Biological functions and therapeutic applications of human mucosal-associated invariant T cells.

Mucosal-associated invariant T (MAIT) cells are a unique subset of innate-like T lymphocytes that bridge innate and adaptive immunity. Characterized by their semi-invariant T cell receptor (TCR) and abundant localization in mucosal tissues, MAIT cells recognize microbial metabolites, primarily derived from the riboflavin biosynthesis pathway, presented by the major histocompatibility complex (MHC)-related protein 1 (MR1). This interaction, along with co-stimulatory signals, triggers rapid immune responses, including cytokine secretion and cytotoxic activity, highlighting their importance in maintaining immune homeostasis and combating infections. This review provides an in-depth overview of MAIT cell biology, including development, activation pathways, and functional diversity, highlighting their protective roles in immunity, contributions to diseases like cancer and inflammatory bowel disease (IBD), and context-dependent dual functions in health and pathology. This review also highlights the emerging therapeutic potential of MAIT cells in immunotherapy. Their unique TCR specificity, abundance, and tissue-homing properties make them ideal candidates for engineering novel therapies, such as chimeric antigen receptor (CAR)-MAIT cells, targeting infections, cancers, and autoimmune diseases. Challenges like antigen escape, T cell exhaustion, and CAR design optimization must be addressed to enhance clinical efficacy. In summary, MAIT cells are integral to immune function, and their therapeutic potential presents exciting opportunities for the treatment of a wide range of diseases. Further research is essential to unlock the full potential of these versatile immune cells

Hydrodynamic parameters of floods and related bank erosion events indicated from tree rings and 2D hydrodynamic model for a small ungauged catchment (Sudeten Mts., Poland)

Small mountain catchments usually lack hydrological monitoring and gauges. Therefore, in such areas, data on past flood and bank erosion are often missing, which makes assessing flood and erosion hazards very limited. We attempt to fill in this gap by dating individual flood and erosion events from growth disturbances produced by trees after their stems are tilted, and their roots are exposed and wounded by transported material. We aimed to develop a conceptual approach to integrate dendrochronology and 2D modelling for indicating and assessing past events of floods and bank erosion on a small mountain river Łomniczka, Sudeten mountains, Poland. We dated growth disturbances resulting from tilting of stems of spruce trees which grow on eroded riverbanks, i.e. tree-ring eccentricity and compression wood. We also dated disturbances resulting from the exposure of roots from under the soil cover, i.e. sudden decreases of cell lumen, and root injuries by debris transported by floods, i. e. scars and traumatic resin ducts. Dendrochronology allow to indicate the occurrence of 28 floods since the 1930s, including 11 floods when bank erosion was also recorded at study sites. The approach enables to identify rates of bank erosion during specific floods which ranged at study sites from 20 to 120 cm. The largest discharge was determined for the 1997 flood (106,7 m3 s 1), and the highest flow velocities were obtained for the 1930 floods (4.59 m/s). Results show that the highest shear stress occurred during the floods in 1943 and 1977 (510,3N/m2) and in 1997 flood (469.1 N/m2). We conclude that dendrochronology combined with 2D modelling allowed us to indicate past floods and bank erosion, and to prepare reliable inventories for analyses of flood and erosion hazard. The approach proposed in this paper can also be used as a tool for flood management, spatial management and planning

Remote sensing monitoring and evaluation of the temporal and spatial changes in the eco-environment of a typical arid land of the Tarim Basin in Western China

The eco-environment provides various spaces, conditions, and resources for human development, and their quality is a significant factor affecting sustainable development in a region. Most drylands face environmental fragility due to problems such as infertile land, scarce suitable living space, and a lack of resources. Therefore, investigating the temporal and spatial changes in the eco-environment of drylands is vital to developing them sustainably. This paper takes Hetian, which is located in the Tarim Basin ofWestern China and has typical features of an arid (or a hyper-arid) region, as the research area. The ecological index (EI) was used to construct a comprehensive ecological evaluation system, and five sub-indices (the biological richness index, vegetation coverage index, water network denseness index, land stress index, and pollution load index) were calculated to identify the quality and changes in the eco-environment of Hetian in 1995, 2009, and 2018. The results show that, from 1995 to 2018, the EI in Hetian showed a continuous downward trend (from 24.76 to 16.32), representing a change (DEI) of 8.44; this indicates significant deterioration in the quality of the local eco-environment. Large fluctuations in the EI also suggests that the environment in Hetian is very sensitive. In addition, the results revealed a degradation of Hetian, which includes a hyper-arid region

A minimal binding footprint on CD1d-glycolipid is a basis for selection of the unique human NKT TCR

Although it has been established how CD1 binds a variety of lipid antigens (Ag), data are only now emerging that show how αβ T cell receptors (TCRs) interact with CD1-Ag. Using the structure of the human semiinvariant NKT TCR–CD1d–α-galactosylceramide (α-GalCer) complex as a guide, we undertook an alanine scanning mutagenesis approach to define the energetic basis of this interaction between the NKT TCR and CD1d. Moreover, we explored how analogues of α-GalCer affected this interaction. The data revealed that an identical energetic footprint underpinned the human and mouse NKT TCR–CD1d–α-GalCer cross-reactivity. Some, but not all, of the contact residues within the Jα18-encoded invariant CDR3α loop and Vβ11-encoded CDR2β loop were critical for recognizing CD1d. The residues within the Vα24-encoded CDR1α and CDR3α loops that contacted the glycolipid Ag played a smaller energetic role compared with the NKT TCR residues that contacted CD1d. Collectively, our data reveal that the region distant to the protruding Ag and directly above the F′ pocket of CD1d was the principal factor in the interaction with the NKT TCR. Accordingly, although the structural footprint at the NKT TCR–CD1d–α-GalCer is small, the energetic footprint is smaller still, and reveals the minimal requirements for CD1d restriction

Flavoured jet algorithms: a comparative study

The accurate identification of heavy-flavour jets — those which originate from bottom or charm quarks — is crucial for precision studies of the Standard Model and searches for new physics. However, assigning flavour to jets presents significant challenges, primarily due to issues with infrared and collinear (IRC) safety. This paper aims to address these challenges by evaluating recently-proposed jet algorithms designed to be IRC-safe and applicable in high-precision measurements. We compare these algorithms across benchmark heavy-flavour production processes and kinematic regimes that are relevant for LHC phenomenology. Exploiting both fixed-order calculations in QCD as well as parton shower simulations, we analyse the infrared sensitivity of these new algorithms at different stages of the event evolution and compare to flavour labelling strategies currently adopted by LHC collaborations. The results highlight that, while all algorithms lead to more robust flavour assignments compared to current techniques, they vary in performance depending on the observable and energy regime. The study lays groundwork for robust, flavour-aware jet analyses in current and future collider experiments to maximise the physics potential of experimental data by reducing discrepancies between theoretical and experimental methods

Generation of allogeneic CAR-NKT cells from hematopoietic stem and progenitor cells using a clinically guided culture method.

Cancer immunotherapy with autologous chimeric antigen receptor (CAR) T cells faces challenges in manufacturing and patient selection that could be avoided by using off-the-shelf products, such as allogeneic CAR natural killer T (AlloCAR-NKT) cells. Previously, we reported a system for differentiating human hematopoietic stem and progenitor cells into AlloCAR-NKT cells, but the use of three-dimensional culture and xenogeneic feeders precluded its clinical application. Here we describe a clinically guided method to differentiate and expand IL-15-enhanced AlloCAR-NKT cells with high yield and purity. We generated AlloCAR-NKT cells targeting seven cancers and, in a multiple myeloma model, demonstrated their antitumor efficacy, expansion and persistence. The cells also selectively depleted immunosuppressive cells in the tumor microenviroment and antagonized tumor immune evasion via triple targeting of CAR, TCR and NK receptors. They exhibited a stable hypoimmunogenic phenotype associated with epigenetic and signaling regulation and did not induce detectable graft versus host disease or cytokine release syndrome. These properties of AlloCAR-NKT cells support their potential for clinical translation

Flavoured jet algorithms: a comparative study

The accurate identification of heavy-flavour jets — those which originate from bottom or charm quarks — is crucial for precision studies of the Standard Model and searches for new physics. However, assigning flavour to jets presents significant challenges, primarily due to issues with infrared and collinear (IRC) safety. This paper aims to address these challenges by evaluating recently-proposed jet algorithms designed to be IRC-safe and applicable in high-precision measurements. We compare these algorithms across benchmark heavy-flavour production processes and kinematic regimes that are relevant for LHC phenomenology. Exploiting both fixed-order calculations in QCD as well as parton shower simulations, we analyse the infrared sensitivity of these new algorithms at different stages of the event evolution and compare to flavour labelling strategies currently adopted by LHC collaborations. The results highlight that, while all algorithms lead to more robust flavour assignments compared to current techniques, they vary in performance depending on the observable and energy regime. The study lays groundwork for robust, flavour-aware jet analyses in current and future collider experiments to maximise the physics potential of experimental data by reducing discrepancies between theoretical and experimental methods