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Abstract Although γδ T cells are known to participate in immune dysregulation in solid tumors, their relevance to human microsatellite-stable (MSS) colorectal cancer (CRC) is still undefined. Here, using integrated gene expression analysis and T cell receptor sequencing, we characterized γδ T cells in MSS CRC, with a focus on Vδ1 + T cells. We identified Vδ1+ T cells with shared motifs in the third complementarity-determining region of the δ-chain, reflective of antigen recognition. Changes in gene and protein expression levels suggested a dysfunctional effector state of Vδ1+ T cells in MSS CRC, distinct from Vδ1+ T cells in microsatellite-instable (MSI). Interaction analysis highlighted an immunosuppressive role of fibroblasts in the dysregulation of Vδ1+ T cells in MSS CRC via the TIGIT-NECTIN2 axis. Blocking this pathway with a TIGIT antibody partially restored cytotoxicity of the dysfunctional Vδ1 phenotype. These results define an operative pathway in γδ T cells in MSS CRC.

The development of biocompatible hydrogels for 3D bioprinting is essential for creating functional tissue models and advancing preclinical drug testing. This study investigates the formulation, printability, mechanical properties, and biocompatibility of a novel Alg-Gel hydrogel blend (alginate and gelatin) for use in extrusion-based 3D bioprinting. A range of hydrogel compositions were evaluated for their rheological behavior, including shear-thinning properties, storage modulus, and compressive modulus, which are crucial for maintaining structural integrity during printing and supporting cell viability. The printability assessment of the 7% alginate–8% gelatin hydrogel demonstrated that the 27T tapered needle achieved the highest normalized Printability Index (POInormalized = 1), offering the narrowest strand width (0.56 ± 0.02 mm) and the highest printing accuracy (97.2%) at the lowest printing pressure (30 psi). In contrast, the 30R needle, with the smallest inner diameter (0.152 mm) and highest printing pressure (80 psi), resulted in the widest strand width (0.70 ± 0.01 mm) and the lowest accuracy (88.8%), resulting in a POInormalized of 0.274. The 30T and 27R needles demonstrated moderate performance, with POInormalized values of 0.758 and 0.558, respectively. The optimized 7% alginate and 8% gelatin blend demonstrated favorable printability, mechanical strength, and cell compatibility with MDA-MB-213 breast cancer cells, exhibiting high cell proliferation rates and minimal cytotoxicity over a 2-week culture period. This formulation offers a balanced approach, providing sufficient viscosity for precision printing while minimizing shear stress to preserve cell health. This work lays the groundwork for future advancements in bioprinted cancer models, contributing to the development of more effective tools for drug screening and personalized medicine.

The complex composite material cement paste (CP) is under high pressures in underwater applications and when impact loading occurs. The mechanical behavior of cement paste to hydrostatic compression results from mechanical deformations of each phase, including unhydrated and hydrated minerals. Molecular Dynamics was used to study the atomistic deformation of individual unhydrated cement phases with increasing hydrostatic pressures. The pressure-specific volume Birch-Murnaghan equation of state (EoS) and the bulk modulus at zero pressure were determined for each phase. Results show that the bulk modulus and compressibility are pressure dependent. For tricalcium silicate (C3S), dicalcium silicate (C2S), and tricalcium aluminate (C3A), the bulk modulus increases, while the volume compression decreases with increasing pressure. The C3S and C3A phases are stable during hydrostatic compression and exhibit isotropic behavior. The C2S phase is not stable and shows anisotropic behavior. These results explain the effect of unreacted cement clinkers on cement paste mechanical behavior under high pressure based on the response of individual phases.

A 30-year-old man presented with fever, hepatosplenomegaly, and a rash over his lower limbs (palpable purpura). Evaluation revealed pancytopenia and hypergammaglobulinemia. A subsequent bone marrow examination and serology confirmed visceral leishmaniasis (kala-azar), while the biopsy of skin lesion suggested leukocytoclastic vasculitis. No alternate cause of vasculitis was forthcoming, and the patient was treated with conventional amphotericin B for 14 days after which resolution of symptoms (including the rash) was noted. Cutaneous vasculitis is an extremely rare complication following visceral leishmaniasis with no known cases reported thus far. Hence, a high index of suspicion is warranted in achieving timely diagnosis and initiation of appropriate therapy.

The thermoresponsive behavior of a Methylcellulose (MC) polymer was systematically investigated to determine its usability in constructing MC based hydrogel systems in cell sheet engineering applications. Solution-gel analyses were made to study the effects of polymer concentration, molecular weight and dissolved salts on the gelation of three commercially available MCs using differential scanning calorimeter and rheology. For investigation of the hydrogel stability and fluid uptake capacity, swelling and degradation experiments were performed with the hydrogel system exposed to cell culture solutions at incubation temperature for several days. From these experiments, the optimal composition of MC-water-salt that was able to produce stable hydrogels at or above 32 °C, was found to be 12% to 16% of MC (Mol. wt. of 15,000) in water with 0.5× PBS (~150mOsm). This stable hydrogel system was then evaluated for a week for its efficacy to support the adhesion and growth of specific cells in culture; in our case the stromal/stem cells derived from human adipose tissue derived stem cells (ASCs). The results indicated that the addition (evenly spread) of ~200 µL of 2 mg/mL bovine collagen type -I (pH adjusted to 7.5) over the MC hydrogel surface at 37 °C is required to improve the ASC adhesion and proliferation. Upon confluence, a continuous monolayer ASC sheet was formed on the surface of the hydrogel system and an intact cell sheet with preserved cell–cell and cell–extracellular matrix was spontaneously and gradually detached when the grown cell sheet was removed from the incubator and exposed to room temperature (~30 °C) within minutes.

Dysregulated immune responses to infection such as those encountered in sepsis can be catastrophic. Sepsis is typically triggered by an overwhelming systemic response to an infectious agent(s) and is associated with high morbidity and mortality even under optimal critical care. Recent studies have implicated unconventional, innate-like T lymphocytes, including CD1d- and MR1-restricted T cells as effectors and/or regulators of inflammatory responses during sepsis. These cell types are typified by invariant natural killer T (iNKT) cells, variant NKT (vNKT) cells and mucosa-associated invariant T (MAIT) cells. iNKT and vNKT cells are CD1d-restricted, lipid-reactive cells with remarkable immunoregulatory properties. MAIT cells participate in antimicrobial defense, and are restricted by MHC-related protein 1 (MR1), which displays microbe-derived vitamin B metabolites. Importantly, NKT and MAIT cells are rapid and potent producers of immunomodulatory cytokines. Therefore, they may be considered attractive targets during the early, hyperinflammatory phase of sepsis when immediate interventions are urgently needed, and also in later phases when adjuvant immunotherapies could potentially reverse the dangerous state of immunosuppression. We will highlight recent findings that point to the significance or the therapeutic potentials of NKT and MAIT cells in sepsis and will also discuss what lies ahead in research in this area.

As the construction industry faces growing environmental concerns and a need for viable practices, this study explores the potential for substituting natural aggregates (NA) with untreated coarse recycled aggregates (CRAs) and pretreated CRAs (PCRAs) in the production of pavement-quality concrete (PQC). The research explores the performance of ambient-cured alkali-activated pavement-quality concrete (AAPQC), chosen as an environmentally friendly alternative to the water cured cement concrete, with the CRAs as the alternative to the traditional NA. The investigation includes a systematic assessment of the properties of PCRAs to determine their suitability for AAPQC production. Furthermore, a series of experimental investigations such as slump, ultrasonic pulse velocity, compressive strength, flexural strength, split tensile strength, water absorption, apparent density, and the volume of permeable voids to evaluate the mechanical and durability properties of the AAPQC mixtures were carried out. Microstructural investigations including FESEM, energy-dispersive X-ray, X-ray diffraction, FTIR, and stereo microscopy were also carried out for deeper understanding and substantiation of the results observed. It was interesting to observe that AAPQC with 100% PCRAs exhibited higher compressive strength (approximately 55.1 MPa) and flexural strength (4.9 MPa) than AAPQC with 100% untreated CRAs. Furthermore, AAPQCs with 100% PCRAs were superior in absorption and permeability compared to AAPQCs with CRAs. With these and many more interesting observations, this study holds promise and contributes valuable insights into viable pavement construction practices by promoting the use of PCRAs in the ambient-cured AAPQC. [ABSTRACT FROM AUTHOR]

The development of biocompatible hydrogels for 3D bioprinting is essential for creating functional tissue models and advancing preclinical drug testing. This study investigates the formulation, printability, mechanical properties, and biocompatibility of a novel Alg-Gel hydrogel blend (alginate and gelatin) for use in extrusion-based 3D bioprinting. A range of hydrogel compositions were evaluated for their rheological behavior, including shear-thinning properties, storage modulus, and compressive modulus, which are crucial for maintaining structural integrity during printing and supporting cell viability. The printability assessment of the 7% alginate–8% gelatin hydrogel demonstrated that the 27T tapered needle achieved the highest normalized Printability Index (POInormalized = 1), offering the narrowest strand width (0.56 ± 0.02 mm) and the highest printing accuracy (97.2%) at the lowest printing pressure (30 psi). In contrast, the 30R needle, with the smallest inner diameter (0.152 mm) and highest printing pressure (80 psi), resulted in the widest strand width (0.70 ± 0.01 mm) and the lowest accuracy (88.8%), resulting in a POInormalized of 0.274. The 30T and 27R needles demonstrated moderate performance, with POInormalized values of 0.758 and 0.558, respectively. The optimized 7% alginate and 8% gelatin blend demonstrated favorable printability, mechanical strength, and cell compatibility with MDA-MB-213 breast cancer cells, exhibiting high cell proliferation rates and minimal cytotoxicity over a 2-week culture period. This formulation offers a balanced approach, providing sufficient viscosity for precision printing while minimizing shear stress to preserve cell health. This work lays the groundwork for future advancements in bioprinted cancer models, contributing to the development of more effective tools for drug screening and personalized medicine. [ABSTRACT FROM AUTHOR]

This work introduces an approach to enhance the real-time monitoring of batch suspension polymerization processes through the integration of real-time calorimetry and state estimation techniques. The challenges inherent in monitoring dynamic and complex processes, particularly in the absence of direct measurements, are effectively addressed through the proposed approach. A dynamic model equation specific to batch operation is employed to assess conversion throughout the process, with timely updates of dynamic parameters in the model equation. A nonlinear high gain cascaded observer with calorimetric measurements estimates the overall heat transfer coefficient and reaction heat. Variations in other parameters such as heat capacity and density are derived from estimated conversion data and updated in the model equation. The study also accounts for the heat loss to the surroundings during isoperibolic batch processes. Validation of the proposed soft sensor model is carried out by comparing the estimated and experimental conversion data by conducting MMA suspension polymerization in a reaction calorimeter. Results demonstrate the potential of calorimetric state estimation as an alternative to direct conversion measurements, offering comprehensive and enhanced monitoring of the batch suspension polymerization process. [ABSTRACT FROM AUTHOR]