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Protein tyrosine phosphatase non-receptor type 18 (PTPN18) is often highly expressed in colorectal cancer (CRC), but its role in this disease remains unclear. We demonstrated that PTPN18 overexpression promotes growth and tumorigenesis in CRC cells and that PTPN18 deficiency yields the opposite results in vitro. Moreover, a xenograft assay showed that PTPN18 deficiency significantly inhibited tumorigenesis in vivo. PTPN18 activated the MYC signaling pathway and enhanced CDK4 expression, which is tightly associated with the cell cycle and proliferation in cancer cells. Finally, we found that MYC interacted with PTPN18 and increased the protein level of MYC. In conclusion, our results suggest that PTPN18 promotes CRC development by stabilizing the MYC protein level, which in turn activates the MYC-CDK4 axis. Thus, PTPN18 could be a novel therapeutic target in the future.

During the preparation of Bi2Sr2CaCu2O8+δ (Bi2212) superconducting thin films by sol-gel method, the complexing agent and sintering conditions can significantly influence the quality and the performance of thin film. In this study, Bi2212 thin films were prepared on single crystal SrTiO3 (001) substrate, and the phase purity, crystallinity, surface morphology and transport properties were studied particularly with different sintering temperature and time, complexing agent and its ratio to metal ions. Due to relatively low carbon content, tartaric acid (TA) as a complexing agent improved the film quality and transport properties compared with the traditional ethylenediamine tetraacetic acid (EDTA). When the complex ratios of TA to metal ions was 1:1, Bi2212 thin films exhibited good epitaxial properties, a high Bi2212 phase purity and a low surface roughness of 12.74 nm. Simultaneously, under these preparation condition, Bi2212 superconducting thin film showed a higher Tc, onset of 93.28 K.

A novel N-doped graphene-like carbon nanosheets (CNs) and carbon nanotubes (CNTs)-encapsulated Co-Co3O4 nanoparticles (NPs) (CN@Co-Co3O4/CNTs) were synthesized successfully by a simple hydrothermal and annealing method with graphite carbon nitride (g-C3N4) as self-template. By annealing Co2+/g-C3N4 under N2 atmosphere, g-C3N4 was transformed into CN/CNTs, and Co2+ was reduced into CoNPs which were embedded in CNs. Further annealing in air, a shell of Co3O4 was formed around CoNPs. The amount of CNs, CNTs, and CoNPs can be adjusted by changing the ratio of Co2+ in Co2+/g-C3N4. The graphene-like CNs provided a large number of active sites and a large specific surface area for loading lots of small CoNPs uniformly. The CNTs with a diameter of 100 nm could not only improve the conductivity but also provide a buffer space for the aggregation and volume expansion of Co3O4. CNTs also enlarged the interlayer distance of CNs, which prevented the re-stacking of CNs and provided great convince for the intercalation and de-intercalation of Li+. When applied for anode material of lithium-ion batteries, CN@Co-Co3O4/CNTs exhibited a high discharge capacity of 460.0 mAh g−1 at 5000 mA g−1 after 300 cycles with a Coulombic efficiency of 98% and excellent higher-rate capacity (401.0 mAh g−1 at 2000 mA g−1 and 329.0 mAh g−1 at 5000 mA g−1).

Sediment samples collected from the river Shitalakhya, Bangladesh, were analyzed using atomic absorption spectroscopy (AAS) to investigate site-to-site (spatial) and seasonal (i.e., dry, premonsoon, post-monsoon) variation of Cr, Mn, Ni, Cu and Zn. The mean concentrations of Cr, Mn, Ni, Cu and Zn were 22.37 ± 6.09, 612.59 ± 160.08, 54.11 ± 11.21, 50.36 ± 9.40 and 103.62 ± 62.74 mg/kg in the dry, 31.58 ± 5.22, 569.71 ± 112.16, 58.35 ± 7.82, 49.93 ± 17.36 and 110.88 ± 95.83 mg/kg in the pre-monsoon and 18.09± 6.32, 567.02 ± 115.55, 50.89 ± 6.58, 39.75 ± 4.56 and 55.22 ± 11.33 mg/kg in the post-monsoon, respectively. Based on the metals’ concentrations, no considerable difference was observed among the three seasons, but the concentrations were slightly elevated in the dry and pre-monsoon compared to that in the post-monsoon with respect to site-to-site variation. Among the metals examined, concentrations of Ni and Cu were elevated because of the use of oxides of these heavy metals as catalysts in the ammonia plant. The following statistical indices i.e., Pearson correlation matrix, geo-accumulation index (Igeo), contamination factor (Cf), degree of contamination (Cd), pollution load index (PLI) and ecological risk potential (RI) factors were taken into account to assess the heavy metals contamination of the sediments. According to the values of the statistical indices for Cr, Mn, Ni, Cu and Zn, it is concluded that the study area was with low contamination while concentrations of Ni and Cu were higher than the Threshold Effect Level (TEL) and Toxicity Reference Value (TRV) values suggesting unsafe to use the sediments for vegetation and other uses.

Bioconversion (e.g. anaerobic fermentation and compost) is the common recycling method of waste activated sludge (WAS) and its hydrolysis, as the rate-limiting step of fermentation, could be accelerated by protease. However, the commercial protease was unstable in a sludge environment, which increased the cost. An endogenous alkaline protease stable in sludge environment was screened in this study and its suitability for treating the sludge was analyzed. The optimal production medium was determined by Response Surface Methodology as starch 20 g/L, KH2PO4 4 g/L, MgSO4·7H2O 1 g/L, sodium carboxy-methyl-cellulose 4 g/L, casein 4 g/L and initial pH 11.3, which elevated the yield of protease by up to 15 times (713.46 U/mL) compared with the basal medium. The obtained protease was active and stable at 35 °C–50 °C and pH 7.0–11.0. Furthermore, it was highly tolerant to sludge environment and maintained high efficiency of sludge hydrolysis for a long time. Thus, the obtained protease significantly hydrolyzed WAS and improved its bioavailability. Overall, this work provided a new insight for enzymatic treatment of WAS by isolating the endogenous and stable protease in a sludge environment, which would promote the resource utilization of WAS by further bioconversion. HIGHLIGHTS A novel protease-producing bacterium was isolated from the sludge.; The screened protease was highly tolerant to the sludge environment.; Treatment of the sludge by the screened protease elevated its bioavailability.; The screened protease was a promising biocatalyst for sludge treatment.

In distant hybridization of fishes, there is a low hatching rate of hybrid progenies. To further understand the causes of low hatchability, in this article, cross-breeding between zebrafish (ZF) and crucian carp (CC) are generated, in which the hatching rate of cross progenies (ZF♀ × CC♂, ZC) is 35.67%, while that of reciprocal cross progenies (CC♀ × ZF♂, CZ) is about zero. The structures and SDS-PAGE protein pattern of egg envelopes in hybrid early embryos are like their maternal fish, however, during the process of embryo development, some differences are detected between the CZ and CC. The hatching enzyme gene 1 (he1) nucleotide sequences from ZF and CC were 85.1% identity, while that of 99.6% identity was between the ZF and ZC, and 98.4% from CC and hybrid of CZ. There are differences in predictive protein physicochemical properties of he1 between CZ and CC, but no significant change in he1 mRNA levels during embryonic development. Our data furtherly verify that the characteristics of egg envelope and hatching enzyme in hybrid progenies are inherited from maternal fish. Moreover, there are obvious differences between CZ and maternal parent in both egg envelope and hatching enzyme during embryonic development, which are considered to be related to its low hatching rate.

A mild method for accessing diazo compounds via aerobic oxidation of hydrazones is described. This catalytic transformation employs a Cu(OAc)2/pyridine catalyst and molecular oxygen from ambient ai...

(H2dabco)[NH4(ClO4)3] (DAP, dabco = 1,4-diazabicyclo[2.2.2]octane) is a recently synthesized ammonium perchlorate-based molecular perovskite energetic material. The high-symmetry perovskite configuration assembles the oxidant ClO4− and fuel H2dabco2+ into a compact cubic crystal, realizing a high energy-releasing efficiency. In this study, the thermal decomposition of DAP has been investigated by thermogravimetric analysis (TG) and differential scanning calorimetry (DSC) coupled with Fourier transform infrared (FTIR) spectroscopy and mass spectroscopy (MS). The TG-DSC profiles show that DAP has an intense one-stage heat release process with a weight loss of 94.7%. The evolved gas products are identified as H2O, CO2, CO, HCl, HCN, NH3, HNCO by FTIR spectrum, in which the infrared characteristic peak at 2283 and 2250 cm−1 is clarified not from N2O and assigned to HNCO. The principal products are H2O and CO2 together with significant amounts of HCl, HCN, NH3 in MS, while few nitrogen oxides and O2 are detected. The experimental results show that organic components have been the prominent media for the degradation of ClO4−. To refine the mechanism observed in experiment, ab initio molecular dynamics simulations are carried out to reveal the atomistic reaction mechanisms. The decomposition of DAP starts with proton transfer from NH4+ and H2dabco2+ to ClO4−. The deprotonated carbon skeleton is preferable to NH3 in capturing O atoms, realizing a faster consumption of O atoms. Amounts of H atoms enter the environment being active free radicals, realizing an efficient autocatalytic chain propagation of degradation of ClO4−. The atomistic thermal decomposition reaction mechanism of DAP uncovers the role of organic components in promoting the degradation of ClO4−, which will help improve the synthesis strategy of molecular perovskite energetic materials with improved performance.

Uranium is a common radionuclide contaminant in groundwater. Recovery of uranium from uranium-containing water can achieve the dual purposes of uranium remediation and uranium resource utilization. However, very few studies have successfully achieved this task. In this study, we developed a microbial fuel cell (MFC) system with a titanium dioxide nanotube array (TNTA) cathode, which could efficiently remove (over 95%) and recover (over 97%) uranium from uranium-containing water. Results demonstrated that the removal of U(VI) in the MFC was through an adsorption–reduction–deposition mechanism. U(VI) was adsorbed by the TNTA cathode, and the adsorbed U(VI) was further electroreduced to U(IV)O2 and deposited on the surface of the TNTA cathode. The reduction of adsorbed U(VI) initiated re-equilibration of the desorption reaction of adsorbed U(VI) and induced re-adsorption of U(VI). The re-adsorbed U(VI) could be further electroreduced to U(IV)O2, which resulted in the continuous removal of U(VI). Finally, 2.95 μmol U(VI) was reduced and deposited as U(IV)O2 on the surface of the TNTAs (1476.22 μmol m−2) without observing capacity saturation. Moreover, the deposited U(IV)O2 can be easily separated from the TNTA cathode with dilute nitric acid, and the TNTA cathode can be used repeatedly with stable performance.

The fabrication, by an electrochemical process, of a new battery-type electrode material, is presented. Such materials are fabricated by direct current electrodeposition of Ni(OH)2 on lamellar Ni3Si. Microstructure and morphology of Ni(OH)2/Ni3Si electrodes were characterised. Cyclic voltammetry and galvanostatic charge–discharge results revealed that they are battery-type electrodes. Increasing deposition time or decreasing discharge current can significantly increase the areal capacity. The areal capacity of Ni(OH)2/Ni3Si-20 with a discharge current of 20 mA is only 2.8% of that with 1 mA. However, the increasing deposition time will reduce the cyclic stability of the electrodes. The initial areal capacity of Ni(OH)2/Ni3Si-20 is twice that of Ni(OH)2/Ni3Si-10 with a discharge current of 10 mA, but after 1000 cycles, it can only maintain 59.3% of the initial value. This Letter is expected to provide a powerful reference and guidance for the preparation of electrodes with large areal capacity and cycle stability.

Background Overexpression of Skp2 plays a critical role in tumorigenesis and correlates with poor prognosis in human malignancies. Thus, Skp2 has been proposed as an attractive target for anti-tumor interventions. Methods The expression of Skp2 in human colorectal cancer (CRC) and the role of Skp2 in tumorigenic properties and irradiation sensitivities of CRC cells were examined by anchorage-dependent and -independent growth assays, immunoblot, flow cytometry, immunohistochemical staining, ubiquitination analysis, co-immunoprecipitation assay, CRISPR-Cas9-based gene knockout, and xenograft experiments. Results Skp2 is highly expressed in CRC patient tissues. Blocking Skp2 expression reduces the tumorigenic properties of CRC cells in vitro and in vivo. Depletion of Skp2 confers sensitivity to irradiation of CRC cells. Skp2 deficiency enhances irradiation-induced intrinsic apoptosis by facilitating E3 ligase FBW7-mediated Mcl-1 ubiquitination and degradation. Knockout of Skp2 sensitizes CRC cells to irradiation treatments in vivo. Conclusion Our findings indicate that Skp2 stabilizes Mcl-1, and targeting Skp2 in combination with traditional radiotherapy might be efficacious in treating CRC.

Dysfunction of epidermal growth factor receptor (EGFR) signalling plays a critical role in the oncogenesis of non–small‐cell lung cancer (NSCLC). Here, we reported the natural product, licochalcone A, exhibited a profound anti‐tumour efficacy through directly targeting EGFR signalling. Licochalcone A inhibited in vitro cell growth, colony formation and in vivo tumour growth of either wild‐type (WT) or activating mutation EGFR‐expressed NSCLC cells. Licochalcone A bound with L858R single‐site mutation, exon 19 deletion, L858R/T790M mutation and WT EGFR ex vivo, and impaired EGFR kinase activity both in vitro and in NSCLC cells. The in silico docking study further indicated that licochalcone A interacted with both WT and mutant EGFRs. Moreover, licochalcone A induced apoptosis and decreased survivin protein robustly in NSCLC cells. Mechanistically, we found that treatment with licochalcone A translationally suppressed survivin through inhibiting EGFR downstream kinases ERK1/2 and Akt. Depletion of the translation initiation complex by eIF4E knockdown effectively inhibited survivin expression. In contrast, knockdown of 4E‐BP1 showed the opposite effect and dramatically enhanced survivin protein level. Overall, our data indicate that targeting survivin might be an alternative strategy to sensitize EGFR‐targeted therapy.

Deoxynivalenol (DON) is a widely distributed mycotoxin that frequently occurs in various foodstuffs, and poses a health risk to human and animals. Biodegradation of DON to less- or non-toxic substances using naturally existing microorganisms is considered the best approach for DON detoxification. Although various microorganisms capable of detoxifying DON have been reported; however, such studies on probiotic strains are scarce. In this study, a bacterial strain (ASAG 216) showed to possess the capability of detoxifying 100 μg/mL DON by 81.1% within 8 h was isolated from the intestine of a donkey. After morphological observation and 16S rDNA sequence analysis, the strain was identified as Bacillus subtilis. The DON-degradation potential of B. subtilis ASAG 216 was predominantly attributed to the culture supernatant, which turned to be sensitive to heat, sodium dodecyl sulfate, and proteinase K treatment, indicating the possible presence of extracellular proteins or enzymes in the supernatant which were responsible for DON degradation. Moreover, B. subtilis ASAG 216 has a broad temperature (35–50 °C) and pH (6.5–9.0) tolerance on DON degradation, apart from its ability to withstand conditions which generally prevail during the intestinal transit. In addition, the tested strain showed antimicrobial activity against Escherichia coli, Staphylococcus aureus and Salmonella typhimurium. These results provide satisfactory grounds for the potential use of B. subtilis ASAG 216 as a new feed additive to address DON contamination.

Herein, a new activated porous carbon (APC) was proposed by carbonizing waste biomass of pinecone which could be obtained in large quantities and subsequently activation of zinc chloride. Then small Co3O4 nanoparticles were loaded on the surface and holes of APC to prepare the final Co3O4/APC nanocomposites. The as-prepared APC had a lotus root-like and layered porous structure with a large number of mesopores and micropores. The APC reduced the agglomeration of small Co3O4 particles which were uniformly anchored on the surface of APC. When applied for the anode of lithium-ion batteries, the Co3O4/APC nanocomposites had a reversible capacity of 625 mAh g−1 after 200 cycles at the current density of 500 mA g−1. The Co3O4/APC nanocomposites also had a good rate performance. Above all, this work could transform waste biomass into sustainable resource, and the raw materials were easy to obtain in large quantities.

Herein we demonstrate a packed bed flow reactor capable of achieving highly regio- and stereoselective C-H functionalization reactions using a newly developed Rh2 (S-2-Cl-5-CF3 TPCP)4 catalyst. To optimize the immobilized dirhodium catalyst employed in the flow reactor, we systematically study both (i) the effects of ligand immobilization position, demonstrating the critical factor that the catalyst-support attachment location can have on the catalyst performance, and (ii) silica support mesopore length, demonstrating that decreasing diffusional limitations leads to increased accessibility of the active site and higher catalyst turnover frequency. We employ the immobilized dirhodium catalyst in a simple packed bed flow reactor achieving comparable yields and levels of enantioselectivity to the homogeneous catalyst employed in batch and maintain this performance over ten catalyst recycles.

Feng Gao,1,2,* Li Zhou,3,* Ming Li,1,4,5,* Wenbin Liu,6 Shuting Yang,2 Wei Li1,7 1Cell Transplantation and Gene Therapy Institute, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, People’s Republic of China; 2Department of Ultrasonography, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, People’s Republic of China; 3Department of Pathology, Xiangya Hospital of Central South University, Changsha, Hunan 410013, People’s Republic of China; 4Changsha Stomatological Hospital, Changsha, Hunan 410004, People’s Republic of China; 5School of Stomatology, Hunan University of Chinese Medicine, Changsha, Hunan 410208, People’s Republic of China; 6Department of Pathology, Hunan Cancer Hospital, Changsha, Hunan 410013, People’s Republic of China; 7Department of Radiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Li Email weililx@csu.edu.cnBackground: Deregulation of Cyclin D1 and cell cycle progression plays a critical role in tumorigenesis. The natural compound piperlongumine (PL) exhibits potential anticancer effects in various cancer models, but the underlying mechanism needs further elucidation.Methods: The inhibitory effect of PL on colorectal cancer (CRC) cells was determined by anchorage-dependent and -independent assays. The protein level of Cyclin D1 was examined by immunoblot (IB) and immunohistochemical staining (IHC). The mRNA level was determined by qRT-PCR. Phosphorylation of histone H3 was analyzed by immunofluorescence (IF). The cell cycle was examined by flow cytometry. The in vivo antitumor effect was validated by the xenograft mouse model.Results: Cyclin D1 was overexpressed in CRC tissues and cells, and was required for maintaining cell growth, colony formation, and in vivo tumorigenesis. PL decreased the protein level of c-Fos, which eventually reduced the transcriptional activity of AP-1 and the mRNA level of Cyclin D1. Mechanism study showed that PL impaired EGF-induced activation of ERK1/2 and Akt signalings, which resulted in a reduction of c-Fos transcription. Furthermore, PL reduced the half-life of c-Fos and caused the ubiquitination-dependent degradation of c-Fos. Finally, the in vivo antitumor effect of PL on CRC cells was examined using a xenograft mouse model.Conclusion: Our data indicate that PL is a promising antitumor agent that deserves further study for CRC treatment.Keywords: colorectal cancer, piperlongumine, c-Fos, Cyclin D1

This study was aimed to explore the effect of Rubimaillin on the survival, migration, and invasion of prostate cancer cell lines DU145 and PC3, and its mechanism. CCK-8 method was used to detect the effects of different concentrations of rubs (0, 5, 10, 20, 40 and 80 μM) on the activity of DU145 cells and PC3 cells. Transwell cell lab test was used to detect the migration and invasion of cells. Western blot was used to detect Notch-1, MMP-2, MMP-9 and Hes-1 protein levels. The CCK-8 assay showed that Rub inhibited the activity of Du145 and PC3 cells in a concentration dependent manner. When the concentration reached 40 μM, the inhibition reached the maximum. After Rub intervention, the migration and invasion ability of Du145 and PC3 cells decreased significantly, while the expression levels of Notch-1, MMP-2, MMP-9 and Hes-1 protein decreased significantly. Rub can inhibit the growth, migration and invasion of prostate cancer cell line DU145 and PC3. The mechanism may be related to the inhibition of Notch-1, MMP-2, MMP-9 and Hes-1 by Rub.

Background: Overexpression of survivin plays a crucial role in the maintaining unlimited cell growth, apoptosis suppression, and correlates with poor prognosis in human malignancies. Methods: A natural product library was used for natural compound screening through MTS assay. The expression of survivin in oral squamous cell carcinoma (OSCC) and the inhibitory effect of xanthohumol (XN) on OSCC were examined through methods of anchorage-dependent and -independent growth assays, immunoblot, immunofluorescence, immunohistochemical staining, ubiquitination analysis, co-immunoprecipitation assay, CRISPR-Cas9-based gene knockout, and xenograft experiment. Results: Survivin is highly expressed in OSCC cells and patient-derived tissues, and required for OSCC cell growth in vitro and in vivo . With a natural compound screening, we identified that xanthohumol exhibited a significant anti-tumor effect against OSCC cells through inhibiting survivin protein. Xanthohumol suppressed anchorage-dependent and independent cell growth and delayed in vivo tumor development of OSCC cells. Xanthohumol inhibited the Akt-Wee1-CDK1 signaling, which in turn decreased survivin phosphorylation on Thr34, and facilitated E3 ligase Fbxl7-mediated survivin ubiquitination. Xanthohumol alone or in combination with radiation overcame radioresistance in OSCC xenograft tumors. Conclusion: Our findings indicate that targeting survivin for degradation might a promising strategy for OSCC treatment. Keywords: Oral squamous cell carcinoma; Xanthohumol; Ubiquitination; Fbxl7

Submarine pipeline was widely used to transport oil and gas in offshore petroleum exploitation. In practice, deep-water pipeline experiences several times of maintenance every year. This periodic o...

Feng Gao,1,2,* Ming Li,1,3,4,* Wenbin Liu,5 Wei Li2,6 1Cell Transplantation and Gene Therapy Institute, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, People’s Republic of China; 2Department of Ultrasonography, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, People’s Republic of China; 3School of Stomatology, Hunan University of Chinese Medicine, Changsha, Hunan 410208, People’s Republic of China; 4Changsha Stomatological Hospital, Hunan University of Chinese Medicine, Changsha, Hunan, 410004, People’s Republic of China; 5Department of Pathology, The Affiliated Hunan Cancer Hospital of Central South University, Changsha, Hunan 410013, People’s Republic of China; 6Department of Radiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Li Tel +86 731-88618643Email weililx@csu.edu.cnBackground: Deregulation of epidermal growth factor receptor (EGFR) signaling plays a critical role in non-small cell lung cancer (NSCLC) tumorigenesis. The natural product Tanshinone IIA (Tan IIA) exhibits significant anti-tumor effect in various human cancers, however, the mechanism remains elusive.Methods: The inhibitory effect of Tan IIA NSCLC cells was determined by MTS and soft agar assays. The activation of EGFR signaling and the protein level of myeloid cell leukemia 1 (Mcl-1) were examined by immunoblot (IB), immunohistochemical staining (IHC), and ubiquitination analysis. The in vivo anti-tumor effect was validated by the xenograft mouse model.Results: Tan IIA inhibits NSCLC cells through suppression of EGFR signaling. Tan IIA decreases cell viability and colony formation in EGFR wild type and activating mutant cell lines. The IB data further confirmed that Tan IIA suppresses EGFR phosphorylation time- and dose-dependently. Tan IIA destabilizes Mcl-1 and shortens the half-life. Ubiquitination analysis showed that treatment with Tan IIA promotes Mcl-1 ubiquitination and degradation. Further study showed that the downregulation of EGFR-Akt signaling is required for Tan IIA-induced Mcl-1 reduction. Ectopic overexpression of constitutively activated Akt1 compromised these antitumor efficacies in Tan IIA-treated NSCLC cells. Finally, Tan IIA inhibited the in vivo tumor growth.Conclusion: Our data indicate that Tan IIA acts as an EGFR signaling inhibitor, and targeting EGFR-Akt-Mcl1 axis could provide a new option for NSCLC treatment.Keywords: non-small cell lung cancer, Tanshinone IIA, epidermal growth factor receptor, Mcl-1, ubiquitination

Background Addiction to aerobic glycolysis is a common metabolic phenotype in human non-small cell lung cancer (NSCLC). The natural product Sinomenine (Sin) exhibits significant anti-tumor effects in various human cancers. However, the underlying mechanism remains elusive. Methods The inhibitory effect of Sin on NSCLC cells was determined by MTS and soft agar assays. The glycolysis efficacy of NSCLC cells was examined by glucose uptake and lactate production. The activation of Akt signaling and the protein level of hexokinases II (HK2) were examined by immunoblot (IB), qRT-PCR, and immunohistochemical staining (IHC). The in vivo anti-tumor effect of Sin was validated by the xenograft mouse model. Results We showed that HK2 is highly expressed in NSCLC tissues and cell lines. Depletion of HK2 suppressed cell viability, anchorage-independent colony formation, and xenograft tumor growth. Sinomenine exhibited a profound inhibitory effect on NSCLC cells by reducing HK2-mediated glycolysis both in vitro and in vivo. Ectopic overexpression of HK2 compromised these anti-tumor efficacies in sinomenine-treated NSCLC cells. Moreover, we revealed that sinomenine decreased Akt activity, which caused the down-regulation of HK2-mediated glycolysis. Knockdown of Akt reduced HK2 protein level and impaired glycolysis. In contrast, overexpression of constitutively activated Akt1 reversed this phenotype. Conclusion This study suggests that targeting HK2-mediated aerobic glycolysis is required for sinomenine-mediated anti-tumor activity.

Tyrosinase is the key enzyme in melanin biosynthesis and inherently involves both monophenolase activity and diphenolase activity. A continuous fluorometric assay method was developed for the first time to directly monitor the real monophenolase activity without the interference of diphenolase reactions through exclusively quenching the native fluorescence of DOPA by borate. Complexation with borate at pH 8.0 allowed for selective quantitation of tyrosine in a binary mixture of tyrosine and DOPA at 335 nm. The time course for consumption of tyrosine was established to measure the initial velocity by recording the tyrosine fluorescence intensity at discrete intervals. The assay worked in the monophenolase activity range from 0.13 to 2.01 U mL-1 with the limit of detection (LOD) of 0.10 U mL-1. The assay method exhibited a promising prospect in application in kinetics of monophenolase and high throughput screening for monophenolase inhibitors.

Chitin-derived hydrogels are commonly used in bone regeneration because of their high cell compatibility; however, their poor mechanical properties and little knowledge of the interaction between the materials and host cells have limited their practical application. Methods: To evaluate osteoinductivity and enhance the mechanical properties of a newly synthesized thermosensitive hydroxypropyl chitin hydrogel (HPCH), a mesenchymal stem cell (MSC)-encapsulated HPCH was infused into a three-dimensional-printed poly (e-caprolactone) (PCL)/ nano-hydroxyapatite (nHA) scaffold to form a hybrid scaffold. The mechanical properties and cell compatibility of the scaffold were tested. The interaction between macrophages and scaffold for angiogenesis and osteogenesis were explored in vitro and in vivo. Results: The hybrid scaffold showed improved mechanical properties and high cell viability. When MSCs were encapsulated in HPCH, osteo-differentiation was promoted properly via endochondral ossification. The co-culture experiments showed that the hybrid scaffold facilitated growth factor secretion from macrophages, thus promoting vascularization and osteoinduction. The Transwell culture proved that MSCs modulated the inflammatory response of HPCH. Additionally, subcutaneous implantation of MSC-encapsulated HPCH confirmed M2 activation. In situ evaluation of calvarial defects confirmed that the repair was optimal in the MSC-loaded HPCH + PCL/nHA group. Conclusions: PCL/nHA + HPCH hybrid scaffolds effectively promoted vascularization and osteoinduction via osteogenesis promotion and immunomodulation, which suggests promising applications for bone regeneration.

Recent developments in controlled C–H functionalization transformations continue to inspire new retrosynthetic disconnections. One tactic in C–H functionalization is the intermolecular C–H insertion reaction of rhodium bound carbenes. These intermediates can undergo highly selective transformations through the modulation of the ligand framework of the rhodium catalyst. This work describes our continued efforts towards differentiating C–H bonds in the same molecule by judicious catalyst choice. Substituted cyclobutanes which exist as a mixture of interconverting conformers and possess neighboring C–H bonds within a highly strained framework are the targets herein for challenging the current suite of catalysts. While most C–H functionalization tactics focus on generating 1,2-disubstituted cyclobutanes via substrate-controlled directing group methods, the regiodivergent methods in this paper provide access to chiral 1,1-disubstituted and cis -1,3-disubstituted cyclobutanes simply by changing the catalyst identity, thus permitting entry to novel chemical space.

In this study, ultrafine and uniform cuprous oxide (Cu2O) nanocubes with different sizes and rough surfaces were prepared via a seed-mediated process. The Cu2O nanocubes were formed by the self-assembly of the subsequently generated Cu2O crystallites on the surface of the introduced seed medium. The obtained samples were used for non-enzymatic glucose detection and exhibited good capabilities. The Cu2O nanocubes obtained from a beaker 3 modified electrode showed the best performance, such as high sensitivity (3213 μA mM−1 cm−2), low limit of detection (LOD, 0.14 μM), acceptable linear range (0.05 to 5.15 mM) and fast electrocatalytic response (

Ubiquitous occurrences of phthalic acid esters (PAEs) or phthalates in a variety of consumer products have been demonstrated. Nevertheless, studies on their occurrence in various types of bottled drinks are limited. In this study, fifteen PAEs were analyzed in six categories of bottled drinks (n = 105) collected from the Chinese market, including mineral water, tea drinks, energy drinks, juice drinks, soft drinks, and beer. Among the 15 PAEs measured, DEHP was the most abundant phthalate with concentrations ranging from below the limit of quantification (LOQ) to 41,000 ng/L at a detection rate (DR) of 96%, followed by DIBP (DR: 88%) and DBP (DR: 84%) with respective concentration ranges of below LOQ to 16,000 and to 4900 ng/L. At least one PAE was detected in each drink sample, and the sum concentrations of 15 PAEs ranged from 770 to 48,004 ng/L (median: 6286 ng/L). Significant differences with respect to both PAE concentrations and composition profiles were observed between different types of bottled drinks. The median sum concentration of 15 PAEs in soft drinks was over five times higher than that detected in mineral water, different from other drink types. Besides DEHP, DBIP, and DBP, a high concentration of BMEP was also detected in a tea drink. The estimated daily dietary intake of phthalates (EDIdrink) through the consumption of bottled drinks was calculated based on the concentrations measured and the daily ingestion rates of bottled drink items. The EDIdrink values for DMP, DEP, DIBP, DBP, BMEP, DAP, BEEP, BBP, DCP, DHP, BMPP, BBEP, DEHP, DOP, and DNP through the consumption of bottled mineral water (based on mean concentrations) were 0.45, 0.33, 12.5, 3.67, 2.10, 0.06, 0.32, 0.16, 0.10, 0.09, 0.05, 0.81, 112, 0.13, and 0.20 ng/kg-bw/d, respectively, for Chinese adults. Overall, the EDIdrink values calculated for phthalates through the consumption of bottled drinks were below the oral reference doses suggested by the United States Environmental Protection Agency (U.S. EPA).

A gas chromatography-mass spectrometry (GC/MS) method for the determination of hexabromocyclododecane (HBCD) in expanded polystyrene and extruded polystyrene foam (EPS/XPS) was developed. The EPS/XPS samples were ultrasonically extracted with acetone and the extracts were purified by filtration through a microporous membrane (0.22 μm) and solid-phase extraction. The samples were analyzed using a GC/MS using the selected ion monitoring mode. The ions 157, 319 and 401 were selected as the qualitative ions, while ion 239 was chosen as the quantitative ion. An HBCD standard working solution with a concentration range of 1.0–50.0 mg/L showed good linearity. The detection limit of HBCD was 0.5 mg/kg, meeting the LPC limit (

Immune thrombocytopenia (ITP) was defined using the International Consensus Guidelines as a platelet count

Aberrant sterol lipid metabolism is associated with physiological dysfunctions in the aging brain and aging-dependent disorders such as neurodegenerative diseases. There is an unmet demand to comprehensively profile sterol lipids spatially and temporally in different brain regions during aging. Here, we develop an ion mobility-mass spectrometry based four-dimensional sterolomics technology leveraged by a machine learning-empowered high-coverage library (>2000 sterol lipids) for accurate identification. We apply this four-dimensional technology to profile the spatially resolved landscapes of sterol lipids in ten functional regions of the mouse brain, and quantitatively uncover ~200 sterol lipids uniquely distributed in specific regions with concentrations spanning up to 8 orders of magnitude. Further spatial analysis pinpoints age-associated differences in region-specific sterol lipid metabolism, revealing changes in the numbers of altered sterol lipids, concentration variations, and age-dependent coregulation networks. These findings will contribute to our understanding of abnormal sterol lipid metabolism and its role in brain diseases., Sterol lipids are crucial for maintaining proper brain function. Here, the authors combine ion mobility-mass spectrometry and machine learning to assemble a sterol lipid library and characterize differences in sterol lipids across ten brain regions and two age groups in mice.

The periosteum is rich in vascular networks, osteoprogenitor cells, and stem cells and plays an important role in bone defect repair. However, existing artificial periosteum materials still have difficulty in meeting clinical requirements, such as good mechanical properties and bionic structure construction, osteogenic differentiation, and vascularization capabilities. Here, a poly-e-caprolactone (PCL)/whitlockite (WH, 5, 10, 15 wt %) artificial periosteum with different doping amounts was prepared by electrospinning technology. According to the results of in vitro mineralization experiments, the rapid ion release from WH promotes the deposition of mineralized hydroxyapatite. Inductively coupled plasma-optical emission spectroscopy, in vitro angiogenesis, and cell migration experiments showed that the bionic periosteum of the 15% WH group had the best release rate of Mg2+ and the best ability to promote the human umbilical vein endothelial cell angiogenesis and migration. In addition, this group promoted collagen formation and calcium deposition. Finally, the subcutaneous implantation model was used to verify the biocompatibility and angiogenesis ability of the proposed membrane in vivo. Overall, this biomimetic PCL/WH nanofiber membrane combines the positive osteogenic differentiation ability and angiogenic ability of calcium phosphate materials and thus has good application prospects in the field of periosteal repair in the future.

Microbial secondary metabolites are one of the main sources of bioactive natural products. It is estimated that around 75% of all antibiotics are derived from secondary metabolites produced by filamentous actinomycete. Gordonia sp. are members of the actinomycete family, their contribution to the environment improvement and environmental protection by their biological degradation ability, but there are few studies on the antimicrobial activity of their secondary metabolites. Our team isolated a Gordonia strain WA 4–31 with anti-Candida albicans activity from the intestinal tract of Periplaneta americana in the early stage. In this study, we firstly identified the strain WA 4–31 by the morphological characteristics and the phylogenetic analyses, and found that it homologous to a strain of Gordonia from the Indian desert by 100%. Then four compounds, Actinomycin D (1), Actinomycin X2 (2), Mojavensin A (3) and cyclic (leucine-leucne) dipeptide (4) were purified from the ethyl acetate extract of the fermented broth of the strain. The compounds 1–4 had activities against Candida albicans, Aspergillus niger, Aspergillus fumigatus and Trichophyton rubrum. They also had activities against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli.coli in different degree. Interestingly, we found that when Mojavensin A was mixed with compound 4 ratio of 1:1, the activity of the mixture on anti-Candida albicans was better than the single. Besides, compounds 1–3 had varying degrees of antiproliferative activity on CNE-2 cells and HepG-2 cells. These indicated that Gordonia rare actinomycete from the intestinal tract of Periplaneta americana possessed a potential as a source of active secondary metabolites.

Removal of uranium from groundwater is of great significance as compared to in situ bioimmobilization technology. In this study, a novel direct electro-reductive method has been developed to efficiently remove and recover uranium from carbonate-containing groundwater, where U(VI)O

Adsorbents from sustainable precursors are highly desirable for practical applications. In this study, carboxymethyl cellulose (CMC) and humic acid (HA) were adopted to fabricate a composite immobilized on precipitates of calcium hydroxide (PCH) and ferric hydroxide (PFH). The as-obtained adsorbent, denoted as HA-CMC/PMH (PCH and PFH were referred to as PMH), was analyzed by infrared spectroscopy, scanning electron microscopy, X-ray photoelectron spectroscopy and thermo gravimetric analysis. When applying for a typical organic pollutant of methylene blue (MB) removal from aqueous solution, a high adsorption capacity of 666.67 mg/g was achieved over HA-CMC/PMH. The adsorption mechanisms of MB involved ion exchanging and π–π interactions, this adsorption process mainly occurred on both anionic and aromatic groups. Adsorption behavior analysis indicated that Langmuir isotherm model and pseudo-second order kinetic model fitted experimental data well, suggesting a mono-layer adsorption of MB onto the adsorbent. Further thermodynamic analysis proved that the adsorption of MB onto HA-CMC/PMH was an exothermal spontaneous process. The developed adsorbent is also reusable with 79.93% of adsorption capacity remaining in the fifth recycle runs. Therefore, the adsorbent of HA-CMC/PMH is suggested to be a promising candidate for adsorption applications.

For the low-concentration oily micro-polluted water formed by the leakage of refined oil products, an unexpensive and high-efficiency magnetic enhanced flocculation method was introduced in this study. First, the performance of magnetic flocculation(MF) to remove oily contaminants was discussed. The results indicated that it achieved more than 95% removal in only 1min with 50mg/L-Polyaluminum chloride(PAC), 50mg/L-Fe3O4 and10mg/L- Polyacrylamide (PAM). The novel indexs Rδand Si were proposed to evaluate the oil removal with UV-Abs in-situ method. According to the adsorption kinetics of oil contaminants, the adsorption kinetics changed from pseudo-first-order to pseudo-second-order kinetics after the addition of Fe3O4 on the basis of conventional coagulation (CF). It was transformed into intraparticle diffusion kinetics when the PAM continued to be added. Combined with the Fe-O-Al bond in the FTIR spectrum of flocs, the main mechanism of MF is enhanced charge neutralization and hydrogen bond adsorption. In addition, it was shown that satisfactory oil removal after recover, which indicated the great potential of a sustainable way by reusing low-cost magnetic seeds.

Background Prevention of epithelial-mesenchymal transition (EMT) provides a novel treatment strategy for tumor metastasis. Our previous studies have shown that diallyl disulfide (DADS) inhibits Ras related C3 botulinum toxin substrate1 (Rac1) expression, being a potential agent that suppresses migration and invasion of colon cancer cells. The study provides information on the underlying mechanisms. Methods The expression of Rac1 and EMT markers (vimentin, N-cadherin and E-cadherin) in colon cancer samples was detected. Colon cancer cell lines treated with or without DADS were used to examine EMT markers, Rac1 and its related molecules. Various cell functions related to metastasis were performed in vitro, and further confirmed in vivo. Results Rac1 was highly expressed in colon cancer, and associated with aberrant expression of EMT markers and poor prognosis. Rac1 overexpression induced cell migration and invasion in vitro and metastasis in vivo with down-regulation of E-cadherin and up-regulation of N-cadherin, vimentin, and snail1, whereas inhibition of Rac1 impaired the oncogenic function. DADS suppressed Rac1 expression and activity via inhibition of PI3K/Akt pathway, thus suppressing EMT and invasion and migration of colon cancer cells. The tumor inhibition of DADS was enhanced by knockdown of Rac1, but antagonized by overexpression of Rac1. We further found that DADS blocked EMT via targeting the Rac1-mediated PAK1-LIMK1-Cofilins signaling. Conclusion Rac1 is a potential target molecule for the inhibitory effect of DADS on EMT and invasion and metastasis of colon cancer cells.

A kind of porous carbon with low cost and abundance in nature derived from loofah sponge (LS) was prepared and applied as three-dimensional (3D) conductive network to support flower-like CoO for lithium-ion batteries' (LIBs) anode. LS, as a natural biomass, was rich in nitrogen source and also had abundantly porous structures. Therefore, the formation of porous LS carbon (LSC) with excellent electrical conductivity and high specific areas made it possible to replace relative expensive graphene or carbon nanotubes. When it was used as the supporting matrix to load the flower-like CoO, 3D conductive carbon network and porous structure could not only improve the electron transport and area of contact with the electrolyte, but also buffer general problem of cracking or pulverization caused by the volume stress of CoO. Finally, the obtained flower-like CoO/LSC nanocomposites exhibited a high capacity of 781 mAh g−1 at 200 mA g−1 after 150 discharging/charging cycles and an outstanding rate capability, which was far better than that of pure LSC, CoO and commercial graphite. The good performance showed that LS might be used widely in LIBs as an effective supporting conductive carbon material due to its accessibility and low cost. It also provided a thinking approach to make good use of many natural resources for energy storage.