Analysis of Factors that Tourists Attach Importance to Rural Tourism Image——Taking Rural Tourism in Ningde Region as Example

Rural tourism was formed with traditional characteristics of the countryside industry naturally.It combined with human ecology,production,and ecological environment.In order to prepare the image of the future shape of rural tourism strategy in Ningde regions.This study classified visitors’importance of image of rural tourism into 6 categories:“leisure recreation”,“improving knowledge”,“service facilities”,“modern function”,“childhood in the countryside”,and“rich theme activities”by using factor analysis and structured questionnaires to a random sample survey for the visitors over 15 years old.The major result was summarized as follows:the research shows that there are significant differences in tourists’views on the importance of rural tourism image at all levels,and the most importance image of visitors to rural tourism was“service facilities”.

Multidimensional autophagy nano-regulator boosts Alzheimer's disease treatment by improving both extra/intraneuronal homeostasis

Intraneuronal dysproteostasis and extraneuronal microenvironmental abnormalities in Alzheimer’s disease(AD)collectively culminate in neuronal deterioration.In the context of AD,autophagy dysfunction,a multi-link obstacle involving autophagy downregulation and lysosome defects in neurons/microglia is highly implicated in intra/extraneuronal pathological processes.Therefore,multidimensional autophagy regulation strategies co-manipulating“autophagy induction”and“lysosome degradation”in dual targets(neuron and microglia)are more reliable for AD treatment.Accordingly,we designed an RP-1 peptide-modified reactive oxygen species(ROS)-responsive micelles(RT-NM)loading rapamycin or gypenoside XVII.Guided by RP-1 peptide,the ligand of receptor for advanced glycation end products(RAGE),RT-NM efficiently targeted neurons and microglia in AD-affected region.This nanocombination therapy activated the whole autophagy-lysosome pathway by autophagy induction(rapamycin)and lysosome improvement(gypenoside XVII),thus enhancing autophagic degradation of neurotoxic aggregates and inflammasomes,and promoting Aβ phagocytosis.Resultantly,it decreased aberrant protein burden,alleviated neuroinflammation,and eventually ameliorated memory defects in 3×Tg-AD transgenic mice.Our research developed a multidimensional autophagy nano-regulator to boost the efficacy of autophagy-centered AD therapy.

Human Placental Mesenchymal Stem Cells Relieve Primary Sclerosing Cholangitis via Upregulation of TGR5 in Mdr2^(-/-)Mice and Human Intrahepatic Cholangiocyte Organoid Models

Primary sclerosing cholangitis(PSC)is a biliary disease accompanied by chronic inflammation of the liver and biliary stricture.Mesenchymal stem cells(MSCs)are used to treat liver diseases because of their immune regulation and regeneration-promoting functions.This study was performed to explore the therapeutic potential of human placental MSCs(hP-MSCs)in PSC through the Takeda G protein-coupled receptor 5(TGR5)receptor pathway.Liver tissues were collected from patients with PSC and healthy donors(n=4)for RNA sequencing and intrahepatic cholangiocyte organoid construction.hP-MSCs were injected via the tail vein into Mdr2^(-/-),bile duct ligation(BDL),and 3,5-diethoxycarbonyl-1,4-dihydrocollidine(DDC)mouse models or co-cultured with organoids to confirm their therapeutic effect on biliary cholangitis.Changes in bile acid metabolic profile were analyzed by liquid chromatography/tandem mass spectrometry(LC-MS/MS).Compared with healthy controls,liver tissues and intrahepatic cholangiocyte organoids from PSC patients were characterized by inflammation and cholestasis,and marked downregulation of bile acid receptor TGR5 expression.hP-MSC treatment apparently reduced the inflammation,cholestasis,and fibrosis in Mdr2^(-/-),BDL,and DDC model mice.By activating the phosphatidylinositol 3 kinase/extracellular signal-regulated protein kinase pathway,hP-MSC treatment promoted the proliferation of cholangiocytes,and affected the transcription of downstream nuclear factorκB through regulation of the binding of TGR5 and Pellino3,thereby affecting the cholangiocyte inflammatory phenotype.

Rational fusion design inspired by cell-penetrating peptide:SS31/S-14 G Humanin hybrid peptide with amplified multimodal efficacy and bio-permeability for the treatment of Alzheimer’s disease

Alzheimer’s disease is a neurodegenerative disease induced by multiple interconnected mechanisms.Peptide drug candidates with multi-modal efficacy generated from fusion strategy are suitable for addressing multi-facet pathology.However,clinical translation of peptide drugs is greatly hampered by their low permeability into brain.Herein,a hybrid peptide HNSS is generated by merging two therapeutic peptides(SS31 and S-14 G Humanin(HNG)),using a different approach from the classical shuttle-therapeutic peptide conjugate design.HNSS demonstrated increased bio-permeability,with a 2-fold improvement in brain distribution over HNG,thanks to its structure mimicking the design of signal peptide-derived cell-penetrating peptides.HNSS efficiently alleviated mitochondrial dysfunction through the combined effects of mitochondrial targeting,ROS scavenging and p-STAT3 activation.Meanwhile,HNSS with increased Aβaffinity greatly inhibited Aβoligomerization/fibrillation,and interrupted Aβinteraction with neuron/microglia by reducing neuronal mitochondrial Aβdeposition and promoting microglial phagocytosis of Aβ.In3×Tg-AD transgenic mice,HNSS treatment efficiently inhibited brain neuron loss and improved the cognitive performance.This work validates the rational fusion design-based strategy for bio-permeability improvement and efficacy amplification,providing a paradigm for developing therapeutic peptide candidates against neurodegenerative disease.

Impact of total organic carbon and chlorine to ammonia ratio on nitrification in a bench-scale drinking water distribution system

Nitrification occurs in chloraminated drinking water systems and is affected by water quality parameters.The aim of this study was to investigate the impact of total organic carbon and chlorine to ammonia ratio on nitrification potential in a simulated drinking water distribution system as during chloramination.The occurrence of nitrification and activity of nitrifying bacteria was primarily monitored using four rotating annular bioreactors(RAB)with different chlorine to ammonia ratios and total organic carbon(TOC)levels.The results indicated that nitrification occurred despite at a low influent concentration of ammonia,and a high concentration of nitrite nitrogen was detected in the effluent.The study illustrated that reactors 1(R1)and 3(R3),with higher TOC levels,produced more nitrite nitrogen,which was consistent with the ammonia-oxidizing bacteria(AOB)counts,and was linked to a relatively more rapid decay of chloramines in comparison to their counterparts(R2 and R4).The AOB and HPC counts were correlated during the biofilm formation with the establishment of nitrification.Biofilm AOB abundance was also higher in the high TOC reactors compared with the low TOC reactors.The chlorine to ammonia ratio did not have a significant impact on the occurrence of nitrification.Bulk water with a high TOC level supported the occurrence of nitrification,and AOB development occurred at all examined chlorine to ammonia dose ratios(3:1 or 5:1).

Numerical modeling of the seasonal circulation in the coastal ocean of the Northern South China Sea

The Finite Volume Community Ocean Model(FVCOM)was adapted to the Northern South China Sea(NSCS)to investigate the seasonality of coastal circulation,as well as along-shelf and cross-shelf transport.In fall and winter,southwestward current dominates the NSCS shelf,while the currenfs direction shifts to northeast in summer.The circulation pattern in spring is more complicated:both southwestward and northeastward currents are detected on the NSCS shelf.The mean shelf circulation pattern in winter does not show the permanent counter-wind South China Sea Warm Current(SCSWC)along the 100-200 m isobaths.Meanwhile,the model results indicate a northeastward current flowing along 50-100 m isobaths in spring.Southwestward along-shelf transport varies from 0.30-1.93 Sv in fall and winter,and it redirects to northeast in summer ranging jfrom 0.44—1.09 Sv.Onshore transport is mainly through the shelf break segment southeast of the Pearl River Estuary.

Escherichia coli inactivation by pressurized CO_2 treatment methods at room temperature: Critical issues

This study aims to increase the inactivation efficiency of CO_2 against Escherichia coli under mild conditions to facilitate the application of pressurized CO_2 technology in water disinfection. Based on an aerating-cycling apparatus, three different treatment methods（continuous aeration, continuous reflux, and simultaneous aeration and reflux） were compared for the same temperature, pressure（0.3–0.7 MPa）, initial concentration, and exposure time（25 min）. The simultaneous aeration and reflux treatment（combined method） was shown to be the best method under optimum conditions, which were determined to be 0.7 MPa, room temperature, and an exposure time of 10 min. This treatment achieved 5.1-log reduction after 25 min of treatment at the pressure of 0.3 MPa and 5.73-log reduction after 10 min at 0.7 MPa. Log reductions of 4.4 and 5.0 occurred at the end of continuous aeration and continuous reflux treatments at 0.7 MPa, respectively.Scanning electron microscopy（SEM） images suggested that cells were ruptured after the simultaneous aeration and reflux treatment and the continuous reflux treatment. The increase of the solubilization rate of CO_2 due to intense hydraulic conditions led to a rapid inactivation effect. It was found that the reduction of intracellular p H caused by CO_2 led to a more lethal bactericidal effect.

Somatic mutations predict prognosis in myelodysplastic syndrome patients with normal karyotypes

Dear Editor,Myelodysplastic syndromes(MDSs)are a group of clonal myeloid stem cell disorders characterized by varying degrees of cytopenias,cytogenetic and molecular genetic abnormalities,and a predisposition to acute myeloid leukemia(AML).The treatments for MDS mainly consist of cytoreductive treatment,such as traditional AML-like chemotherapy,hypomethylating agents(HMAs),allogeneic hematopoietic stem cell transplantation(alio-HSCT)and immunoregulation according to risk stratification.

Investigation of UV–TiO_2 photocatalysis and its mechanism in Bacillus subtilis spore inactivation

The inactivation levels of Bacillus subtilis spores for various disinfection processes （ultraviolet （UV）, TiO2 and UV-TiO2） were compared. The results showed that the inactivation effect of B. subtilis spores by UV treatment alone was far below that for bacteria without endospores. TiO2 alone in the dark, as a control experiment, exhibited almost no inactivation effect. Compared with UV treatment alone, the inactivation effect increased significantly with the addition of TiO2. Increases of the UV irradiance and Ti02 concentration both contributed to the increase of the inactivation effect. Lipid peroxidation was found to be the underlying mechanism of inactivation. Malondialdehyde （MDA）, the degradation product of lipid peroxidation, was used as an index to determine the extent of the reaction. The MDA concentration surged surprisingly to 3.24 nmol/mg dry cell with the combination disinfection for 600 see （0.10 mW/cm2 irradiance and 10 mg/L TiO2）. In contrast, for UV alone or TiO2 in the dark, the MDA concentration was 0.38 and 0.25 nmol/mg dry cell, respectively, under the same conditions. This indicated that both UV and TiO2 were essential for lipid peroxidation. Changes in cell ultrastructure were observed by transmission electron microscopy. The cell membrane was heavily damaged and cellular contents were completely lysed with the UV-TiO2 process, suggesting that lipid peroxidation was the root of the enhancement in inactivation efficiency.

Deformation mechanisms for a new medium-Mn steel with 1.1 GPa yield strength and 50% uniform elongation

A new medium-Mn steel was designed to achieve unprecedented tensile properties,with a yield strength beyond 1.1 GPa and a uniform elongation over 50%.The tensile behavior shows a heterogeneous deforma-tion feature,which displays a yield drop followed by a large Lüders band strain and several Portevin-Le Châtelier bands.Multiple strain hardening mechanisms for excellent tensile properties were revealed.Firstly,non-uniform martensite transformation occurs only within a localized deformation band,and ini-tiation and propagation of every localized deformation band need only a small amount of martensite transformation,which can provide a persistent and complete transformation-induced-plasticity effect dur-ing a large strain range.Secondly,geometrically necessary dislocations induced from macroscopic strain gradient at the front of localized deformation band and microscopic strain gradient among various phases provide strong heter-deformation-induced hardening.Lastly,martensite formed by displacive shear trans-formation can inherently generate a high density of mobile screw dislocations,and interstitial C atoms segregated at phase boundaries and enriched in austenite play a vital role in the dislocation multipli-cation due to the dynamic strain aging effect,and these two effects provide a high density of mobile dislocations for strong strain hardening.