Accessing Functionalized Ultra-High Molecular Weight Poly(α-olefin)s via Hafnium-Mediated Highly Isospecific Copolymerization.

Inspired by the favorable impact of heteroatom-containing groups in phenoxy-imine titanium and late transition metal catalysts, a series of novel pyridylamido hafnium catalysts bearing ─OMe (Cat-OMe), ─CF3 (Cat-CF3), and ─C6F5 (Cat-C6F5) substituents are designed and synthesized. Together with the established hafnium catalysts Cat-H and Cat-iPr by Dow/Symyx, these catalysts are applied in the polymerization of α-olefins, including 1-hexene, 1-octene, and 4M1P, as well as in the copolymerization of these α-olefins with a specifically designed polar monomer. The enhancement of polymer molecular weight derived from catalyst modification and the incorporation of polar monomers is discussed in detail. Notably, the new catalysts are all highly active for α-olefins polymerization, with catalyst Cat-CF3 producing isotactic polymers with the highest molecular weight (Mw = 1649 kg mol-1); in copolymerization with polar monomers, catalyst Cat-OMe yields isotactic copolymer with the highest molecular weight (Mw = 2990 kg mol-1). Interestingly, catalyst Cat-C6F5 bearing a ─C6F5 group in the N-aryl moiety gives rise to poly(α-olefin) with reduced stereoselectivity. The findings of this study underscore the potential of heteroatom-containing groups in the development of early transition metal catalysts and the synthesis of polymer with novel structures.

Effects of follicle-stimulating hormone on the proliferation and apoptosis of infantile hemangioma stem cells.

Objective: To investigate the effects of different concentrations of follicle-stimulating hormone (FSH) on the proliferation and apoptosis of human hemangioma stem cells, it will provide a basis for studying the mechanism of FSH in treating hemangioma. Methods: Hemangioma specimens were collected from the Longgang District Maternity & Child Healthcare Hospital of Shenzhen City. Hemangioma stem cells were treated with different concentrations of FSH. Cell viability was detected by CCK8 method and cell apoptosis was analyzed by flow cytometry. Results: Hemangioma stem cells (HemSCs) were extracted from fresh tissue of infantile hemangioma by the CD133 immunomagnetic bead method. Under the influence of FSH at different concentrations (0, 100, 1000 IU/L), the cell viability of hemangioma stem cells increased significantly in a concentration-dependent manner (P < 0.05). At the same time, the apoptosis of hemangioma stem cells decreased with increasing concentrations of follicle-stimulating hormone (P < 0.05). Specifically, 1000 IU/L FSH significantly promoted the proliferation of hemangioma stem cells and inhibited their apoptosis. Conclusion: High concentration of follicle-stimulating hormone can maintain the growth of hemangioma by promoting the proliferation and inhibiting the apoptosis of hemangioma stem cells.

Exosomal transfer leads to chemoresistance through oxidative phosphorylation-mediated stemness phenotype in colorectal cancer.

Background: Recently years have seen the increasing evidence identifying that OXPHOS is involved in different processes of tumor progression and metastasis and has been proposed to be a potential therapeutical target for cancer treatment. However, the exploration in oxidative phosphorylation-mediated chemoresistance is still scarce. In our study, we identify exosomal transfer leads to chemoresistance by reprogramming metabolic phenotype in recipient cells. Methods: RNA sequencing analysis was used to screen altered targets mediating exosome transfer-induced chemoresistance. Seahorse assay allowed us to measure mitochondrial respiration. Stemness was measured by spheroids formation assay. Serum exosomes were isolated for circ_0001610 quantification. Results: The induced oxidative phosphorylation leads to more stem-like properties, which is dependent on the transfer of exosomal circ_0001610. Exosome transfer results in the removal of miR-30e-5p-mediated suppression of PGC-1a, a master of mitochondrial biogenesis and function. Consequently, increased PGC-1a reshapes cellular metabolism towards oxidative phosphorylation, leading to chemoresistance. Inhibition of OXPHOS or exosomal si-circ_0001610 increases the sensitivity of chemotherapy by decreasing cell stemness in vitro and in vivo. Conclusion: Our data suggests that exosomal circ_0001610-induced OXPHOS plays an important role in chemoresistance and supports a therapeutical potential of circ_0001610 inhibitors in the treatment of oxaliplatin-resistant colorectal cancer by manipulating cell stemness.

Exosomal transfer of miR-181b-5p confers senescence-mediated doxorubicin resistance via modulating BCLAF1 in breast cancer.

BACKGROUND: Doxorubicin resistance represents a major clinical challenge for treating patients with advanced breast cancer (BC). Exosomes, exchanging genetic cargo between heterogeneous populations of tumour cells, have been proposed to mediate drug resistance and cancer progression in other cancer types. However, their specific role in mediating doxorubicin resistance in BC remains unclear. Here, we demonstrate the important role of exosomal miR-181b-5p (exo-miR-181b-5p) in mediating doxorubicin resistance. METHODS: Small-RNA sequencing and bioinformatic analyses were used to screen miRNAs mediating doxorubicin resistance in BC, which were further verified by RT-qPCR. SA-ß-gal staining assays allowed us to measure cellular senescence. Exosomes from patients' serum before and after neoadjuvant chemotherapy were isolated for exo-miR-181b-5p quantification. RESULTS: Doxorubicin-resistant BC cell lines exhibited upregulated exosomal miR-181b-5p. Addition of exo-miR-181b-5p actively fused with recipient cells and transferred a drug-resistant phenotype. Overexpression of miR-181b-5p downregulated p53/p21 levels and inhibited doxorubicin-induced G1 arrest and senescence by suppressing BCLAF1 expression in vitro. Further, in vivo experiments showed treatment of exo-miR-181b-5p inhibitors exhibited superior tumour control and reversed the doxorubicin-resistance phenotype, accompanied with increased tumoral BCLAF1. CONCLUSION: Our data suggests exo-miR-181b-5p as a prognostic biomarker and a therapeutic potential for exo-miR-181b-5p inhibitors in the treatment of doxorubicin-resistant BC patients.

Prognostic Significance of Cuproptosis-Related Gene Signatures in Breast Cancer Based on Transcriptomic Data Analysis.

Breast cancer (BRCA) remains a serious threat to women's health, with the rapidly increasing morbidity and mortality being possibly due to a lack of a sophisticated classification system. To date, no reliable biomarker is available to predict prognosis. Cuproptosis has been recently identified as a new form of programmed cell death, characterized by the accumulation of copper in cells. However, little is known about the role of cuproptosis in breast cancer. In this study, a cuproptosis-related genes (CRGs) risk model was constructed, based on transcriptomic data with corresponding clinical information relating to breast cancer obtained from both the TCGA and GEO databases, to assess the prognosis of breast cancer by comprehensive bioinformatics analyses. The CRGs risk model was constructed and validated based on the expression of four genes (NLRP3, LIPT1, PDHA1 and DLST). BRCA patients were then divided into two subtypes according to the CRGs risk model. Furthermore, our analyses revealed that the application of this risk model was significantly associated with clinical outcome, immune infiltrates and tumor mutation burden (TMB) in breast cancer patients. Additionally, a new clinical nomogram model based on risk score was established and showed great performance in overall survival (OS) prediction, confirming the potential clinical significance of the CRGs risk model. Collectively, our findings revealed that the CRGs risk model can be a useful tool to stratify subtypes and that the cuproptosis-related signature plays an important role in predicting prognosis in BRCA patients.

Deep Adsorption Desulfurization of Fluid Catalytic Cracking Light Gasoline on NiO/ZnO-TiO2 Adsorbents with a High Breakthrough Sulfur Capacity.

Two kinds of NiO/ZnO-TiO2 adsorbents were prepared by equal volume impregnation (NiO/ZnO-TiO2-1) and kneading (NiO/ZnO-TiO2-2) methods. The adsorbents were characterized by X-ray diffraction, mercury intrusion porosimetry, scanning electron microscopy, energy dispersive X-ray spectroscopy, H2 temperature-programmed reduction, and H2 temperature-programmed desorption. It was found that NiO/ZnO-TiO2-2 had a smaller average pore diameter and a larger specific surface area as well as a more uniform distribution of the nickel element. Additionally, more Ni0 active sites together with a stronger interaction between the active component and the support were detected on the surface of NiO/ZnO-TiO2-2, which was beneficial to the inhibition of olefin saturation during desulfurization. The desulfurization performance of the adsorbents was investigated in a fixed bed reactor with fluid catalytic cracking light gasoline as a feed oil. The evaluation results confirmed NiO/ZnO-TiO2-2 with a better desulfurization performance with less olefin saturation. It could reduce the total sulfur content from 300 ppmw to less than 5 ppmw, and the breakthrough time and breakthrough sulfur capacity were 91 h and 6.71% (67.1 mg S/g adsorbent), respectively.

Tanshinone I and Tanshinone IIA/B attenuate LPS-induced mastitis via regulating the NF-κB.

BACKGROUND: Mastitis is a common disease occurs in breast-feeding mothers, but published data are poor. This study aimed to study the effects of Tanshinones on treating mastitis. METHODS: Clinical trials performed in 58 breast-feeding mothers were carried out. B-ultrasound and blood test were used to measure the size of breast mass and the change of blood cell counts. BALB/c mice were injected with LPS and then treated by Tanshinone I or Tanshinone IIA/B. Myeloperoxidase (MPO) activity and the release of inflammatory cytokines were tested by MPO kit, RT-qPCR and ELISA. Mouse mammary epithelial cells (mMECs) were isolated and the effects of Tanshinones were measured by conducting CCK-8 assay, flow cytometry, RT-qPCR and ELISA. RESULTS: Patients treated by Cefprozil combined with Tanshinone got better outcomes than patients treated by Cefprozil alone. In animal trials, Tanshinone I and Tanshinone IIA/B significantly reduced MPO activity, and the levels of TNF-α, IL-1ß and IL-6 in serum and mammary gland tissues. In mMECs, Tanshinone I and Tanshinone IIA/B attenuated LPS-induced viability loss and apoptosis. And they effectively inhibited the release of TNF-α, IL-1ß and IL-6. Also, Tanshinone I and Tanshinone IIA/B significantly attenuated LPS-evoked NF-κB activation. CONCLUSION: Tanshinone I and Tanshinone IIA/B have potentials in treating mastitis. The beneficial effects might be through regulating NF-κB activation.

Effect of the pore structure of an active alumina catalyst on isobutene production by dehydration of isobutanol.

An alumina catalyst was prepared by mixing and pinching with pseudo-boehmite, and the catalyst was reamed with polyethylene glycol. The catalysts prepared were characterized by means of XRD, mercury injection and NH3-TPD, and the dehydration properties of the catalysts prepared with different amounts of reamer were evaluated in a 10 mL fixed bed reactor with 5% water as a raw material. The results showed that the addition of reamer did not affect the crystal structure and the amount of acid of the catalyst. With the increase of the amount of reamer, the pore volume of the catalyst increased continuously, the number of large pores increased, the conversion rate of isobutanol increased, and the selectivity of isobutene remained basically unchanged. When the amount of reamer is 30%, the isobutanol conversion rate is the best. The isobutanol conversion rate and the isobutene selectivity were 97% and 93% respectively under the conditions of 330 °C, 0.1 MPa and 12 h-1 air velocity of the body liquid.

Performance of gamma-Al2O3 decorated with potassium salts in the removal of CS2 from C5 cracked distillate.

Deep desulfurization is a key process for the production of high value-added products from C5 distillates. In this work, different potassium salt modified gamma-Al2O3 adsorbents were prepared by an incipient-wetness impregnation method and characterized by N2 adsorption-desorption, SEM-EDS, TEM, CO2-TPD, XRD, FT-IR, and IC. The C5 distillate with a 1200 µg mL-1 sulfur content is desulfurized to less than 10 µg mL-1 within 24 hours by the static adsorption method. For the desulfurization in the fix-bed reactor, the breakthrough sulfur capacity of K2CO3-decorated gamma-Al2O3 reaches 0.76 wt% under the optimized conditions, viz., at 30 °C, with a sulfur content of 50 µg mL-1 in the raw oil, and a liquid hourly space velocity of 1 h-1. The desulfurization activity of the exhausted adsorbent can be recovered after regeneration. Selective adsorption of CS2 includes three processes: adsorption, hydrolysis, and oxidation. CS2 is first adsorbed on the adsorbent and hydrolyzed to form H2S. H2S is further oxidized to form S/SO4 2-, and then deposits on the surface of the adsorbent. Adsorption, hydrolysis, and oxidation all play essential roles in the removal process of CS2.

Centromere protein U (CENPU) enhances angiogenesis in triple-negative breast cancer by inhibiting ubiquitin-proteasomal degradation of COX-2.

Triple-negative breast cancer (TNBC) is characterized by high vascularity, but anti-angiogenic therapies show poor efficacy. Centromere protein U (CENPU), a centromere component essential for mitosis, is associated with tumorigenesis in multiple cancers; however, little is known of its role in breast cancer. Here, we investigate its expression and function of promoting angiogenesis in TNBC. Immunohistochemical staining revealed high CENPU expression in TNBC tissue and high CENPU levels correlated significantly with poor distant metastasis-free and overall survival. Knockdown of CENPU in TNBC cells inhibited vascular endothelial growth factor A (VEGFA) production and significantly reduced tube formation and migration of human umbilical vein endothelial cells in vitro. In a mouse xenograft model, CENPU knockdown reduced TNBC tumor growth concomitant with a reduction in CD31 + microvessel density. Mechanistic studies revealed that CENPU promoted angiogenesis by inhibiting the ubiquitination and proteasomal degradation of cyclooxygenase-2 (COX-2), leading to increased activation of the COX-2-p-ERK-HIF-1α-VEGFA signaling pathway. Taken together, our results demonstrate a critical role for CENPU in COX-2-mediated signaling for angiogenesis, and identify a role of CENPU in regulating angiogenesis in TNBC.

Fe3O4@C Core-Shell Carbon Hybrid Materials as Magnetically Separable Adsorbents for the Removal of Dibenzothiophene in Fuels.

Herein, we demonstrate a new class of core-shell magnetic carbon hybrid materials (Fe3O4@C) for remarkable adsorptive desulfurization of dibenzothiophene (DBT), which have been successfully prepared through hydrocarbonization of glucose on the surface of Fe3O4 and the subsequent pyrolyzation process. The as-obtained Fe3O4@C retains amorphous nature of carbon shells with a large surface area and displays an increase of iron atoms as active sites under elevated pyrolyzation temperature which is favorable in the adsorption of sulfur-containing species through physical and chemical adsorption, respectively. We investigate the adsorption capacity and efficiency of Fe3O4@C as a magnetically adsorbent for the removal of DBT in model oils under various experimental conditions including the adsorbent obtained at different temperatures, the amount of adsorbents, the DBT initial concentration, the regeneration approach, as well as the interference species. Our results demonstrated that the as-obtained Fe3O4@C at 650 °C (Fe3O4@C-650) displays a remarkable estimated adsorption performance (57.5 mg DBT/g for 200 ppmw), extraordinary high desulfurization efficiency (99% for 200 ppmw), and a high selectivity for DBT compared with its derivatives. Moreover, Fe3O4@C can be recovered in a quite easy, economical, and eco-friendly manner by an external magnet after five cycles without significant weight loss, which significantly simplifies the operation procedure and favors the recycle of Fe3O4@C. Combined with the economic and eco-friendly merits, Fe3O4@C offers a new avenue to employ the magnetic carbon materials for industrial applications and provides a promising substitute for adsorptive desulfurization in view of academic, industrial, and environmental aspects.

A new nonlinear method for calculating growing degree days.

Precise calculations of growing degree days (GDD) are an important component in crop simulation models and managerial decisions. Traditional methods for calculating GDD assume linear developmental responses to temperature and cannot precisely account for the delay in growth or development at temperatures above the optimal temperature (Topt). A new nonlinear method for calculating GDD was developed. Variations in the prediction of the dates since sowing to various developmental stages and performance measures for describing the accumulation of dry matter by GDD for two widely planted crops (corn and wheat) were used to evaluate the new method in comparison with the traditional methods. The new method predicted the dates of the developmental stages more precisely (date variations reduced by 1 d), and the errors for the predictions of the accumulation of dry matter for winter wheat and corn were smaller. The method was most promising for spring wheat. The new method was more stable and more precise than traditional methods, especially when Topt was lower than the maximum air temperature.

USP18 promotes breast cancer growth by upregulating EGFR and activating the AKT/Skp2 pathway.

Recent studies have suggested that ubiquitin-specific peptidase (USP)18 may act as an oncogene in various types of cancer. Although the role of USP18 in breast cancer cell lines has been elucidated, the underlying mechanisms and clinical role of USP18 in breast cancer are currently not well understood. The bioinformatics analysis and experimental results of the present study demonstrated that aberrant promoter methylation led to increased expression of USP18 in breast cancer. In addition, correlation analysis suggested that a negative correlation between methylation and USP18 mRNA expression was observed in The Cancer Genome Atlas database. USP18 promoted cell proliferation, colony formation and cell cycle progression in vitro. Furthermore, the Gene Set Enrichment Analysis results demonstrated that USP18 may be negatively associated with apoptosis in patients with breast cancer. Bioinformatics analysis results indicated that USP18 was also revealed to be associated with the protein kinase B (AKT) signaling pathway and mammary tumorigenesis in vivo. In addition, the results indicated that USP18 may promote the epidermal growth factor (EGF)-mediated EGF receptor (EGFR)/AKT/S­phase kinase-associated protein 2 (Skp2) pathway by upregulating EGFR and Skp2 in a AKT/forkhead box O3-dependent manner in breast cancer. The results of bioinformatics analysis revealed that increased USP18 expression was associated with a higher TNM stage and unfavorable prognosis in clinical patients. USP18 was also significantly enhanced in patients with human epidermal growth factor receptor 2-positive breast cancer; furthermore, Kaplan­Meier curve demonstrated that combining USP18 and Skp2 expression improved prognostic capability in breast cancer. Taken together, these results suggested that USP18 may serve a key role in breast cancer development by upregulating EGFR and subsequently activating the AKT/Skp2 feedback loop pathway. The role of USP18 in breast cancer provides a novel insight into the clinical application of the USP18/AKT/Skp2 pathway.

HSP90 inhibitor AUY922 can reverse Fulvestrant induced feedback reaction in human breast cancer cells.

Hormone therapy has become one of the main strategies for breast cancer, however, many estrogen receptor (ER) positive patients end in tumor collapse due to initial or acquired resistance to hormone treatment, which includes Fulvestrant. Here we report that ErbB receptors and downstream PI3K/AKT and ERK pathway have been reactivated after treatment of Fulvestrant in ER positive MCF-7 and T47D cells, which are related to Fulvestrant resistance. HSP90 is a universally expressed chaperone protein and plays a vital role in both normal and cancer cells, HSP90 inhibitor AUY922 can reverse this feedback reactivation effect of Fulvestrant by targeting multiple proteins related in ErbB receptors, PI3K/AKT and ERK pathway, which is much better than single targeting inhibitors. We also consolidate these effects in human fresh breast tumors. Combination of AUY922 and Fulvestrant may become a promising therapy strategy in breast cancer treatment.

Selective Hydrodeoxygenation of 5-Hydroxymethylfurfural to 2,5-Dimethylfuran over Heterogeneous Iron Catalysts.

This work provided the first example of selective hydrodeoxygenation of 5-hydroxymethylfurfural (HMF) to 2,5-dimethylfuran (DMF) over heterogeneous Fe catalysts. A catalyst prepared by the pyrolysis of an Fe-phenanthroline complex on activated carbon at 800 °C was demonstrated to be the most active heterogeneous Fe catalyst. Under the optimal reaction conditions, complete conversion of HMF was achieved with 86.2 % selectivity to DMF. The reaction pathway was investigated thoroughly, and the hydrogenation of the C=O bond in HMF was demonstrated to be the rate-determining step during the hydrodeoxygenation, which could be accelerated greatly by using alcohol solvents as additional H-donors. The excellent stability of the Fe catalyst, which was probably a result of the well-preserved active species and the pore structure of the Fe catalyst in the presence of H2 , was demonstrated in batch and continuous flow fixed-bed reactors.

Correlations between lncRNA-SOX2OT polymorphism and susceptibility to breast cancer in a Chinese population.

AIM: We evaluated the effect of lncRNA SOX2OT expression and its SNP in tumorigenesis and development of breast cancer (BC) in a case-control study. METHODS: A total of 1106 individuals, 505 newly diagnosed BC patients and 601 age-matched controls (±2 years) were testified. Real-time PCR was adopted for testing tissues' SOX2OT expression. Genotyping of rs9839776 were conducted by using SNaPshot assays. RESULTS: SOX2OT were overexpressed in BC tissues (p < 0.001). SOX2OT SNP rs9839776 was strongly associated with the higher expression of SOX2OT and an increased risk of BC in Chinese women (odds ratio: 1.42; 95% CI: 1.06-1.90; p = 0.018). CONCLUSION: These results confirmed that BC was conspicuously associated with higher SOX2OT expression. SOX2OT SNP rs9839776 was significantly associated with the onset of BC possibly via influencing the expression of SOX2OT.

Preparation, characterization and relative bioavailability of oral elemene o/w microemulsion.

The objective was to develop an elemene oil/water (o/w) microemulsion and evaluate its characteristics and oral relative bioavailability in rats. Elemene was used as the oil phase and drug, polysorbate 80 as a surfactant along with ethanol, propylene glycol, and glycerol as the cosurfactants. The microemulsion was prepared by mixing method, or ultrasonication method in an ultrasonic bath. Its three-dimensional response surface diagram was drawn by Mathcad software. The microemulsion was characterized by visual observation, cross-polarized microscopy, size, zeta potential, acidity, viscosity, and surface tension measurement. The drug content and entrapment efficiency were determined by ultra fast liquid chromatography (UFLC) and liquid surface method. Blood was drawn from rats at different time points after oral administration of an elemene microemulsion or a commercial elemene emulsion for measurement of the drug in plasma by UFLC to establish the pharmacokinetic parameters and relative bioavailability. The elemene microemulsion as a clarified and isotropic system containing 1% elemene (w/v), 5% ethanol (v/v), 15% propylene glycol (v/v), 15% glycerol (v/v), and 5% polysorbate 80 (w/v), was characterized as (57.7 ± 2.8) nm in size, 0.485 ± 0.032 in polydispersity index, (3.2 ± 0.4) mv in zeta potential, (5.19 ± 0.08) in pH, 6 mpa·s in viscosity, (31.8 ± 0.3) mN·m(-1) in surface tension, (8.273 ± 0.018) mg·mL(-1) in content of ß-elemene, and (99.81 ± 0.24)% in average entrapment efficiency. The area under the concentration-time curves from 0 h to 24 h (AUC(0→24h)) of the elemene microemulsion and commercial elemene emulsion were integrated to be 3.092 mg·h·L(-1) and 1.896 mg·h·L(-1) respectively, yielding a relative bioavailability of 163.1%. The present study demonstrates the elemene microemulsion as a new formulation with ease of preparation, high entrapment efficiency, excellent clarity, good stability, and improved bioavailability.

[Repair of the soft tissue defect of the fifth finger with a reversed ulnar fasciocutaneous flap from the fifth metacarpal side].

OBJECTIVE: To introduce a method by reversed ulnar fasciocutaneous flap incised form the ulnar side of the fifth metacarpal area for repairing the soft tissue defect of the fifth finger. METHODS: From May 2001 to September 2001, ten patients with the soft tissue defects of the thenar side, dorsal side or ulnar side of the fifth finger were treated with the reversed ulnar fasciocutaneous flap incised from the fifth metacarpal area. The axial line of the flap was the line from ulnar side of the head of the fifth metacarpal bone to the pisiform level. The revolving point of the flap pedicle was 0.5-1 cm near the proximal end of the metacarpal-phalangeal joint.The area of the flap was form 5.0 cm x 3.5 cm to 1.5 cm x 1.0 cm. RESULTS: All flaps of the ten cases were alive. 5-7 months followed-up show that, after operation, the flap present sensation in 6-12 mm, with soft texture and good appearances. CONCLUSIONS: The advantages of this operative method were as follows: the reversed ulnar fasciocutaneous flap of the fifth metacarpal area have reliable blood supply, it was easily dissected and with good texture. So far this kind of flap is a good choice in repairing the soft tissue of the fifth finger.