IL-12Fc. In a single dose NHP study, masked att IL-12Fc was well tolerated up to 31.8 mg/kg, while wt IL-12Fc demonstrated a maximum tolerated dose of below 1.3 mg/kg. Despite the reduced potency of att IL-12Fc in vitro, in in vivo efficacy studies in a human PBMC engrafted xenograft model the masked att IL-12Fc was able to control tumor growth whereas masked wt IL-12Fc and wt IL-12Fc showed limited anti-tumor activity, suggesting the approach of masked, protease activated att IL-12Fc might be able to achieve a higher exposure of active cytokine in the tumor in comparison to the masked wt IL-12Fc and wt IL-12 comparator. To further investigate the potentially superior exposure response relationship of masked att IL-12Fc, we developed a quantitative systems pharmacology (QSP) model based on our experimental data and literature data. In this model the predicted ratio of IL-12-receptor occupancy by active IL-12Fc in the tumor vs. blood was 18x greater for masked att IL-12Fc than for wt IL-12Fc, whereas the ratio was under 10x greater for masked wt IL-12Fc vs. wt IL-12Fc. In summary, the affinity attenuated, masked IL-12Fc lead ZW270 has potent and superior anti-tumor activity to wt IL-12Fc and masked wt IL-12Fc, and is well tolerated in NHPs to >30 mg/kg. Our data suggests that the combined strategy of masked, protease activated IL-12Fc and attenuated IL-12 potency has the potential to widen the therapeutic index and to have superior activity to masked, protease cleavable wt IL-12 and unmasked wt IL-12 fusions. Citation Format: Maya C. Poffenberger, Jennifer L. Bishop, Ryan J. Blackler, Kevin G. Haworth, Steven Booth, Shalla Hanson, Jeff R. Proctor, I-Ting Shao, Nichole K. Escalante, Dayananda Siddappa, Joel Smith, Gursev Anmole, Saki Konomura, Nicholas A. Dawson, Sifa Arrafi, Desmond Lau, Gerry Rowse, Rupert H. Davies, Thomas Spreter von Kreudenstein. ZW270, a conditionally masked IL-12 cytokine fusion protein displaying potent anti-tumor activity absent systemic toxicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2935.

Virus-induced asthma is prevalent among children, but its underlying mechanisms are unclear. Accumulated evidence indicates that early-life respiratory virus infection increases susceptibility to allergic asthma. Nonetheless, the relationship between systemic virus infections, such as enterovirus infection, and the ensuing effects on allergic asthma development is unknown. Early-life enterovirus infection was correlated with higher risks of allergic diseases in children. Adult mice exhibited exacerbated mite allergen-induced airway inflammation following recovery from EV-A71 infection in the neonatal period. Bone marrow-derived macrophages (BMDMs) from recovered EV-A71-infected mice showed sustained innate immune memory (trained immunity) that could drive naïve T helper cells toward Th2 and Th17 cell differentiation when in contact with mites. Adoptive transfer of EV-A71-trained BMDMs induced augmented allergic inflammation in naïve recipient mice, which was inhibited by 2-deoxy-D-glucose (2-DG) pretreatment, suggesting that trained macrophages following enterovirus infection are crucial in the progression of allergic asthma later in life.

The optical performance of fused silica optics used in high-power lasers is known to depend not only on their surface damage resistance, but also on their surface quality. Previous studies have shown that good fused silica damage performance and surface quality can be achieved by the use of reactive ion etching (RIE), followed by HF-based wet shallow etching (3 μm). In this study, two kinds of HF-based etchants (aqueous HF and HF/NH4F solutions) were employed to investigate the effect of HF-based etching on the optical performance of reactive-ion-etched fused silica surfaces at various HF-based shallow etching depths. The results showed that the addition of NH4F to HF solution makes it possible to produce a high-quality optical surface with a high laser-induced damage threshold, which is strongly associated with the surface roughness and fluorescence defect density. Additionally, changing the HF-based etching depth over the range from 1 μm to 3 μm can affect the surface damage resistance and absorption performance of RIE-treated fused silica. The light-scattering results indicate that the point defect density plays an important role in the determination of the HF-based etching depth. Understanding these trends can enable the advantages of the combined technique of RIE and HF-based etching during the fabrication of high-quality fused silica optics.

Simultaneous enhancement in water flux and removal efficiency during the filtration process remains a big challenge for separation membranes. The porous structure of the filter paper can provide many channels for water transportation, but the separation performance is generally poor. The purpose of this study is to develop a new kind of filter paper consisting of ultralong hydroxyapatite (HAP) nanowires, cellulose fibers (CFs) and double metal oxide (LDO) nanosheets, and to achieve the simultaneous enhancement of both water flux and removal efficiency for high-performance dye separation. In this work, a novel kind of LDO/HAP/CF nanocomposite filter paper consisting of ultralong HAP nanowires and CFs and LDO nanosheets has been developed for rapid water filtration and highly efficient dye adsorption. Positively charged LDO nanosheets can adsorb on the surface of negatively charged ultralong HAP nanowires and embed in the porous networked structure of the LDO/HAP/CF nanocomposite filter paper, which can provide a porous structure for rapid water transportation and can adjust the pore size of the nanocomposite filter paper. As a result, the pure water flux of the LDO/HAP/CF nanocomposite filter paper can be adjusted. The optimized pure water flux of the LDO/HAP/CF nanocomposite filter paper can reach 783.6 L m-2 h-1 bar-1, which is 1.51 times that of the HAP/CF filter paper without LDO nanosheets (518.6 L m-2 h-1 bar-1). More importantly, the adsorption capacity of LDO nanosheets is high for dye molecules, the rejection percentage of Congo red (CR) by the as-prepared HAP/CF filter paper is only 59.8%, and its water flux is 534.7 L m-2 h-1 bar-1. The optimized rejection percentage and water flux of the LDO/HAP/CF nanocomposite filter paper for CR are significantly enhanced (98.3% and 736.8 L m-2 h-1 bar-1, respectively) compared to those of the HAP/CF filter paper. The size of LDO nanosheets has a significant effect on the water flux and dye rejection percentage of the LDO/HAP/CF nanocomposite filter paper. The as-prepared LDO/HAP/CF nanocomposite filter paper is promising for the applications in highly efficient purification of wastewater containing dye molecules.

Chloromethylisothiazolinone (CMIT) has been extensively used as antimicrobial in cosmetics, detergents, wall paints, and anti-fouling products. To prevent the potential ecological and health risks, the degradation mechanisms and toxicity changes of CMIT by Vacuum-Ultraviolet/Ultraviolet (VUV/UV) irradiation were investigated in this study. VUV/UV irradiation showed better performance on CMIT degradation compared to sole UV photolysis. The removal efficiency of CMIT with photon fluence of 0.6 μEinstein/cm

Under the background of big data, citizens can freely access and use open data to create value through the open government data platform (OGDP). The sustainable use of OGDP can meet the needs of citizens. The value created by citizens can also improve quality of life, which is of great significance to the sustainable development of society. From the citizens’ perspective, we constructed an evaluation model of citizens’ sustainable use of OGDP, including 12 indicators in four dimensions: Data, platform, outcome, and citizen. We have built the complete evaluation system with the DANP (Decision-Making Trial and Evaluation Laboratory-Based Analytic Network Process) method. It explores the main influencing factors and mutual influence of citizens’ sustainable use of OGDP. Empirical research is done on four provincial OGDPs in China’s Shanghai, Zhejiang, Guizhou, and Fujian provinces. The TOPSIS (Technique for Order Preference by Similarity to an Ideal Solution) method was used to rank the OGDPs in four pilot areas in empirical research. The results demonstrate that the improvement priorities of dimensions have the following order: Citizen, outcome, data, and platform, in which data and platform are cause dimensions, and outcome and citizen are result dimensions. The satisfaction indicator has the highest weight among all evaluation indicators, followed by the quality and quantity of outcomes. The one with the lowest weight is non-discrimination. The empirical results show that the OGDP in Zhejiang ranks the highest overall, followed by the OGDPs of Shanghai, Fujian, and Guizhou provinces. In the outcome and citizen dimensions, Zhejiang provincial OGDP does the best. Fujian provincial OGDP does the best in the platform dimension. The citizens’ sustainable use of OGDP can be promoted by timely opening of data that citizens need urgently, perfecting the policy of privacy protection and user guide of OGDP, holding open data innovation competition, providing data visualization function, providing various download formats of data sets, and simplifying the download procedures for citizens.

Methylisothiazolinone (MIT) is frequently used as antimicrobial in household and industrial products, and poses ecological and health risks to aquatic organisms and humans. In this study, vacuum ultraviolet (VUV)/ultraviolet (UV) irradiation was found highly efficient for removal of MIT. The rate constant of MIT degradation (k

Autophagy has been demonstrated to play important roles in the infection and pathogenesis of many viruses. We previously found that porcine parvovirus (PPV) infection can induce autophagy in porcine placental trophoblast cells (PTCs), but its underlying mechanism has not yet been fully revealed. In this study, we showed that PPV infection inhibited the activation of mTORC1 and promoted the expression of Beclin 1 and LC3II in PTCs. Treatment with a mTOR activator inhibited the expression of Beclin 1 and LC3II, as well as autophagy formation, and reduced viral replication in PPV-infected PTCs. Furthermore, we found that inhibition of AMPK expression, but not the inhibition of PI3K/Akt, p53, or MAPK/ERK1/2 pathway activation, can significantly increase mTOR phosphorylation in PPV-infected PTCs. Then, we found that the regulation of mTOR phosphorylation by AMPK was mediated by Raptor. AMPK expression knockout inhibited the activation of Raptor, decreased the expression of Beclin 1 and LC3II, suppressed the formation of autophagosomes, and reduced viral replication during PPV infection. Together, our results showed that PPV infection induces autophagy to promote viral replication by inhibiting the activation of mTORC1 through activation of the AMPK/Raptor pathway. These findings provide information to understand the molecular mechanisms of PPV-induced autophagy.

Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a distinct entity with a conspicuous tumor microenvironment compared with EBV-negative gastric carcinoma. However, the exact role of EBV in gastric carcinogenesis remains elusive. In the present study, we found that EBV upregulated CXCL8 expression, and CXCL8 significantly promoted vasculogenic mimicry (VM) formation of gastric carcinoma (GC) cells. In accordance with these observations, overexpression of CXCL8 increased cell proliferation and migration of AGS and BGC823 cells, while knockdown of CXCL8 with siRNA inhibited cell proliferation and migration of AGS-EBV cells. In addition, activation of NF-κB signaling was involved in VM formation induced by CXCL8, which was blocked by NF-κB inhibitors BAY 11-7082 and BMS345541. Furthermore, EBV-encoded lncRNA RPMS1 activated the NF-κB signaling cascade, which is responsible for EBV-induced VM formation. Both xenografts and clinical samples of EBVaGC exhibit VM histologically, which are correlated with CXCL8 overexpression. Finally, CXCL8 is positively correlated with overall survival in GC patients. In conclusion, EBV-upregulated CXCL8 expression promotes VM formation in GC

Background: Emerging studies have showed that circular RNAs (circRNAs) are important regulators for tumorigenesis by modulating malignant behaviors of tumor cells. However, the functions of EBV-encoded circRNAs in EBV-associated gastric carcinoma (EBVaGC) remain poorly understood. Methods: The expression of ebv-circRPMS1 in EBVaGC tissues, xenografts and cell lines were analyzed by BaseScope, qRT-PCR and in situ hybridization (ISH). The effects of ebv-circRPMS1 on gastric carcinoma (GC) cell proliferation, apoptosis, migration and invasion were measured by CCK8, EdU, immunofluorescence (IF), FACS and Transwell assays. qRT-PCR, Western blotting, ChIP, RNA fluorescence in situ hybridization (RNA-FISH), luciferase reporter assays, mass spectrum, RNA immunoprecipitation (RIP), and pulldown assays were used to investigate the molecular mechanisms. Xenograft mouse model was also used to analyze the effect of ebv-circRPMS1 on GC growth and metastasis in vivo.Results: We demonstrated that ebv-circRPMS1 promoted the proliferation, migration, invasion and anti-apoptosis of EBVaGC cells. Mechanistically, ebv-circRPMS1 recruited the Sam68 complex to the promoter of METTL3 and enhanced its transcription. Moreover, overexpression of METTL3 induced transcriptional activation of downstream genes (such as SNAI1, ZMYM1 and SOCS2) via m6A modifications on their mRNAs, which were associated with tumor progression. Besides, RNA binding proteins (RBPs) such as QKI, DHX9 and ILF3, might involve in ebv-circRPMS1 biogenesis. In clinical EBVaGC samples, ebv-circRPMS1 was associated with distant metastasis and poor prognosis. Conclusion: These findings indicated that ebv-circRPMS1 contributed to EBVaGC progression through recruiting the Sam68 complex to activate METTL3 expression and its downstream targets. Ebv-circRPMS1, Sam68 and METTL3 may serve as therapeutic targets for EBVaGC.

Metformin has been widely used as an oral drug for the treatment of diabetes mellitus. However, its consumption can be influenced by many economic and social factors. In this study, we investigated the spatial consumption pattern of metformin in China through wastewater-based epidemiology (WBE) approach. Influent wastewater samples were collected from 21 wastewater treatment plants (WWTPs) in 19 cities of the northeast China. A method using solid-phase extraction combined with N-Methyl-bis (trifluoroacetamide) derivatization for GC-MS detection was applied for metformin analysis. In 21 days, metformin showed high stability in wastewater at 24 °C and −20 °C. The mean concentrations of metformin in all WWTPs ranged from 2.42 μg L−1 to 53.6 μg L−1. The consumption of metformin was 0.66–15.6 mg d−1 capita−1 with the mean value of 5.54 ± 4.28 mg d−1 capita−1. The prevalence of metformin ranged from 0.09% to 2.10% with an average of 0.74%. Both the consumption and prevalence of metformin displays significant spatial variations in northeast China. A statistical correlation analysis indicated that the consumption of metformin increases with the decrease of per capita disposable income of urban residents. To further predict the use of metformin in China, we developed a regress model and depicted a consumption map. The annual consumption of urban residents in Chinese provinces range from 1085-63,828 kg yr−1 with mean value of 25,347 kg yr−1, which would provide a certain reference value for public health care and diabetes control.

In this paper, we report a novel approach to fabricate gradient doped porous material via the slope-rotation method. By using dibutyl phthalate as the solvent, benzoin methyl ether as the photoinitiator, and silica sub-microsphere as filler, gradient doped trimethylolpropane trimethacrylate (TMPTMA) foams were fabricated after rotating and mixing, ultraviolet curing, and CO2 supercritical drying. The microstructure and gradient distribution of silica fillers were characterized by nitrogen adsorption, scanning electron microscopy, UV–visible absorption spectrum, and thermogravimetric analysis. The mechanical property was obtained by dynamic mechanical analysis. The results indicated that the approach was an effective method to fabricate gradient doped TMPTMA foams and had the potential to prepare any kind of gradient doped porous material derived from a sol–gel process. The mechanical property was further reinforced by gradient doping of silica sub-microspheres.

In the history of civilization, Xuan paper with its superior texture, durability and suitable characteristics for writing and painting, has played an important role in the dissemination of culture and art. Xuan paper has won the reputation of "the king of paper that lasts for 1000 years" and was inscribed on the Representative List of the Intangible Cultural Heritage of Humanity by the Educational, Scientific and Cultural Organization of the United Nations in 2009. However, the surface of the commercial unprocessed Xuan paper has a large number of large-sized pores with a poor resistance to water, allowing ink droplets to easily spread during the writing and painting process. In this study, we report a new kind of nanocomposite Xuan (HNXP) paper comprising ultralong hydroxyapatite (HAP) nanowires and plant cellulose fibers with unique ink wetting performance, high whiteness and excellent durability. The as-prepared HNXP paper sheets with various weight ratios of ultralong HAP nanowires ranging from 10% to 100% are all superhydrophilic with a water contact angle of zero. In contrast, the ink contact angle of the HNXP paper can be well controlled by adjusting the weight ratio of ultralong HAP nanowires, and the ink contact angle of the HNXP paper increases with increasing weight ratio of ultralong HAP nanowires. The experimental results show the unique ink wetting behavior of the as-prepared HNXP paper, which is absent in the traditional Xuan paper. This new kind of nanocomposite Xuan paper comprising ultralong hydroxyapatite nanowires and plant cellulose fibers is promising for applications in calligraphy and painting arts.