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Supplementary Figure from IFNα Potentiates Anti–PD-1 Efficacy by Remodeling Glucose Metabolism in the Hepatocellular Carcinoma Microenvironment

The adsorption performance and mechanism of the amino-modified zirconium-based metal organic framework (UiO-66-NH2) for the removal of U(VI) in aqueous solution were studied. Compared with UiO-66, UiO-66-NH2 shows better adsorption performance due to the introduction of amino groups. The adsorption characteristics of factors such as pH, UiO-66-NH2 dosage and contact time were investigated. The results show that the maximum adsorption capacity is 384.6 mg g−1 at pH = 6 and T = 313 K. The adsorption conforms to the quasi-second-order kinetic model and the Langmuir isotherm model. The thermodynamic parameters indicate that the adsorption process of U(VI) is endothermic and spontaneous. After five cycles, the removal rate of U(VI) still exceeded 83.53%. The results indicate that UiO-66-NH2 is a promising adsorbent that can effectively remove U(VI) in radioactive wastewater.

Polyethyleneimine (PEI) modified magnetic yeast biomaterials composites (MY@SiO2-PEI) were prepared through a two-step solution polymerization method to remove U(VI) from aqueous solutions. The impact of six anions on U(VI) removal efficiency with MY@SiO2-PEI in single- and multi-ion systems was conducted in this article. A 26–2 Fractional factorial design (FFD) and Visual MINTEQ were employed to identify primary or interacting factors and the uranium chemical speciation calculations, respectively. In the single-ion systems, PO43−, humic acids (HA) slightly increased the U(VI) removal efficiency with MY@SiO2-PEI at low pH, whereas the U(VI) removal efficiency was largely reduced with SO42−, CO32−. The factorial effects of the six selected species on U(VI) removal efficiency via FFD in the multi-ion system were in the following sequence: CO32− > Cl− > HA > PO43− > SO42− > NO3−, and U(VI) removal was affected significantly by the combined of AB (Cl− × NO3−), BD (NO3− × SO42−).

The overall response rate for anti–PD-1 therapy remains modest in hepatocellular carcinoma (HCC). We found that a combination of IFNα and anti–PD-1–based immunotherapy resulted in enhanced antitumor activity in patients with unresectable HCC. In both immunocompetent orthotopic and spontaneous HCC models, IFNα therapy synergized with anti–PD-1 and the combination treatment led to significant enrichment of cytotoxic CD27+CD8+ T cells. Mechanistically, IFNα suppressed HIF1α signaling by inhibiting FosB transcription in HCC cells, resulting in reduced glucose consumption capacity and consequentially establishing a high-glucose microenvironment that fostered transcription of the T-cell costimulatory molecule Cd27 via mTOR–FOXM1 signaling in infiltrating CD8+ T cells. Together, these data reveal that IFNα reprograms glucose metabolism within the HCC tumor microenvironment, thereby liberating T-cell cytotoxic capacities and potentiating the PD-1 blockade–induced immune response. Our findings suggest that IFNα and anti–PD-1 cotreatment is an effective novel combination strategy for patients with HCC. Significance: Our study supports a role of tumor glucose metabolism in IFNα-mediated antitumor immunity in HCC, and tumor-infiltrating CD27+CD8+ T cells may be a promising biomarker for stratifying patients for anti–PD-1 therapy. See related commentary by Kao et al., p. 1615. This article is highlighted in the In This Issue feature, p. 1599

Spinal fusion is widely used for patients with spinal disorders; however, patients often suffer from back pain following fusion surgery. Substance P (SP) acts as a pain neurotransmitter via the sensory nerve afferent fibres up to the spinal cord, and is involved in the conduction and modulation of pain. The use of specific SP neurokinin receptor (NKR) antagonists may decrease postoperative pain. In the present study, the effects of alterations in the quantity of SP and NKRs in the early spinal fusion process were investigated. The results of the present study revealed that SP and NKRs began to appear 1 week post‑surgery in fibrous tissues. The abundance of SP and NKRs peaked at 3 weeks post‑surgery; the majority of SP and NKRs were distributed around the allograft and the new microvessels. In conclusion, SP and NKRs are involved in early spinal fusion, a finding that may facilitate the development of novel strategies to promote spinal fusion from a neurogenesis perspective.

Objectives Patients with traumatic vertebral fractures often have major associated postoperative morbidities such as healing failure and kyphosis. Low-intensity pulsed ultrasound (US) has been found to promote bone fracture healing. The objectives of our study were to determine whether low-intensity pulsed US could promote traumatic vertebral fracture healing and to explore its inner mechanisms. Methods A rat model of traumatic vertebral fracture was created and treated with low-intensity pulsed US after surgery. At 4 weeks after surgery, radiographic, micro-computed tomography, and 3-dimensional reconstruction were used to assess the radiologic healing status; a histologic analysis was performed to evaluate the pathologic process and relationship between osteogenesis and type H microvessels. Results Well-remodeled trabecular meshworks were found in the low-intensity pulsed US treatment group compared to the control group. Micro-computed tomography and 3-dimensional reconstruction revealed more and thicker trabeculae after low-intensity pulsed US treatment. Abundant chondrocytes, a newly formed bone marrow cavity, trabeculae, and microvessels were formed at the fracture sites. More osterix-positive osteoblasts were circling the newly formed bone meshwork and were situated at the interface of chondrocytes in the low-intensity pulsed US treatment group. Type H microvessels were spreading around the newly formed trabecula, bone marrow cavity, osteoblasts, and interface of chondrocytes, with a larger mean vascular density in the low-intensity pulsed US group. Conclusions Low-intensity pulsed US could accelerate traumatic vertebral fracture healing by temporally and spatially increasing chondrogenesis and osteoblast-induced osteogenesis coupled with angiogenesis of type H microvessels in a rat model of traumatic vertebral fracture.