We had the opportunity to investigate the bacterial population in air samples, condensation water, and inner wall swabs from the Russian space station Mir. From the first and second air samples ...during the mission, 29 and 7 bacterial colonies were collected, respectively. The values were equivalent to 16.8 and 4.0 cfu/100 liter air, respectively. Condensation water was collected from three different sites. The total viable bacterial counts were 2.1 × 106, 5.2 × 102, and 3.0 × 101 cfu/ml. The phylogenetic position of each isolate was determined by total 16S rDNA sequencing. Bacteria from air samples were mainly Gram‐positive (35/36 colonies), and staphylococci occupied dominant specifically (23/36 colonies). On the other hand, Gram‐negative bacteria were mainly isolated from condensation water samples. Most strains were thought to be opportunistic pathogens or environmental bacteria (such as those that inhabit soil, water, or air) found on earth. However, 6 of 23 isolates were suspected to be new species according to phylogenetic analysis and quantitative DNA‐DNA hybridization data. The isolation of the other levels 3 and 2 bacteria, using specific selective media, was unsuccessful because all samples were heavily contaminated with fungi. To overcome this situation, PCR methods were applied to survey most levels 3 and 2 pathogenic bacteria in the condensation water samples. Up to 380 different primers for bacterial pathogens were used in this study. Only Mycobacterium avium 16S DNA sequences, however, could be amplified from the three water samples. The average bacteria count was estimated to be about 104 organisms/ml water.
Two new inorganic–organic hybrid polyoxovanadates, Cu(2,2′-bipy)
3
2H
4V
16O
38(Cl)·4H
2O
1 and Cu(2,2′-bipy)
3
3V
15O
36(Cl)·3H
2O
2 (2,2′-bipy=2,2′-bipyridine), have been prepared under the ...hydrothermal conditions and structurally characterized by elemental analysis, IR spectra, EPR spectra, TG analyses and single-crystal X-ray diffraction. Compounds
1 and
2 are based on V
16O
38(Cl)
8− and V
15O
36(Cl)
6− building block, respectively. They were synthesized under the same reaction condition but in different pH range, which shows that the pH value of the reaction plays a key role in the structural control of self-assemble process.
Development of novel tumor-targeted drug vehicles for cancer therapy is very important and has become one of major topics for designing nanoscale chemotherapeutics delivery systems. In the present ...study, selenium nanoparticles (SeNPs) was decorated with hyaluronic acid (HA) to prepare HA-SeNPs nanoparticles which were used to load doxorubicin (DOX) to fabricate tumor-targeted functionalized selenium nanoparticles HA-Se@DOX. In vitro and in vivo antitumor activities of HA-Se@DOX in human cervical carcinoma treatment were investigated. HA-Se@DOX showed selective cellular uptakes between cervical cancer HeLa cells and human umbilical vein endothelial cells (HUVEC). In vitro release result indicated that DOX was released from HA-SeNPs faster in acidic environment in comparison with normal physiological environment and 76.9% DOX was released in pH 5.4 during initial 30 h. HA-Se@DOX showed high activity to inhibit HeLa cell proliferation and triggered HeLa cell apoptosis via activating Bcl-2 signaling pathway. In vivo antitumor study showed that HA-Se@DOX inhibited tumor growth through suppressing cancer cells proliferation and inducing cancer cells apoptosis. Interestingly, HA-Se@DOX exhibited stronger anticancer activity than free DOX and Se@DOX in vitro and in vivo. Additionally, HA-Se@DOX did not cause damage to major organs at the used dose. HA-Se@DOX is a promising antitumor agent for human cervical carcinoma treatment and this research provides a novel therapeutic strategy for cancer therapy.
•Novel functionalized nanoparticles HA-Se@DOX for delivery of doxorubicin with anticancer activity.•HA-Se@DOX efficiently deliver doxorubicin without cytotoxicity.•HA-Se@DOX shows selective cellular uptake between HeLa cervical carcinoma cells and human normal cells.•HA-Se@DOX exhibit great antitumor efficacy in HeLa cervical carcinoma tumor model.
自2019年12月底以来，湖北省武汉市陆续发现多例新型冠状病毒肺炎（简称：新冠肺炎，2019 novel coronavirus ...disease，COVID-19），并在全国范围内蔓延。随着新冠肺炎疫情的蔓延，肺癌患者的常规医疗受到影响。由于肺癌患者接受抗肿瘤治疗后免疫力低，合并感染后症状重，应是疫情防治的重点对象，肺癌患者对新冠肺炎的防范措施日益受到关注。复杂严峻的新冠肺炎疫情下，接受抗肿瘤治疗的肺癌患者如出现发热及呼吸道症状，更需要仔细地进行鉴别诊断，评估新冠肺炎感染的风险。对于肺癌患者，在新冠肺炎疫情期间，需要进行精细化和个体化的管理，最大程度地保护患者，有效防范新冠肺炎。 Since late December 2019, an outbreak of 2019 novel coronavirus disease (COVID-19) in Wuhan, China has spread quickly nationwide. With the spread of COVID-19, the routine clinical diagnosis and treatment for lung cancer patients has been disturbed. Due to the systemic immunosuppressive of lung cancer patients caused by the malignancy and anticancer treatments, lung cancer patients are more susceptible to infection than healthy individuals. Furthermore, patients with cancer had poorer prognosis from infection. Lung cancer patients should be the priority group for COVID-19 prevention. The protection provisions and control measures aiming to protect lung cancer patients from COVID-19 have been increasingly concerned. During
Congenital hyperinsulinism (CHI) is a severe heterogeneous disorder due to dysregulation of insulin secretion from the pancreatic β-cells leading to severe hypoglycemia in infancy. ...18-fluoro-l-3,4-dihydroxyphenylalanine positron emission tomography (18F‑DOPA‑PET)/CT is a useful tool in distinguishing between focal and diffuse disease preoperatively. But recent studies have suggested that the scanning may not be accurate as initially estimated. In this study we characterize a case of CHI with a compound heterozygous mutation of ABCC8 gene. The results of clinical investigation, gene mutation analysis, 18F‑DOPA‑PET/CT scan, and pathological examination showed some new characteristics that have never been reported. The patient was unresponsive to medical therapy with diazoxide and received pancreatectomy twice. Genetic analysis identified a compound heterozygous mutation in ABCC8 genes. Imaging with 18F‑DOPA‑PET/CT indicated a focal lesion in the head of the pancreas. The pathological diagnosis was an atypical form of CHI. The patient presented with a phenotype of atypical CHI unresponsive to diazoxide. It is considered that a relationship existed between the compound heterozygous mutation and the atypical form. 18F‑DOPA‑PET/CT is a useful tool in distinguishing between focal and diffuse forms preoperatively but the accuracy is not 100%. The scan result is best combined with genetic analysis and intra-operative biopsy to confirm the histological subtypes. The combination will provide the optimal strategy for the surgical treatment of patients with CHI.
•Our study finds a novel compound heterozygous mutation of ABCC8 gene.•The reported mutation of ABCC8 gene was linked to an atypical form of CHI.•18F‑DOPA‑PET/CT scan does not always tell the truth of histological subtypes of CHI.•Intra-operative biopsy is necessary for the surgical treatment of patients with CHI.
Cyclobentinib was designed and synthesized as a novel anti-CML agent, its in vitro activity against K562 cells was evaluated by MTT assay. CB1107 showed remarkable cytotoxicity against K562 cell line ...with an IC
50
of 0.037 ± 0.028 μmol/L, and thus it was 17-fold more potent than the reference drug Imatinib. Inducing cell apoptosis and affecting cell cycling of this compound in K562 cells were estimated by using flow cytometry and Acridine Orange/Ethidium Bromide (AO/EB) staining. The results showed that CB1107 was capable of arresting cell cycle at G0/G1 phase as well as inducing cell apoptosis significantly. Molecular mechanism of CB1107 was detected by the protein expression of Bcr-Abl
P210
using western blotting analysis. Downregulation of expression of Bcr-Abl
P210
was obviously revealed in the treatment of this tetralin amide compound. Of note, the results of these investigations suggested that CB1107 is more potent than the reference drug Imatinib against K562 cells. Additionally, in vivo results indicated that CB1107 significantly decreased tumor growth in K562 tumor-bearing Non-obese Diabetic/Severe Combined Immunodeficiency (NOD/SCID) mice. Histopathological investigation revealed that CB1107 without notable toxicity in a given dose range. These findings collectively demonstrate CB1107 is a promising candidate as a novel anti-CML agent.
In this paper we present an investigation of the energy performance of a mini trapezoidal solar pond (with surface of 2.4m×2.4m and depth of 1.5 m) which was built in Dalian, China. The pond was ...filled with salty water to form the upper convective zone (UCZ), the non-convective zone (UCZ), and the lower convective zone (LCZ). Energy efficiency, the ratio of available energy to the total energy, was defined basing on the first law of thermodynamics at each zone of the solar pond. The energy efficiency of the three layers were analyzed separately accounting to the simulation results of the temperature distribution in the trapezoidal solar pond. It shows that the energy efficiency of the solar pond is relatively high at the beginning of the operation, and the energy efficiency of the UCZ is the lowest while the LCZ is the highest.
Totarol is a plant-derived natural product and has been reported to exhibit important pharmacological activities. However, the anticancer activity of totarol has not been evaluated yet. Therefore, ...the present research work was designed to evaluate the antitumor effects of totarol in SGC-7901 human gastric cancer cells and human gastric epithelial mucosa cell line GES-1 (used as normal cell line model) together with examining its effects on induction of apoptosis, cell cycle phase distribution and cell migration.
The effect of totarol on cell cytotoxicity was evaluated by MTT cell viability assay. Inverted phase contrast microscopy was used to identify the effects on cell morphology, while transmission electron microscopy indicated the apoptosis-driven morphological changes in cancer cells. The effects on cell apoptosis were also evaluated by annexin V/PI staining, while cell cycle analysis was done by flow cytometry. In vitro wound healing assay estimated the effects of totarol on cell migration.
The results indicated that totarol induced selective cytotoxic effects in SGC-7901 human gastric cancer cells concentration-dependently and exhibited lower toxicity in GES-1 normal cells. The totarol-treated cells showed significant alterations in cell morphology including rounding and cellular shrinkage. Untreated SGC-7901 cells exhibited normal cellular morphology with undamaged plasma membrane. However, treating cells with totarol led to damaged plasma membrane along with appearance of rounded protrusions (apoptotic bodies) containing damaged and broken chromatin material. Treatment with different doses of totarol led to profound suppression of wound healing. Totarol treatment also led to G2/M phase cell cycle arrest in these cells in a concentration-dependent manner.
The present study indicated that totarol diterpene has the tendency to show selective anticancer effects in SGC-7901 human gastric cancer cells along with inducing apoptosis, cell cycle arrest and inhibition of cell migration.
Aqua‐coordinated sandwich‐type polyoxometalates (POMs), {WZnTM2(H2O)2(ZnW9O34)2}n− (TM=RhIII, PdII, and PtII), catalyze olefin epoxidation with hydrogen peroxide and have been well established, and ...they present an advance toward the utilization of olefins. To elucidate the epoxidation mechanism, we systematically performed density functional calculations. The reaction proceeds through a two‐step mechanism: activation of H2O2 and oxygen transfer. The aqua‐coordinated complexes show two distinct H2O2 activation pathways: “two‐step” and “concerted”. The concerted processes are more facile and proceed with similar and rate‐determining energy barriers at the Rh‐, Pd‐, and Pt‐containing transition states, which agrees well with the experimental results. Next, the resulting TM−OH−(μ‐OOH) intermediate transfers an O atom to olefin to form an epoxide. The higher reactivity of the Rh‐containing POM is attributed to more interactions between the Rh and hydroperoxo unit. We also calculated all active oxygen positions to locate the most favorable pathway. The higher reactivity of the two‐metal‐bonded oxygen position is predominantly ascribed to its lower stereoscopic hindrance. Furthermore, the presence of one and two explicit water solvent molecules significantly reduces the energy barriers, making these sandwich POMs very efficient for the olefin epoxidation with H2O2.
POM‐cats: The viability of the epoxidation mechanism of olefins catalyzed by aqua‐coordinated polyoxometalates (POMs) is investigated, and the roles of the substituted noble metal, active oxygen position, and solvent are analyzed. Computational analyses of the catalytic mechanism with larger POM systems, such as those reported in this study, remain a challenge for computational chemistry and will be very helpful to evaluate and improve epoxidation catalysts.
DHCR24
encodes 3β-hydroxysterol-Δ
24
-reductase (DHCR24) catalyzing the cholesterol synthesis from desmosterol using the flavin adenine dinucleotide (FAD) as a co-factor. It is generally accepted ...that U18666a inhibits the reductase activity of DHCR24, but the detailed mechanism remains elusive. To explore the mechanism of the inhibitory effect of U18666a on DHCR24, we performed molecular dynamics (MD) simulations of two complexes including complexes of DHCR24-FAD-desmosterol enzymatic reactive components with and without the inhibitor U18666a. We found that the U18666a bound into the hydrophobic package near the FAD package of DHCR24. Furthermore, binding free energy of DHCR24 and desmosterol without U18666a is −54.86 kcal/mol, while the system with U18666a is −62.23 kcal/mol, suggesting that the affinity of the substrate desmosterol to DHCR24 was increased in response to the U18666a. In addition, U18666a interacts with FAD by newly forming three hydrogen bonds with Lys292, Lys367, and Gly438 of DHCR24. Finally, secondary structural analysis data obtained from the surrounding hot spots showed that U18666a induced dramatic secondary structural changes around the key residues in the interaction of DHCR24, FAD, and desmosterol. Taken together, these results for the first time demonstrate at the molecular structure level that U18666a blocks DHCR24 activity through an allosteric inhibiting mechanism, which may provide new insight into the development of a new type of cholesterol-lowering drug targeting to block the activity of DHCR24.
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