<i>Trans</i>-vaccenic acid reprograms CD8⁺ T cells and anti-tumour immunity

Diet-derived nutrients are inextricably linked to human physiology by providing energy and biosynthetic building blocks and by functioning as regulatory molecules. However, the mechanisms by which circulating nutrients in the human body influence specific physiological processes remain largely unknown. Here we use a blood nutrient compound library-based screening approach to demonstrate that dietary trans-vaccenic acid (TVA) directly promotes effector CD8+ T cell function and anti-tumour immunity in vivo. TVA is the predominant form of trans-fatty acids enriched in human milk, but the human body cannot produce TVA endogenously. Circulating TVA in humans is mainly from ruminant-derived foods including beef, lamb and dairy products such as milk and butter, but only around 19% or 12% of dietary TVA is converted to rumenic acid by humans or mice, respectively. Mechanistically, TVA inactivates the cell-surface receptor GPR43, an immunomodulatory G protein-coupled receptor activated by its short-chain fatty acid ligands. TVA thus antagonizes the short-chain fatty acid agonists of GPR43, leading to activation of the cAMP–PKA–CREB axis for enhanced CD8+ T cell function. These findings reveal that diet-derived TVA represents a mechanism for host-extrinsic reprogramming of CD8+ T cells as opposed to the intrahost gut microbiota-derived short-chain fatty acids. TVA thus has translational potential for the treatment of tumours

Semiconducting Pavonites CdMBi₄Se₈ (M = Sn and Pb) and Their Thermoelectric Properties

Two new compounds CdPbBi₄Se₈ and CdSnBi₄Se₈ adopt the pavonite structure type and crystallize in the monoclinic space group <i>C</i>2/<i>m</i> with <i>a</i> = 13.713(3) Å, <i>b</i> = 4.1665(8) Å, <i>c</i> = 15.228(3) Å, β = 115.56(3)° for CdPbBi₄Se₈; <i>a</i> = 13.679 Å, <i>b</i> = 4.153 Å, <i>c</i> = 15.127 Å, β = 115.51° for CdSnBi₄Se₈. Their crystal structures are composed of two different types of polyhedral slabs, one containing a mixture of one octahedron [MSe₆] block and paired squared pyramids [MSe₅], while the other forms distorted galena-type (or NaCl-type) lattices with three [MSe₆] octahedral chains (M = Pb, Cd, Bi, Sn). Both CdPbBi₄Se₈ and CdSnBi₄Se₈ are stable up to ∼970 K. Density functional theory (DFT) calculations show that both CdPbBi₄Se₈ and CdSnBi₄Se₈ are indirect band gap semiconductors. DFT phonon dispersion calculations performed on CdSnBi₄Se₈ give valuable insights as to the origin of the observed low experimental lattice thermal conductivities of ∼0.58 W m^–1 K^–1 at 320 K. The title compounds exhibit n-type conduction, and they exhibit promising thermoelectric properties with a maximum thermoelectric figure of merit, ZT, reaching 0.63 for CdPbBi₄Se₈, and 0.40 for CdSnBi₄Se₈ at 850 K

Semiconducting Pavonites CdMBi₄Se₈ (M = Sn and Pb) and Their Thermoelectric Properties

Two new compounds CdPbBi₄Se₈ and CdSnBi₄Se₈ adopt the pavonite structure type and crystallize in the monoclinic space group <i>C</i>2/<i>m</i> with <i>a</i> = 13.713(3) Å, <i>b</i> = 4.1665(8) Å, <i>c</i> = 15.228(3) Å, β = 115.56(3)° for CdPbBi₄Se₈; <i>a</i> = 13.679 Å, <i>b</i> = 4.153 Å, <i>c</i> = 15.127 Å, β = 115.51° for CdSnBi₄Se₈. Their crystal structures are composed of two different types of polyhedral slabs, one containing a mixture of one octahedron [MSe₆] block and paired squared pyramids [MSe₅], while the other forms distorted galena-type (or NaCl-type) lattices with three [MSe₆] octahedral chains (M = Pb, Cd, Bi, Sn). Both CdPbBi₄Se₈ and CdSnBi₄Se₈ are stable up to ∼970 K. Density functional theory (DFT) calculations show that both CdPbBi₄Se₈ and CdSnBi₄Se₈ are indirect band gap semiconductors. DFT phonon dispersion calculations performed on CdSnBi₄Se₈ give valuable insights as to the origin of the observed low experimental lattice thermal conductivities of ∼0.58 W m^–1 K^–1 at 320 K. The title compounds exhibit n-type conduction, and they exhibit promising thermoelectric properties with a maximum thermoelectric figure of merit, ZT, reaching 0.63 for CdPbBi₄Se₈, and 0.40 for CdSnBi₄Se₈ at 850 K

Figure S11 from <i>NRAS</i> Mutant Dictates AHCYL1-Governed ER Calcium Homeostasis for Melanoma Tumor Growth

Supplementary Figure 11. There is positive correlation between ATF2 and AHCYL1 mRNA levels in human cutaneous melanoma patients by TCGA analysis.</p

Figure S7 from <i>NRAS</i> Mutant Dictates AHCYL1-Governed ER Calcium Homeostasis for Melanoma Tumor Growth

Supplementary Figure 7. AHCYL1 deficiency attenuates cell proliferation, decreases ER calcium levels, and activates the UPR.</p

Figure S10 from <i>NRAS</i> Mutant Dictates AHCYL1-Governed ER Calcium Homeostasis for Melanoma Tumor Growth

Supplementary Figure 10. CREB doesn’t positively regulate AHCYL1 transcription.</p

Figure S3 from <i>NRAS</i> Mutant Dictates AHCYL1-Governed ER Calcium Homeostasis for Melanoma Tumor Growth

Supplementary Figure 3. AHCYL2 does not overexpress and is not critical in human NRAS-mutated melanoma as AHCYL1.</p

Figure S1 from <i>NRAS</i> Mutant Dictates AHCYL1-Governed ER Calcium Homeostasis for Melanoma Tumor Growth

Supplementary Figure 1. AHCYL1 is selectively critical for NRAS-mutated but not for BRAF-mutated human melanoma cells.</p

Figure S2 from <i>NRAS</i> Mutant Dictates AHCYL1-Governed ER Calcium Homeostasis for Melanoma Tumor Growth

Supplementary Figure 2. AHCYL1 knockout selectively causes cell cycle arrest in NRAS-mutant expressing human melanoma cells.</p