Millijoule Terahertz Radiation from Laser Wakefields in Nonuniform Plasmas.

We report the experimental measurement of millijoule terahertz (THz) radiation emitted in the backward direction from laser wakefields driven by a femtosecond laser pulse of few joules interacting with a gas target. By utilizing frequency-resolved energy measurement, it is found that the THz spectrum exhibits two peaks located at about 4.5 and 9.0 THz, respectively. In particular, the high frequency component emerges when the drive laser energy exceeds 1.26 J, at which electron acceleration in the forward direction is detected simultaneously. Theoretical analysis and particle-in-cell simulations indicate that the THz radiation is generated via mode conversion from the laser wakefields excited in plasma with an up-ramp profile, where radiations both at the local electron plasma frequency and its harmonics are produced. Such intense THz sources may find many applications in ultrafast science, e.g., manipulating the transient states of matter.

Living Cell-Target Responsive Accessibility Profiling Reveals Silibinin Targeting ACSL4 for Combating Ferroptosis.

We report a living cell-target responsive accessibility profiling (LC-TRAP) approach to identify the targetome of silibinin (SIL), a well-established hepatoprotective natural product (NP), in HepG2 cells. Proteins showing accessibility changes, probed by covalent lysine labeling reagents and leveraged by multiplexed quantitative proteomics, following the administration of SIL to the living cells were assigned as potential targets. Among the assigned targetome, ACSL4, an enzyme essential for ferroptosis induction, might be involved in the hepatoprotective effects of SIL and hence was intensively validated. We first demonstrated that SIL protected HepG2 cells from ferroptosis dependent on ACSL4. Then, we used biophysical assays and a SIL-derivatized chemical probe to corroborate that SIL can bind to ACSL4. The ensuing enzymatic assays showed that SIL inhibited ACSL4 enzymatic activity, thereby mitigating the ACSL4-mediated ferroptosis. As such, we revealed that ACSL4 inhibition, using SIL as a model compound, represents a promising hepatoprotective strategy. Further, since TRAP probes the accessibility changes of reactive proteinaceous lysines, it can pinpoint the proximal regions where the ligand engagement may occur. Thus, the LC-TRAP analysis of SIL, the newly discovered ligand of ACSL4, and arachidonic acid (AA), the substrate, intriguingly showed that SIL and AA both affected the conformation of the K536-proximal region of ACSL4, albeit through distinct binding patterns. Collectively, we describe a straightforward LC-TRAP workflow that does not involve ligand-derived probe synthesis and is widely applicable to target discovery of NPs.

Neospora caninum inhibits tumor development by activating the immune response and destroying tumor cells in a B16F10 melanoma model.

BACKGROUND: Melanoma is a malignant tumor with a high mortality rate. Some microorganisms have been shown to activate the immune system and limit cancer progression. The objective of this study is to evaluate the anti-melanoma effect of Neospora caninum, a livestock pathogen with no pathogenic activity in humans. METHODS: Neospora caninum tachyzoites were inoculated into a C57BL/6 mouse melanoma model by intratumoral and distal subcutaneous injections. Tumor volumes were measured, and cell death areas were visualized by hematoxylin and eosin staining and quantified. Apoptosis in cell cultures and whole tumors was detected by propidium iodide (PI) and TUNEL staining, respectively. Cytokine and tumor-associated factor levels in tumors and spleens were detected by real-time quantitative polymerase chain reaction. Infiltration of macrophages and CD8+ T cells in the tumor microenvironment (TME) were detected by immunohistochemistry with anti-CD68 and anti-CD8 antibodies, respectively. Finally, 16S rRNA sequencing of mice cecal contents was performed to evaluate the effect of N. caninum on gut microbial diversity. RESULTS: Intratumoral and distal subcutaneous injections of N. caninum resulted in significant inhibition of tumor growth (P < 0.001), and more than 50% of tumor cells were dead without signs of apoptosis. Neospora caninum treatment significantly increased the mRNA expression levels of IL-12, IFN-γ, IL-2, IL-10, TNF-α, and PD-L1 in the TME, and IL-12 and IFN-γ in the spleen of tumor-bearing mice (P < 0.05). An increase in the infiltration of CD8+ T cells and macrophages in the TME was observed with these cytokine changes. Neospora caninum also restored the abundance of gut microbiota Lactobacillus, Lachnospiraceae, Adlercreutzia, and Prevotellaceae associated with tumor growth, but the changes were not significant. CONCLUSION: Neospora caninum inhibits B16F10 melanoma by activating potent immune responses and directly destroying the cancer cells. The stable, non-toxic, and efficacious properties of N. caninum demonstrate the potential for its use as a cancer treatment.

Removal of NO in flue gas simulated by the Fe2+/Cu2+-activated double oxidant system.

⋅OHThe wet denitrification technology has a good development prospect due to its simple system and mild reaction conditions, and related research has become a hot topic in the field of flue gas purification. In this work, a novel simultaneous removal technology of NO from flue gas using Fe2+/Cu2+-catalytic H2O2/(NH4)2S2O8 system was developed for the first time. The feasibility of this new flue gas cleaning technology was explored through a series of experiments and performance analyses. The mechanism of oxidation products, free radicals and simultaneous removal of NO was revealed. The effects of the main process parameters on the removal of NO were investigated. Relevant results demonstrated that the removal efficiency of NO was elevated when the concentration of (NH4)2S2O8 or reacting temperature increased, while it was decreased after increasing the raising of Fe2+, Cu2+ and H2O2 concentrations. The main radicals were and·SO4-, using the electron spin resonance technique in the solution, and played a very important role in NO removal. The main products were carried out by ion chromatography and elemental N material accountancy, and the results showed that it was sulfate and nitrate in the solution, which provided theoretical guidance for the subsequent treatment and resource utilization of the absorption solution. The results of the study provided a theoretical basis for the industrial application of wet denitrification.

Attosecond betatron radiation pulse train.

High-intensity X-ray sources are essential diagnostic tools for science, technology and medicine. Such X-ray sources can be produced in laser-plasma accelerators, where electrons emit short-wavelength radiation due to their betatron oscillations in the plasma wake of a laser pulse. Contemporary available betatron radiation X-ray sources can deliver a collimated X-ray pulse of duration on the order of several femtoseconds from a source size of the order of several micrometres. In this paper we demonstrate, through particle-in-cell simulations, that the temporal resolution of such a source can be enhanced by an order of magnitude by a spatial modulation of the emitting relativistic electron bunch. The modulation is achieved by the interaction of the that electron bunch with a co-propagating laser beam which results in the generation of a train of equidistant sub-femtosecond X-ray pulses. The distance between the single pulses of a train is tuned by the wavelength of the modulation laser pulse. The modelled experimental setup is achievable with current technologies. Potential applications include stroboscopic sampling of ultrafast fundamental processes.

Prevalence and molecular identification of Balantioides coli isolates from pet guinea pigs in Central China.

Balantioides coli is the only known zoonotic ciliate that can infect humans and is usually acquired from swine. It has, however, been reported in other mammals, including guinea pigs, where infection prevalence and molecular characterization are relatively unknown. In the present study, 32 guinea pigs from two different pet markets in Luoyang city of the Henan province in China were evaluated for ciliate-like trophozoites or cysts by direct fecal smear microscopy. Positive samples were further characterized using 18S rDNA and ITS1-5.8S rDNA-ITS2 sequence analysis. Microscopy indicated that ciliate-like cysts were observed in the fecal samples of several guinea pigs, were spherical in shape, and exhibited sizes of 40-65 µm in diameter. The average cyst-positive prevalence in guinea pigs was 62.5%. Sequence analysis indicated that the guinea pig-derived ciliate isolates belonged to B. coli and included two genetic variants (A and B), of which genetic variant A was more dominant among the guinea pig samples. To the best of our knowledge, the present study is the first molecular identification of B. coli in guinea pigs and provides some important information for investigating the molecular epidemiology of B. coli.

Cytosolic ME1 integrated with mitochondrial IDH2 supports tumor growth and metastasis.

NADPH is a pivotal cofactor that maintains redox homeostasis and lipogenesis in cancer cells and interference with NADPH production is a promising approach for treating cancer. However, how normal and cancer cells differentially exploit NADPH-producing pathways is unclear, and selective approaches to targeting NADPH are lacking. Here, we show that the assayed cancer cell lines preferentially depend on ME1-mediated NADPH production. ME1 knockdown increases intracellular ROS levels and impairs lipogenesis in cancer cells, leading to retarded proliferation and increased anoikis, while sparing normal cells. Notably, ME1 interference ultimately resulted in adaptive upregulation of mitochondrial IDH2 dependent of AMPK-FoxO1 activation to replenish the NADPH pool and mitigate cytosolic ROS. Combining ME1 ablation and IDH2 inhibition drastically reduces intracellular NADPH and prevents resistance to ME1 interference, resulting in increased apoptosis and impeded tumor growth and metastasis. This study demonstrates that cytosolic ME1 integrated with mitochondrial IDH2 is essential for tumor growth and metastasis, thereby highlighting the blockade of metabolic compensation by disrupting mitochondrial-cytosol NADPH transport as a promising approach to selectively targeting NADPH in cancer cells that rely on NADPH-driven antioxidant systems.

First molecular identification of Buxtonella ciliates from captive-bred mangabeys (Cercocebus torquatus) from China.

Buxtonella species are large cyst-forming ciliates that infect ruminants and monkeys, and are morphologically similar to Balantidium coli ciliates that infect pigs, humans, monkeys, and other animals. In this study, we isolated spherical cysts of ciliates that were similar to those of Balantidium and Buxtonella species within collared mangabeys (Cercocebus torquatus) from the Wangcheng Zoo of Luoyang in the Henan Province of central China. The cysts were further identified and designated as belonging to the Buxtonella monkey genotype based on molecular analyses of 18S rRNA, 5.8S rRNA, and ITS1-5.8S rRNA-ITS2 genetic markers. To our knowledge, this is the first report of Buxtonella monkey genotype within monkeys in China. These results will help clarify the classification of species of cyst-forming ciliate infections in monkeys.

A novel serine/threonine protein phosphatase type 5 from second-generation merozoite of Eimeria tenella is associated with diclazuril-induced apoptosis.

Screening the anticoccidial drug targets is very important for developing novel drugs and revealing the molecular basis of drug resistance in coccidia. Due to high effectivity and safety, diclazuril was used widely in the poultry industry. To assess the roles of the serine/threonine protein phosphatase type 5 of second-generation merozoites in Eimeria tenella (EtPP5) in the anticoccidial activity of diclazuril against chicken coccidiosis, EtPP5 was cloned using reverse transcriptase polymerase chain reaction and rapid amplification of cDNA ends. Ultrastructural changes in second-generation merozoites and mRNA expression level of EtPP5 were monitored by transmission electron microscopy (TEM) and quantitative real-time PCR, respectively. The results showed that the full length of the cloned EtPP5 cDNA (2,495 bp) encompassed a 1,647-bp open reading frame encoding a polypeptide of 548 residues with an estimated molecular mass of 60.82 kDa and a theoretical isoelectric point of 5.89. Molecular analysis of EtPP5 reveals the presence of a C-terminal phosphatase domain and an extended N-terminal tetratricopeptide repeat motif, a typical feature of protein phosphatases. The cDNA sequence has been submitted to the GenBank database with accession number JX987508. EtPP5 shared 89% homology with the published sequence of a PP5 ortholog of Toxoplasma gondii at the amino acid level (GenBank XP_002364442.1). TEM observed that diclazuril induced ultrastructural changes in second-generation merozoites. Quantitative real-time PCR analysis showed that compared with the control group, the level of EtPP5 mRNA expression was significantly downregulated by 51.4% by diclazuril treatment. The high similarity of EtPP5 to previously described PP5 of other organisms, as well as its downregulated expression and connection with apoptosis in the second-generation merozoites induced by diclazuril, suggests that it could act an important role in understanding the signaling mechanism underlining the diclazuril-induced merozoites apoptosis.

Morphological and molecular characterization of Sarcocystis miescheriana from pigs in the central region of China.

Sarcocystosis is an important food-borne parasitosis in humans and various animals. Sarcocystis miescheriana and Sarcocystis suihominis are pathogenic to pigs; S. suihominis is also distinctly pathogenic to humans. Intermediate and final hosts can harbor more than one Sarcocystis species, so the exact identification for Sarcocystis infection in various hosts is essential to control sarcocystosis in humans and important economic animals including pigs. In this study, four isolates of sarcocysts from slaughtered pigs (SmJY1-SmJY4) in the central region of China, in Henan province, were collected and examined by transmission electron microscopy and 18S rRNA sequence analysis to identify the Sarcocystis species in pigs in China. The results showed that cysts in the diaphragm muscles have a thick cyst wall with a number of palisade-like protrusions up to 4.38 µm in length. Inside these protrusions, there were 13-16 fibrils per protrusion. Bradyzoites in cysts showed typical characteristics of Apicomplexa including a conoid, many micronemes, dense bodies, one big nucleus, and a number of amylopectin granules. These ultrastructural results suggest that characteristics of tissue cysts of the isolates SmJY1-SmJY4 were similar to those of S. miescheriana. The sequence similarities of SmJY1-SmJY4 with S. miescheriana were 99-99.5 %, and the sequence similarities of SmJY1-SmJY4 with S. suihominis were much lower. Results of the ultrastructural observation in combination with molecular characterization based on the 18S rRNA sequence represent the first demonstration of S. miescheriana in pigs in China. In addition, results of the histological examination showed that the cysts of S. miescheriana had two types of cyst wall, a palisade-like thick wall and another smoothly thin wall, and could cause obvious atrophy, degeneration, and necrosis of muscle fibers in the diaphragm of naturally infected pigs. These findings will provide an important reference for the examination of Sarcocystis species in the slaughter quarantine of live pigs and in the control of sarcocystosis in pigs.

Function of the iron-binding chelator produced by Coriolus versicolor in lignin biodegradation.

An ultrafiltered low-molecular-weight preparation of chelating compounds was isolated from a wood-containing culture of the white-rot basidiomycete Coriolus versicolor. This preparation could chelate Fe3+ and reduce Fe3+ to Fe2+, demonstrating that the substance may serve as a ferric chelator, oxygen-reducing agent, and redox-cycling molecule, which would include functioning as the electron transport carrier in Fenton reaction. Lignin was treated with the iron-binding chelator and the changes in structure were investigated by 1H-NMR, 13C-NMR, difference spectrum caused by ionization under alkaline conditions and nitrobenzene oxidation. The results indicated that the iron-binding chelator could destroy the beta-O-4 bonds in etherified lignin units and insert phenolic hydroxyl groups. The low-molecular-weight chelator secreted by C. versicolor resulted in new phenolic substructures in the lignin polymer, making it susceptible to attack by laccase or manganese peroxidase. Thus, the synergic action of the iron-binding chelator and the lignocellulolytic enzymes made the substrate more accessible to degradation.