Fangchinoline induces antiviral response by suppressing STING degradation

The stimulator of interferon genes(STING),an integral adaptor protein in the DNA-sensing pathway,plays a pivotal role in the innate immune response against infections.Additionally,it presents a valuable therapeutic target for infectious diseases and cancer.We observed that fangchinoline(Fan),a bis-benzylisoquinoline alkaloid(BBA),effectively impedes the replication of vesicular stomatitis virus(VSV),encephalomyocarditis virus(EMCV),influenza A virus(H1N1),and herpes simplex virus-1(HSV-1)in vitro.Fan treatment significantly reduced the viral load,attenuated tissue inflammation,and improved survival in a viral sepsis mouse model.Mechanistically,Fan activates the antiviral response in a STING-dependent manner,leading to increased expression of interferon(IFN)and interferon-stimulated genes(ISGs)for potent antiviral effects in vivo and in vitro.Notably,Fan interacts with STING,preventing its degradation and thereby extending the activation of IFN-based antiviral responses.Collectively,our findings highlight the potential of Fan,which elicits antiviral immunity by suppressing STING degradation,as a promising candidate for antiviral therapy.

Protective eff ect and mechanism of nanoantimicrobial peptide ND-C14 against Streptococcus pneumoniae infection

BACKGROUND:Streptococcus pneumoniae(S.pneumoniae)is a common pathogen that causes bacterial pneumonia.However,with increasing bacterial resistance,there is an urgent need to develop new drugs to treat S.pneumoniae infections.Nanodefensin with a 14-carbon saturated fatty acid(ND-C14)is a novel nanoantimicrobial peptide designed by modifying myristic acid at the C-terminus of humanα-defensin 5(HD5)via an amide bond.However,it is unclear whether ND-C14 is effective against lung infections caused by S.pneumoniae.METHODS:In vitro,three groups were established,including the control group,and the HD5 and ND-C14 treatment groups.A virtual colony-count assay was used to evaluate the antibacterial activity of HD5 and ND-C14 against S.pneumoniae.The morphological changes of S.pneumoniae treated with HD5 or ND-C14 were observed by scanning electron microscopy.In vivo,mice were divided into sham,vehicle,and ND-C14 treatment groups.Mice in the sham group were treated with 25μL of phosphate-buffered saline(PBS).Mice in the vehicle and ND-C14 treatment groups were treated with intratracheal instillation of 25μL of bacterial suspension with 2×108 CFU/mL(total bacterial count:5×10^(6) CFU),and then the mice were given 25μL PBS or intratracheally injected with 25μL of ND-C14(including 20μg or 50μg),respectively.Survival rates were evaluated in the vehicle and ND-C14 treatment groups.Bacterial burden in the blood and bronchoalveolar lavage fluid were counted.The lung histology of the mice was assessed.A propidium iodide uptake assay was used to clarify the destructive eff ect of ND-C14 against S.pneumoniae.RESULTS:Compared with HD5,ND-C14 had a better bactericidal eff ect against S.pneumoniae because of its stronger ability to destroy the membrane structure of S.pneumoniae in vitro.In vivo,ND-C14 significantly delayed the death time and improved the survival rate of mice infected with S.pneumoniae.ND-C14 reduced bacterial burden and lung tissue injury.Moreover,ND-C14 had a membrane permeation eff ect on S.pneumoniae,and its destructive ability increased with increasing ND-C14 concentration.CONCLUSION:The ND-C14 may improve bactericidal eff ects on S.pneumoniae both in vitro and in vivo.

Decadal variation of thermocline-sea surface temperature feedback in the tropical Indian Ocean and the underlying mechanisms

The thermocline-sea surface temperature(SST)feedback is the most important component of the Bjerknes feedback,which plays an important role in the development of the air-sea coupling modes of the Indian Ocean.The thermocline-SST feedback in the Indian Ocean has experienced significant decadal variations over the last40 a.The feedback intensified in the late twentieth century and then weakened during the hiatus in global warming at the early twenty-first century.The thermocline-SST feedback is most prominent in the southeastern and southwestern Indian Ocean.Although the decadal variations of feedback are similar in these two regions,there are still differences in the underlying mechanisms.The decadal variations of feedback in the southeastern Indian Ocean are dominated by variations in the depth of the thermocline,which are modulated by equatorial zonal wind anomalies.Whereas the decadal variation of feedback in the southwestern Indian Ocean is mainly controlled by the intensity of upwelling and thermocline depth in winter and spring,respectively.The upwelling and thermocline depth are both affected by wind stress curl anomalies over the southeastern Indian Ocean,which excite anomalous Ekman pumping and influence the southwestern Indian Ocean through westward propagating Rossby waves.

Efficiency Assessment of Land Use Types in Tan Binh Commune,Dak Doa District,Gia Lai Province,Vietnam

Land resource depletion causes a range of consequences,such as threats to food security,increasing poverty,and social unrest.Therefore,reasonable and effective land use has become a crucial issue of the nation and localities nationwide.Research results in Tan Binh commune,Dak Doa district,Gia Lai Province in Vietnam showed that long-term industrial and agricultural land occupies most of the commune's agroforestry land.The study also had shown that there are six common land use types(LUTs)in the commune.In particular,the LUT of pepper cultivation had the highest economic benefit,whereas the LUT of coffee brought the highest social benefit.However,the LUT of chayote was the highest in overall benefits with Ect of 0.93;thus,this LUT should be widely applied throughout Tan Binh commune.The research results were a crucial scientific basis for proposing a group of suitable plants to local natural conditions to bring effective and sustainable efficiency in land-use types.

Suppressing FXR promotes antiviral effects of bile acids via enhancing the interferon transcription

Bile acids(BAs)are natural metabolites in mammals and have the potential to function as drugs against viral infection.However,the limited understanding of chenodeoxycholic acid(CDCA)receptors and downstream signaling,along with its lower suppression efficiency in inhibiting virus infection limits its clinical application.In this study,we demonstrate that farnesoid X receptor(FXR),the receptor of CDCA,negatively regulates interferon signaling,thereby contributing to the reduced effectiveness of CDCA against virus replication.FXR deficiency or pharmacological inhibition enhances interferon signaling activation to suppress virus infection.Mechanistically,FXR impairs the DNA binding and transcriptional abilities of activated interferon regulatory factor 3(IRF3)through interaction.Reduced IRF3 transcriptional activity by FXReIRF3 interaction significantly undermines the expression of Interferon Beta 1(IFNB1)and the antiviral response of cells,especially upon the CDCA treatment.In FXR-deficient cells,or when combined with Z-guggulsterone(GUGG)treatment,CDCA exhibits a more potent ability to restrict virus infection.Thus,these findings suggest that FXR serves as a limiting factor for CDCA in inhibiting virus replication,which can be attributed to the“signaling-brake”roles of FXR in interferon signaling.Targeting FXR inhibition represents a promising pharmaceutical strategy for the clinical application of BAs metabolites as antiviral drugs.

钱江源国家公园叶附生苔类植物的物种多样性

本文报道钱江源国家公园叶附生苔类植物4科9属19种,较之前记录增加3科8属17种。与钱江源处于同纬度的我国其他地区相比,钱江源叶附生苔类植物的种数仅次于西藏墨脱,排名第二。鳞叶疣鳞苔(Cololejeunea longifolia)和尖叶薄鳞苔(Leptolejeunea subacuta)是钱江源国家公园最常见的2种叶附生苔类植物。丰富的叶附生苔类植物表明钱江源国家公园具有较合适的叶附生苔类植物生长环境,这可能与该地区长期有效的保护密切相关。