聚偏氟乙烯-六氟丙烯纳米纤维膜3D微/纳米串珠构建及性能

文中以聚偏氟乙烯-六氟丙烯(PVDF-HFP)为成纤聚合物、SiO_(2)为无机添加剂,通过静电纺丝法与静电喷涂法制备了PVDF-HFP/(PVDF-HFP/SiO_(2))复合纳米纤维膜,并研究了SiO_(2)添加量和喷涂时间对其结构和性能的影响。结果发现,所得复合纳米纤维膜由下层PVDF-HFP纳米纤维和上层PVDF-HFP/SiO_(2)微/纳米串珠构成。当SiO_(2)质量分数为2%、喷涂时间为2 h时,所得膜的水接触角高达123°,具有优异的疏水性,呈现出优异的油水分离性能,分离通量可达9800 L/(m^(2)·h),分离效率大于99%。此外,所得膜循环使用10次后分离效率仍可达98%以上。

Expression of cyclooxygenase-2 and clinicopathologic features in human gastric adenocarcinoma

AIM: To study the expression of cyclooxygenase-2 (COX-2)gene in gastric cancer and the relationship between COX-2expression and clinicopathologic features of gastric cancer.METHODS: With reference to the expression of β-actin gene,COX-2 mRNA level was examined in cancerous tissues andadjacent noncancerous mucosa from 33 patients bysemiquantitative reverse transcription- polymerase chainreaction (RT-PCR). Quantitation of relative band Adj volumecounts was performed using molecular Analyst for windowssoftware. The COX-2 index was determined from the band Adjvolume counts ratio of COX-2 to constitutively expressed actin.RESULTS: The COX-2 index in gastric carcinoma wassignificantly higher than that in normal mucosa (0.5966±0.2659vs 0.2979+0.171, u=5.4309, P＜0.01). Significantly higherexpression of COX-2 mRNA was also observed in patientswith lymph node involvement than that in those without(0.6775±0.2486 vs 0.4105±0.2182, t=2.9341, P＜0.01).Furthermore, the staging in the UICC TNM classificationsignificantly correlated with COX-2 overexpression (F＝3.656,P＜0.05), the COX-2 index in stage Ⅲ and IV was significantlyhigher than those in stage Ⅰ and Ⅱ(q=3.2728 and q=3.4906, P＜0.05). The COX-2 index showed no correlationwith patient's age, sex, blood group, tumor location, grosstyping, depth of invasion, differentiation, and the greatesttumor dimension (P＞0.05).CONCLUSION: Expression of COX-2 mRNA in gastriccarcinoma was significantly higher, which may enhancelymphatic metastasis in patients with gastric carcinoma. Thestaging in the UICC TNM classification was significantlycorrelated with COX-2 over-expression. COX-2 may contributeto progression of tumor in human gastric adenocarcinoma.

Association between endogenous gene expression and growth regulation induced by TGF-β1 in human gastric cancer cells

AIM: To investigate the association between endogenous gene expression and growth regulation including proliferation and apoptosis induced by transforming growth factor-β1(TGF-β1) in human gastric cancer (GC) cells.METHODS: Reverse transcription polymerase chain reaction (RT-PCR) was performed to detect the main components of the TGF-β1/Smads signal pathway in human poorly differentiated GC cell line BGC-823. Localization of Smad proteins was also determined using immunofluorescence.Then, the BGC-823 cells were cultured in the presence or absence of TGF-β1 (10 ng/mL) for 24 and 48 h, and the effects of TGF-β1 on proliferation and apoptosis were measured by cell growth curve and flow cytometry (FCM)analysis. The ultrastructural features of BGC-823 cells with or without TGF-β1 treatment were observed under transmission electron microscope. The apoptotic cells were visualized by means of the terminal deoxynucleotidyl transferase (TdT)-mediated dTUPin situ nick end-labeling (TUNEL) method. Meanwhile, the expression levels of endogenous p15, p21 and Smad7 mRNA and the corresponding proteins in the cells were detected at 1, 2and 3 h after culture in the presence or absence of TGF-β1(10 ng/mL) by semi-quantitative RT-PCR and Western blot,respectively.RESULTS: The TGF-β1/Smad signaling was found to be intact and functional in BGC-823 cells. The growth curve revealed the most evident inhibition of cell proliferation by TGF-β1 at 48 h, and FCM assay showed G1 arrest accompanied with apoptosis induced by TGF-β1. The typical morphological changes of apoptosis were observed in cells exposed to TGF-β1. The apoptosis index (AI) in TGF-β1-treated cells was significantly higher than that in the untreated controls (10.7±1.3% vs 0.32±0.06%, P＜0.01).The levels of p15, p21 and Smad7mRNA and corresponding proteins in cells were significantly up-regulated at 1 h, but gradually returned to basal levels at 3 h following TGF-β1(10 ng/mL) treatment.CONCLUSION: TGF-β1 affects both proliferation and apoptosis of GC cells through the regulation of p15 and p21,and induces transient expression of Smad 7 as a negative feedback modulation of TGF-β1 signal. Our results suggest a novel functional role of p21 as an accelerant of TGF-β1-mediated apoptosis in GC cells.

Apoptosis of human gastric adenocarcinoma cells induced by β-ionone

AIM:To investigate the effect of β-ionone on the growth and apoptosis of gastric adenocarcinoma cell line SGC-7901.METHODS: Using M-IT, fluorescence dye (Hoechst-33258),transmission electron microscopy and the TUNEL assay,we examined growth and apoptosis of SGC-7901 cells treated with β-ionone at various concentrations (i.e. 25, 50, 100 and 200μmol/L) for 24h,48h.RESULTS:The growth of SGC-7901 cells was inhibited by β-ionone. Seven days after treatment with β-ionone at four concentrations, the inhibition rates were 12.04%, 30.59%,78.25% and 94.15%, respectively. The IC50 value of β-ionone for SGC-7901 cells was estimated to be 89μmol/L.The apoptotic morphology was demonstrated in SGC-7901 cells treated with β-ionone by Hoechst-33258 staining and electron microscopy. Apoptosis was also shown in β-iononetreated SGC-7901 cells by the TUNEL assay.CONCLUSION:β-ionone can inhibit cell proliferation and induce apoptosis of SGC-7901 cells.However, the mechanism needs to be further investigated.

Effects of cg,t11-conjugated linoleic acid on adhesion of human gastric carcinoma cell line SGC-7901

AIM: To investigate the effect of c9, t11-conjugated linoleic acid (c9,t11-CLA) on the adhesion of human gastric carcinoma cell line (SGC-7901).METHODS: SGC-7901 cells were at first treated with different concentrations (25, 50, 100, 200 μmol/L) of c9,t111-CLA and 1 mL/L ethanol (as a negative control) for 24 h.Using adhesion assay and Western blot, we investigated the ability of SGC-7901 cells to adhere to intracellular matrix and examined the expression of E-cadherin (ECD), α-catenin,intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in these cells.RESULTS: The attachment rate to laminin of SGC-7901 cells treated with different concentrations of c9,t11-CLA (0,25, 50, 100, and 200 μmol/L) was 100.0±3.3, 95.7±4.0,89.2±4.6, 87.9±6.1, and 65.9±5.8, respectively. The attachment rate to fibronectin was 100.0±4.7, 96.8±3.8,94.5±4.1, 76.5±4.3, and 61.8±4.8, respectively. The attachment rate to Matrigel was 99.9±6.6, 91.4±6.8,85.5±7.4, 79.3±5.6, and 69.6±5.1, respectively. Besides,c9,t11-CLA could increase the level of ECD and α-catenin,and decrease the level of ICAM-1 and VCAM-1 in SGC-7901 cells.CONCLUSION: c9, t11-CLA can reduce the adhesion of human gastric carcinoma cells to laminin, fibronectin and Matrigel. c9,t11-CLA can increase the level of ECD and α-catenin, and decrease the level of ICAM-1 and VCAM-1 in human gastric carcinoma cells.

Enhancement of oral bioavailability and anti-Parkinsonian efficacy of resveratrol through a nanocrystal formulation

Resveratrol(RES),a non-flavonoid polyphenol extracted from a wide variety of plants,exhibits neuroprotective activities against Parkinson’s disease(PD).However,undesirable water solubility of RES reduces its oral bioavailability and demonstrates lowefficacy in blood and brain,thus limiting its application.In present study,a nanocrystal formulation of RES(RES-NCs)was developed to enhance its oral bioavailability and delivery into brain for PD treatment.RES-NCs were fabricated with hydroxypropyl methylcellulose(HPMC)stabilizer via antisolvent precipitation approach.The obtained RES-NCs displayed the particle size of 222.54±1.66 nm,the PDI of 0.125±0.035,the zeta potential of−9.41±0.37mV,and a rapid in vitro dissolution rate.Molecular dynamics simulation of RES and HPMC revealed an interaction energy of−68.09 kJ/mol and a binding energy of−30.98±0.388 kJ/mol,indicating that the spontaneous binding between the two molecules is through van der Waals forces.RES-NCs conferred enhanced cellular uptake as well as improved permeability relative to pure RES.In addition,RES-NCs were able to protect neurons against cytotoxicity induced by MPP+.Meanwhile,RES-NCs exerted no significant toxic effects on zebrafish embryos and larvae,and did not influence their survival and hatching rates.When orally administered to rats,RES-NCs exhibited more favorable pharmacokinetics than pure RES,with higher plasma and brain concentrations.More importantly,MPTP-induced PD mice showed notable improvements in behavior,attenuated dopamine deficiency,and elevated levels of dopamine and its metabolites after the treatment with RES-NCs.Furthermore,immunoblot analysis revealed that the neuroprotective role of RES-NCsmay be at least partially mediated by Akt/Gsk3βsignaling pathway.Taken altogether,RES-NCs can serve as a potential treatment modality for PD,offering means of improving RES oral bioavailability and brain accumulation.

Effect of cornel iridoid glycoside on experimental autoimmune encephalomyelitis attenuation through JAK/STAT signaling pathway,at least partially

OBJECTIVE In order to investigate whether cornel iridoid glycoside(CIG),the main component extracted from Cornus officinalis,can treat demyelinating diseases of the central nervous system(CNS)such as multiple sclerosis(MS).METHODS CIG(30,60 and 120mg·kg-1)or vehicle was intragastrically administered once daily to rats,starting immediately after purified myelin basic protein(MBP)68-86 peptides immunization until day 20 post immunization(p.i.).Histopathological staining,enzyme-linked immunosorbent assay,biochemical methods and Western blotting approaches were used to evaluate the disease incidence and severity,neuroinflammatory and neurotrophic response in the CNS.RESULTS Neurological deficit and proportion of incidence seen in EAE rats were significantly reduced by CIG treatment in a dose-dependent manner.Histopathological staining showed that CIG treatment alleviated demyelination and inflammatory infiltration,increased the number of oligodendrocytes,enhanced the expression of brain-derived neurotrophic factor(BDNF).Production of proinflammatory molecules such as interleukin-1β(IL-1β),tumour necrosis factor-αand interferon-γwere also inhibited by CIG administration.CIG could ameliorate phosphorylation of STAT1,STAT3 and JAK1 as well as IL-6/IL-6 Rexpression,which involved in immune response and inflammation.CONCLUSION Our results demonstrated that CIG may ameliorate EAE rats through down-regulation of JAK/STAT signaling pathway.This study gave new insight into the novel regulatory mechanism of CIG and highlight novel therapeutic targets and a potential therapeutic agent for the treatment of MS.

Molecular Simulation on Transport Properties of Confined Water

The diffusivity and viscosity of water confined in micropores were studied by molecular dynamics simulations. The effects of pore width and density were analyzed at pore widths from 0.9 to 2.6 nm. The diffusivity in micropores is lower than that of the bulk, and it decreases as pore width decreases and as density increases. But the viscosity in micropores is much larger than that of the bulk, and it increases as pore width decreases and as density increases. The diffusivity in channel parallel direction is obviously larger than that in channel perpendicular directions.

Study of Benign and Malignant Intraductal Lesions of the Breast by Fiberoptic Ductoscopy

OBJECTIVE To observe and subtype the appearance of intraductal papilloma (lesions) and of infiltrating ductal carcinoma or early infiltrating ductal carcinoma using a fiberoptic ductoscope (FDS) examination, and to discuss the differentiation and diagnosis of benign and malignant tumors,by FDS.METHODS The characteristics of FDS images and diagnostic data for 229 patients with intraductal papilloma (lesions) and 50 patients with ductal carcinoma, who were confirmed by surgical pathology from October 1998 to December 2003, were analyzed retrospectively.RESULTS The appearance of the lesions observed by FDS were grouped into 4types: a monothelia (type Ⅰ), polythelia (type Ⅱ), superficies (type Ⅲ) and a mixture (type Ⅳ). Intraductal papillomas (lesions) were more commonly seen in type Ⅰ and Ⅱ, and intraductal carcinomas, or early infiltrating ductal carcinomas were more commonly seen in type Ⅲ and Ⅳ;there was a statistically significant difference in the distribution of the ductoscopic types, except in type Ⅱ, between the two types of lesions, P<0.001. The focal detection rate by FDS for intraductal papilloma and papillomatosis was 99.6% (228/229) and for breast cancer was 96.0% (48/50). The diagnostic accuracy was 97.8% (224/229) and 82.0% (41/50),respectively.CONCLUSION FDS can be a guide for the treament of benign and malignant intraductal tumors, with early discovery and accurate diagnosis.

Effects of zero-valent iron added in the flooding or drainage process on cadmium immobilization in an acid paddy soil

Zero-valent iron(ZVI)is a promising material for the remediation of Cd-contaminated paddy soils.However,the effects of ZVI added during flooding or drainage processes on cadmium(Cd)retention remain unclear.Herein,Cd-contaminated paddy soil was incubated for 40days of flooding and then for 15 days of drainage,and the underlying mechanisms of Cd immobilization coupled with Fe/S/N redox processes were investigated.The addition of ZVI to the flooding process was more conducive to Cd immobilization.Less potential available Cd was detected by adding ZVI before flooding,which may be due to the increase in paddy soil pH and newly formed secondary Fe minerals.Moreover,the reductive dissolution of Fe minerals promoted the release of soil colloids,thereby increasing significantly the surface sites and causing Cd immobilization.Additionally,the addition of ZVI before flooding played a vital role in Cd retention after soil drainage.In contrast,the addition of ZVI in the drainage phase was not conducive to Cd retention,which might be due to the rapid decrease in soil pH that inhibited Cd adsorption and further immobilization on soil surfaces.The findings of this study demonstrated that Cd availability in paddy soil was largely reduced by adding ZVI during the flooding period and provide a novel insight into the mechanisms of ZVI remediation in Cd-contaminated paddy soils.

Impact of short-term ambient air pollution exposure on the risk of severe COVID-19

Ecological studies suggested a link between air pollution and severe COVID-19 outcomes,while studies accounting for individual-level characteristics are limited.In the present study,we aimed to investigate the impact of short-term ambient air pollution exposure on disease severity among a cohort of 569 laboratory confirmed COVID-19 patients admitted to designated hospitals in Zhejiang province,China,from January 17 to March 3,2020,and elucidate the possible biological processes involved using transcriptomics.Compared with mild cases,severe cases had higher proportion of medical conditions as well as unfavorable results in most of the laboratory tests,and manifested higher air pollution exposure levels.Higher exposure to air pollutants was associated with increased risk of severe COVID-19 with odds ratio(OR)of 1.89(95%confidence interval(CI):1.01,3.53),2.35(95%CI:1.20,4.61),2.87(95%CI:1.68,4.91),and 2.01(95%CI:1.10,3.69)for PM_(2.5),PM_(10),NO_(2)and CO,respectively.OR for NO_(2)remained significant in two-pollutant models after adjusting for other pollutants.Transcriptional analysis showed 884 differentially expressed genes which mainly were enriched in virus clearance related biological processes between patients with high and low NO_(2)exposure levels,indicating that compromised immune response might be a potential underlying mechanistic pathway.These findings highlight the impact of shortterm air pollution exposure,particularly for NO_(2),on COVID-19 severity,and emphasize the significance in mitigating the COVID-19 burden of commitments to improve air quality.

N6-methyladenosine-modified DBT alleviates lipid accumulation and inhibits tumor progression in clear cell renal cell carcinoma through the ANXA2/YAP axis-regulated Hippo pathway

Background:The mechanism of metabolism reprogramming is an unsolved problem in clear cell renal cell carcinoma(ccRCC).Recently,it was discovered that the Hippo pathway altered tumor metabolism and promoted tumor progression.Thus,this study aimed at identifying key regulators of metabolism reprogramming and the Hippo pathway in ccRCC and pinpointing potential therapeutic targets for ccRCC patients.Methods:Hippo-related gene sets and metabolic gene sets were used to screen potential regulators of the Hippo pathway in ccRCC.Public databases and samples from patients were applied to investigate the association of dihydrolipoamide branched chain transacylase E2(DBT)with ccRCC and Hippo signaling.The role of DBT was confirmed by gain or loss of function assays in vitro and in vivo.Mechanistic results were yielded by luciferase reporter assay,immunoprecipitation,mass spectroscopy,and mutational studies.Results:DBT was confirmed as a Hippo-related marker with significant prognostic predictive value,and its downregulationwas caused bymethyltransferaselike-3(METTL3)-mediated N6-methyladenosine(m6A)modification in ccRCC.Functional studies specified DBT as a tumor suppressor for inhibiting tumor progression and correcting the lipid metabolism disorder in ccRCC.Mechanistic findings revealed that annexin A2(ANXA2)interacted with the lipoyl-binding domain of DBT to activate Hippo signaling which led to decreased nuclear localization of yes1-associated transcriptional regulator(YAP)and transcriptional repression of lipogenic genes.Conclusions:This study demonstrated a tumor-suppressive role for the DBT/ANXA2/YAP axis-regulated Hippo signaling and suggested DBT as a potential target for pharmaceutical intervention in ccRCC.

三元共轭聚合物用于NIR-Ⅱ荧光成像及光热/光动力联合治疗

为获得同时具有光热性能、光动力性能及近红外二区(NIR-Ⅱ,1000-1700 nm)荧光发射的共轭聚合物,将一种电子受体单元和2种电子供体单元进行共聚得到一种新型三元共轭聚合物,进一步利用两亲性Pluronic F127作为包覆材料,通过简单的纳米沉淀方法制备得到基于该共轭聚合物的水溶性纳米颗粒.该纳米颗粒具有优异的生物相容性、较好的稳定性、高的近红外一区(NIR-Ⅰ,650~900 nm)光学吸收及NIR-Ⅱ荧光发射能力.在单一激光照射下,该纳米颗粒可以同时产生过高热、活性氧及NIR-Ⅱ荧光信号,可用于NIR-Ⅱ荧光成像指导下的肿瘤光热/光动力联合治疗.