Design and characterization of a bifunctional bybrid antibacterial peptide LLH for bactericidal/endotoxin neutralization effects

Objective:To design a bi-functional antimicrobial peptide with bactericidal and endotoxin neutralization activity,and explore its bactericidal properties.Methods:The LBP(86-99)peptides and HLF(1-11)peptides were connected by a GGGS flexible 4-peptide linker to obtain the bi-functional antimicrobial peptide,which was named LLH.The secondary structure characteristics of LLH were analyzed by Emboss software.The minimum inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)of LLH against Escherichia coli ATCC25922 and DH5αwere determined by the microtiter broth dilution method.The bactericidal kinetics of LLH was characterized and its effect on endotoxin neutralization was determined.The hemolysis of LLH was evaluated.Results:LLH carried a positive charge of+9,exhibitedβ-folding andβ-corner structure,and had strong hydrophobicity.The MIC of LLH against Escherichia coli ATCC25922 and DH5αwas 4μM,and the MBC of LLH against Escherichia coli ATCC25922 and DH5αwas 8 and 4μM,respectively.LLH showed rapid bactericidal effects and significantly neutralized the endotoxin released in the sterilization process as well as reducing release of endotoxin.LLH showed no significant hemolysis at concentrations up to 400μg/mL.Conclusion:LLH produces dual effects of rapid sterilization and endotoxin neutralization,and does not induce significant hemolysis.

Application of a concrete thermal pile in cooling the warming permafrost under climate change

Permafrost degradation caused by climate warming is posing a serious threat to the stability of cast-in-place pile foundations in warm permafrost regions.Ambient cold energy can be effectively utilized by two-phase closed thermosyphons(TPCTs)to cool the permafrost.Therefore,we installed TPCTs in a cast-in-place pile foundation to create a unique structure called a thermal pile,which effectively utilizes the TPCTs to regulate ground temperature.And we conducted a case study and numerical simulation to exhibit the cooling performance,and optimize the structure of the thermal pile.The purpose of this study is to promote the application of thermal piles in unstable permafrost regions.Based on the findings,the thermal pile operated for approximately 53%of the entire year and effectively reduced the deep ground temperature at a rate of at least-0.1℃per year.Additionally,it successfully raised the permafrost table that is 0.35 m shallower than the natural ground level.These characteristics prove highly beneficial in mitigating the adverse effects of permafrost degradation and enhancing infrastructure safety.Expanding the length of the condenser section and the diameter of the TPCT in a suitable manner can effectively enhance the cooling capability of the thermal pile and ensure the long-term mechanical stability of the pile foundation even under climate warming.

Protective effects of Foeniculum vulgare root bark extract against carbon tetrachloride-induced hepatic fibrosis in mice

AIM To investigate the protective effects of Foeniculum vulgare root bark(FVRB), a traditional Uyghur medicine, against carbon tetrachloride(CCl4)-induced hepatic fibrosis in mice. METHODS Mice were randomly divided into eight groups(n = 20 each). Except for the normal control group, mice in the rest groups were intraperitoneally injected(i.p.) with 0.1% CCl4-olive oil mixture at 10 m L/kg twice a week to induce liver fibrosis. After 4 wk, mice were treated concurrently with the 70% ethanol extract of FVRB(88, 176, 352 and 704 mg/kg, respectively) daily by oral gavage for 4 wk to evaluate its protective effects. Serum aspartate aminotransferase(AST), alanine aminotransferase(ALT), triglyceride(TG), hexadecenoic acid(HA), laminin(LN), glutathione(GSH), superoxide dismutase(SOD), and malondialdehyde(MDA) in liver tissues were measured. Hematoxylin-eosin(H and E) staining and Masson trichrome(MT) staining were performed to assess histopathological changes in the liver. The expression of transforming growth factor β1(TGF-β1), matrix metalloprotein 9(MMP-9) and metallopeptidase inhibitor 1(TIMP-1) was detected by immunohistochemical analysis. Additionally, TGF-β1 and alpha-smooth muscle actin(α-SMA) protein expression was measured by Western blot.RESULTS A significant reduction in serum levels of AST, ALT, TG, HA and LN was observed in the FVRB-treated groups, suggesting that FVRB displayed hepatoprotective effects. Also, the depletion of GSH, SOD, and MDA accumulation in liver tissues was suppressed by FVRB. The expression of TGF-β1, MMP-9 and TIMP-1 determined by immunohistochemistry was markedly reduced in a dose-dependent manner by FVRB treatment. Furthermore, protective effects of FVRB against CCl4-induced liver injury were confirmed by histopathological studies. Protein expression of TGF-β1 and α-SMA detected by Western blot was decreased by FVRB treatment.CONCLUSION Our results indicate that FVRB may be a promising agent against hepatic fibrosis and its possible mechanisms are inhibiting lipid peroxidation and reducing collagen formation in liver tissue of liver fibrosis mice.

Hepatoprotective effect of Cichorium intybus L.,a traditional Uighur medicine,against carbon tetrachloride-induced hepatic fibrosis in rats

AIM:To investigate the hepatoprotective effect of a Cichorium intybus L.extract(CIE)on CCl4-induced hepatic fibrosis in rats.METHODS:Seventy-two male Wistar albino rats were randomly divided into six groups of twelve rats each.The normal control group was allowed free access to food and water.Liver injury was performed in the remaining five groups with an i.p.injection of a 1.0mL/kg CCl4 and olive oil(2:3 v/v)mixture,twice weekly for 8 weeks.All rats,with the exception of the injury model group,were intragastrically(i.g.,)administered quantum satis(q.s.)dosages[CIE group:6,18,and 54 mg/kg,respectively;Fu Fang Bie Jia Ruan Gan Pian(FFBJRGP)group:780 mg/kg].The oral administration of different drugs was performed on the day before CCl4 administration and subsequently once per day for8 wk.The serum levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),hexadecenoic acid(HA),laminin(LN),hydroxyproline(Hyp),and glutathione(GSH),malondialdehyde(MDA)and superoxide dismutase(SOD)in the rat livers were measured.Histopathological changes in the liver were assessed for each group using HE staining and a Masson Trichrome examination.The expression of transforming growth factor-β1(TGF-β1)andα-smooth muscle actin(α-SMA)was examined by immunohistochemical analysis.RESULTS:CIE at oral doses of 6,18,and 54 g/kg per day showed a significant hepatoprotective effect,especially at a dose of 54 g/kg per day.CIE doses reduced the levels of AST(149.04±34.44,P<0.01),ALT(100.72±27.19,P<0.01),HA(548.50±65.09,P<0.01),LN(28.69±3.32,P<0.01)and Hyp(263.33±75.82,P<0.01).With regards to hepatoprotective activity,the CIE dose of 54 g/kg per day produced the largest significant effect by increasing GSH(3.11±0.81),SOD(269.98±33.77,P<0.01)and reducing MDA(2.76±0.51,P<0.01)levels in the liver.The expressions of TGF-β1 andα-SMA were measured by immunohistology and found to be significantly reduced by CIE in a dose-dependent manner.

Permafrost degradation along the Qinghai-Tibet Highway from 1995 to 2020

Permafrost degradation significantly affects engineering infrastructure,hydrologic processes,landscape and geomorphic processes,ecosystems and carbon cycling in cold regions.The permafrost degradation along the Qinghai–Tibet Highway(QTH)on the Qinghai–Tibet Plateau,China,introduces an adverse effect on the deformation of the highway subgrade.At present,observation of a long series of ground temperatures is lacking.From 1995 to 2020,a monitoring system of ground temperature in 10 natural sites along QTH was built and maintained.Ground temperatures at different depths were continuously observed semi-monthly.In this study,permafrost changes along QTH were quantitatively investigated based on these records.The main results showed that both the permafrost table depth(PTD)and ground temperature at different depths exhibited an increasing trend from 1995 to 2020 with widespread spatiotemporal differences.The higher the annual mean and range of PTD were,the higher the increase rate in PTD.The increase rates in PTDs in the warm permafrost regions were 6.18 cm per year larger than those in the cold ones.Overall,the increase rates in ground temperature decreased with the increase in depth at each site.At different depths,the smaller the mean annual ground temperature(MAGT)was,the larger the increase rate in the permafrost temperatures.The larger the range of ground temperatures was,the bigger the increase rate in the permafrost temperatures.At a depth of 6.0 m,the increase rate in the ground temperature in cold permafrost regions was twice that in warm permafrost regions.Information on the magnitudes and differences in permafrost degradation along QTH is necessary for the design of effective adaption strategies for engineering construction and environment protection in permafrost regions under climatic warming.

Viscous creep of ice-rich permafrost debris in a recently uncovered proglacial area in the Tianshan Mountains, China

Since the Little Ice Age and as a consequence of climate warming,many recently deglaciated forefields have become and will continue to evolve into large ice-debris complexes exposed to periglacial processes and environment.Such transitional processes have significant implications for geomorphologic shaping and water supply for the downstream communities,especially in arid regions,but our understanding of their evolutionary processes and their potential geomorphic and hydrological impacts is stil limited.A landform transition from partly debris-covered glaciers to ice-rich permafrost debris undergoing slow viscous creep was revealed in the Aerzailaikunai Valley in the eastern Tianshan Mountains in China based on the results of in-situ observations and measurements(boreholes,ground temperature monitoring,electrical resistivity tomography surveys,and continuous global positioning system measurements,among others).The internal structure of ice-tll mixture contains pure ice layers,supersaturated frozen sands with ice lenses,and ice-bearing blocks with maximum volumetric contents of heterogeneous ice at 35%-60%.Beneath an 1.5-m-thick active layer,permafrost reached far into the underlying bedrock with the mean annual ground temperature of-2.1℃ at the depth of 20 m.The higher surface velocities(with an accumulative displacement of 65 mm from October 2019 to May 2020)and extremely high electrical resistivity(several million Ω m)of the debris-covered glacier margin were in sharp contrast to those of the progressively stabilizing ground surface(up to 16 mm)and the lower zones with relatively smaler electrical resistivity(several thousand Ω m).Combined with the borehole stratigraphy(higher rock content),monitored ground temperatures(permafrost environment),lower electrical resistance(ice-rich moraine),and continuous global positioning system results(viscous creeping),this study documents a transition from glacial to periglacial conditions,materials and processes characteristic of cold-dry ice-clad mountains,and reinforces the theory of the transition from debris-covered glaciers into morainically originated rock glaciers.