Anti-proliferative effect of olmesartan on Tenon's capsule fibroblasts

AIM： To evaluate the inhibitive effect of olmesartan to fibroblast proliferation and the anti-scarring effect in Tenon＇s capsule, both in vitro and in vivo.· METHODS： Human primary Tenon＇s capsule fibroblasts were cultured in vitro, treated with up titrating concentrations of olmesartan. The rate of inhibition was tested with methyl thiazol tetrazolium（MTT） method.Real-time PCR was performed to analyze changes in m RNA expressions of the fibrosis-related factors： matrix metalloproteinase-2（MMP-2）, tissue inhibitor of metalloproteinase（TIMP-1,2） and proliferating cell nuclear antigen（PCNA）. Thirty rabbits were divided into5 groups（3, 7, 14, 21, and 28d）. A rabbit conjunctiva flap model was created in each eye. Olmesartan solution was injected subconjunctivally and then evaluated its anti-proliferation and anti-fibrosis effects through the histological morphology and immunohistochemistry of MMP-2 and PCNA in each group. Only the 7d group was treated with Masson＇s trichrome to compare the neovascularization in the subconjunctiva area.·RESULTS： In vitro, cultured Tenon＇s capsule human fibroblasts showed a dose dependent inhibition by olmesartan in MTT. Olmesartan reduced m RNA expressions of MMP-2 and PCNA but increased m RNA expressions of TIMP-1 and TIMP-2. In vivo, the rabbit eyes treated with olmesartan at 3rd, 7th, 14 thand 21stdays demonstrated a significant reduced expressions of MMP-2 and PCNA compared with control eye, no significant difference observed in 28 thday group. The cellular proliferation and neovascularization was suppressed by olmesartan in Masson＇s trichrome observation.·CONCLUSION： By inhibiting fibroblasts in vitro and in vivo, olmesartan prevents the proliferation and activity of fibroblasts in scar tissue formation, which might benefit glaucoma filtering surgery.

Anti-proliferative effect of Annona extracts on breast cancer cells

Backgorund:Fruits and seed extracts of Annona montana have significant cytotoxic potential in several cancer cells.This study evaluates the effect of A.montana leaves hexane extract on several signaling cascades and gene expression in metastatic breast cancer cells upon insulin-like growth factor-1(IGF-1)stimulation.Methods:MTT assay was performed to determine the proliferation of cancer cells.Propidium iodide staining and flow cytometry analysis of Annexin V binding was utilized to measure the progression of the cell cycle and the induction of apoptosis.Protein expression and phosphorylation were determined by western blotting analysis to examine the underlying cellular mechanism triggered upon treatment with A.montana leaves hexane extract.Results:A.montana leaves hexane(subfraction V)blocked the constitutive stimulation of the PI3K/mTOR signaling pathways.This inhibitory effect was associated with apoptosis induction as evidenced by the positivity with Annexin V and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNNEL)staining,activation of caspase-3,and cleavage of PPAR.It also limited the expression of various downstream genes that regulate proliferation,survival,metastasis,and angiogenesis(i.e.,cyclin D1,survivin,COX-2,and VEGF).It increased the expression of p53 and p21.Interestingly,we also observed that this extract blocked the activation of AKT and ERK without affecting the phosphorylation of the IGF-1 receptor and activation of Ras upon IGF-1 stimulation.Conclusion:Our study indicates that A.montana leaves(sub-fraction V)extract exhibits a selective anti-proliferative and proapoptotic effect on the metastatic MDA-MB-231 breast cancer cells through the involvement of PI3K/AKT/mTOR/S6K1 pathways.

Anti-proliferative activity of phlorotannin extracts from brown algae Laminaria japonica Aresch

In this study, we evaluated the anti-proliferative activity of phlorotannins derived from brown algae Laminariajaponica Aresch extracts on the human hepatocellular carcinoma cell （BEL-7402） and on routine leukemic cells （P388） by MTT assay. Cells were incubated with 100 μg/mL of the phlorotannin extract （PE） for 48 h. The inhibitory rate of PE on BEL-7402 and P388 cells was 30.20±1.16% and 43.44±1.86%, respectively, and the half-inhibitory concentration of PE （IC50） on P388 and BEL-7402 cells was 120 μg/mL and 〉200 μg/mL, respectively. Microscopic observation shows that the morphologic features of tumor cells treated with PE and 5-fluorouracil are markedly different from the normal control group. The inhibitory rate of fraction A2 isolated from PE by sephadex LH-20 for BEL-7402 and P388 cells at the sample concentration of 70.42 μg/mL was 61.96±7.02% and 40.47±8.70%, respectively. The apoptosis peak for fraction A2 was the most profound of all fractions used in the flow cytometry assay. The results indicate that the anti-proliferative of this algal extract is associated with the total phlorotannin content.

Potential of four marine-derived fungi extracts as anti-proliferative and cell death-inducing agents in seven human cancer cell lines

Objective:To evaluate the in vitro anticancer activity of crude ethyl acetate extracts of the culture of four marine-derived fungi Aspergillus similanensis KUFA 0013(E1),Neosartorya paulistemis KUFC 7897(E2),Neosartorya siamensis KUFA 0017(E4) and Talaromyces trachyspermus KUFC 0021(E3) on a panel of seven human cancer cell lines.Methods:Effects on cell proliferation,induction of DNA damage and cell death were assessed by MTT and clonogenic assays,comet assay and nuclear condensation assay,respectively.Results:The proliferation of HepG2,HCTl 16 and A375 cells decreased after incubation with the extracts E2 and E4.The anti-proliterative effect was confirmed by morphologic alterations and by clonogenic assay.Both extracts also induced cell death in HepG2 and HCT116 cells.Doxorubicin was used as a positive control and showed in vitro anticancer activity.Conclusions:This study demonstrated,for the first time,that extracts of Neosartorya paulistensis and Neosartorya siamensis have selective anti-proliferative and cell death activities in HepG2,HCT16 and A375 cells.The bioactivity of these extracts suggests a potential for biotechnological applications and substantiates that both should be further considered for the elucidation of the molecular targets and signal transduction pathways involved.

A new cerebroside and its anti-proliferation effect on VSMCs from the radix of Cyperus rotundus L.

A new cerebroside,1-O-(β-D-glucopyranosyloxy)-(2S,3R,4E,8Z)-2-[(2′R)-2’-hydroxylignoceranoylamino]-4,8-tetradecene-3- diol was isolated from the 60%EtOH extract of traditional Chinese medical plant Cyperus rotundus L.Its structure was determined on the basis of spectroscopic data.This new compound showed anti-proliferation effect on vascular smooth muscle cells(VSMCs).

Design,synthesis and anti-proliferative studies of a novel series of indirubin derivatives

A series of novel derivatives of indirubin were synthesized and evaluated for their anti-proliferative activity against human cancer cell lines of SGC7901,A549,HL-60,SK-BR-3 and HCT116.Most of the compounds displayed more potent activity than Sunitinib.In addition,the derivatives showed improved water solubility,which may be favorable to their pharmacokinetic performances.

240 nm AlGaN-based deep ultraviolet micro-LEDs:size effect versus edge effect

240 nm AlGaN-based micro-LEDs with different sizes are designed and fabricated.Then,the external quantum efficiency(EQE)and light extraction efficiency(LEE)are systematically investigated by comparing size and edge effects.Here,it is revealed that the peak optical output power increases by 81.83%with the size shrinking from 50.0 to 25.0μm.Thereinto,the LEE increases by 26.21%and the LEE enhancement mainly comes from the sidewall light extraction.Most notably,transversemagnetic(TM)mode light intensifies faster as the size shrinks due to the tilted mesa side-wall and Al reflector design.However,when it turns to 12.5μm sized micro-LEDs,the output power is lower than 25.0μm sized ones.The underlying mechanism is that even though protected by SiO2 passivation,the edge effect which leads to current leakage and Shockley-Read-Hall(SRH)recombination deteriorates rapidly with the size further shrinking.Moreover,the ratio of the p-contact area to mesa area is much lower,which deteriorates the p-type current spreading at the mesa edge.These findings show a role of thumb for the design of high efficiency micro-LEDs with wavelength below 250 nm,which will pave the way for wide applications of deep ultraviolet(DUV)micro-LEDs.

Evaluation of the intracellular lipid-lowering effect of polyphenols extract from highland barley in HepG2 cells

Active ingredients from highland barley have received considerable attention as natural products for developing treatments and dietary supplements against obesity.In practical application,the research of food combinations is more significant than a specific food component.This study investigated the lipid-lowering effect of highland barley polyphenols via lipase assay in vitro and HepG2 cells induced by oleic acid(OA).Five indexes,triglyceride(TG),total cholesterol(T-CHO),low density lipoprotein-cholesterol(LDL-C),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),were used to evaluate the lipidlowering effect of highland barley extract.We also preliminary studied the lipid-lowering mechanism by Realtime fluorescent quantitative polymerase chain reaction(q PCR).The results indicated that highland barley extract contains many components with lipid-lowering effects,such as hyperoside and scoparone.In vitro,the lipase assay showed an 18.4%lipase inhibition rate when the additive contents of highland barley extract were 100μg/m L.The intracellular lipid-lowering effect of highland barley extract was examined using 0.25 mmol/L OA-induced HepG2 cells.The results showed that intracellular TG,LDL-C,and T-CHO content decreased by 34.4%,51.2%,and 18.4%,respectively.ALT and AST decreased by 51.6%and 20.7%compared with the untreated hyperlipidemic HepG2 cells.q PCR results showed that highland barley polyphenols could up-regulation the expression of lipid metabolism-related genes such as PPARγand Fabp4.

Engineering Strategies for Suppressing the Shuttle Effect in Lithium–Sulfur Batteries

Lithium–sulfur(Li–S)batteries are supposed to be one of the most potential next-generation batteries owing to their high theoretical capacity and low cost.Nevertheless,the shuttle effect of firm multi-step two-electron reaction between sulfur and lithium in liquid electrolyte makes the capacity much smaller than the theoretical value.Many methods were proposed for inhibiting the shuttle effect of polysulfide,improving corresponding redox kinetics and enhancing the integral performance of Li–S batteries.Here,we will comprehensively and systematically summarize the strategies for inhibiting the shuttle effect from all components of Li–S batteries.First,the electrochemical principles/mechanism and origin of the shuttle effect are described in detail.Moreover,the efficient strategies,including boosting the sulfur conversion rate of sulfur,confining sulfur or lithium polysulfides(LPS)within cathode host,confining LPS in the shield layer,and preventing LPS from contacting the anode,will be discussed to suppress the shuttle effect.Then,recent advances in inhibition of shuttle effect in cathode,electrolyte,separator,and anode with the aforementioned strategies have been summarized to direct the further design of efficient materials for Li–S batteries.Finally,we present prospects for inhibition of the LPS shuttle and potential development directions in Li–S batteries.

Isolation, purification and characterization of an N-acetyl-D-lactosamine binding mitogenic and anti-proliferative lectin from tubers of a cobra lily Arisaema utile Schott

Lectins are the carbohydrate-binding proteins of non-immune origin which have been the subject of intense investigation over the last few decades owing to the variety of interesting biological properties. Most of the lectins which have been purified and characterized from plants have been obtained from dicotyledons. In the present study a lectin was purified from tubers of a monocot plant Arisaema utile (AUL) Schott by affinity chromatography on asialofetuin-linked amino activated silica beads. AUL gave a single band in SDS-PAGE at pH 8.3 corresponding to subunit Mr 13.5 kDa. The native molecular mass of AUL was 54 kDa suggesting a homotetrameric structure. AUL gave multiple bands in isoelectric focusing and in native PAGE at pH 8.3. AUL was inhibited by N-acetyl-D-lactosamine (Lac NAc), a disaccharide and asialofetuin, a complex desialylated serum glycoprotein. When treated with denaturing agents, the lectin was stable in the presence of urea (3 M), thiourea (4 M) and guanidine HCl (4 M). AUL was a glycoprotein with a carbohydrate content of 1.2%. Complete loss of activity was observed upon modification of tryptophan residues of the lectin. The activity was reduced to 25% after modification of tyrosine. Chemical modification of arginine, histidine, serine and cysteine residues of AUL did not affect its activity. Using Far UV CD spectra the estimated secondary structure was 37% α-helix, 25% β-sheet and 38% random contributions. The lectin showed potent mitogenic response towards human lymphocytes. In vitro anti-proliferative assay using 11 human cancer cell lines resulted in 50% inhibition of six cell lines viz. SW-620, HCT-15, SK-N-SH, IMR-32, Colo-205 and HT-29 at 38, 42, 43, 49, 50 and 89 µg/ml, respectively.

Experimental study on the effect of water absorption level on rockburst occurrence of sandstone

To investigate the mechanism of rockburst prevention by spraying water onto the surrounding rocks,15 experiments are performed considering different water absorption levels on a single face.High-speed photography and acoustic emission(AE)system are used to monitor the rockburst process.The effect of water on sandstone rockburst and the prevention mechanism of water on sandstone rockburst are analyzed from the perspective of energy and failure mode.The results show that the higher the ab-sorption degree,the lower the intensity of the rockburst after absorbing water on single side of sand-stone.This is reflected in the fact that with the increase in the water absorption level,the ejection velocity of rockburst fragments is smaller,the depth of the rockburst pit is shallower,and the AE energy is smaller.Under the water absorption level of 100%,the magnitude of rockburst intensity changes from medium to slight.The prevention mechanism of water on sandstone rockburst is that water reduces the capacity of sandstone to store strain energy and accelerates the expansion of shear cracks,which is not conducive to the occurrence of plate cracking before rockburst,and destroys the conditions for rockburst incubation.

Anti-Biofilm, Anti-Quorum Sensing, and Anti-Proliferative Activities of Methanolic and Aqueous Roots Extracts of Carica papaya L. and Cocos nucifera L.

Objective: This study focused on the antibacterial and anti-proliferative activity of extracts from Carica papaya and Cocos nucifera roots. Methodology: The minimum inhibitory concentration and the minimum bactericidal concentration of the extracts on Escherichia coli, Pseudomonas aeruginosa, Streptococcus mutans, and Staphylococcus aureus were deduced by the microdilution method. The anti-biofilm activity was determined on all four strains and anti-quorum sensing activity by inhibition of violacein production in Chromobacterium violaceum. Anti-proliferative activity on prostate cultured cancer cells was evaluated by MTT assay. Sterols and triterpenes were also assayed in this study. Results: The methanolic extract of Carica papaya showed the best anti-biofilm effect with a percentage inhibition of 66.10 ± 1.79. The methanolic extract of Cocos nucifera had the strongest inhibition on the production of quorum sensing (61.42 ± 0.28). In addition, the methanolic extract of Cocos nucifera roots showed the best cytotoxic effect on prostate cancer LNCaP cell lines (IC50 = 26.98 ± 2.6 μg/mL) and Carica papaya on the PC-3 lines (IC50 = 127.20 ± 5.99 μg/mL). The extracts were also rich in triterpenes and sterols. Conclusion: This study provides support for the ethnomedical use of Carica papaya and Cocos nucifera roots as an antimicrobial and anticancer.

High responsivity photodetectors based on graphene/WSe_(2) heterostructure by photogating effect

Graphene, with its zero-bandgap electronic structure, is a highly promising ultra-broadband light absorbing material.However, the performance of graphene-based photodetectors is limited by weak absorption efficiency and rapid recombination of photoexcited carriers, leading to poor photodetection performance. Here, inspired by the photogating effect, we demonstrated a highly sensitive photodetector based on graphene/WSe_(2) vertical heterostructure where the WSe_(2) layer acts as both the light absorption layer and the localized grating layer. The graphene conductive channel is induced to produce more carriers by capacitive coupling. Due to the strong light absorption and high external quantum efficiency of multilayer WSe_(2), as well as the high carrier mobility of graphene, a high photocurrent is generated in the vertical heterostructure. As a result, the photodetector exhibits ultra-high responsivity of 3.85×10~4A/W and external quantum efficiency of 1.3 × 10~7%.This finding demonstrates that photogating structures can effectively enhance the sensitivity of graphene-based photodetectors and may have great potential applications in future optoelectronic devices.

“Buckets effect”in the kinetics of electrocatalytic reactions

In this study,we systematically investigated the effect of proton concentration on the kinetics of the oxygen reduction reaction(ORR)on Pt(111)in acidic solutions.Experimental results demonstrate a rectangular hyperbolic relationship,i.e.,the ORR current excluding the effect of other variables increases with proton concentration and then tends to a constant value.We consider that this is caused by the limitation of ORR kinetics by the trace oxygen concentration in the solution,which determines the upper limit of ORR kinetics.A model of effective concentration is further proposed for rectangular hyperbolic relationships:when the reactant concentration is high enough to reach a critical saturation concentration,the effective reactant concentration will become a constant value.This could be due to the limited concentration of a certain reactant for reactions involving more than one reactant or the limited number of active sites available on the catalyst.Our study provides new insights into the kinetics of electrocatalytic reactions,and it is important for the proper evaluation of catalyst activity and the study of structureperformance relationships.

Cumulative effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease in China

BACKGROUND Within the normal range,elevated alanine aminotransferase(ALT)levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the associations between repeated high-normal ALT measurements and the risk of new-onset MAFLD prospectively.METHODS A cohort of 3553 participants followed for four consecutive health examinations over 4 years was selected.The incidence rate,cumulative times,and equally and unequally weighted cumulative effects of excess high-normal ALT levels(ehALT)were measured.Cox proportional hazards regression was used to analyse the association between the cumulative effects of ehALT and the risk of new-onset MAFLD.RESULTS A total of 83.13%of participants with MAFLD had normal ALT levels.The incidence rate of MAFLD showed a linear increasing trend in the cumulative ehALT group.Compared with those in the low-normal ALT group,the multivariate adjusted hazard ratios of the equally and unequally weighted cumulative effects of ehALT were 1.651[95%confidence interval(CI):1.199-2.273]and 1.535(95%CI:1.119-2.106)in the third quartile and 1.616(95%CI:1.162-2.246)and 1.580(95%CI:1.155-2.162)in the fourth quartile,respectively.CONCLUSION Most participants with MAFLD had normal ALT levels.Long-term high-normal ALT levels were associated with a cumulative increased risk of new-onset MAFLD.

Impact of effective stress on permeability for carbonate fractured-vuggy rocks

To gain insight into the flow mechanisms and stress sensitivity for fractured-vuggy reservoirs,several core models with different structural characteristics were designed and fabricated to investigate the impact of effective stress on permeability for carbonate fractured-vuggy rocks(CFVR).It shows that the permeability performance curves under different pore and confining pressures(i.e.altered stress conditions)for the fractured core models and the vuggy core models have similar change patterns.The ranges of permeability variation are significantly wider at high pore pressures,indicating that permeability reduction is the most significant during the early stage of development for fractured-vuggy reservoirs.Since each obtained effective stress coefficient for permeability(ESCP)varies with the changes in confining pressure and pore pressure,the effective stresses for permeability of four representative CFVR show obvious nonlinear characteristics,and the variation ranges of ESCP are all between 0 and 1.Meanwhile,a comprehensive ESCP mathematical model considering triple media,including matrix pores,fractures,and dissolved vugs,was proposed.It is proved theoretically that the ESCP of CFVR generally varies between 0 and 1.Additionally,the regression results showed that the power model ranked highest among the four empirical models mainly applied in stress sensitivity characterization,followed by the logarithmic model,exponential model,and binomial model.The concept of“permeability decline rate”was introduced to better evaluate the stress sensitivity performance for CFVR,in which the one-fracture rock is the strongest,followed by the fracture-vug rock and two-horizontalfracture rock;the through-hole rock is the weakest.In general,this study provides a theoretical basis to guide the design of development and adjustment programs for carbonate fractured-vuggy reservoirs.

Carbon Emission Effects Driven by Evolution of Chinese Dietary Structure from 1987 to 2020

Exploring carbon emission effects based on the evolution of residents’ dietary structure to achieve the carbon neutrality goal and mitigate climate change is an important task.This study took China as the research object(data excluding Hong Kong,Macao and Taiwan) and used the carbon emission coefficient method to quantitatively measure the food carbon emissions from 1987–2020,then analyzed the carbon emission effects under the evolution of dietary structure.The results showed that during the study period,the Chinese dietary structure gradually changed to a high-carbon consumption pattern.The dietary structure of urban residents developed to a balanced one,while that of rural residents developed to a high-quality one.During the study period,the per capita food carbon emissions and total food consumption of Chinese showed an increasing trend.The per capita food carbon emissions of residents in urban and rural showed an overall upward trend.The total food carbon emissions in urban increased significantly,while that in rural increased first and then decreased.The influence of beef and mutton on carbon emissions is the highest in dietary structure.Compared with the balanced dietary pattern,the food carbon emissions of Chinese residents had not yet reached the peak,but were evolving to a high-carbon consumption pattern.

Rockburst criterion and evaluation method for potential rockburst pit depth considering excavation damage effect

Excavation-induced disturbances in deep tunnels will lead to deterioration of rock properties and formation of excavation damaged zone(EDZ).This excavation damage effect may affect the potential rockburst pit depth.Taking two diversion tunnels of Jinping II hydropower station for example,the relationship between rockburst pit depth and excavation damage effect is first surveyed.The results indicate that the rockburst pit depth in tunnels with severe damage to rock masses is relatively large.Subsequently,the excavation-induced damage effect is characterized by disturbance factor D based on the Hoek-Brown criterion and wave velocity method.It is found that the EDZ could be further divided into a high-damage zone(HDZ)with D=1 and weak-damage zone(WDZ),and D decays from one to zero linearly.For this,a quantitative evaluation method for potential rockburst pit depth is established by presenting a three-element rockburst criterion considering rock strength,geostress and disturbance factor.The evaluation results obtained by this method match well with actual observations.In addition,the weakening of rock mass strength promotes the formation and expansion of potential rockburst pits.The potential rockburst pit depth is positively correlated with HDZ and WDZ depths,and the HDZ depth has a significant contribution to the potential rockburst pit depth.

Electrode/Electrolyte Interfacial Chemistry Modulated by Chelating Effect for High-Performance Zinc Anode

Although Zn metal has been regarded as the most promising anode for aqueous batteries,its practical application is still restricted by side reactions and dendrite growth.Herein,an in-situ solid electrolyte interphase(SEI)film formed on the interface of electrode/electrolyte during the plating/stripping of zinc anodes by introducing trace amounts of multidentate ligand sodium diethyldithiocarbamate(DDTC)additive into 1 M ZnSO_(4).The synergistic effect of in-situ solid electrolyte interphase forming and chelate effect endows Zn^(2+)with uniform and rapid interface-diffusion kinetics against dendrite growth and surface side reactions.As a result,the Zn anode in 1 M ZnSO_(4)+DDTC electrolytes displays an ultra-high coulombic efficiency of 99.5%and cycling stability(more than 2000 h),especially at high current density(more than 600 cycles at 40 mA cm^(-2)).Moreover,the Zn//MnO_(2)full cells in the ZnSO_(4)+DDTC electrolyte exhibit outstanding cyclic stability(with 98.6%capacity retention after 2000 cycles at 10 C).This electrode/electrolyte interfacial chemistry modulated strategy provides new insight into enhancing zinc anode stability for high-performance aqueous zinc batteries.

Review on synergistic damage effect of irradiation and corrosion on reactor structural alloys

The synergistic damage effect of irradiation and corrosion of reactor structural materials has been a prominent research focus.This paper provides a comprehensive review of the synergistic effects on the third-and fourth-generation fission nuclear energy structural materials used in pressurized water reactors and molten salt reactors.The competitive mechanisms of multiple influencing factors,such as the irradiation dose,corrosion type,and environmental temperature,are summarized in this paper.Conceptual approaches are proposed to alleviate the synergistic damage caused by irradiation and corrosion,thereby promoting in-depth research in the future and solving this key challenge for the structural materials used in reactors.