Evaluation of protective immunity induced by a DNA vaccine encoding SAG2 and SRS2 against Toxoplasma gondii infection in mice.

Toxoplasma gondii is an important protozoan pathogen, which can cause severe diseases in the newborns and immunocompromised individuals. Developing an effective vaccine against Toxoplasma infection is a critically important global health priority. Immunofluorescence staining analysis revealed that TgSAG2 and TgSRS2 are membrane associated and displayed on the surface of the parasite. Immunizations with pBud-SAG2, pBud-SRS2 and pBud-SAG2-SRS2 DNA vaccines significantly increased the production of specific IgG antibodies. Immunization with pBud-SAG2-SRS2 elicited cellular immune response with higher concentrations of IFN-γ and IL-4 compared to the control group. Antigen-specific lymphocyte proliferations in the pBud-SRS2 and pBud-SAG2-SRS2 groups were significantly higher compared to that in the control group. Furthermore, 30 % of mice immunized with pBud-SAG2-SRS2 survived after the challenge infection with virulent T. gondii RH tachyzoites. This study revealed that immunization with pBud-SAG2-SRS2 induced potent immune responses, and has the potential as a promising vaccine candidate for the control of T. gondii infection.

Multiple small-dose infusions of G-CSF-mobilized haploidentical lymphocytes after autologous haematopoietic stem cell transplantation for acute myeloid leukaemia.

This retrospective study analysed 106 acute myeloid leukaemia (AML) patients undergoing autologous haematopoietic stem cell transplantation (ASCT) to assess the impact of multiple small-dose infusions of granulocyte-colony-stimulating factor (G-CSF)-mobilized haploidentical lymphocytes as post-ASCT maintenance therapy. Among them, 50 patients received lymphocyte maintenance therapy, 21 received alternative maintenance therapy, and 35 received no maintenance therapy. Patients receiving lymphocyte maintenance therapy demonstrated significantly higher overall survival (OS) and disease-free survival (DFS) compared to those without maintenance therapy, with 4-year OS and DFS rates notably elevated. While there were no significant differences in recurrence rates among the three groups, lymphocyte maintenance therapy showcased particular benefits for intermediate-risk AML patients, yielding significantly higher OS and DFS rates and lower relapse rates compared to alternative maintenance therapy and no maintenance therapy. The study suggests that multiple small-dose infusions of G-CSF-mobilized haploidentical lymphocytes may offer promising outcomes for AML patients after ASCT, particularly for those classified as intermediate-risk. These findings underscore the potential efficacy of lymphocyte maintenance therapy in reducing disease relapse and improving long-term prognosis in this patient population.

AMPK targets PDZD8 to trigger carbon source shift from glucose to glutamine.

The shift of carbon utilization from primarily glucose to other nutrients is a fundamental metabolic adaptation to cope with decreased blood glucose levels and the consequent decline in glucose oxidation. AMP-activated protein kinase (AMPK) plays crucial roles in this metabolic adaptation. However, the underlying mechanism is not fully understood. Here, we show that PDZ domain containing 8 (PDZD8), which we identify as a new substrate of AMPK activated in low glucose, is required for the low glucose-promoted glutaminolysis. AMPK phosphorylates PDZD8 at threonine 527 (T527) and promotes the interaction of PDZD8 with and activation of glutaminase 1 (GLS1), a rate-limiting enzyme of glutaminolysis. In vivo, the AMPK-PDZD8-GLS1 axis is required for the enhancement of glutaminolysis as tested in the skeletal muscle tissues, which occurs earlier than the increase in fatty acid utilization during fasting. The enhanced glutaminolysis is also observed in macrophages in low glucose or under acute lipopolysaccharide (LPS) treatment. Consistent with a requirement of heightened glutaminolysis, the PDZD8-T527A mutation dampens the secretion of pro-inflammatory cytokines in macrophages in mice treated with LPS. Together, we have revealed an AMPK-PDZD8-GLS1 axis that promotes glutaminolysis ahead of increased fatty acid utilization under glucose shortage.

A Review of Brain-Inspired Cognition and Navigation Technology for Mobile Robots.

Brain-inspired navigation technologies combine environmental perception, spatial cognition, and target navigation to create a comprehensive navigation research system. Researchers have used various sensors to gather environmental data and enhance environmental perception using multimodal information fusion. In spatial cognition, a neural network model is used to simulate the navigation mechanism of the animal brain and to construct an environmental cognition map. However, existing models face challenges in achieving high navigation success rate and efficiency. In addition, the limited incorporation of navigation mechanisms borrowed from animal brains necessitates further exploration. On the basis of the brain-inspired navigation process, this paper launched a systematic study on brain-inspired environment perception, brain-inspired spatial cognition, and goal-based navigation in brain-inspired navigation, which provides a new classification of brain-inspired cognition and navigation techniques and a theoretical basis for subsequent experimental studies. In the future, brain-inspired navigation technology should learn from more perfect brain-inspired mechanisms to improve its generalization ability and be simultaneously applied to large-scale distributed intelligent body cluster navigation. The multidisciplinary nature of brain-inspired navigation technology presents challenges, and multidisciplinary scholars must cooperate to promote the development of this technology.

Lightweight semantic segmentation network for tumor cell nuclei and skin lesion.

In the field of medical image segmentation, achieving fast and accurate semantic segmentation of tumor cell nuclei and skin lesions is of significant importance. However, the considerable variations in skin lesion forms and cell types pose challenges to attaining high network accuracy and robustness. Additionally, as network depth increases, the growing parameter size and computational complexity make practical implementation difficult. To address these issues, this paper proposes MD-UNet, a fast cell nucleus segmentation network that integrates Tokenized Multi-Layer Perceptron modules, attention mechanisms, and Inception structures. Firstly, tokenized MLP modules are employed to label and project convolutional features, reducing computational complexity. Secondly, the paper introduces Depthwise Attention blocks and Multi-layer Feature Extraction modules. The Depthwise Attention blocks eliminate irrelevant and noisy responses from coarse-scale extracted information, serving as alternatives to skip connections in the UNet architecture. The Multi-layer Feature Extraction modules capture a wider range of high-level and low-level semantic features during decoding and facilitate feature fusion. The proposed MD-UNet approach is evaluated on two datasets: the International Skin Imaging Collaboration (ISIC2018) dataset and the PanNuke dataset. The experimental results demonstrate that MD-UNet achieves the best performance on both datasets.

Effects of a rainwater harvesting system on the soil water, heat and growth of apricot in rain-fed orchards on the Loess Plateau.

Rainwater is the main water source in arid and semiarid areas of the Loess Plateau, where rainfall is generally insufficient, ineffective and underutilized during the growing season. Thus, improving rainwater utilization efficiency is essential for sustainable agricultural development. A new system composed of rainwater harvesting, an infiltrator bucket with multiple holes and mulching (RHM), was designed to maintain soil moisture at a proper level in rain-fed orchards in arid and semiarid areas of the Loess Region of China. However, there is a lack of clarity on the effectiveness of RHM. In this study, changes in the soil environment and the growth and physiology of apricot trees were monitored via two treatments: (1) Rain-harvesting irrigation system (RHM) treatment and (2) traditional orchard treatment (CK) as a baseline. The results showed that (1) RHM could effectively improve soil water storage at depths of 0-45 cm and at a horizontal distance of 40 cm from the trunk. For the 1.4 mm light rain event, the soil water content increased by 6.3-12%, and for the two moderate rains, the soil water content increased by 12-25%. The change in the soil relative water content predicted by the LSTM model is consistent with the overall trend of the measured value and gradually decreases, and the prediction accuracy is high, with an error of 0.65. (2) The average soil temperatures at 5 cm, 20 cm and 40 cm under RHM were 17.0% (2.4 °C), 13.6% (1.9 °C) and 7.5% (1 °C) greater than those under CK, respectively. (3) Compared with the control treatment, RHM improved the growth and WUEL of apricot trees. The results highlighted the efficiency of the RHM system in enhancing the soil environment and regulating the growth and physiology of apricot trees, which has greater popularization value in arid and semiarid areas.

Vaccination with structurally adapted fungal protein fibrils induces immunity to Parkinson's disease.

The pathological misfolding and aggregation of soluble α-synuclein into toxic oligomers and insoluble amyloid fibrils causes Parkinson's disease, a progressive age-related neurodegenerative disease for which there is no cure. HET-s is a soluble fungal protein that can form assembled amyloid fibrils in its prion state. We engineered HET-s(218-298) to form four different fibrillar vaccine candidates, each displaying a specific conformational epitope present on the surface of α-synuclein fibrils. Vaccination with these four vaccine candidates prolonged the survival of immunized TgM83+/- mice challenged with α-synuclein fibrils by 8% when injected into the brain to model brain-first Parkinson's disease or by 21% and 22% when injected into the peritoneum or gut wall, respectively, to model body-first Parkinson's disease. Antibodies from fully immunized mice recognized α-synuclein fibrils and brain homogenates from patients with Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Conformation-specific vaccines that mimic epitopes present only on the surface of pathological fibrils but not on soluble monomers, hold great promise for protection against Parkinson's disease, related synucleinopathies and other amyloidogenic protein misfolding disorders.

Overcoming research challenges: In vitro cultivation of Ameson portunus (Phylum Microsporidia).

Ameson portunus is an intracellular pathogen that infects marine crabs Portunus trituberculatus and Scylla paramamosain, causing significant economic losses. However, research into this important parasite has been limited due to the absence of an in vitro culture system. To address this challenge, we developed an in vitro cultivation model of A. portunus using RK13 cell line in this study. The fluorescent labeling assay indicated a high infection rate (∼60 %) on the first day post-infection and quantitative PCR (qPCR) detection demonstrated successful infection as early as six hours post-inoculation. Fluorescence in situ hybridization (FISH) and qPCR were used for the detection of A. portunus infected cells. The FISH probe we designed allowed detection of A. portunus in infected cells and qPCR assay provided accurate quantification of A. portunus in the samples. Transmission electron microscopy (TEM) images revealed that A. portunus could complete its entire life cycle and produce mature spores in RK13 cells. Additionally, we have identified novel life cycle characteristics during the development of A. portunus in RK 13 cells using TEM. These findings contribute to our understanding of new life cycle pathways of A. portunus. The establishment of an in vitro culture model for A. portunus is critical as it provides a valuable tool for understanding the molecular and immunological events that occur during infection. Furthermore, it will facilitate the development of effective treatment strategies for this intracellular pathogen.

Unpacking the mediating role of classroom interaction between student satisfaction and perceived online learning among Chinese EFL tertiary learners in the new normal of post-COVID-19.

Online learning has become increasingly prevalent in the era of digitalization, impacted by both internet penetration and the COVID-19 pandemic. Classroom interaction, as a key factor in evaluating students' learning experience in online settings, has been identified to be associated with their academic achievement. While previous research has underscored the significance of classroom interaction in language learning settings, there is relatively limited research on its relationships with student satisfaction and learning. This research intends to explore classroom interaction and its mediating role in the correlation between student satisfaction and perceived online learning in online contexts. Given this, the paper reports a quantitative-method study that examined how Chinese EFL tertiary students perceived three types of classroom interaction (i.e., learner-learner, learner-instructor, and learner-content), their satisfaction, and its influences on their perceived online learning. Data was collected from 319 Chinese university students through convenience sampling and a self-designed questionnaire, and then analyzed with the help of SPSS. The results showed that: 1) the students had moderately positive perceptions of classroom interaction and online learning, but were neutral about their satisfaction; 2) positive correlations were observed between classroom interaction, student satisfaction, and online learning; and 3) student satisfaction predicted perceived online learning, with classroom interaction partially mediating this relationship. The findings of this research have implications for strengthening the effectiveness of online language teaching in the post-COVID-19 era.

Anti-Toxoplasma gondii effect of tylosin in vitro and in vivo.

BACKGROUND: Toxoplasma gondii is an important protozoan pathogen with medical and veterinary importance worldwide. Drugs currently used for treatment of toxoplasmosis are less effective and sometimes cause serious side effects. There is an urgent need for the development of more effective drugs with relatively low toxicity. METHODS: The effect of tylosin on the viability of host cells was measured using CCK8 assays. To assess the inhibition of tylosin on T. gondii proliferation, a real-time PCR targeting the B1 gene was developed for T. gondii detection and quantification. Total RNA was extracted from parasites treated with tylosin and then subjected to transcriptome analysis by RNA sequencing (RNA-seq). Finally, murine infection models of toxoplasmosis were used to evaluate the protective efficacy of tylosin against T. gondii virulent RH strain or avirulent ME49 strain. RESULTS: We found that tylosin displayed low host toxicity, and its 50% inhibitory concentration was 175.3 µM. Tylsoin also inhibited intracellular T. gondii tachyzoite proliferation, with a 50% effective concentration of 9.759 µM. Transcriptome analysis showed that tylosin remarkably perturbed the gene expression of T. gondii, and genes involved in "ribosome biogenesis (GO:0042254)" and "ribosome (GO:0005840)" were significantly dys-regulated. In a murine model, tylosin treatment alone (100 mg/kg, i.p.) or in combination with sulfadiazine sodium (200 mg/kg, i.g.) significantly prolonged the survival time and raised the survival rate of animals infected with T. gondii virulent RH or avirulent ME49 strain. Meanwhile, treatment with tylosin significantly decreased the parasite burdens in multiple organs and decreased the spleen index of mice with acute toxoplasmosis. CONCLUSIONS: Our findings suggest that tylosin exhibited potency against T. gondii both in vitro and in vivo, which offers promise for treatment of human toxoplasmosis.

Mechanisms by which sheep milk consumption ameliorates insulin resistance in high-fat diet-fed mice.

Sheep milk is rich in fat, protein, vitamins and minerals and is also one of the most important sources of natural bioactives. Several biopeptides in sheep milk have been reported to possess antibacterial, antiviral and anti-inflammatory properties, and they may prevent type 2 diabetes (T2D), disease and cancer. However, the precise mechanism(s) underlying the protective role of sheep milk against T2D development remains unclear. Therefore, in the current study, we investigated the effect of sheep milk on insulin resistance and glucose intolerance in high-fat diet (HFD)-fed mice, by conducting intraperitoneal glucose tolerance tests, metabolic cage studies, genomic sequencing, polymerase chain reaction, and biochemical assays. Hyperinsulinemic-euglycemic clamp-based experiments revealed that mice consuming sheep milk exhibited lower hepatic glucose production than mice in the control group. These findings further elucidate the mechanism by which dietary supplementation with sheep milk alleviates HFD-induced systemic glucose intolerance.

SERS probing of fungal HET-s fibrils formed at neutral and acidic pH conditions.

Advances in precision medical diagnostics require accurate and sensitive characterization of pathogens. In particular, health conditions associated with protein misfolding require an identification of proteinaceous amyloid fibrils or their precursors. These pathogenic entities express specific molecular structures, which require ultra-sensitive, molecular-level detection methods. A potentially transformative technique termed nanoplasmonics employs electro-optical phenomena in the vicinity of specially engineered metal nanostructures. A signature application of nanoplasmonics exploits enhancement of inelastic scattering of light in specific locations near metallic nanostructures, known as surface-enhanced Raman scattering (SERS). We applied SERS complemented with confocal microscopy imaging for ultra-sensitive, non-invasive, and label-free characterization of the fungal prion HET-s (218-289) as a model for ß-sheet rich amyloid structures. This characterization employed Au-coated dielectric supports as plasmonic substrates. After confirming the formation of HET-s fibrils at both pH 7.5 and 2.8 using negative staining transmission electron microscopy, we subjected the fibril-containing solutions to multimodal analysis using confocal microscopy and SERS. The SERS spectral fingerprints from all HET-s samples expressed vibrational markers for ß-structure, unstructured backbone, and aromatic side-chains. However, relative intensities of major SERS bands were pronouncedly different for the two pH levels. We have analyzed potential origins of the most pronounced SERS bands and proposed hypothetical mechanistic models that could explain the observed SERS fingerprints from HET-s fibrils grown at pH 7.5 and 2.8.

Treatment outcomes and cognitive function following electroconvulsive therapy in patients with severe depression.

BACKGROUND: Traditional treatments for major depressive disorder (MDD), including medication and therapy, often fail and have undesirable side effects. Electroconvulsive therapy (ECT) uses electrical currents to induce brief seizures in the brain, resulting in rapid and potent antidepressant effects. However, owing to misconceptions and controversies, ECT is not as widely used as it could and often faces stigmatization. AIM: To evaluate the efficacy and safety of ECT compared to those of medication and/or therapy in patients with severe MDD. METHODS: This prospective cohort study included 220 individuals with severe MDD who were divided into the ECT and non-ECT groups. The patients in the ECT group underwent bilateral ECT three times a wk until they either achieved remission or reached a maximum of 12 sessions. The non-ECT group received medication and/or therapy according to clinical guidelines for MDD. The primary outcome was the variation in the hamilton depression rating scale (HDRS) score from treatment/ECT initiation to week 12. In addition, patients' quality of life, cognitive abilities, and biomarkers were measured throughout the study. RESULTS: Although both groups showed significant improvements in their HDRS scores over time, the improvement was more pronounced in the ECT group than in the non-ECT group. Additionally, the ECT group exhibited a more substantial improvement in the quality of life and cognitive function than those of the non-ECT group. Compared with the non-ECT group, the ECT group exhibited evi-dently lower variations in the brain-derived neurotrophic factor (BDNF) and cytokine interleukin-6 (IL-6) levels. The side effects were generally mild and comparable between the two groups. ECT is safer and more potent than medication and/or therapy in mitigating depressive symptoms, enhancing well-being, and bolstering cognitive capabilities in individuals with severe MDD. ECT may also affect the levels of BDNF and IL-6, which are indicators of neuroplasticity and inflammation, respectively. CONCLUSION: ECT has emerged as a potentially advantageous therapeutic approach for patients with MDD who are unresponsive to alternative treatments.

Polycarbosilane/Divinylbenzene-Modified Magnesium Hydroxide to Enhance the Flame Retardancy of Ethylene-Vinyl Acetate Copolymer.

The thermal decomposition product of magnesium hydroxide (MH) is magnesium oxide (MgO), which serves as the foundational material for fireproof layer construction in the condensed phase. However, the weak interaction force between particles of MgO generated by thermal decomposition leads to the insufficient strength and poor adhesion ability of the fireproof layer. The fireproof layer was easily damaged and detached in this study, resulting in the low flame-retardant efficiency of MH. In this work, polycarbosilane (PCS) and divinyl benzene (DVB) were used to modify MH, and EVA/MH/PCS/DVB composites were made via melt blending. The flame-retardant properties of EVA/MH/PCS/DVB were evaluated using the limiting oxygen index (LOI), vertical combustion (UL-94), and a cone calorimeter (CONE). The thermal stability of the composites and flame retardants was analyzed using a thermogravimetric analyzer. The char layer structure was observed and analyzed using scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS), respectively. The results indicate that the LOI of the EVA/MH/PCS/DVB with 50 wt.% flame retardants in total was as high as 65.1, which increased by 160% in comparison with EVA/MH. Furthermore, the total smoke production (TSP) of the EVA/MH/PCS/DVB composite decreased by 22.7% compared to EVA/MH/PCS; the thermal stability of the MH/PCS/DVB and EVA/MH/PCS/DVB improved to some extent; and the compact residual char after the combustion of EVA/MH/PCS/DVB had fewer cracks due to the adhesive effect induced by PCS/DVB.

The effect of initial electrons generation approaches on nanosecond pulsed breakdown characteristics.

In this paper, the effects of initial electrons generation approaches on nanosecond pulsed breakdown characteristics are analyzed. Based on the numerical simulations with a 3D PIC-MCC model, the impacts of field-enhancement factor and initial electron concentration on nanosecond pulsed breakdown characteristics are investigated. Three types of switches are designed and subjected to testing under pulse voltages with rise times of 40, 70, and 120 ns, respectively. The results can be summarized as follows. First, the field-enhancement factor and initial electron concentration have significant influences on the development of the discharge channel. Second, the cathode-grooved self-triggered switch exhibits lower breakdown time delay jitter than the hemispherical self-breakdown switch at low pressure, while the differences in jitter between the two switches become negligible at high pressure. Third, the cathode-grooved self-triggered switch shows a lower breakdown time delay jitter compared to the pre-ionization self-triggered switch for pulse voltages with rise times of 40 and 70 ns. Conversely, this trend reverses for pulse voltage with a rise time of 120 ns. Finally, the breakdown time delay jitter for both the cathode-grooved self-triggered switch and the pre-ionization self-triggered switch has been reduced, and both switches are suitable for different operating requirements and conditions.

The predicting role of EFL teachers' immediacy behaviors in students' willingness to communicate and academic engagement.

BACKGROUND: Teacher-student interactions and proximity have been shown influential in second/foreign (L2) education. However, the role of L2 teachers' immediacy behaviors on students' willingness to communicate (WTC) and academic engagement remains relatively unexamined in the context of English as a foreign language (EFL). PURPOSE: This study intended to examine the association among EFL teachers' immediacy behaviors and students' WTC and engagement. METHODS: In this quantitative study, three online questionnaires were completed by 400 Chinese EFL students in different universities out of which 364 were valid. RESULTS: The results of statistical analysis and structural equation modeling (SEM) indicated that teachers' immediacy behaviors (verbal, nonverbal) had a highly significant influence on EFL students' WTC (ß=0.89, p = .000) and academic engagement (ß=0.71, p = .000). It was also revealed that teachers' immediacy could predict 89% and 71% of variances in students' WTC academic engagement, respectively. CONCLUSIONS: Based on the results, I could be concluded that EFL teachers' interpersonal communication abilities (e.g., immediacy) foster the establishment and growth of other positive outcomes among learners. IMPLICATIONS: The study presents some conclusions and practical implications for EFL teachers, materials developers, and trainers to integrate the nonverbal cues of L2 communication into their practices. Such practices have the potential to enhance students' willingness to communicate (WTC) and improve academic engagement.