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1.
Eur J Med Chem ; 183: 111731, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31577977

RESUMO

With the expectation to find out new anti-gastric cancer agents with high efficacy and selectivity, a series of novel tertiary sulfonamide derivatives were synthesized and the anti-cancer activity was studied in three selected cancer cell lines (MGC-803, PC-3, MCF-7) in vitro. Some of the synthesized compounds could significantly inhibit the proliferation of these tested cancer cells and were more potent than the positive control (5-Fu). The structure-activity relationship of tertiary sulfonamide derivatives was explored in this report. Among the tested compounds, compound 13g containing benzimidazole moiety showed the best anti-proliferation activities against MGC-803 cells (IC50 = 1.02 µM), HGC-27 cells (IC50 = 1.61 µM), SGC-7901 (IC50 = 2.30 µM) cells as well as the good selectivity between the cancer and normal cells. Cellular mechanism studies elucidated compound 13g inhibited the colony formation of gastric cancer cell lines. Meanwhile, compound 13g arrested cell cycle at G2/M phase and induced cell apoptosis. Mechanistically, compound 13g markedly decreased p-Akt and p-c-Raf expression, which revealed that compound 13g targeted gastric cancer cell lines via interfering with AKT/mTOR and RAS/Raf/MEK/ERK pathways. All the findings suggest that compound 13g might be a valuable lead compound for the anti-gastric cancer agents.

2.
PLoS One ; 14(9): e0222091, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31509561

RESUMO

Quantitative analysis of the contribution rate of China's hydraulic science and technology and analysis of the underlying reasons behind changes provide an important foundation upon which the government can formulate water policies. This paper abandons the assumption of a scale economy and separates the changes of benefits brought about by the scale from scientific and technological progress, thus changing the C-D production function from linear to nonlinear. Based on a feedforward neural network, it calculates the coefficient of the output elasticity, the economic contribution rate of China's hydraulic science and technology and the scale economies for each year using relevant data from 1981 to 2016. The results show that (1) the average contribution rate of capital investment from 1981 to 2016 was 47.3%, and the average contribution rate of labor from 1981 to 2016 was 9.1%. It is not obvious that the significant increase in the labor force has contributed to the growth of China's water conservancy industry. (2) The average contribution rate of scale economies in 1981-2016 was 26.7%, and the contribution rate of scale economies is negatively correlated with the capital contribution rate. (3) The average contribution rate of China's hydraulic science and technology was 43.6% from 1981 to 2016, and the average contribution rate of the total factor productivity after removing scale economies from 1981 to 2016 was 16.9%. During the period of the 6th Five-Year Plan(1981~1985), the contribution rate of water conservancy science and technology was relatively high. Since that time, it has remained at 40%. In recent years, as water conservancy reforms in key areas have made positive progress, scientific and technological progress has increased the growth of water conservancy benefits annually.

3.
Nat Commun ; 10(1): 4244, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31534125

RESUMO

Sodium metal batteries have potentially high energy densities, but severe sodium-dendrite growth and side reactions prevent their practical applications, especially at high temperatures. Herein, we design an inorganic ionic conductor/gel polymer electrolyte composite, where uniformly cross-linked beta alumina nanowires are compactly coated by a poly(vinylidene fluoride-co-hexafluoropropylene)-based gel polymer electrolyte through their strong molecular interactions. These  beta alumina nanowires combined with the gel polymer layer create dense and homogeneous solid-liquid hybrid sodium-ion transportation channels through and along the nanowires, which promote uniform sodium deposition and formation of a stable and flat solid electrolyte interface on the sodium metal anode. Side reactions between the sodium metal and liquid electrolyte, as well as sodium dendrite formation, are successfully suppressed, especially at 60 °C. The sodium vanadium phosphate/sodium full cells with composite electrolyte exhibit 95.3% and 78.8% capacity retention after 1000 cycles at 1 C at 25 °C and 60 °C, respectively.

4.
Cancer Med ; 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31476109

RESUMO

BACKGROUND: Marital status has long been widely recognized as a determinant of cancer survival. However, only few analytical studies have been conducted on this issue considering heterogeneous factors. The aim of this study was to assess the effects of marital status on postoperative survival of patients with less differentiated (poor/anaplastic) hepatocellular carcinoma (HCC). METHODS: We retrospectively analyzed 1581 postoperative patients diagnosed with poor/anaplastic HCC from the Surveillance, Epidemiology, and End Results database between 2004 and 2015. Patients were classified into married, never married, divorced/separated and widowed groups. Kaplan-Meier analysis and multivariate Cox regression analysis were used to analyze the effects of marital status on HCC cause-specific survival (HCSS). RESULTS: Compared with married patients, there were no significant differences in HCSS for unmarried, never married, divorced/separated and widowed patients both in univariate (5-year HCSS: 36.0% vs 36.3%, 36.0% vs 32.4%, 36.0% vs 40.2%, 36.0% vs 36.3%, respectively, all P > .05) and multivariate analysis (all P > .05). Furthermore, in stratified analyses according to sex, age, and tumor size, compared with married patients, there were also no significant differences for never married, divorced/separated, and widowed patients both in univariate (all P > .05) and multivariate analysis (all P > .05). CONCLUSIONS: For patients with poor/anaplastic differentiated HCC treated with surgical resection, marital status has no prognostic role in survival.

5.
Sci Rep ; 9(1): 13303, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527770

RESUMO

Gyroviruses (GyVs) are small, single-stranded, circular DNA viruses in the genus Gyrovirus, which consists of the chicken anemia virus (CAV) prototype and nine other viral species. These different GyV species have been reported in chickens, humans, mice, and companion animals. To date, CAV has been identified in the feces of domestic cats, while the circulation of other GyV species in cats is currently unknown. In the present study, 197 fecal samples were collected from pet cats in northeast China, and samples were screened for different GyV species by PCR. Twelve GyV strains were identified from the feces of pet cats. These included 4 positive for CAV, 3 for HGyV/AGV2, 3 for GyV3 and 2 positive for GyV6. The complete genome sequences of the 12 cat-sourced GyV strains showed 93.9-99.7% nucleotide identities to the homologous reference GyV strains. Phylogenetic analyses based on the complete genomes, VP1, VP2 and VP3 genes showed the identical classification of GyV species with previous reports. Moreover, one and four unique amino acid substitutions were identified in the VP1 protein of the cat-sourced HGyV/AGV2 and GyV6 strains, respectively, and one substitution was also observed in the VP2 protein of one GyV6 strain identified in this study. In conclusion, our investigation demonstrates that the diverse GyV species were circulating in domestic cats, and provides the first molecular evidence for the circulation of HGyV/AGV2, GyV3 and GyV6 in domestic cats. These cat-origin GyVs possessed considerable genetic diversity. This study also raises the possibility that domestic cats, as reservoirs for gyroviruses, may inadvertently disseminate viruses to other species, e.g., humans and chickens.

6.
Anal Chem ; 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31529947

RESUMO

The nitrogen-containing imine or hydrazone linked covalent organic frameworks (COFs) are poorly luminescent due to the fluorescence quenching by nitrogen atoms in the linkages, even if highly luminescent units and linkers are employed. The fluorescence quenching pathway to prevent linkage-originated to mitigate the inherent limitations of the linkage is a promising method for luminescent COFs. The generation of N- by deprotonation of the N-H unit eliminates the electron transfer from N lone pair to COF (TpPa-1) and enhances the luminescence. In this work, TpPa-1 achieved turn-on luminescence response with good sensitivity and reproducibility toward triethylamine (TEA) vapor in the process of deprotonation. The fabricated detector offers a viable approach for sensing ppm-level TEA, which can remind people to take timely measures to reduce the environmental hazards caused by TEA. The fluorescent sensor TpPa-1@LE constructed by the products of TpPa-1 and TEA can quantitatively trace biomarker methylglyoxal (MGO) for diabetes mellitus diagnosis in serum system. Furthermore, using TEA and MGO as input signals and the two fluorescence emissions G476 and Y525 as output signals, an advanced analytical device based on two Boolean logic gates with INH and AND function is constructed. This work provides a new strategy for improving the weak luminescence of COF in aqueous solution and realizes selective response to biomarker (MGO) for diabetes mellitus diagnosis.

7.
Biomed Pharmacother ; 118: 109407, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545290

RESUMO

The purpose of this study was to observe the functions of preconditioning with endoplasmic reticulum stress (ERS) whether alleviated heart ischemia/reperfusion injury (HI/RI) via modulating IRE1/ATF6/RACK1/PERK and PGC-1α expressions in diabetes mellitus (DM) or not. Diabetic rats were pretreated with 0.6 mg/kg tunicamycin (TM, 0.6 mg/kg tunicamycin was administered via intraperitoneal injection 30 minutes prior to the I/R procedures), and then subjected to 45 minutes of ischemia and 3 hours of reperfusion. Blood and myocardial tissues were collected, myocardial pathological injuries were investigated, serum creatine kinase-MB (CK-MB) and cardiac troponin T (cTnT) levels were measured, left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), maximum rate of left ventricular pressure rise (+dp/dtmax) and maximum rate of left ventricular pressure drop (-dp/dtmax) were evaluated, reactive oxygen species (ROS) and caspase-3 levels were observed, ΔΨm level and ROS expression were measured, and activated transcript factor 6 (ATF6), receptor for activated C kinase 1 (RACK1), PRK-like ER kinase (PERK), glucose regulated protein 78 (GRP78) and peroxisome proliferator-activated receptor γ co-activator 1-α (PGC-1α) expressions were assessed. The TM ameliorated the pathological damages, reduced myocardial oxidative stress damages, restrained apoptosis, and upregulated the expressions of ATF6, RACK1, PERK, GRP78 and PGC-1α compared with those of the ischemia/reperfusion (I/R) group in DM. This study suggested the preconditioning with endoplasmic reticulum stress (TM) strategy that could enhance protection against HI/RI in DM in clinical myocardial diseases.

8.
Cells ; 8(10)2019 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-31546722

RESUMO

A brief episode of transient ischemia (TI) can confer cerebral ischemic tolerance against a subsequent severer TI under standard condition. The brain under obesity's conditions is more sensitive to ischemic injury. However, the impact of a brief episode of TI under obesity's conditions has not been fully addressed yet. Thus, the objective of this study was to determine the effect of a brief TI in the hippocampus of high-fat diet (HFD)-induced obese gerbils and related mechanisms. Gerbils were maintained on HFD or normal diet (ND) for 12 weeks and subjected to 2 min TI. HFD gerbils were heavier, with higher blood glucose, serum total cholesterol, triglycerides, and leptin levels. Massive loss of pyramidal neurons occurred in the hippocampal cornu ammonis 1 (CA1) field of HFD animals at 5 days after 2 min of TI, but 2 min of TI did not elicit death of pyramidal neurons in ND gerbils. The HFD group showed significantly increased levels of oxidative stress indicators (dihydroethidium and 4-hydroxynonenal) and proinflammatory cytokines (tumor necrosis factor-α and interleukin-1ß) and microglial activation in pre- and/or post-ischemic phases compared to the ND group. Levels of mammalian target of rapamycin (mTOR) and phosphorylated-mTOR in the CA1 field of the HFD group were also significantly higher than the ND group. On the other hand, inhibition of mTOR activation by rapamycin (an allosteric mTOR inhibitor) significantly attenuated neuronal death induced by HFD, showing reduction of HFD-induced increases of oxidative stress indicators and proinflammatory cytokines, and microglia activation. Taken together, a brief episode of TI can evoke neuronal death under obesity's conditions. It might be closely associated with an abnormal increase of mTOR activation-mediated, severe oxidative stress and neuroinflammation in pre- and/or post-ischemic phases.

9.
Mol Brain ; 12(1): 76, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31484535

RESUMO

Central sensitization plays a pivotal role in the maintenance of chronic pain induced by chronic pancreatitis (CP), but cortical modulation of painful CP remains elusive. This study was designed to examine the role of anterior insular cortex (aIC) in the pathogenesis of hyperalgesia in a rat model of CP. CP was induced by intraductal administration of trinitrobenzene sulfonic acid (TNBS). Abdomen hyperalgesia and anxiety were assessed by von Frey filament and open field tests, respectively. Two weeks after surgery, the activation of aIC was indicated by FOS immunohistochemical staining and electrophysiological recordings. Expressions of VGluT1, NMDAR subunit NR2B and AMPAR subunit GluR1 were analyzed by immunoblottings. The regulatory roles of aIC in hyperalgesia and pain-related anxiety were detected via pharmacological approach and chemogenetics in CP rats. Our results showed that TNBS treatment resulted in long-term hyperalgesia and anxiety-like behavior in rats. CP rats exhibited increased FOS expression and potentiated excitatory synaptic transmission within aIC. CP rats also showed up-regulated expression of VGluT1, and increased membrane trafficking and phosphorylation of NR2B and GluR1 within aIC. Blocking excitatory synaptic transmission significantly attenuated abdomen mechanical hyperalgesia. Specifically inhibiting the excitability of insular pyramidal cells reduced both abdomen hyperalgesia and pain-related anxiety. In conclusion, our findings emphasize a key role for aIC in hyperalgesia and anxiety of painful CP, providing a novel insight into cortical modulation of painful CP and shedding light on aIC as a potential target for neuromodulation interventions in the treatment of CP.

10.
ACS Appl Mater Interfaces ; 11(40): 37357-37364, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31532614

RESUMO

Li4Ti5O12 (LTO) as the anode of lithium (Li) ion batteries has high interfacial side reactivity with the electrolyte, which leads to severe gassing behavior and poor cycling stability. Herein, the capacity loss mechanism of the high-tap density LTO microsphere anode under different temperatures (25, 45, and 60 °C) and charge/discharge rates (1 and 5 C) is systematically investigated. The capacity retentions of the LTO/Li cell after 500 cycles at 1 C are 95.6, 90.0, and 87.1% under three temperatures, which drop to 91.9, 58.3, and 20.9% when cycling at 5 C, respectively. Results show that the high temperature and rate almost do not damage the structure of LTO, but greatly affect the thickness and components of the solid electrolyte interface (SEI), and consequently reduce the performance of the LTO/Li cells. An SEI mainly consisting of inorganic species forms on LTO after 500 cycles at 1 C, while organic compounds are observed after 500 cycles at 5 C. The capacity of cycled LTO cannot recover again because of the thick SEI although using new Li metal anodes, separators, and electrolytes. This work demonstrates that it is of great significance for LTO to construct a stable SEI for achieving excellent cycling performance at a high rate and temperature.

11.
J Food Biochem ; 43(8): e12945, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31368575

RESUMO

α-l-Rhamnosidase is a biotechnologically important enzyme in food industry and in the preparation of drugs and drug precursors. To expand the functionality of our previously cloned α-l-rhamnosidase from Aspergillus niger JMU-TS528, 14 mutants were constructed based on the changes of the folding free energy (ΔΔG), predicted by the PoPMuSiC algorithm. Among them, six single-site mutants displayed higher thermal stability than wild type (WT). The combinational mutant K573V-E631F displayed even higher thermostability than six single-site mutants. The spectra analyses displayed that the WT and K573V-E631F had almost similar secondary and tertiary structure profiles. The simulated protein structure-based interaction analysis and molecular dynamics calculation were further implemented to assess the conformational preferences of the K573V-E631F. The improved thermostability of mutant K573V-E631F may be attributed to the introduction of new cation-π and hydrophobic interactions, and the overall improvement of the enzyme conformation. PRACTICAL APPLICATIONS: The stability of enzymes, particularly with regards to thermal stability remains a critical issue in industrial biotechnology and industrial processing generally tends to higher ambient temperature to inhibit microbial growth. Most of the α-l-rhamnosidases are usually active at temperature from 30 to 60°C, which are apt to denature at temperatures over 60°C. To expand the functionality of our previously cloned α-l-rhamnosidase from Aspergillus niger JMU-TS528, we used protein engineering methods to increase the thermal stability of the α-l-rhamnosidase. Practically, conducting reactions at high temperatures enhances the solubility of substrates and products, increases the reaction rate thus reducing the reaction time, and inhibits the growth of contaminating microorganisms. Thus, the improvement on the thermostability of α-l-rhamnosidase on the one hand can increase enzyme efficacy; on the other hand, the high ambient temperature would enhance the solubility of natural substrates of α-l-rhamnosidase, such as naringin, rutin, and hesperidin, which are poorly dissolved in water at room temperature. Protein thermal resistance is an important issue beyond its obvious industrial importance. The current study also helps in the structure-function relationship study of α-l-rhamnosidase.

12.
Chem Commun (Camb) ; 55(68): 10084-10087, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31380530

RESUMO

Pd-encapsulated porous carbon materials (Pd-PCMs) were prepared from the coupling polymerization of an aryl halide and aryl alkyne under mild conditions. Combining its porous microstructure and encapsulated Pd nanoparticles, Pd-PCMs with high sulfur loading reach a capacity of 920 mA h g-1 after 200 cycles at 0.3C.

13.
Ann Surg Oncol ; 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31407178

RESUMO

BACKGROUND: Routine performance of internal mammary sentinel lymph node biopsy (IM-SLNB) remains a subject of debate due to no clinical relevance in breast cancer, because it was performed only in clinically axillary lymph node (ALN)-negative patients. In this study, IM-SLNB was performed in clinically ALN-positive patients, and its impact on nodal staging and therapeutic strategy were subsequently analyzed. METHODS: Clinically ALN-positive patients who underwent IM-SLNB were enrolled in this prospective study. Statistical analysis was performed using Chi square test, Mann-Whitney U and logistic regression models with a significance level of 0.05. RESULTS: Among the 352 recruited patients, the internal mammary sentinel lymph node (IMSLN) visualization rate of patients who received initial surgery and neoadjuvant systemic therapy (NST) was 71.9% (123/171) and 33.1% (60/181), respectively. The 183 patients who underwent IM-SLNB successfully had the average time duration of 7 min and the median IMSLN number of 2. There were 87 positive IMSLNs in all the 347 removed IMSLNs, which were mainly concentrated in the second (50.6%) and third (34.5%) intercostal space. The IMSLN metastasis rate was 39.8% (initial surgery) and 13.3% (NST), respectively. All of the 183 IM-SLNB patients received more accurate nodal staging, 57 of whom had stage elevated, which might have prompted modifications to the therapeutic strategy. CONCLUSIONS: IM-SLNB should be routinely performed in clinically ALN-positive patients, and thus more accurate nodal staging and perfect pathologic complete response definition could be put forward. The identification of IMLN metastases by IM-SLNB might potentially influence therapeutic strategies.

14.
J Cell Biochem ; 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31407397

RESUMO

BACKGROUND: In this study, we established both an animal model and a cellular model of hyperuricemia (HUC). Subsequently, we treated these models with allopurinol (ALLO) to study the effect of uric acid (UA) and ALLO on the differentiation and proliferation of osteoblasts and vascular smooth muscle cells (VSMC). METHODS: Western Blot, immunohistochemistry assay, and real-time polymerase chain reaction were conducted to measure the changes in the expression of differentiation-related factors in osteoblasts and VSMCs in HUC and HUC+ALLO groups. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and flow cytometry were utilized to observe the changes in the proliferation of osteoblasts in HUC and HUC+ALLO groups. Von Kossa staining was performed along with calcium content measurement to investigate the effect of HUC/ALLLO on vascular calcification. RESULTS: In this study, the levels of Wnt3a and differentiation-related factors, including Runx2, Sp7, Ibsp, Bglap, Dmp1, and Col1a1, were all evidently decreased in HUC rats, while the presence of ALLO increased the levels of above factors. In addition, the viability of osteoblasts was reduced while their apoptosis was elevated in the HUC group, and ALLO treatment reduced the apoptosis and increased the viability of osteoblasts to a certain extent. Moreover, HUC elevated the levels of Wnt3a, Runx2, Sp7, Bglap, Col1a1, SM22a, and Acta2 in VSMCs of HUC rats, leading to greatly increased calcium content and obvious vascular calcification. In contrary, ALLO treatment reduced the effect of HUC. Furthermore, the effect of UA and ALLO on osteoblasts and VSMCs was also validated in cellular models treated with monosodium urate (MSU) crystals or MSU+ALLO. CONCLUSIONS: HUC can suppress the differentiation and proliferation of osteoblasts while promoting the differentiation of VSMCs both in vivo and in vitro. The treatment by ALLO exhibited a therapeutic effect on HUC by promoting the differentiation and proliferation of osteoblasts while reducing vascular calcification.

15.
Nat Commun ; 10(1): 3906, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31467269

RESUMO

Mycobacterium tuberculosis infection remains a major threat to human health worldwide. Drug treatments against tuberculosis (TB) induce expression of several mycobacterial proteins, including IniA, but its structure and function remain poorly understood. Here, we report the structures of Mycobacterium smegmatis IniA in both the nucleotide-free and GTP-bound states. The structures reveal that IniA folds as a bacterial dynamin-like protein (BDLP) with a canonical GTPase domain followed by two helix-bundles (HBs), named Neck and Trunk. The distal end of its Trunk domain exists as a lipid-interacting (LI) loop, which binds to negatively charged lipids for membrane attachment. IniA does not form detectable nucleotide-dependent dimers in solution. However, lipid tethering indicates nucleotide-independent association of IniA on the membrane. IniA also deforms membranes and exhibits GTP-hydrolyzing dependent membrane fission. These results confirm the membrane remodeling activity of BDLP and suggest that IniA mediates TB drug-resistance through fission activity to maintain plasma membrane integrity.

16.
World Neurosurg ; 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31465849

RESUMO

OBJECTIVE: To explore the risk factors of delayed facial paralysis (DFP) after microvascular decompression (MVD) for hemifacial spasm (HFS) METHODS: :A retrospective study was conducted on 636 patients who had undergone MVD for HFS by the same neurosurgery department of China-Japan Friendship Hospital from January 2006 to May 2016. Of all patients, 7.9% (50 of 636) presented DFP, which occurred from the 2nd day to the 60th day after operation, with an average of 12.9 days (SD = 10.0005). All of 50 patients with DFP recovered completely from 10 to 300 days after the onset of DFP, with an average of 88.7 days (SD = 61.389). We randomly selected 100 patients from 586 patients without DFP as the control group. Univariate and multivariate logistic analysis was used to analyze the risk factors involved in the occurrence of DFP RESULTS: : Univariate analysis showed that course of disease was the only factor associated with DFP (P = 0.003). Furthermore, in the multivariate logistic analysis,the course of HFS was the only risk factor associated with DFP (P = 0.01). Additionally, Spearman test revealed a positive correlation between the time of DFP onset and the duration of DFP symptoms (rs = 0.682, P < 0.001) CONCLUSION: Although DFP frequently occurred after MVD, it can recover spontaneously. The longer the course of HFS lasts, the more frequently DFP will occur after MVD. The earlier DFP occurs, the shorter it takes to recover. Hemifacial spasm (HFS) is characterized by involuntary paroxysmal convulsions of one side facial muscles. The main cause of HFS is vascular compression of the root exit zoon (REZ) of facial nerve. 1-3 Microvascular decompression (MVD) is the only effective method to cure HFS. Complications of MVD includes hearing impairment, facial paralysis, meningitis, intracranial hemorrhage, intracranial infection, and delayed facial paralysis (DFP). 4,5 DFP refers to the facial paralysis which occurs more than 24 hours after MVD,and it can generally recover spontaneously. 6 It is common in the clinical observation and its mechanism is still unclear.7-9 To study the risk factors of DFP after MVD for HFS is of great significance for exploring the mechanism of DFP and further understanding the intrinsic pathophysiological process of cranial nerve diseases.

17.
Bioorg Chem ; 92: 103190, 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31465969

RESUMO

A series of novel indoline derivatives were synthesized and evaluated for antiproliferative activity against four selected cancer cell lines (Hela, A549, HepG2 and KYSE30). Among them, compound 20 displayed the potent inhibition activity against esophageal cancer cells (Kyse30, Kyse450, Kyse510 and EC109). Cellular mechanism studies in esophageal squamous cell carcinoma (ESCC) cells elucidated compound 20 inhibited cell growths in vitro and in vivo, reduced colony formation, arrested cell cycle at M phase, and induced Noxa-dependent apoptosis in ESCC. Importantly, compound 20 was identified as a novel Noxa mediated apoptosis inducer. These results suggested that compound 20 might be a promising anticancer agent with potential for development of further clinical applications.

18.
J Am Chem Soc ; 141(36): 14043-14047, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31386352

RESUMO

Simultaneously monitoring label-free nanoparticles (NPs) and fluorescent biomolecules inside the live cell in real time is challenging because both imaging methods require different instrumentation and measuring principles. Here we report a novel scattered light imaging (SLi) technique that allows label-free NPs to be monitored using a conventional confocal microscope. The method shows a high spatial resolution and can distinguish label-free silver nanoparticles (AgNPs) with a 10 nm size difference in live cells. We performed SLi to observe the uptake, movement, distribution, and transformation of AgNPs in live cells at a single-particle level. The method is applicable to accurately track the localization of a variety of nanomaterials inside the cell. With this approach, label-free NP and fluorescent-labeled biomolecules are imaged simultaneously making it possible to real-time monitor nanobio interactions.

19.
Int J Mol Sci ; 20(16)2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31408956

RESUMO

This paper first reports on the selective separation of volatile fatty acids (VFAs) (acetic and hexanoic acids) using polymer inclusion membranes (PIMs) containing quaternary ammonium and phosphonium ionic liquids (ILs) as the carrier. The affecting parameters such as IL content, VFA concentration, and the initial pH of the feed solution as well as the type and concentration of the stripping solution were investigated. PIMs performed a much higher selective separation performance toward hexanoic acid. The optimal PIM composed of 60 wt% quaternary ammonium IL with the permeability coefficients for acetic and hexanoic acid of 0.72 and 4.38 µm s-1, respectively, was determined. The purity of hexanoic acid obtained in the stripping solution increased with an increase in the VFA concentration of the feed solution and decreasing HCl concentration of the stripping solution. The use of Na2CO3 as the stripping solution and the involvement of the electrodialysis process could dramatically enhance the transport efficiency of both VFAs, but the separation efficiency decreased sharply. Furthermore, a coordinating mechanism containing hydrogen bonding and ion exchange for VFA transport was demonstrated. The highest purity of hexanoic acid (89.3%) in the stripping solution demonstrated that this PIM technology has good prospects for the separation and recovery of VFAs from aqueous solutions.

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