CD4+ T cells display a spectrum of recall dynamics during re-infection with malaria parasites.

Children in malaria-endemic regions can experience repeated Plasmodium infections over short periods of time. Effects of re-infection on multiple co-existing CD4+ T cell subsets remain unresolved. Here, we examine antigen-experienced CD4+ T cells during re-infection in mice, using scRNA-seq/TCR-seq and spatial transcriptomics. TCR transgenic TEM cells initiate rapid Th1/Tr1 recall responses prior to proliferating, while GC Tfh counterparts are refractory, with TCM/Tfh-like cells exhibiting modest non-proliferative responses. Th1-recall is a partial facsimile of primary Th1-responses, with no upregulated effector-associated genes being unique to recall. Polyclonal, TCR-diverse, CD4+ T cells exhibit similar recall dynamics, with individual clones giving rise to multiple effectors including highly proliferative Th1/Tr1 cells, as well as GC Tfh and Tfh-like cells lacking proliferative capacity. Thus, we show substantial diversity in recall responses mounted by multiple co-existing CD4+ T cell subsets in the spleen, and present graphical user interfaces for studying gene expression dynamics and clonal relationships during re-infection.

Plasmodium infection induces phenotypic, clonal, and spatial diversity among differentiating CD4+ T cells.

Naive CD4+ T cells must differentiate in order to orchestrate immunity to Plasmodium, yet understanding of their emerging phenotypes, clonality, spatial distributions, and cellular interactions remains incomplete. Here, we observe that splenic polyclonal CD4+ T cells differentiate toward T helper 1 (Th1) and T follicular helper (Tfh)-like states and exhibit rarer phenotypes not elicited among T cell receptor (TCR) transgenic counterparts. TCR clones present at higher frequencies exhibit Th1 skewing, suggesting that variation in major histocompatibility complex class II (MHC-II) interaction influences proliferation and Th1 differentiation. To characterize CD4+ T cell interactions, we map splenic microarchitecture, cellular locations, and molecular interactions using spatial transcriptomics at near single-cell resolution. Tfh-like cells co-locate with stromal cells in B cell follicles, while Th1 cells in red pulp co-locate with activated monocytes expressing multiple chemokines and MHC-II. Spatial mapping of individual transcriptomes suggests that proximity to chemokine-expressing monocytes correlates with stronger effector phenotypes in Th1 cells. Finally, CRISPR-Cas9 gene disruption reveals a role for CCR5 in promoting clonal expansion and Th1 differentiation. A database of cellular locations and interactions is presented: https://haquelab.mdhs.unimelb.edu.au/spatial_gui/.

Gut microbiome and serum amino acid metabolome alterations in autism spectrum disorder.

Gut microbiota and their metabolic products might play important roles in regulating the pathogenesis of autism spectrum disorder (ASD). The purpose of this study was to characterize gut microbiota and serum amino acid metabolome profiles in children with ASD. A non-randomized controlled study was carried out to analyze the alterations in the intestinal microbiota and their metabolites in patients with ASD (n = 30) compared with neurotypical controls (NC) (n = 30) by metagenomic sequencing to define the gut microbiota community and liquid chromatography/mass spectrometry (LC/MS) analysis to characterize the metabolite profiles. Compared with children in the NC group, those in the ASD group showed lower richness, higher evenness, and an altered microbial community structure. At the class level, Deinococci and Holophagae were significantly lower in children with ASD compared with TD. At the phylum level, Deinococcus-Thermus was significantly lower in children with ASD compared with TD. In addition, the functional properties (such as galactose metabolism) displayed significant differences between the ASD and NC groups. Five dominant altered species were identified and analyzed (LDA score > 2.0, P < 0.05), including Subdoligranulum, Faecalibacterium_praushitzii, Faecalibacterium, Veillonellaceae, and Rumminococcaceae. The peptides/nickel transport system was the main metabolic pathway involved in the differential species in the ASD group. Decreased ornithine levels and elevated valine levels may increase the risk of ASD through a metabolic pathway known as the nickel transport system. The microbial metabolism in diverse environments was negatively correlated with phascolarctobacterium succinatutens. Our study provides novel insights into compositional and functional alterations in the gut microbiome and metabolite profiles in ASD and the underlying mechanisms between metabolite and ASD.

Carbon-Atom Exchange between [MC2]+ (M = Os and Ir) and Methane: on the Thermodynamic and Dynamic Aspects.

Gas-phase reactions of [OsC2]+ and [IrC2]+ with methane at ambient temperature have been studied using quadrupole-ion trap mass spectrometry combined with quantum chemical calculations. Both [OsC2]+ and [IrC2]+ undergo carbon-atom exchange reactions with methane. The associated mechanisms for the two systems are found to be similar. The differences in the rates of carbon isotope exchange reactions of methane with [MC2]+ (M = Os and Ir) are explained by several factors like the energy barrier for the initial H3C-H bond breaking processes, the molecular dynamics, orbital interactions, and the H-binding energies of the pivotal steps. Besides, the number of participating valence orbitals might be one of the keys to regulate the rate in the key step. The present findings may provide useful ideas and inspiration for designing similar processes.

Bupleurum exerts antiarrhythmic effects by inhibiting L-type calcium channels in mouse ventricular myocytes.

BACKGROUND: Bupleurum (Bup), is a traditional effective medicine to treat colds and fevers in clinics. Multiple studies have demonstrated that Bup exhibites various biological activities, including cardioprotective effects, anti-inflammatory, anticancer, antipyretic, antimicrobial, and antiviral effects, etc. Currently, the effects of Bup on cardiac electrophysiology have not been reported yet. METHODS: Electrocardiogram recordings were used to investigate the effects of Bup on aconitine-induced arrhythmias. Patch-clamp techniques were used to explore the effects of Bup on APs and ion currents. RESULTS: Bup reduced the incidence of ventricular fibrillation (VF) and delayed the onset time of ventricular tachycardia (VT) in mice. Additionally, Bup (40 mg/mL) suppressed DADs induced by high-Ca2+ and shortened action potential duration at 50 % completion of repolarization (APD50) and action potential duration at 90 % completion of repolarization (APD90) to 60.89 % ± 8.40 % and 68.94 % ± 3.24 % of the control, respectively. Moreover, Bup inhibited L-type calcium currents (ICa.L) in a dose-dependent manner, with an IC50 value of 25.36 mg/mL. Furthermore, Bup affected the gated kinetics of L-type calcium channels by slowing down steady-state activation, accelerating the steady-state inactivation, and delaying the inactivation-recovery process. However, Bup had no effects on the Transient sodium current (INa.T), ATX II-increased late sodium current (INa.L), transient outward current (Ito), delayed rectifier potassium current (IK), or inward rectifier potassium current (IK1). CONCLUSION: Bup is an antiarrhythmic agent that may exert its antiarrhythmic effects by inhibiting L-type calcium channels.

Intestinal SURF4 is essential for apolipoprotein transport and lipoprotein secretion.

OBJECTIVE: Lipoprotein assembly and secretion in the small intestine are critical for dietary fat absorption. Surfeit locus protein 4 (SURF4) serves as a cargo receptor, facilitating the cellular transport of multiple proteins and mediating hepatic lipid secretion in vivo. However, its involvement in intestinal lipid secretion is not fully understood. In this study, we investigated the role of SURF4 in intestinal lipid absorption. METHODS: We generated intestine-specific Surf4 knockout mice and characterized the phenotypes. Additionally, we investigated the underlying mechanisms of SURF4 in intestinal lipid secretion using proteomics and cellular models. RESULTS: We unveiled that SURF4 is indispensable for apolipoprotein transport and lipoprotein secretion. Intestine-specific Surf4 knockout mice exhibited ectopic lipid deposition in the small intestine and hypolipidemia. Deletion of SURF4 impeded the transport of apolipoprotein A1 (ApoA1), proline-rich acidic protein 1 (PRAP1), and apolipoprotein B48 (ApoB48) and hindered the assembly and secretion of chylomicrons and high-density lipoproteins. CONCLUSIONS: SURF4 emerges as a pivotal regulator of intestinal lipid absorption via mediating the secretion of ApoA1, PRAP1 and ApoB48.

Enhancement of the organic acid content and antioxidant capacity of yellow whey through fermentation with Lacticaseibacillus casei YQ336.

Fermentation is considered an effective tool for improving the functional characteristics of food. In this study, Lacticaseibacillus casei YQ336 was used to ferment yellow whey, and physical and chemical analysis was performed to identify the changes in the nutritional components and antioxidant activity of the fermented yellow whey. Non-targeted metabolomics was used to study the transformation of small molecular substances in the fermented yellow whey. After 48 h of pure culture fermentation with L. casei YQ336, the pH of yellow whey decreased significantly (p < 0.05). Meanwhile, the content of total acids, organic acids, sugars, total phenols, and total flavonoids and the antioxidant activity showed a significant increase (p < 0.05). A total of 628 differential metabolites were identified between fermented and unfermented yellow whey samples, of which 293 were upregulated and 335 were downregulated. After fermentation, due to the growth and metabolic activity of L. casei YQ336, meaningful metabolites such as homovanillic acid, lactic acid, oxalic acid, L-glutamic acid, and phenylalanine, as well as phenyllactic acid, gallic acid, and genistein were produced. This increased the organic acid content and antioxidant activity of yellow whey. The findings provide a theoretical and practical basis for further research on the bio-functional activity of yellow whey and the recycling and utilization of food by-products.

Fermentation improves antioxidant capacity and γ-aminobutyric acid content of Ganmai Dazao Decoction by lactic acid bacteria.

Introduction: Ganmai Dazao Decoction is a traditional Chinese recipe, and is composed of licorice, floating wheat, and jujube. Methods: Effects of lactic acid bacteria fermentation on the physicochemical properties, antioxidant activity, and γ-aminobutyric acid of Ganmai Dazao Decoction were studied. The changes of small and medium molecules in Ganmai Dazao Decoction before and after fermentation were determined by LC-MS non-targeted metabolomics. Results: The results showed that the contents of lactic acid, citric acid, acetic acid, and total phenol content increased significantly, DPPH free radical clearance and hydroxyl free radical clearance were significantly increased. γ-aminobutyric acid content was 12.06% higher after fermentation than before fermentation. A total of 553 differential metabolites were detected and identified from the Ganmai Dazao Decoction before and after fermentation by partial least squares discrimination and VIP analysis. Discussion: Among the top 30 differential metabolites with VIP values, the content of five functional substances increased significantly. Our results showed that lactic acid bacteria fermentation of Ganmai Dazao Decoction improves its antioxidant effects and that fermentation of Ganmai Dazao Decoction with lactic acid bacteria is an innovative approach that improves the health-promoting ingredients of Ganmai Dazao Decoction.

On the performance of the M-C (M = Fe, Ru, Os) unit toward methane activation.

Gas-phase reactions of [MC]+ (M = Os and Ru) with methane at ambient temperature have been studied by using quadrupole-ion trap (Q-IT) mass spectrometry combined with quantum chemical calculations. Theoretical calculations reveal the influence of electronic signatures and that it is the energy gap of the associated frontier molecular orbitals that dominates the ability of the cluster in the initial H3C-H bond breaking. By extension, a theoretical consideration upon changing the ligand from carbide to carbyne and eventually to carbene reveals that the reactivities of the M-complex (M = Os, Ru and Fe) are determined by the energy gap of the involved orbitals. In addition, a few factors like the dipole moment, spin density and charge distributions influence the orbital energy gap to different extents. Thus, altering the local structure of the active center to modulate the orbital distribution may be a possible means of regulation of the activity.

Methane Activation by [OsC3]+: Implications for Catalyst Design.

Gas-phase reactions of [OsC3]+ with methane at ambient temperature have been studied by using quadrupole-ion trap mass spectrometry combined with quantum chemical calculations. The comparison of [OsC3]+ with the product clusters revealed significant changes in cluster reactivity. In particular, with different ligands, the cluster may produce multiple products or, alternatively, just a single product. Theoretical calculations reveal the influence of electronic features such as molecular polarity index, charge and spin distribution, and HOMO-LUMO gap on the reactivity of the Os complexes. Fundamentally, it is the polarity of the clusters that leads to the cluster reactivity in the methane activation. Furthermore, reducing the local polarity of the catalyst active site may be one means of reducing the number of byproducts in the reaction.

Naringin exerts antiarrhythmic effects by inhibiting channel currents in mouse cardiomyocytes.

INTRODUCTION: Naringin, a flavonoid extracted from citrus plants, has a variety of biological effects. Studies have shown that increasing the consumption of flavonoid-rich foods can reduce the incidence of cardiac arrhythmia. Naringin has been reported to have beneficial cardiovascular effects and thus can be used to prevent cardiovascular diseases, but the electrophysiological mechanism through which it prevents arrhythmias has not been elucidated. This study was conducted to investigate the effect of naringin on the transmembrane ion channel currents in mouse ventricular myocytes and the antiarrhythmic effect of this compound on Langendorff-perfused mouse hearts. METHODS: Action potentials (APs) and ionic currents were recorded in isolated ventricular myocytes using the whole-cell patch-clamp technique. Anemone toxin II (ATX II) and CaCl2 were used to induce early afterdepolarizations (EADs) and delayed afterdepolarizations (DADs), respectively. Electrocardiogram (ECG) recordings were conducted in Langendorff-perfused mouse hearts with a BL-420F biological signal acquisition and analysis system. RESULTS: At the cellular level, naringin shortened the action potential duration (APD) of ventricular myocytes and decreased the maximum depolarization velocity (Vmax) of APs.Naringin inhibited the L-type calcium current (ICa.L) and ATX II enhanced the late sodium current (INa.L) in a concentration-dependent manner with IC50 values of 508.5 µmol/L (n = 9) and 311.6 µmol/L (n = 10), respectively. In addition, naringin also inhibited the peak sodium current (INa·P) and delayed the rectifier potassium current (IK) and the transient outward potassium current (Ito). Moreover, naringin reduced ATX II-induced APD prolongation and EADs and had a significant inhibitory effect on CaCl2-induced DADs as well. At the organ level, naringin reduced the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) induced by ATX II and shortened the duration of both in isolated hearts. CONCLUSION: Naringin can inhibit the occurrence of EADs and DADs at the cellular level; furthermore, it can inhibit INa.L, ICa.L, INa·P, IK, and Ito in ventricular myocytes. Naringin also inhibits arrhythmias induced by ATX II in hearts. By investigating naringin with this electrophysiological method for the first time, we determined that this flavonoid may be a multichannel blocker with antiarrhythmic effects.

Expansion of MAIT cells in the combined absence of NKT and γδ-T cells.

Mucosal-associated invariant T (MAIT) cells, natural killer T (NKT) cells, and γδT cells are collectively referred to as 'unconventional T cells' due to their recognition of non-peptide antigens and restriction to MHC-I-like molecules. However, the factors controlling their widely variable frequencies between individuals and organs are poorly understood. We demonstrated that MAIT cells are increased in NKT or γδT cell-deficient mice and highly expand in mice lacking both cell types. TCRα repertoire analysis of γδT cell-deficient thymocytes revealed altered Trav segment usage relative to wild-type thymocytes, highlighting retention of the Tcra-Tcrd locus from the 129 mouse strain used to generate Tcrd-/- mice. This resulted in a moderate increase in distal Trav segment usage, including Trav1, potentially contributing to increased generation of Trav1-Traj33+ MAIT cells in the Tcrd-/- thymus. Importantly, adoptively transferred MAIT cells underwent increased homeostatic proliferation within NKT/gdT cell-deficient tissues, with MAIT cell subsets exhibiting tissue-specific homing patterns. Our data reveal a shared niche for unconventional T cells, where competition for common factors may be exploited to collectively modulate these cells in the immune response. Lastly, our findings emphasise careful assessment of studies using NKT or γδT cell-deficient mice when investigating the role of unconventional T cells in disease.

Do your friends stress you out? A field study of the spread of stress through a community network.

In this study, we seek to understand how stress changes in dynamic social systems. Where prior work on the interpersonal transmission of stress focused on pairs of individuals and small groups, we adopt a network perspective to investigate how the distribution of stress in an individual's social environment influences their stress appraisal process. We conducted a 6-month longitudinal study of 315 early to midcareer adults in professional master's programs as they encountered the stress of everyday academic life. We follow the dynamics of the participants' networks and their concomitant stress at four key time points during those 6 months. We find that the perceived stress of one's social contacts affects their experience of stress in this setting. Yet, not everyone is equally susceptible to this social influence. In particular, we find that social influence is substantially amplified under conditions of relative consensus among one's social contacts. Also, a low level of neuroticism, a high level of conscientiousness, and a high level of internal control orientation help buffer the transmission of stress. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The effect of fine service on customer loyalty in rural homestays: The mediating role of customer emotion.

Rural homestay is an important driver for developing rural tourism, which still grows against the wind in the post-epidemic era of the COVID-19 virus and shows unique attributes that are different from those of the traditional hospitality industry. Based on the five-dimensional model of fine service theory, this study introduces culture as a unique dimension to construct a six-dimensional model of rural homestay fine service and explores the influencing mechanism of rural homestay fine service on customer loyalty. This study successively used expert interviews and questionnaires to develop the structural equation model through SPSS 26.0 and AMOS 24.0. The results showed that culture, as a unique attribute of rural homestay, is another important factor influencing the level of rural homestay fine service besides privacy, responsiveness, empathy, comfort, and psychological quality. Customer emotion of rural homestays significantly impacts customer loyalty and fully mediates the relationship between fine service and customer loyalty. This study verifies the effectiveness of fine service theory in the research of rural homestay good service and provides a new measuring tool, which has the potential to enrich and develop the exploration of fine service.

CD8 coreceptor engagement of MR1 enhances antigen responsiveness by human MAIT and other MR1-reactive T cells.

Mucosal-associated invariant T (MAIT) cells detect microbial infection via recognition of riboflavin-based antigens presented by the major histocompatibility complex class I (MHC-I)-related protein 1 (MR1). Most MAIT cells in human peripheral blood express CD8αα or CD8αß coreceptors, and the binding site for CD8 on MHC-I molecules is relatively conserved in MR1. Yet, there is no direct evidence of CD8 interacting with MR1 or the functional consequences thereof. Similarly, the role of CD8αα in lymphocyte function remains ill-defined. Here, using newly developed MR1 tetramers, mutated at the CD8 binding site, and by determining the crystal structure of MR1-CD8αα, we show that CD8 engaged MR1, analogous to how it engages MHC-I molecules. CD8αα and CD8αß enhanced MR1 binding and cytokine production by MAIT cells. Moreover, the CD8-MR1 interaction was critical for the recognition of folate-derived antigens by other MR1-reactive T cells. Together, our findings suggest that both CD8αα and CD8αß act as functional coreceptors for MAIT and other MR1-reactive T cells.

Chitosan-based thermal insulation compressible foam enhanced with high performance of piezoelectric generation and sensing.

A series of chitosan (CS)-konjac glucomannan (KGM) foams with excellent thermal insulation property has been prepared using a directional freezing method, which exhibit high strain recovery, excellent piezoelectric generation and sensing properties. Layered lamellar or honeycomb morphologies in CS-KGM foams attributes a low thermal conductivity coefficient of ca. 0.03 W/(m·K). Bridge-like structure that mainly observed in CS-KGM foams from horizontal freezing endows them with excellent compression recovery performance even after 200 compression cycles. This along with piezoelectricity of CS contributes a long-lasting piezoelectric generation performance, ranging from 0.809 to 2.460 V during compression cycle process. Piezoelectric signals generated from pressing with certain strain and rate, finger taping and hand grasping can be sensed profoundly by CS-KGM. As thus, fully renewable source-based CS-KGM foams with outstanding thermal insulation and piezoelectric performance shows great potential in application as wearable thermal insulation and piezoelectric devices.

Applying finite-time lyapunov exponent to study the tidal dispersion on oil spill trajectory in Burrard Inlet.

This study used a combination of Finite-Time Lyapunov Exponent (FTLE) values, residual currents, and tidal excursion lengths to systematically investigate the effects of tidal dispersion on oil spill trajectories in Burrard Inlet, BC, Canada, which is a tidally dominated estuary. The FTLE analysis results showed that tidal type and tidal phase significantly influenced the FTLE fields because the flow structure and the location of saddle points varied as a function of the tidal type and tidal phase. Some transport barriers formed in the Inner Harbour, which blocked the water exchange between the western and eastern parts of the inlet. Moreover, tidal mixing in the wider regions of Burrard Inlet (i.e., the western Outer Harbour) was relatively weak than in the narrower areas (i.e., First Narrows and Second Narrows). The observations from the FTLE analysis agreed well with the residual currents and tidal excursion results. The drifter trajectories were consistent with the Lagrangian coherent structure lines extracted from the FTLE analysis. To verify the tidal dispersion impact on an oil spill trajectory in the inlet, the FTLE fields were compared with a real oil spill that occurred in Burrard Inlet in 2015 (the M/V Marathassa oil spill). The FTLE fields reasonably explained the spilled oil's trajectories from the real event. In addition, a set of stochastic oil spill models were run in this study and found that the FTLE analysis was a reliable tool for oil spill tracking. Overall, the FTLE method would be a valuable addition to practical oil spill response planning.

DBWM: A diluted bitumen weathering model.

To help better assist the management of Diluted bitumen (DilBit) spills in marine environment, a model named as DilBit Weathering Model (DBWM) was developed in this study to simulate DilBits weathering in marine environment. The DBWM was developed based on specific algorithms for evaporation, dispersion, biodegradation, as well as density and viscosity changes for DilBit weathering and other widely used algorithms for conventional oil weathering in marine environment. To validate the model, a series of DilBit weathering simulation were conducted and compared with the experimental data. Furthermore, the performance of DBWM was compared with a widely used oil weathering model (Automated Data Inquiry for Oil Spills, ADIOS2). The results demonstrated the feasibility and advantages of the developed DBWM in simulating the weathering of marine DilBit spills. Thus, the proposed DBWM can provide effective decision support to marine DilBit spill management.

Saccharomyces boulardii alleviates DSS-induced intestinal barrier dysfunction and inflammation in humanized mice.

Recent clinical studies have demonstrated a beneficial effect of Saccharomyces boulardii (S. boulardii) in inflammatory bowel disease (IBD). However, the underlying mechanisms remain poorly defined. In this study, we investigated the modulating effect of S. boulardii on the intestinal microbiota in humanized mice with dextran sulfate sodium (DSS)-induced colitis. The mice were fed an S. boulardii-supplement diet for 16 days before DSS treatment. The results showed that feeding S. boulardii significantly ameliorated the colon damage and regulated inflammatory responses by modulating the cytokine profile. These changes were found to be associated with an altered microbiome composition and short-chain fatty acid (SCFA) metabolism. Further analysis demonstrated that S. boulardii-derived polysaccharides and polypeptides promoted the growth of certain probiotics and increased the microbial metabolite SCFAs levels. Overall, these findings demonstrated the role of S. boulardii as a potential gut microbiota modulator to prevent and treat IBD.

On the origin of reactivity variation upon sequential ligation: the [Re(Cl)x]+/CH4 (x = 1-3) couples.

The potential of [ReClx]+ (x = 1-3) in activating methane has been explored by using a combination of gas-phase experiments and high-level quantum calculations. When the number of Cl ligands increases, the reactivity towards methane activation varies accordingly. While [ReClx]+ (x = 1-2) are able to dehydrogenate methane by a three-state reactivity scenario, [ReCl3]+ shows inertness towards methane at ambient conditions. Furthermore, the product ion [ClRe(H)CH]+ of the [ReCl]+/CH4 couple could continue to activate methane and liberate molecular dihydrogen but another product ion [Cl2ReCH2]+ is unreactive with methane. Obviously, the nature and the number of ligands make a difference to the reactivity towards methane activation. The associated reaction mechanism and the electron origins for the rather different reactivities are discussed in detail. Finally and more importantly, instructive information concerning the rational design of Re-catalysts for methane conversion is obtained.