DAB2IP stabilizes p27Kip1 via suppressing PI3K/AKT signaling in clear cell renal cell carcinoma.

Renal cell carcinoma (RCC) is the most lethal of the urologic malignancies. We previously discovered that DAB2IP, a novel Ras GTPase-activating protein, was frequently epigenetically silenced in RCC, and DAB2IP loss was correlated with the overall survival of RCC patients. In this study, we determined the biological functions of DAB2IP in clear cell RCC (ccRCC) and its potential mechanisms of action. Correlations between DAB2IP expression level and ccRCC tumor size and patient survival were analyzed, and the results showed that ccRCC patients with high DAB2IP mRNA level exhibited smaller tumor size and better survival than the patients with low DAB2IP. Compared to control, DAB2IP knockdown significantly increased cell proliferation, promoted cell cycle progression in G1/S phase, and decreased p27 expression. Mechanism studies demonstrated that loss of DAB2IP promoted p27 protein phosphorylation, cytosolic sequestration, and subsequently ubiquitination-mediated degradation in ccRCC cells. Further studies confirmed that the proline-rich domain in C terminal (CPR) of DAB2IP suppressed AKT phosphorylation and p27 phosphorylation on S10. Hence, DAB2IP is essential for p27 protein stabilization in ccRCC, which is at less partly mediated by PI3K/AKT signaling pathway.

Adverse event profiles of PCSK9 inhibitors alirocumab and evolocumab: Data mining of the FDA adverse event reporting system.

BACKGROUND: Proprotein convertase subtilisin/kexin type (PCSK9) inhibitor is a new drug class approved for treating dyslipidemias. Herein, we aimed to investigate the safety profiles of PCSK9 inhibitors (alirocumab and evolocumab) using the Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: We included adverse event (AE) reports regarding alirocumab and evolocumab submitted to the FAERs between 2015Q3 to 2021Q1. Disproportionality analyses, including reporting odds ratio (ROR), were performed to detect risk signals from the FAERs data to identify potential drug-AE associations. A signal was considered when the lower limit of the 95% confidence interval of ROR exceeded 1 and ≥3 AEs were reported. The definition relied on system organ class and preferred terms established by the Medical Dictionary for Regulatory Activities. RESULTS: The FAERS database documented 31 475 reports regarding PCSK9 inhibitors (alirocumab and evolocumab) from July 1, 2015, to March 31, 2021. Although some differences were detected, alirocumab and evolocumab shared considerably similar safety profiles. The most significant RORs and most common reports were injection-site reactions (eg, injection-site pain, bruising, haemorrhage, erythema), muscle-related AEs (eg, myalgia, back pain, arthralgia, muscle spasms), influenza-like illness, pain and headache. CONCLUSION: Data mining of the FAERs is useful for examining PCSK9 inhibitor-induced AEs. Herein, our findings were largely consistent with clinical experience and could help clinicians improve the safety of PCSK9 inhibitors in clinical practice.

Interactions between intestinal morphology, digestion, inflammatory responses, and gut microbiota of juvenile channel catfish elicited by dietary enzymatic rice protein.

The reduction of fishmeal in aquafeeds has been the concern of researchers. Replacing fishmeal with plant proteins affects intestinal function and inflammation, but the interaction between the intestinal responses and gut microbiota remains unclear. In this study, juvenile channel catfish (Ictalurus punctatus) was fed with four diets in which enzymatic rice protein (RP) replaced fishmeal at levels of 0 (FM), 2.5% (RP2.5), 5.0% (RP5.0), and 7.5% (RP7.5) for 8 weeks to solve the problem mentioned above. Quantification of intestinal morphology showed that 2.5% or 5.0% RP significantly increased villus length and goblet cell number, accompanied by higher activities of intestinal trypsin, alkaline phosphatase (AKP), and Na+/K+-ATPase (NKA) in RP2.5 group (P < 0.05). In contrast, 7.5% RP slightly damaged the intestinal mucosa and significantly reduced the activities of amylase, AKP, and NKA, as well as decreased serum complement 4 (C4) and immunoglobulin M (IgM). Noteworthy, RT-qPCR showed that 2.5% RP significantly down-regulated intestinal mRNA expression level of il8, while up-regulated mif, tlr4, tlr7, tgfß3, and cldn2. In contrast, 7.5% RP up-regulated the mRNA expression levels of il1ß, il8, and mif, while down-regulated cldn3d. Analysis of gut microbiota showed that 2.5% RP increased the relative abundance of Bacteroidetes and significantly activated potential functions of gut microbiota involved in carbohydrate metabolism. The 7.5% RP increased the diversity of the gut microbiota, accompanied by a significant increase in the relative abundance of conditionally pathogenic bacteria such as Vibrio, Serratia, and Aeromonas (classified as Proteobacteria). Notably, Vibrio was the biomarker species with the greatest difference between the FM and RP7.5 groups (genus level). Correlation analysis indicated that Vibrio may affect immunity through the C4 pathway and further lead to gut inflammation and digestive impairment. Taken above, these results indicated that RP could affect intestinal morphology, digestion, and inflammation, and interact with the composition and potential function of gut microbiota. The low RP supplement (2.5%) improved intestinal morphology and digestion, while high supplement (7.5%) disrupted gut microbiota homeostasis, resulting in damage to intestinal mucosa and inflammatory response.

PYCR1 promotes bladder cancer by affecting the Akt/Wnt/ß-catenin signaling.

Pyrroline-5-carboxylate reductase 1 (PYCR1) plays a significant role in the malignant progression of various cancers. However, the role of PYCR1 in bladder cancer has not been well studied. This study was performed to evaluate the potential relevance of PYCR1 in bladder cancer. Our data revealed that PYCR1 expression was increased in bladder cancer tissues, and increased expression of PYCR1 was predictive of decreased survival rates. In bladder cancer cell lines, knockdown of PYCR1 caused significantly retarded cell growth and invasion, while PYCR1 overexpression accelerated cellular proliferation and invasion. Moreover, PYCR1 knockdown decreased levels of phosphorylated Akt, and enhanced activation of Wnt/ß-catenin signaling. Akt inhibition markedly abrogated of PYCR1 overexpression-mediated activation of Wnt/ß-catenin signaling. In addition, overexpression of ß-catenin partially reversed PYCR1 knockdown-mediated tumor suppression. Notably, PYCR1 knockdown significantly impeded tumor formation and growth in bladder cancer cells in vivo. In conclusion, these data demonstrate that PYCR1 is highly expressed in bladder cancer and knockdown of PYCR1 exerts a remarkable inhibitory effect on tumor formation via downregulation of Akt/Wnt/ß-catenin signaling. Our study suggests a potential role for PYCR1 in promoting bladder cancer progression and indicates that PYCR1 may be utilized as an attractive and promising anticancer target for treatment of bladder cancer.

Administration of dietary recombinant hepcidin on grass carp (Ctenopharyngodon idella) against Flavobacterium columnare infection under cage aquaculture conditions.

Hepcidin links iron metabolism with innate immunity during the inhibition of bacterial infection. Our previous studies had shown that recombinant hepcidin can significantly reduce the mortality rate of Ctenopharyngodon idella infected with Flavobacterium columnare under laboratory conditions. Here, we studied the preventive and therapeutic effects of feed supplemented with different doses of recombinant hepcidin on F. columnare-challenged C. idella reared in a cage culture environment. The results showed that in the prevention groups, 30 and 90 mg/kg of added purified and unpurified hepcidin respectively resulted in a higher survival rate in the early post-infection period, while 60 mg/kg of purified hepcidin significantly improved the survival rate in the therapy group (all compared to the control group). In the hepatopancreas, the expression of hepcidin and ferritin was significantly up-regulated, and the levels of ferroportin and serum iron were significantly decreased, especially in the therapy group. In addition, the expression of iron-related genes in spleen and intestine exhibited a similar trend to that in hepatopancreas. Meanwhile, immune genes were up-regulated to varying degrees, and the therapy group exhibited a significantly improved expression of pro-inflammatory cytokines and specific immunity. In summary, our study shows that different doses of recombinant hepcidin had protective effects against bacterial infection by regulating the iron distribution and immune gene expression, which provides a strong foundation for the application of recombinant hepcidin in aquaculture.

Chitosan reduces the protective effects of IFN-γ2 on grass carp (Ctenopharyngodon idella) against Flavobacterium columnare infection due to excessive inflammation.

IFN-γ is an immunomodulatory factor that has been extensively studied in phenotypes of mammalian macrophages and multifarious inflammatory responses. Usually these studies relied on the classical synergistic activation of IFN-γ with LPS (LipoPolySaccharides). However, non-mammalian vertebrates, and in particular fish, are not very susceptible to LPS, and easily acquire tolerance upon repeated exposure. Therefore, for studies in fish, it is necessary to replace the classical IFN-γ+LPS immune system activation method, and find other pathogen-associated molecular patterns (PAMPs) capable of stimulating the fish immune system. Here we used an important farmed fish species, Ctenopharyngodon idella, to study the effects of CiIFN-γ2 (C. idella IFN-γ2) and chitosan (CS) on its immune responses in vivo and vitro. Our results showed that the combination of CS and CiIFN-γ2 significantly enhanced the activation of macrophages, with an activation intensity even stronger than in CiIFN-γ2 and CiIFN-γ2+LPS groups. In vivo, injection of CiIFN-γ2 could improve the survival rate of C. idella infected with Flavobacterium columnare, while a combined injection of CiIFN-γ2+CS only improved protection in the early stages after the challenge. Notably, both injections reduced the bacterial load of viscera and improved the levels of several plasma parameters (TP, T-SOD, LA, and NO). However, a dramatic up-regulation of inflammatory factors, severe inflammatory damage in the intestines and hepatopancreas, and increased mortality in late stages of infection were observed in the CiIFN-γ2+CS group. Our findings provide new insights into the macrophage activation phenotypes and inflammatory responses in fish. They also demonstrate that CiIFN-γ2 could be used as a potential immunopotentiator, but not in combination with CS. This suggests that selection of immunological adjuvants should be carefully tested experimentally.

Dietary conjugated linoleic acid modulates morphology, selective immune parameters, and gene expressions in the intestine of grass carp.

Conjugated linoleic acid (CLA) has been shown to exhibit anti-inflammatory properties in the intestine in mammals. However, the effect of CLA on intestinal immune response in fish is still unknown. Therefore, a 65-day growth trial was conducted to investigate the effects of dietary conjugated linoleic acid (CLA) on morphology, selective immune parameters, and gene expressions in the intestine of grass carp. Seven isonitrogenous and isolipidic diets were formulated as follows: 0 (control), 0.5 (CLA0.5), 1 (CLA1), 1.5 (CLA1.5), 2 (CLA2), 2.5 (CLA2.5), and 3 (CLA3) g CLA per 100g of feed. RESULTS: showed that dietary supplementation of 1.5-3% CLA significantly (P < 0.05) increased the fold and enterocyte heights in the PI and MI of grass carp. Complement 3 (C3) and immunoglobulin M (IgM) contents in three intestinal segments were significantly (P < 0.05) higher in fish fed with CLA1.5 to CLA2.5 diets compared to fish fed the control diet. CLA1.5 to CLA2.5 diets significantly (P < 0.05) increased the mRNA expression levels of anti-inflammatory cytokines (IL-10 and TGFß1) and significantly (P < 0.05) reduced the mRNA expression levels of pro-inflammatory cytokines (IL-1ß, IL-8, and TNF-α) in the PI, MI, and DI. This improved expression of anti-inflammatory cytokines and the inhibited expression of pro-inflammatory cytokines in the intestine of grass carp, might be mediated via TLR4/NF-κB-signaling pathway. Our results suggested that CLA1.5 to CLA2 diets improved intestinal morphology, increased the expression of anti-inflammatory cytokines, and inhibited the expression of pro-inflammatory cytokines in the intestine of grass carp. In conclusion, dietary supplementation of 1.5%-2% CLA show the anti-inflammatory therapeutic potential in the intestine of grass carp. The anti-inflammatory therapeutic potential of CLA might be mediated via TLR4/NF-κB-signaling pathway.

Photochromic Inorganic/Organic Thermoplastic Elastomers.

Photochromic materials are an important class of "smart materials" and are broadly utilized in technological devices. However, most photochromic materials reported so far are composed of inorganic compounds that are challenging to process and suffer from poor mechanical performance, severely limiting their applications in various markets. In this paper, inorganic photochromic tungsten trioxide (WO3 ) nanocrystals are conveniently grafted with polymers to hurdle the deficiency in processability and mechanical properties. This new type of photochromic material can be thermally processed into desired geometries like disks and dog-bone specimens. Fully reversible photochromic response under UV light is also achieved for WO3 -graft polymers, exhibiting tunable response rate, outperforming the pristine WO3 nanocrystals. Notably, the resulted graft polymers show extraordinary mechanical performance with excellent ductility (≈800% breaking strain) and relatively high breaking strength (≈2 MPa). These discoveries elucidate an effective pathway to design smart inorganic/organic hybrid thermoplastic elastomers endowed with outstanding photochromic and mechanical properties as well as exceptional processability.

MicroRNA-613 represses prostate cancer cell proliferation and invasion through targeting Frizzled7.

A growing number of studies have indicated that microRNAs (miRNAs) are critical regulators of carcinogenesis and cancer progression and may serve as potential therapeutic tools for cancer therapy. Frizzled7 (Fzd7), the most important receptor of the Wnt signaling pathway, is extensively involved in cancer development and progression. However, the role of Fzd7 in prostate cancer remains unclear. In this study, we aimed to explore the expression of Fzd7 in prostate cancer and test whether modulating Fzd7 expression by miR-613 would have an impact on prostate cancer cell proliferation and invasion. We found that Fzd7 was highly expressed in prostate cancer cell lines. Through bioinformatics analysis, Fzd7 was predicted as a target gene of miR-613, which was validated by dual-luciferase reporter assays, real-time quantitative polymerase chain reaction and Western blot analysis. By gain of function experiments, we showed that overexpression of miR-613 significantly suppressed prostate cancer cell proliferation and invasion. Furthermore, miR-613 overexpression markedly downregulated the Wnt signaling pathway. Through a rescue experiment, we showed that overexpression of Fzd7 could abrogate the inhibitory effect of miR-613 on cell proliferation and invasion as well as Wnt signaling. Additionally, these results were further strengthened by data showing that miR-613 was significantly downregulated in prostate cancer tissues, exhibiting an inverse correlation with Fzd7 expression. In conclusion, our study suggests that miR-613 functions as a tumor suppressor, partially through targeting Fzd7, and is a potential therapeutic target for prostate cancer.

Noninvasive Staging of Kidney Dysfunction Enabled by Renal-Clearable Luminescent Gold Nanoparticles.

As a "silent killer", kidney disease is often hardly detected at an early stage but can cause lethal kidney failure later on. Thus, a preclinical imaging technique that can readily differentiate between the stages of kidney dysfunction is highly desired for improving our fundamental understanding of kidney disease progression. Herein, we report that in vivo fluorescence imaging, enabled by renal-clearable near-infrared-emitting gold nanoparticles, can noninvasively detect kidney dysfunction, report on the dysfunctional stages, and even reveal adaptive function in a mouse model of unilateral obstructive nephropathy, which cannot be diagnosed with routine kidney function markers. These results demonstrate that low-cost fluorescence kidney functional imaging is highly sensitive and useful for the longitudinal, noninvasive monitoring of kidney dysfunction progression in preclinical research.

Structural and luminescence properties of Y(2-x)GeMoO8:REx (RE = Eu, Tb) phosphors.

Y(2-x)GeMoO8:REx (RE = Eu, Tb) phosphors were synthesized using a facile sol-gel method. The morphology and structure of the phosphors were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD); while their luminescent properties were investigated by photoluminescence (PL) spectrometry. Our results reveal that all of these Y(2-x)GeMoO8:REx (RE = Eu, Tb) phosphors adopted the tetragonal phase, belonging to Scheelite (CaWO4 ) structure. The obtained YGeMoO8:Eu phosphors exhibit a strong emission in the red light range which can be assigned to the (5)D0 → (7)F2 transition of Eu(3+) when it is excited at 459 nm. Under 392 and 489 nm excitation, the YGeMoO8:Tb phosphors present predominant green emission ((5)D4 → (7)F5) at 540 nm. The highest emission of the phosphors can be achieved by adjusting the doping concentration to be 0.25 for Eu(3+) and 0.15 for Tb(3+), respectively. The promising luminescence properties of these materials indicate that they can be potentially applied to white-light-emitting diodes.

[DAB2IP expression in bladder transitional cell carcinoma and its correlation with clinical outcome].

OBJECTIVE: To investigate the expression of DAB2IP in bladder transitional cell carcinoma (BTCC) and its correlation with clinical characteristics and prognosis of BTCC patients. METHODS: Immunohistochemical staining was applied to detect DAB2IP protein level in 79 cases of TCCB tissues and 11 cases of normal bladder tissues, and the relationships of the staining results with pathological grade, stage, lymph node metastasis, gender, age and the 3-year survival rate of the patients were analyzed. RESULTS: The expression of DAB2IP in BTCC tissues was significantly lower than that in normal bladder epithelium, and the expression score and rate of DAB2IP in the high-grade, invasive and metastatic BTCC were significantly lower than those in low-grade, superficial and non-metastatic BTCC (P < 0.05). The 3-year survival rate of the patients with high DAB2IP expression was significantly higher than that of the patients with low DAB2IP expression. CONCLUSION: DAB2IP may be one of the important inhibitory factors during the occurrence and progression of BTCC.

Homogeneous and Heterogeneous Frustrated Lewis Pairs for the Activation and Transformation of CO2.

Due to the serious ecological problems caused by the high CO2 content in the atmosphere, reducing atmospheric CO2 has attracted widespread attention from academia and governments. Among the many ways to mitigate CO2 concentration, the capture and comprehensive utilization of CO2 through chemical methods have obvious advantages, whose key is to develop suitable adsorbents and catalysts. Frustrated Lewis pairs (FLPs) are known to bind CO2 through the interaction between unquenched Lewis acid sites/Lewis base sites with the O/C of CO2, simultaneously achieving CO2 capture and activation, which render FLP better potential for CO2 utilization. However, how to construct efficient FLP targeted for CO2 utilization and the mechanism of CO2 activation have not been systematically reported. This review firstly provides a comprehensive summary of the recent advances in the field of CO2 capture, activation, and transformation with the help of FLP, including the construction of homogeneous and heterogeneous FLPs, their interaction with CO2, reaction activity, and mechanism study. We also illustrated the challenges and opportunities faced in this field to shed light on the prospective research.

IFN-γ enhances protective efficacy against Nocardia seriolae infection in largemouth bass (Micropterus salmoides).

Introduction: Nocardia seriolae adversely impacts a diverse range of fish species, exhibiting significant pathogenic characteristics that substantially impede the progress of aquaculture. N. seriolae infects in fish has a long incubation period, and clinical symptoms are not obvious in the early stages. There is presently no viable and eco-friendly approach to combat the spread of the disease. According to reports, N. seriolae primarily targets macrophages in tissues after infecting fish and can proliferate massively, leading to the death of fish. Interferon-gamma (IFN-γ) is a crucial molecule that regulates macrophage activation, but little is known about its role in the N. seriolae prevention. Methods: IFN-γ was first defined as largemouth bass (Micropterus salmoides, MsIFN-γ), which has a highly conserved IFN-γ characteristic sequence through homology analysis. The recombinant proteins (rMsIFN-γ) were obtained in Escherichia coli (E. coli) strain BL21 (DE3). The inflammatory response-inducing ability of rMsIFN-γ was assessed in vitro using monocytes/macrophages. Meanwhile, the protective effect of MsIFN-γ in vivo was evaluated by N. seriolae infection largemouth bass model. Results: In the inflammatory response of the monocytes/macrophages activated by rMsIFN-γ, various cytokines were significantly increased. Interestingly, interleukin 1ß (IL-1ß) and tumor necrosis factor alpha (TNF-a) increased by 183- and 12-fold, respectively, after rMsIFN-γ stimulation. rMsIFN-γ improved survival by 42.1% compared with the control. The bacterial load in the liver, spleen and head kidney significantly decreased. rMsIFN-γ was also shown to better induce increased expression of IL-1ß, TNF-α, hepcidin-1(Hep-1), major histocompatibility complex I (MHCI), and MHC II in head kidney, spleen and liver. The histopathological examination demonstrated the transformation of granuloma status from an early necrotic foci to fibrosis in the infection period. Unexpectedly, the development of granulomas was successfully slowed in the rMsIFN-γ group. Discussion: This work paves the way for further research into IFN-γ of largemouth bass and identifies a potential therapeutic target for the prevention of N. seriolae.

Integration of Co Single Atoms and Ni Clusters on Defect-Rich ZrO2 for Strong Photothermal Coupling Boosts Photocatalytic CO2 Reduction.

We report a solvothermal method for the synthesis of an oxygen vacancy-enriched ZrO2 photocatalyst with Co single atoms and Ni clusters immobilized on the surface. This catalyst presents superior performance for the reduction of CO2 in H2O vapor, with a CO yield reaching 663.84 µmol g-1 h-1 and a selectivity of 99.52%. The total solar-to-chemical energy conversion efficiency is up to 0.372‰, which is among the highest reported values. The success, on one hand, depends on the Co single atoms and Ni clusters for both extended spectrum absorption and serving as dual-active centers for CO2 reduction and H2O dissociation, respectively; on the other hand, this is attributed to the enhanced photoelectric and thermal effect induced by concentrated solar irradiation. We demonstrate that an intermediate impurity state is formed by the hybridization of the d-orbital of single-atom Co with the molecular orbital of H2O, enabling visible-light-driven excitation over the catalyst. In addition, Ni clusters play a crucial role in altering the adsorption configuration of CO2, with the localized surface plasmon resonance effect enhancing the activation and dissociation of CO2 induced by visible-near-infrared light. This study provides valuable insights into the synergistic effect of the dual cocatalyst toward both efficient photothermal coupling and surface redox reactions for solar CO2 reduction.

SETD7 Promotes Cell Proliferation and Migration via Methylation-mediated TAF7 in Clear Cell Renal Cell Carcinoma.

SET domain containing 7(SETD7), a member of histone methyltransferases, is abnormally expressed in multiple tumor types. However, the biological function and underlying molecular mechanism of SETD7 in clear cell renal cell carcinoma (ccRCC) remain unclear. Here, we explored the biological effects of SETD7-TAF7-CCNA2 axis on proliferation and metastasis in ccRCC. We identified both SETD7 and TAF7 were up-regulated and significantly promoted the proliferation and migration of ccRCC cells. Concurrently, there was a significant positive correlation between the expression of SETD7 and TAF7, and the two were colocalized in the nucleus. Mechanistically, SETD7 methylates TAF7 at K5 and K300 sites, resulting in the deubiquitination and stabilization of TAF7. Furthermore, re-expression of TAF7 could partially restore SETD7 knockdown inhibited ccRCC cells proliferation and migration. In addition, TAF7 transcriptionally activated to drive the expression of cyclin A2 (CCNA2). And more importantly, the methylation of TAF7 at K5 and K300 sites exhibited higher transcriptional activity of CCNA2, which promotes formation and progression of ccRCC. Our findings reveal a unique mechanism that SETD7 mediated TAF7 methylation in regulating transcriptional activation of CCNA2 in ccRCC progression and provide a basis for developing effective therapeutic strategies by targeting members of SETD7-TAF7-CCNA2 axis.

Concentrated solar CO2 reduction in H2O vapour with >1% energy conversion efficiency.

H2O dissociation plays a crucial role in solar-driven catalytic CO2 methanation, demanding high temperature even for solar-to-chemical conversion efficiencies <1% with modest product selectivity. Herein, we report an oxygen-vacancy (Vo) rich CeO2 catalyst with single-atom Ni anchored around its surface Vo sites by replacing Ce atoms to promote H2O dissociation and achieve effective photothermal CO2 reduction under concentrated light irradiation. The high photon flux reduces the apparent activation energy for CH4 production and prevents Vo from depletion. The defects coordinated with single-atom Ni, significantly promote the capture of charges and local phonons at the Ni d-impurity orbitals, thereby inducing more effective H2O activation. The catalyst presents a CH4 yield of 192.75 µmol/cm2/h, with a solar-to-chemical efficiency of 1.14% and a selectivity ~100%. The mechanistic insights uncovered in this study should help further the development of H2O-activating catalysts for CO2 reduction and thereby expedite the practical utilization of solar-to-chemical technologies.

Synthesis mechanism of dimethylhexane-1,6-dicarbamate from 1,6-hexamethylenediamine, urea and methanol: A molecular scale study based on density functional theory.

This work provides a molecular scale insight into non-phosgene synthesis based on the reaction of dimethylhexane-1,6-dicarbamate from 1,6-hexamethylenediamine, urea and methanol with computational electronic method. By exploring almost all possible reaction modes and comparing the effective barrier of each channel, this work analyzes the optimal reaction mechanism for both non-catalytic and self-catalytic systems. The mechanism without catalysis has a high effective free energy barrier (FEB) of 47.0 kcal mol-1. As for self-catalytic system, after sorting out the reaction pathway network, an effective FEB of 24.6 kcal mol-1 is confirmed which corresponds to dissociation of urea.

Thermodynamically controlled multiphase separation of heterogeneous liquid crystal colloids.

Phase separation is a universal physical transition process whereby a homogeneous mixture splits into two distinct compartments that are driven by the component activity, elasticity, or compositions. In the current work, we develop a series of heterogeneous colloidal suspensions that exhibit both liquid-liquid phase separation of semiflexible binary polymers and liquid crystal phase separation of rigid, rod-like nanocellulose particles. The phase behavior of the multicomponent mixture is controlled by the trade-off between thermodynamics and kinetics during the two transition processes, displaying cholesteric self-assembly of nanocellulose within or across the compartmented aqueous phases. Upon thermodynamic control, two-, three-, and four-phase coexistence behaviors with rich liquid crystal stackings are realized. Among which, each relevant multiphase separation kinetics shows fundamentally different paths governed by nucleation and growth of polymer droplets and nanocellulose tactoids. Furthermore, a coupled multiphase transition can be realized by tuning the composition and the equilibrium temperature, which results in thermotropic behavior of polymers within a lyotropic liquid crystal matrix. Finally, upon drying, the multicomponent mixture undergoes a hierarchical self-assembly of nanocellulose and polymers into stratified cholesteric films, exhibiting compartmentalized polymer distribution and anisotropic microporous structure.

Twist confers chemoresistance to anthracyclines in bladder cancer through upregulating P-glycoprotein.

BACKGROUND: The membrane transporter P-glycoprotein (P-gp) was found to mediate chemoresistance, which is one of the obstacles to effective chemotherapy in several types of human cancer. The transcription factor Twist, which has been reported to participate in cancer invasion and metastasis, also plays a vital role in the progression of chemoresistance. However, the effect of Twist on P-gp-related chemoresistance remains dubious. METHODS AND RESULTS: We found that Twist can regulate the expression of P-gp and then confer resistance to anthracycline drugs in human bladder cancer cells. Firstly, Twist was found to be coexpressed with P-gp in human bladder cancer cells and tissues, which were associated with enhanced chemoresistance to anthracycline drugs. Secondly, knockdown of Twist by specific siRNA treatment significantly sensitized bladder cancer cells to anthracycline drugs via inhibiting P-gp expression. Bladder cancer cells that survived transient exposure to anthracycline drugs showed higher levels of P-gp expression and more nuclear localization of Twist than untreated cells. CONCLUSION: We report a novel mechanism of anthracycline chemoresistance in bladder cancer in which activated Twist mediates P-gp expression in addition to its antiapoptotic roles. Therapeutic strategies targeting Twist may improve the management of recurrent bladder cancer after chemotherapy.