tert-Butyl Nitrite-Induced Radical Nitrile Oxidation Cycloaddition: Synthesis of Isoxazole/Isoxazoline-Fused Benzo 6/7/8-membered Oxacyclic Ketones.

A practical metal-free and additive-free approach for the synthesis of 6/7/8-membered oxacyclic ketone-fused isoxazoles/isoxazolines tetracyclic or tricyclic structures is reported through Csp3-H bond radical nitrile oxidation and the intramolecular cycloaddition of alkenyl/alkynyl-substituted aryl methyl ketones. This convenient approach enables the simultaneous formation of isoxazole/isoxazoline and 6/7/8-membered oxacyclic ketones to form polycyclic architectures by using tert-butyl nitrite (TBN) as a non-metallic radical initiator and N-O fragment donor.

C24-Ceramide Drives Gallbladder Cancer Progression Through Directly Targeting Phosphatidylinositol 5-Phosphate 4-Kinase Type-2 Gamma to Facilitate Mammalian Target of Rapamycin Signaling Activation.

BACKGROUND AND AIMS: The wide prevalence of chemoresistance and compromised early diagnosis of gallbladder cancer (GBC) has led to poor patient prognosis, requiring sustained efforts for the identification of effective biomarkers and therapeutic intervention. Ceramides have emerged as intracellular signaling molecules linked to tumorigenesis and therapeutic response in cancers. However, the clinical relevance of ceramides with GBC has not been investigated. APPROACH AND RESULTS: In the present study, we revealed aberrant gene expressions (e.g., serine palmitoyltransferase 1 [SPTLC1] and ceramide synthase 2 [CERS2]) of de novo ceramide biosynthesis and length-specific ceramide production in GBC tissues. Analyses of serum ceramide pattern in healthy controls, gallbladder stone, and GBC patients identified C24-Ceramide as a potential diagnostic biomarker for patients with GBC. Importantly, elevation of SPTLC1, CERS2, and its product, C24-Ceramide, was associated with tumor staging, distal metastasis, and worse prognosis. In line with this, C24 -Ceramide promoted GBC cell proliferation and migration in vitro and in vivo. Mechanistically, C24-Ceramide directly bound to phosphatidylinositol 5-phosphate 4-kinase type-2 gamma (PIP4K2C), a regulator of mammalian target of rapamycin (mTOR), to facilitate mTOR complex formation and activation. C6-Ceramide, an analogue of natural ceramide, competed with C24-Ceramide for PIP4K2C binding, thereby abrogating C24-Ceramide-mediated mTOR signaling activation and oncogenic activity. Furthermore, stimulation with C6-Ceramide significantly suppressed the proliferative and metastatic capacity of GBC cells in vitro and in vivo, which was dependent on PIP4K2C. CONCLUSIONS: Our findings highlight the clinical relevance of ceramide metabolism with GBC progression and identify C24-Ceramide as a diagnostic biomarker for GBC. We propose that PIP4K2C is indispensable for C6-Ceramide as a potential therapeutic intervention for GBC through a direct competition with C24-Ceramide.

Comparative Analysis of Acanthopanacis Cortex and Periplocae Cortex Using an Electronic Nose and Gas Chromatography-Mass Spectrometry Coupled with Multivariate Statistical Analysis.

Chinese Herbal Medicines (CHMs) can be identified by experts according to their odors. However, the identification of these medicines is subjective and requires long-term experience. The samples of Acanthopanacis Cortex and Periplocae Cortex used were dried cortexes, which are often confused in the market due to their similar appearance, but their chemical composition and odor are different. The clinical use of the two herbs is different, but the phenomenon of being confused with each other often occurs. Therefore, we used an electronic nose (E-nose) to explore the differences in odor information between the two species for fast and robust discrimination, in order to provide a scientific basis for avoiding confusion and misuse in the process of production, circulation and clinical use. In this study, the odor and volatile components of these two medicinal materials were detected by the E-nose and by gas chromatography-mass spectrometry (GC-MS), respectively. An E-nose combined with pattern analysis methods such as principal component analysis (PCA) and partial least squares (PLS) was used to discriminate the cortex samples. The E-nose was used to determine the odors of the samples and enable rapid differentiation of Acanthopanacis Cortex and Periplocae Cortex. GC-MS was utilized to reveal the differences between the volatile constituents of Acanthopanacis Cortex and Periplocae Cortex. In all, 82 components including 9 co-contained components were extracted by chromatographic peak integration and matching, and 24 constituents could be used as chemical markers to distinguish these two species. The E-nose detection technology is able to discriminate between Acanthopanacis Cortex and Periplocae Cortex, with GC-MS providing support to determine the material basis of the E-nose sensors' response. The proposed method is rapid, simple, eco-friendly and can successfully differentiate these two medicinal materials by their odors. It can be applied to quality control links such as online detection, and also provide reference for the establishment of other rapid detection methods. The further development and utilization of this technology is conducive to the further supervision of the quality of CHMs and the healthy development of the industry.

Apoptosis of Acanthamoeba castellanii Trophozoites Induced by Oleic Acid.

Acanthamoeba spp. can be parasitic in certain situations and are responsible for serious human infections, including Acanthamoeba keratitis, granulomatous amoebic encephalitis, and cutaneous acanthamoebiasis. We analyzed the fatty acid composition of Acanthamoeba castellanii trophozoites and tested the inhibitory activity of the main fatty acids, oleic acid and arachidonic acid, in vitro. Oleic acid markedly inhibited the growth of A. castellanii, with trophozoite viability of 57.4% at a concentration of 200 µM. Caspase-3 staining and annexin V assays showed that apoptotic death occurred in A. castellanii trophozoites. Quantitative PCR and dot blot analysis showed increased levels of metacaspase and interleukin-1ß converting enzyme, which is also an indication of apoptosis. In contrast, arachidonic acid showed negligible inhibition of growth of A. castellanii trophozoites. Stimulated expression of Atg3, Atg8 and LC3A/B genes and monodansylcadaverine labeling suggested that oleic acid induces apoptosis by triggering autophagy of trophozoites.

Hippocalcin-like 1 suppresses hepatocellular carcinoma progression by promoting p21(Waf/Cip1) stabilization by activating the ERK1/2-MAPK pathway.

UNLABELLED: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death. However, the underlying mechanism during hepatocarcinogenesis remains unclarified. Stable isotope labeling by amino acids in cell culture (SILAC) is a powerful quantitative strategy for proteome-wide discovery of novel biomarkers in cancers. Hippocalcin-like 1 (HPCAL1) is a calcium sensor protein. However, the biological function of HPCAL1 is poorly understood in cancers, including HCC. Herein, HPCAL1 was identified by SILAC as a novel hepatocarcinogenesis suppressor down-regulated in HCC cell lines and tissues. Importantly, lost expression of HPCAL1 was associated with worse prognosis of HCC patients. Interestingly, secreted HPCAL1 protein in the plasma dropped dramatically in HCC patients compared with healthy donors. Receiver operating characteristic curve analysis showed that serum HPCAL1 at a concentration of 8.654 ng/mL could better predict HCC. Furthermore, ectopic expression of HPCAL1 suppresses cell proliferation, while depletion of HPCAL1 led to increased cell growth both in vitro and in vivo. Mechanistically, HPCAL1 directly interacted with p21(Waf/Cip1) in the nucleus, which requires the EF-hand 4 motif of HPCAL1 and the Cy1 domain of p21. This interaction stabilized p21(Waf/Cip1) in an extracellular signal-regulated kinase 1/2-mitogen-activated protein kinase-dependent manner, which subsequently prevented p21(Waf/Cip1) proteasomal degradation by disrupting SCF(Skp2) and CRL4(Cdt2) E3 ligase complexes, resulting in increased protein stability and inhibitory effect of p21(Waf/Cip1). Notably, the tumor suppressive function of HPCAL1 was dependent on p21 in vitro and in vivo. Consistent with this observation, expression of HPCAL1 and p21(Waf/Cip1) was positively correlated in HCC tissues. CONCLUSION: These findings highlight a novel tumor suppressor upstream of p21(Waf/Cip1) in attenuating cell cycle progression and provide a promising diagnostic and prognostic factor, as well as a potential therapeutic target for HCC.

Total synthesis and biological evaluation of spirotryprostatin A analogs.

Based on the spirotryprostatin A structure, a series of compounds belonging to spiro-indolyl diketopiperazine structural class were designed and synthesized, which embody an oxindole with an all-carbon quaternary stereocenter. The total synthesis can efficiently be accessed in a seven-step reaction sequence with 18-28% overall yield from commercially available materials, and a highly enantioselective 1,3-dipolar cycloaddition, N-acylation of the resulting stereochemically complex spiro[pyrrolidin-3,3'-oxindole]s core with Fmoc-L-pro-Cl and spontaneous ring closure upon N-deprotection were obtained. The synthesized compounds 13a-e and 15a-e were evaluated for their antibacterial activities. The result showed that compounds 13b and 15b were active only against Gram-positive bacteria, and selective antibacterial activity was exhibited by compounds 13d and 13e against Streptococcus lactis. Further, all the remaining compounds showed a certain degree of antibacterial activity. In addition, the structure-activity relationship is also discussed.

A new p-hydroxybenzoic acid derivative from an endophytic fungus Penicillium sp. of Nerium indicum.

A new p-hydroxybenzoic acid derivative named 4-(2'R, 4'-dihydroxybutoxy) benzoic acid (1) was isolated from the fermentation of Penicillium sp. R22 in Nerium indicum. The structure was elucidated by means of spectroscopic (HR-ESI-MS, NMR, IR, UV) and X-ray crystallographic methods. The antibacterial and antifungal activity of compound 1 was tested, and the results showed that compound 1 revealed potent antifungal activity against Colletotrichum gloeosporioides, Alternaria alternata, and Alteranria brassicae with MIC value of 31.2 µg/ml.

[Transcriptome analysis reveals genes involved in biosynthesis of secondary metabolism in Cornus officinalis].

In order to explore genetic basis for the biosynthesis of secondary metabolism,the transcriptome of Cornus officinalis was sequenced by the new generation of high-throughput sequencing technology,A total of 96 032 unigenes were assembled with an average length of 590.53 bp. Among them, 35 478 unigenes were annotated in the public databases NR,Swissprot,COG,GO,KOG,Pfam and KEGG. Based on the assignment of KEGG pathway, 84 involved in ridoid biosynthesis and 487 unigenes involved in others secondary metabolites biosynthesis were found. Additionally,53 unigenes and 72 unigenes were predicted to have potential functions of cytochome P450 and UDP- glycosyltransferases based on the annotation result, which may encode responsible for secondary metabolites modification. This study was the first comprehensive transcriptome analysis for C. officinalis, and the candidate genes involved in the biosynthesis of secondary metabolites were obtained. The transcriptome data constitutes a much more abundant genetic resource that can be utilized to benefit further molecular biology studies on C. officinalis.

Transmission of Mycobacterium tuberculosis in China: a population-based molecular epidemiologic study.

BACKGROUND: Understanding the transmission of Mycobacterium tuberculosis is essential for the development of efficient tuberculosis control strategies. China has the second-largest tuberculosis burden in the world. Recent transmission and infection with M. tuberculosis, particularly drug-resistant strains, may account for many new tuberculosis cases. METHODS: We performed a population-based molecular epidemiologic study of pulmonary tuberculosis in China during 1 July 2009 to 30 June 2012. We defined clusters as cases with identical variable number tandem repeat genotype patterns and identified the risk factors associated with clustering, by logistic regression. Relative transmission rates were estimated by the sputum smear status and drug susceptibility status of tuberculosis patients. RESULTS: Among 2274 culture-positive tuberculosis patients with genotyped isolates, there were 705 (31.0%) tuberculosis patients in 287 clusters. Multidrug-resistant (MDR) tuberculosis (adjusted odds ratio [aOR], 1.86; 95% confidence interval [CI], 1.25-2.63) and infection with a Beijing family strain (aOR, 1.56; 95% CI, 1.23-2.96) were associated with clustering. Eighty-four of 280 (30.0%) clusters had a putative source case that was sputum smear negative, and 30.6% of their secondary cases were attributed to transmission by sputum smear-negative patients. The relative transmission rate for sputum smear negative compared with sputum smear-positive patients was 0.89 (95% CI, .68-1.10), and was 1.51 (95% CI, 1.00-2.24) for MDR tuberculosis vs drug-susceptible tuberculosis. CONCLUSIONS: Recent transmission of M. tuberculosis, including MDR strains, contributes substantially to tuberculosis disease in China. Sputum smear-negative cases were responsible for at least 30% of the secondary cases. Interventions to reduce the transmission of M. tuberculosis should be implemented in China.

Opto-mechanisms design of extreme-ultraviolet camera onboard Chang E lunar lander.

The extreme-ultraviolet camera mounted on the Lander of China Chang-E lunar exploration project launched in 2013 is the first instrument used to imaging from the lunar surface to the whole plasmasphere around the earth. Taking into account both the lunar environment conditions and the weight and volume constraints, a single spherical mirror and a spherical microchannel plate detector make up the compact optical system. An optimized opto-mechanical design was presented using Finite Element Analysis Model, and the detail design for the important assemblies of the 2-axis platform, the primary mirror, the aperture door mechanism and MCP detector were all specially addressed for their environmental adaptability and reliability. Tests of mechanical characteristics have demonstrated that the position and pointing accuracy and its stability meets the operation requirements of 2'. Vibration results have shown that the EUVC has adequate stiffness and strength safety margin to survive in launch and the moon environments. The imaging performance with the resolution of 0.08° is measured after vibration, in agreement with the predicted performance.

Quaternized chitosan-based organic-inorganic nanohybrid nanoparticles loaded with prothioconazole for efficient management of fungal diseases with minimal environmental impact.

Poor foliar deposition and retention of pesticides results in serious pesticide residues and environmental pollution. Organic-inorganic hybridized nanoparticles (OIHN), combining the advantages of organic and inorganic materials, can be used as carriers to load pesticides for efficient and safe application. Herein, a novel multifunctional OIHN composed of mesoporous silica nanoparticles (MSNs) and cationic chitosan quaternary ammonium salt (HACC) was constructed and used as a delivery system for prothioconazole (PTC). The resultant PTC@MSNs-HACC exhibited a remarkable loading capacity of 39.07 wt% and demonstrated enhanced PTC release (31.47 %) under alkaline conditions. The UV-shielding properties of MSNs efficiently shielded PTC from photodegradation, increasing its photostability by over threefold. The strong positive charge of HACC conferred excellent adhesion of PTC@MSNs-HACC to fungal cell membranes, leading to high deposition on wheat leaves with improved rain-wash resistance (increased by 30 %). Consequently, PTC@MSNs-HACC (EC50: 12.48 mg/L) exhibited superior wheat scab control compared to PTC emulsifiable concentrate (EC50: 28.49 mg/L). Additionally, PTC@MSNs-HACC displayed excellent uptake and transport in plants, ensuring plant safety and reducing toxicity to zebrafish by >1-fold. The potential application of the developed PTC@MSNs-HACC in agricultural production holds significant promise and is anticipated to find widespread use in the future.

Enhanced control efficacy of spinosad on corn borer using polylactic acid encapsulated mesoporous silica nanoparticles as a smart delivery system.

Asion corn borer (Ostrinia furnacalis (Guenee)) is one of the most important factors affecting the normal growth and yield of corn. However, chemical control methods currently in use cause severe pollution. In the present study, aminated mesoporous silica nanoparticles (MSNs-NH2) and polylactic acid (PLA) were used as the carrier and capping agent respectively to construct an insect gut microenvironment nano-response system that loaded spinosad, a biopesticide used to control O. furnacalis. The resulting spinosad@MSNs-PLA demonstrated high loading capacity (38.6 %) and improved photostability of spinosad. Moreover, this delivery system could intelligently respond to the intestinal microenvironment of the corn borer's gut and achieve the smart release of spinosad. Compared with the conventional pesticide, spinosad@MSNs-PLA exhibited superior efficacy in controlling the O. furnacalis and could uptake and transport in maize plants without adverse effects on their growth. Furthermore, the toxicity of spinosad@MSNs-PLA on zebrafish was reduced by over 50 times. The prepared spinosad@MSNs-PLA has great potential and could be widely applied in agricultural production in the future. This approach could improve the utilization of pesticide and reduce environmental pollution. In addition, MSNs-PLA nano vectors provide new ideas for the control of other borer pests.

Reduced SUMOylation of Nrf2 signaling contributes to its inhibition induced by amyloid-ß.

Oxidative stress induced by amyloid-ß (Aß) has been considered as one of the important mechanisms in the development of Alzheimer disease (AD). The inhibition of endogenous antioxidant Nrf2 signaling in the brain of AD patients aggravates the oxidative damage, however, the causes of Nrf2 signaling inhibition are unclear. It is reported that smallubiquitin-like modification (SUMOylation) is involved in the process of oxidative injury. To investigate whether and how SUMOylation was involved in the inhibition of Nrf2 signaling pathway induced by Aß, Aß intrahippocampal injection rat model and Aß treated SH-SY5Y cell model were used in the current study. Small interfering RNA and lentivirus transfection were used to intervene SUMOylation, and the level of SUMOylation was assessed by immunoprecipitation. The present in vivo and in vitro studies revealed that SUMOylation levels of Nrf2 and MafF, as well as the overall SUMOylation level were reduced under long-term Aß insult. Meanwhile, the binding of Nrf2 to MafF was decreased, accompanied by low interaction with antioxidant response element (ARE) area of gene. Down-regulation of SUMO protein exacerbated the Aß-induced inhibition of Nrf2 signaling pathway, while, enhancement of SUMOylation of Nrf2 and MafF by overexpression of Ubc9 reversed this process. These results imply that reduction in SUMOylation induced by Aß contributed to the inhibition of Nrf2 signaling, and SUMOylation might be a potential therapeutic target of AD.

Protease inhibitor ASP enhances freezing tolerance by inhibiting protein degradation in kumquat.

Cold acclimation is a complex biological process leading to the development of freezing tolerance in plants. In this study, we demonstrated that cold-induced expression of protease inhibitor FmASP in a Citrus-relative species kumquat [Fortunella margarita (Lour.) Swingle] contributes to its freezing tolerance by minimizing protein degradation. Firstly, we found that only cold-acclimated kumquat plants, despite extensive leaf cellular damage during freezing, were able to resume their normal growth upon stress relief. To dissect the impact of cold acclimation on this anti-freezing performance, we conducted protein abundance assays and quantitative proteomic analysis of kumquat leaves subjected to cold acclimation (4°C), freezing treatment (-10°C) and post-freezing recovery (25°C). FmASP (Against Serine Protease) and several non-specific proteases were identified as differentially expressed proteins induced by cold acclimation and associated with stable protein abundance throughout the course of low-temperature treatment. FmASP was further characterized as a robust inhibitor of multiple proteases. In addition, heterogeneous expression of FmASP in Arabidopsis confirmed its positive role in freezing tolerance. Finally, we proposed a working model of FmASP and illustrated how this extracellular-localized protease inhibitor protects proteins from degradation, thereby maintaining essential cellular function for post-freezing recovery. These findings revealed the important role of protease inhibition in freezing response and provide insights on how this role may help develop new strategies to enhance plant freezing tolerance.

Mycobacterium tuberculosis Beijing strains favor transmission but not drug resistance in China.

BACKGROUND: The Mycobacterium tuberculosis Beijing strains are widespread globally. We aimed to determine whether Beijing strains in China are more likely than other strains to spread, and whether they are more likely to become drug resistant. We also sought to determine whether different Beijing sublineages have distinct phenotypic characteristics. METHODS: We conducted a population-based molecular epidemiologic study in 6 provinces in China from 2009 to 2010. We analyzed data and specimens from culture-confirmed pulmonary tuberculosis patients. Each patient's isolate was genotyped using 16-loci variable number of tandem repeats and 6 single-nucleotide polymorphisms. RESULTS: By genotyping, 75.0% (1031/1375) of the strains of M. tuberculosis were Beijing strains. Beijing strains were more likely than non-Beijing strains to be in a genotypic cluster (odds ratio, 2.40, P < .001), and were significantly associated with younger age (P(trend) < .05). There was no significant difference in the proportion of Beijing strains and non-Beijing strains that were drug resistant, even when stratified by new vs retreatment patients. We identified 6 sublineages of Beijing strains in the study population. The modern sublineage of Beijing strains were more likely than the ancient sublineages to be clustered (odds ratio, 2.27, P < .001). CONCLUSIONS: Beijing strains of M. tuberculosis were significantly associated with genotypic clustering, reflecting recent transmission, and younger age, but were not associated with drug resistance. Future studies of Beijing family strains should avoid assuming and attributing characteristics to the entire family and should assess strains of specific sublineages and/or settings.

The differences in learning motivation of college freshmen in Northwest China.

The study aimed to investigate the learning motivation of freshmen from a university in Northwest China, which can supply a reference for improving their learning quality and objectives. Data were collected from 800 freshmen of different majors with a learning motivation questionnaire. Differences in learning motivation between different majors, genders, regions, and students are studied. The results show that gender, seeking knowledge orientation, and material pursuit have significant effects on students' learning motivation. The gender had a significant impact on personal achievement and the only child or not had an obvious effect on material pursuit, while other factors had no obvious difference in gender, regional, and only child or not, while other factors on the gender, regional, and whether the one-child had no obvious difference. According to the results of the research, measures to improve learning motivation are proposed. Our research results provide a reference for improving learning attitude and the quality of universities.

AMPK induces degradation of the transcriptional repressor PROX1 impairing branched amino acid metabolism and tumourigenesis.

Tumour cell metabolic plasticity is essential for tumour progression and therapeutic responses, yet the underlying mechanisms remain poorly understood. Here, we identify Prospero-related homeobox 1 (PROX1) as a crucial factor for tumour metabolic plasticity. Notably, PROX1 is reduced by glucose starvation or AMP-activated protein kinase (AMPK) activation and is elevated in liver kinase B1 (LKB1)-deficient tumours. Furthermore, the Ser79 phosphorylation of PROX1 by AMPK enhances the recruitment of CUL4-DDB1 ubiquitin ligase to promote PROX1 degradation. Downregulation of PROX1 activates branched-chain amino acids (BCAA) degradation through mediating epigenetic modifications and inhibits mammalian target-of-rapamycin (mTOR) signalling. Importantly, PROX1 deficiency or Ser79 phosphorylation in liver tumour shows therapeutic resistance to metformin. Clinically, the AMPK-PROX1 axis in human cancers is important for patient clinical outcomes. Collectively, our results demonstrate that deficiency of the LKB1-AMPK axis in cancers reactivates PROX1 to sustain intracellular BCAA pools, resulting in enhanced mTOR signalling, and facilitating tumourigenesis and aggressiveness.

The Relationship Between Perceived Stress, State-Trait Anxiety, and Sleep Quality Among University Graduates in China During the COVID-19 Pandemic.

The study aimed to investigate the relationship among perceived stress, state-trait anxiety, and sleep quality of graduates to provide a reference for improving their psychological status and attitude adjustment of job-searching during the COVID-19 pandemic. The research was conducted in a descriptive cross-sectional online survey between May 2020 and August 2020. The data were collected from 1,200 participants by using the personal information form prepared by the researchers in line with the literature, the Perceived Stress Scale, the State-Trait Anxiety Inventory, and the Pittsburgh Sleep Quality Index (PSQI). Among the surveyed participants, 47.67% were female, and 10.92% were medical students. The mean perceived stress, state anxiety, trait anxiety, and sleep quality were moderate and found as 31.4±6.69, 46.67±5.80, 49.45±5.54, and 5.94±2.47, respectively. The detection rates of state anxiety and trait anxiety were 48.63 and 49.50%, respectively. There was no significant difference in the detection rate of state anxiety and trait anxiety among different genders and majors (p >0.05). The detection rate of state anxiety and trait anxiety of rural family students was higher than that of urban family students (p <0.01). The score on the PSQI was positively associated with the scores on the perceived stress, state anxiety, and trait anxiety scales (p <0.001 for each model). Sleep quality was associated with increased perceived stress, state anxiety, and trait anxiety among graduates in China. Collectively, the study revealed the relationship between perceived stress, state-trait anxiety, and sleep quality among university graduates in China during the COVID-19 pandemic. Our results offer novel practical implications for all circles of the society to ensure students' health under the context of the COVID-19 epidemic.

Mg/ZrO2 Metal Matrix Nanocomposites Fabricated by Friction Stir Processing: Microstructure, Mechanical Properties, and Corrosion Behavior.

Magnesium (Mg) and its alloys have attached more and more attention because of their potential as a new type of biodegradable metal materials. In this work, AZ31/ZrO2 nanocomposites with good uniformity were prepared successfully by friction stir processing (FSP). The scanning electron microscope (SEM) and transmission electron microscope (TEM) were used to characterize the microstructure of the composites. The mechanical properties, electrochemical corrosion properties and biological properties were evaluated. In addition, the effect of reinforced particles (ZrO2) on the microstructure and properties of the composite was studied comparing with FSP AZ31 Mg alloy. The results show that compared with the base metal (BM), the AZ31/ZrO2 composite material achieves homogenization, densification, and grain refinement after FSP. The combination of dynamic recrystallization and ZrO2 particles leads to grain refinement of Mg alloy, and the average grain size of AZ31/ZrO2 composites is 3.2 µm. After FSP, the c-axis of grain is deflected under the compression stress of shoulder and the shear stress of pin. The ultimate tensile strength (UTS) and yield strength (YS) of BM were 283 and 137 MPa, respectively, the UTS and YS of AZ31/ZrO2 composites were 427 and 217 MPa, respectively. The grain refinement and Orowan strengthening are the major strengthening mechanisms. Moreover, the corrosion resistance in simulated body fluid of Mg alloy is improved by grain refinement and the barrier effect of ZrO2.

Autophagy Activated by Peroxiredoxin of Entamoeba histolytica.

Autophagy, an evolutionarily conserved mechanism to remove redundant or dangerous cellular components, plays an important role in innate immunity and defense against pathogens, which, in turn, can regulate autophagy to establish infection within a host. However, for Entamoeba histolytica, an intestinal protozoan parasite causing human amoebic colitis, the interaction with the host cell autophagy mechanism has not been investigated. In this study, we found that E. histolytica peroxiredoxin (Prx), an antioxidant enzyme critical for parasite survival during the invasion of host tissues, could activate autophagy in macrophages. The formation of autophagosomes in macrophages treated with recombinant Prx of E. histolytica for 24 h was revealed by immunofluorescence and immunoblotting in RAW264.7 cells and in mice. Prx was cytotoxic for RAW264.7 macrophages after 48-h treatment, which was partly attributed to autophagy-dependent cell death. RNA interference experiments revealed that Prx induced autophagy mostly through the toll-like receptor 4 (TLR4)-TIR domain-containing adaptor-inducing interferon (TRIF) pathway. The C-terminal part of Prx comprising 100 amino acids was the key functional domain to activate autophagy. These results indicated that Prx of E. histolytica could induce autophagy and cytotoxic effects in macrophages, revealing a new pathogenic mechanism activated by E. histolytica in host cells.