Non-contact 3D point cloud phenotyping reduces the time and animal disturbance of manual livestock measurement, yet the genetic architecture of automatically derived body conformation traits remains underexplored. Here, we extracted body length (BL) and body height (BH) from 3D point cloud data of 510 Wens Black pigs and mapped their genetic basis. Pearson correlations between automated and manual measurements were 0.79 for BL and 0.74 for BH, with mean absolute percentage errors of 2.30% and 3.55%, respectively. The corresponding genetic correlation estimates were 1.00 ± 0.13 for BL and 0.92 ± 0.14 for BH. Combined single- and multi-locus genome-wide association study (GWAS) identified 43 candidate quantitative trait nucleotides (QTNs), including the BL-associated SNP detected at the suggestive significance level by the single-locus model and 42 additional loci at LOD ≥ 3. Among these, eight BL-associated and six BH-associated QTNs were detected by at least two multi-locus methods, including two BL-associated QTNs detected by all four methods. The maximum estimated proportions of phenotypic variance explained by individual QTNs were 6.00% for BL and 4.71% for BH. Functional enrichment implicated skeletal and cellular development pathways, prioritizing ACKR3, PLCB1 and COL11A1 for BL, and BDNF, PLEKHM1, ANKRD11 and RHOBTB2 for BH, as positional candidate genes. These findings demonstrate that 3D point cloud phenotyping captures heritable body-size variation in pigs and provide loci and candidate genes for validation and future genomic breeding.
Mitochondria have emerged as central regulators of anti-tumor immunity, extending beyond their canonical role in energy production. In cancer immunology, mitochondrial fitness—a multifaceted state encompassing mitochondrial quantity, quality, metabolic adaptability, and stress resilience—emerges as an important component shaping T cell fate across the continuum from activation to exhaustion. During early activation, mitochondrial remodeling supports calcium signaling, redox regulation, and metabolic reprogramming required for clonal expansion and effector differentiation. However, tumor-infiltrating T cells encounter a metabolically hostile tumor microenvironment (TME) characterized by hypoxia, nutrient deprivation, and immunosuppressive metabolite accumulation. To sustain functionality, T cells must maintain mitochondrial plasticity through coordinated regulation of oxidative phosphorylation, fatty acid oxidation, mitochondrial dynamics, biogenesis, and quality control pathways. Persistent antigen exposure and chronic metabolic stress progressively impair mitochondrial fitness, promoting defective oxidative metabolism, excessive reactive oxygen species accumulation, disrupted mitochondrial quality control, and ultimately T cell exhaustion. Mitochondrial fitness has emerged as a defining feature of stem-like progenitor exhausted (Tpex) and memory T cells, which retain self-renewal capacity and mediate durable immune checkpoint blockade responses. Recent studies uncovered novel links between mitochondrial metabolism, epigenetic regulation, and T cell differentiation, highlighting mitochondria as active drivers of immune cell fate rather than passive bioenergetic organelles. This review considers how mitochondrial fitness orchestrates T cell activation, adaptation, exhaustion, and memory formation within the TME, and highlights emerging concepts including mitochondrial control of stem-like T cell maintenance and metabolic reprogramming strategies for restoring mitochondrial function. A deeper understanding of mitochondrial fitness may provide opportunities to enhance cancer immunotherapy and improve long-term anti-tumor immune responses.
The interaction between semen and the female reproductive tract is a critical step in fertilization and pregnancy establishment. In most mammals, insemination induces a transient inflammatory response in the uterus, but the specific semen constituent(s) responsible remain unclear. Using ex vivo and in vivo caprine models, we examined whether sperm and seminal plasma (SP) differentially regulate endometrial and systemic immune responses. Goat endometrial explants were co-cultured with increasing concentrations of sperm or SP for 0, 1, 3, or 6 h. Viable sperm and SP, but not heat-inactivated sperm, induced a rapid, dose-dependent, and transient pro-inflammatory response characterized by increased expression of TNFA, IL-1B, IL-6, and IL-8, together with reduced IL-4 and IL-10 transcript abundance. In vivo, estrus-synchronized nanny goats mated with fertile bucks showed time-dependent changes in serum cytokines and a pro-inflammatory response in peripheral blood cells, whereas non-mated controls showed no comparable changes. Mechanistically, semen exposure was associated with a selective increase in TLR2 mRNA expression in the endometrium, with only minor changes in TLR4, suggesting that TLR2 may contribute to semen-induced uterine immune activation in goats. Collectively, these findings indicate that semen constituents can prime the caprine endometrium toward a pro-inflammatory state and are consistent with a potential role for TLR2-associated signaling in reproductive tract immune modulation.
Platelet surface adhesion receptors and intracellular signaling proteins have been the focus of platelet research for decades, with the aim of understanding how they contribute to hemostatic and thrombotic functions. However, membrane transporters and their respective roles in platelets and megakaryocytes have received relatively little attention, despite their importance for cellular regulation. Platelets harbor members of two principal structurally dissimilar large families of transporters differing in their energy source: ABC (ATP-binding cassette) transporter family and the solute carrier (SLC) family. Family members comprise integral membrane proteins that control the uptake, distribution and excretion of a variety of nutrients and metabolites, lipids, iron and drugs across concentration gradients, thereby exerting significant influence over cellular metabolism and platelet activation. In addition to transporters found in the plasma membrane, platelet transporters may also localize to lysosomal, mitochondrial and secretion granule membranes or to additional organelles. Interestingly, the impact of platelet transporters does not appear to be limited to canonical platelet functions but may extend to recently established platelet interactions with immune cells and selected tissues, with repercussions on health and disease. More recently, members of these two families have been recognized as modulators of drug efficacy and proposed as therapeutic targets. In this review we describe transporter structure, corresponding molecular mechanisms of cargo transport, functional significance, and transporter regulation, within a platelet framework.
Interleukin-15 (IL-15) is an immunoregulatory cytokine also recognized as a myokine, with experimentally demonstrated cytoprotective and metabolic effects. Renal tubular epithelial cells (TECs) and podocytes express components of the IL-15 receptor system, but the role of IL-15 in exercise-associated renal adaptation remains unclear. This review distinguishes evidence from renal experimental models from hypotheses regarding exercise-induced renoprotection. Cell-culture and preclinical studies support a role for IL-15 in promoting TEC survival and attenuating profibrotic responses. Separate studies in podocytes demonstrate a functional role for STAT5 in autophagy regulation and improvements in mitochondrial fusion and respiration in response to IL-15, with optic atrophy 1 (OPA1) implicated in the latter response. These findings do not establish a single integrated pathway or demonstrate that the same protective mechanisms operate during exercise. Strenuous exercise may transiently increase tubular stress- or injury-associated biomarkers; however, these increases do not necessarily indicate clinically significant acute kidney injury (AKI) and should be interpreted alongside measures of renal function and the clinical context. We outline a conceptual framework that distinguishes potentially protective responses in renal parenchymal cells from IL-15-dependent immune activation that may contribute to injury in selected disease settings. Cytokine availability, exposure duration, mode of presentation, receptor composition, and inflammatory context may influence these outcomes, but their roles in renal responses to exercise remain to be established. An increase in circulating IL-15 alone does not establish its skeletal muscle origin, delivery to the kidney, or biological activity in renal target cells. The key unresolved question is whether IL-15 produced by skeletal muscle in response to exercise reaches renal target cells in a biologically active form and confers measurable renoprotection.
