The FOXK1-CCDC43 Axis Promotes the Invasion and Metastasis of Colorectal Cancer Cells

Background/Aims: The CCDC43 gene is conserved in human, rhesus monkey, mouse and zebrafish. Bioinformatics studies have demonstrated the abnormal expression of CCDC43 gene in colorectal cancer (CRC). However, the role and molecular mechanism of CCDC43 in CRC remain unknown. Methods: The functional role of CCDC43 and FOXK1 in epithelial-mesenchymal transition (EMT) was determined using immunohistochemistry, flow cytometry, western blot, EdU incorporation, luciferase, chromatin Immunoprecipitation (ChIP) and cell invasion assays. Results: The CCDC43 gene was overexpressed in human CRC. High expression of CCDC43 protein was associated with tumor progression and poor prognosis in patients with CRC. Moreover, the induction of EMT by CCDC43 occurred through TGF-β signaling. Furthermore, a positive correlation between the expression patterns of CCDC43 and FOXK1 was observed in CRC cells. Promoter assays demonstrated that FOXK1 directly bound and activated the human CCDC43 gene promoter. In addition, CCDC43 was necessary for FOXK1- mediated EMT and metastasis in vitro and vivo. Taken together, this work identified that CCDC43 promoted EMT and was a direct transcriptional target of FOXK1 in CRC cells. Conclusion: FOXK1-CCDC43 axis might be helpful to develop the drugs for the treatment of CRC

The Local Land Finance Transformation with the Synergy of Increment and Inventory: A Case Study in China

Since 1998, the land finance model based on residential and commercial land transfer revenue has played an important role in Chinese social and economic growth, especially in urban infrastructure construction. With China’s population peak and stable urbanization, the “incremental” land-transfer-heavy development paradigm is unsustainable. At the same time, as a developing country, local governments in China must have enough fiscal revenue to encourage high-quality growth. The transformation of land finance is a practical issue that needs to be explored urgently. This article, which was based on the local government financial balance theory, proposed supporting the optimization of the land finance incremental model with the reform of the property tax system. A local land finance transformation mechanism with increment and inventory synergy was then created. Specifically, to avoid a cliff-like fall in the local government’s land-transfer fee, it was proposed that the land-transfer fee change from the original collection, from ordinary commercial housing to improved housing. The property tax should be levied on the second set of ordinary commercial housing to obtain fiscal revenue from the “inventory”. Concurrently, the fiscal money from property taxes could be utilized to build cheap rental housing or to support housing vouchers for new urban residents and young people

Geochemical Characteristics of the Mineral Assemblages from the Niukutou Pb-Zn Skarn Deposit, East Kunlun Mountains, and Their Metallogenic Implications

The Niukutou Pb-Zn deposit is typical of skarn deposits in the Qimantagh metallogenic belt (QMB) in the East Kunlun Mountains. In this study, based on detailed petrographical observations, electron microprobe analyses (EMPAs), and laser-ablation–inductively coupled plasma–mass spectrometry (LA-ICP-MS) analyses, we report the major and trace element compositions of the typical skarn mineral assemblages (garnet, pyroxene, ilvaite, epidote, and chlorite) in this deposit. Three hydrothermal mineralization stages with different mineral assemblages of the prograde metamorphic phase were determined, which were distributed from the inside to the outside of the ore-forming rock mass. Grt1+Px1 (Stage 1), Grt2+Px2 (Stage 2), and Px3 (Stage 3) were distinguished in the Niukutou deposit. Furthermore, the ilvaites in the retrograde metamorphic phase can be divided into three stages, namely Ilv1, Ilv2, and Ilv3. The ore-forming fluid in Stage 1 exhibited high ∑REE, U, and Nd concentrations and δEu, δCe, and LREE/HREE values, which were likely derived from a magmatic–hydrothermal source and formed at high temperatures, high fO2 values, and mildly acidic pH conditions, and probably experienced diffusive metasomatism in a closed system with low water/rock ratios. In Stages 2 and 3, the ore-forming exhibited lower ∑REE, U, and Nd concentrations and δEu, δCe, and LREE/HREE values, with high Mn content that had likely experienced infiltrative metasomatism in an open system with high water/rock ratios. From Ilv1 to Ilv3, the δEu and U contents decreased, whereas the Mn content increased, indicating that the oxygen fugacity of mineralization was in decline. The ore-forming fluid evolution of the Niukutou deposit can be characterized as follows: from Stage 1 to Stage 3, the hydrothermal fluid migrated from the deep plutons to the shallow skarn and marble; the environment altered from the high fO2 and temperature conditions to low fO2 and temperature values, and the pH and Mn contents increased. The fluids contained considerable metal ore-forming materials that were favorable for the enrichment and precipitation of the Fe content. In the retrograde metamorphic phase, with the decrease in oxygen fugacity (from Ilv1 to Ilv3), the temperature and oxygen fugacity of the theore-forming fluid environment decreased, ultimately becoming conducive to the dissolution and precipitation of Pb and Zn elements

Esterification of Alginate with Alkyl Bromides of Different Carbon Chain Lengths via the Bimolecular Nucleophilic Substitution Reaction: Synthesis, Characterization, and Controlled Release Performance

To extend the alginate applicability for the sustained release of hydrophobic medicine in drug delivery systems, the alkyl alginate ester derivative (AAD), including hexyl alginate ester derivative (HAD), octyl alginate ester derivative (OAD), decyl alginate ester derivative (DAD), and lauryl alginate ester derivative (LAD), were synthesized using the alkyl bromides with different lengths of carbon chain as the hydrophobic modifiers under homogeneous conditions via the bimolecular nucleophilic substitution (SN2) reaction. Experimental results revealed that the successful grafting of the hydrophobic alkyl groups onto the alginate molecular backbone via the SN2 reaction had weakened and destroyed the intramolecular hydrogen bonds, thus enhancing the molecular flexibility of the alginate, which endowed the AAD with a good amphiphilic property and a critical aggregation concentration (CAC) of 0.48~0.0068 g/L. Therefore, the resultant AAD could form stable spherical self-aggregated micelles with the average hydrodynamic diameter of 285.3~180.5 nm and zeta potential at approximately −44.8~−34.4 mV due to the intra or intermolecular hydrophobic associations. With the increase of the carbon chain length of the hydrophobic side groups, the AAD was more prone to self-aggregation, and therefore was able to achieve the loading and sustained release of hydrophobic ibuprofen. Additionally, the swelling and degradation of AAD microcapsules and the diffusion of the loaded drug jointly controlled the release rate of ibuprofen. Meanwhile, the AAD also displayed low cytotoxicity to the murine macrophage RAW264.7 cells. Thanks to the good amphiphilic property, colloidal interface activity, hydrophobic drug-loading performance, and cytocompatibility, the synthesized AAD exhibited a great potential for the development of hydrophobic pharmaceutical formulations

Decentralized wastewater treatment in an urban setting: a pilot study of the circulating fluidized bed bioreactor treating septic tank effluent

To meet the increasing wastewater treatment demand while minimizing the land footprint of the treatment systems and plants, more efficient and compact processes are needed. The circulating fluidized bed bioreactor (CFBBR) has been proven to achieve high levels of biological nutrient removal. Past studies at the lab and pilot scale achieved 94% COD removal and 80% nitrogen removal at HRT's of 2-4 h. A collaborative project between Western University and the Guangzhou Institute of Energy Conversion (GIEC), in Guangzhou, China, further explored the treatment of municipal wastewater with the CFBBR. A pilot CFBBR, with aerobic and anoxic columns for nitrification and denitrification, was constructed at the GIEC for in-situ treatment of septic tank effluent from a residential building. Due to high concentrations of ammonia (NH4-N), the wastewater had a COD/N ratio of 2-3. Thus, operating at a longer HRT and supplementing COD, in the form of glucose, was necessary to achieve a high nitrogen removal efficiency. The system was run both with and without supplemental COD at HRT's between 16 and 21 h, treating approximately 1000-1270 L/d. Overall, a COD removal efficiency of at least 92%, ammonia removal of 97%, and nitrogen removal of 82% was achieved. The CFBBR system achieved an effluent with BOD and NH4-N concentrations both below 5 mg/L, a NO3-N concentration below 15 mg/L, and a total nitrogen concentration below 25 mg/L. The compact design of this pilot-CFBBR, coupled with its high BNR performance make it an excellent option for decentralized treatment of urban wastewaters

The association between elevated serum uric acid levels and islet β-cell function indexes in newly diagnosed type 2 diabetes mellitus: a cross-sectional study

Background Serum uric acid (UA) has been reported as a risk factor for type 2 diabetes mellitus (T2DM). However, whether serum UA is associated with insulin resistance and insulin secretion, and the effect of gender on it in the case of the existed association, both remain undefined. Methods A cross-sectional study was designed and performed, which enrolled a total of 403 newly diagnosed T2DM patients (mean age, 50.21 ± 13.34 years (62.5% males)). Clinical characteristics and islet function indexes of all participants were analyzed based on gender-specific tertiles of serum UA levels. In addition, multiple linear regression analysis was conducted to investigate covariates associated with islet function indexes. Results The mean levels of serum UA were 331.05 μmol/L (interquartile range (IQR): 60.6, 400.9 μmol/L) and 267.9 μmol/L (IQR: 204.7, 331.9 μmol/L) in men and women, respectively. The values of insulin secretion indexes involving AUCins30/glu30, AUCins120/glu120 and total insulin disposition index (DI120) in females were significantly higher than those in males. Apart from the homeostasis model assessment insulin resistance of men, serum UA was positively associated with insulin secretion and insulin resistance indexes both in men and women. Multivariable linear regression analysis showed serum UA exerted an independent impact on insulin secretion in females, but not on insulin resistance. In males, islet function was simultaneously affected by serum UA age, body mass index (BMI), and serum lipids. Conclusion Serum UA harbored a positive correlation with insulin secretion and insulin resistance indexes in newly diagnosed T2DM patients, which was influenced by gender, BMI, serum lipids. Hence, serum UA may be considered as a predictor for islet function in clinical practice

Cathode interfacial layer-free all small-molecule solar cells with efficiency over 12%

While nonfullerene small-molecule solar cells (NF-SMSCs) have relatively inferior performance compared with nonfullerene polymer solar cells, their performance is improving. In this work, a weak crystalline molecular donor BSFTR, was designed and synthesized to achieve efficient NF-SMSCs. By blending with a strong crystalline acceptor NBDTP-F-out, BSFTR achieves a well-intermixed blending morphology, which favors the formation of efficient charge percolation pathways with suppressed recombination. The BSFTR:NBDTP-F-out device obtains a power-conversion efficiency (PCE) of approximately 11.97% by achieving an efficient cathode interfacial layer (CIL)-free device that delivers an even higher PCE of 12.3%, which ranks among the top values for the reported NF-SMSCs. This work provides a simple solution for achieving high-performance NF-SMSCs by identifying the key factors for designing efficient, cost-saving, mass production-favorable CIL-free organic photovoltaic devices

Fusobacterium nucleatum promotes tumor progression in KRAS p.G12D-mutant colorectal cancer by binding to DHX15

Abstract Fusobacterium nucleatum (F. nucleatum) promotes intestinal tumor growth and its relative abundance varies greatly among patients with CRC, suggesting the presence of unknown, individual-specific effectors in F. nucleatum-dependent carcinogenesis. Here, we identify that F. nucleatum is enriched preferentially in KRAS p.G12D mutant CRC tumor tissues and contributes to colorectal tumorigenesis in Villin-Cre/Kras G12D+/- mice. Additionally, Parabacteroides distasonis (P. distasonis) competes with F. nucleatum in the G12D mouse model and human CRC tissues with the KRAS mutation. Orally gavaged P. distasonis in mice alleviates the F. nucleatum-dependent CRC progression. F. nucleatum invades intestinal epithelial cells and binds to DHX15, a protein of RNA helicase family expressed on CRC tumor cells, mechanistically involving ERK/STAT3 signaling. Knock out of Dhx15 in Villin-Cre/Kras G12D+/- mice attenuates the CRC phenotype. These findings reveal that the oncogenic effect of F. nucleatum depends on somatic genetics and gut microbial ecology and indicate that personalized modulation of the gut microbiota may provide a more targeted strategy for CRC treatment