Targeting OXCT1-mediated ketone metabolism reprograms macrophages to promote antitumor immunity via CD8+ T cells in hepatocellular carcinoma.

BACKGROUND & AIMS: The liver is the main organ of ketogenesis, while ketones are mainly metabolized in peripheral tissues via the critical enzyme 3-oxoacid CoA-transferase 1 (OXCT1). We previously found that ketolysis is reactivated in hepatocellular carcinoma (HCC) cells through OXCT1 expression to promote tumor progression; however, whether OXCT1 regulates antitumor immunity remains unclear. METHODS: To investigate the expression pattern of OXCT1 in HCC in vivo, we conducted multiplex immunohistochemistry experiments on human HCC specimens. To explore the role of OXCT1 in mouse HCC tumor-associated macrophages (TAMs), we generated LysMcreOXCT1f/f (OXCT1 conditional knockout in macrophages) mice. RESULTS: Here, we found that inhibiting OXCT1 expression in tumor-associated macrophages reduced CD8+ T-cell exhaustion through the succinate-H3K4me3-Arg1 axis. Initially, we found that OXCT1 was highly expressed in liver macrophages under steady state and that OXCT expression was further increased in TAMs. OXCT1 deficiency in macrophages suppressed tumor growth by reprogramming TAMs toward an antitumor phenotype, reducing CD8+ T-cell exhaustion and increasing CD8+ T-cell cytotoxicity. Mechanistically, high OXCT1 expression induced the accumulation of succinate, a byproduct of ketolysis, in TAMs, which promoted Arg1 transcription by increasing the H3K4me3 level in the Arg1 promoter. In addition, pimozide, an inhibitor of OXCT1, suppressed Arg1 expression as well as TAM polarization toward the protumor phenotype, leading to decreased CD8+ T-cell exhaustion and slower tumor growth. Finally, high expression of OXCT1 in macrophages was positively associated with poor survival in patients with HCC. CONCLUSIONS: In conclusion, our results demonstrate that OXCT1 epigenetically suppresses antitumor immunity, suggesting that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer. IMPACT AND IMPLICATIONS: The intricate metabolism of liver macrophages plays a critical role in shaping hepatocellular carcinoma progression and immune modulation. Targeting macrophage metabolism to counteract immune suppression presents a promising avenue for hepatocellular carcinoma treatment. Herein, we found that the ketogenesis gene OXCT1 was highly expressed in tumor-associated macrophages (TAMs) and promoted tumor growth by reprogramming TAMs toward a protumor phenotype. Pharmacological targeting or genetic downregulation of OXCT1 in TAMs enhances antitumor immunity and slows tumor growth. Our results suggest that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer.

First principles calculation of interface interactions and photoelectric properties of ZnSe/SnSe heterostructure.

Heterostructure engineering is an effective technology to improve photo-electronic properties of two dimensional layered semiconductors. In this paper, based on first principles method, we studied the structure, stability, energy band, and optical properties of ZnSe/SnSe heterostructure change with film layer. Results show that all heterostructures are the type-II band arrangement, and the interlayer interaction is characterized by van der Waals. The electron concentration and charge density difference implies the electron (holes) transition from SnSe to monolayer ZnSe. By increasing the layer of SnSe films, the quantum effects are weakened leading to the band gap reduced, and eventually show metal properties. The optical properties also have obvious change, the excellent absorption ability of ZnSe/SnSe heterostructures mainly near the infrared spectroscopy. These works suggest that ZnSe/SnSe heterostructure has significant potential for future optoelectronic applications.

[Effects of Different Nutritional Scoring Systems on Prognosis of Elderly Patients with Multiple Myeloma].

OBJECTIVE: To analyze the prognostic nutritional index (PNI), controlling nutritional status (CONUT) and fibrinogen/albumin ratio (FAR) levels in elderly patients with multiple myeloma (MM) and their prognostic impact. METHODS: The clinical data of 74 elderly MM patients diagnosed in Gansu Provincial Hospital from January 2020 to July 2022 were retrospectively analyzed. The optimal cut-off values for PNI, CONUT score and FAR were obtained by receiver operating characteristic (ROC) curve, which were used for grouping patients. The correlation of above three indexes with clinical parameters such as sex, serum calcium (Ca), ß2-microglobulin (ß2-MG), serum creatinine (Cr) in elderly MM patients were analyzed. The survival rates of patients with different levels of each index were compared. Univariate and multivariate analysis of the impact of clinical indicators on the prognosis of patients were performed. RESULTS: The optimal cut-off values for PNI, CONUT score and FAR were 39.775, 3.5 and 0.175, respectively, according to which the patients were divided into high and low group. Statistical analysis showed that there were significant differences in albumin level among different groups (all P < 0.05). In addition, there was a significant difference in hemoglobin between high-PNI group and low-PNI group (P < 0.05), while in sex distribution between high-FAR and low-FAR group (P < 0.05). The survival rate of elderly MM patients with increased PNI, decreased CONUT score and FAR was higher (all P < 0.05). Univariate and multivariate analysis showed that ß2-MG, Cr, PNI, CONUT score and FAR were independent prognostic factors for elderly MM patients. CONCLUSION: PNI, CONUT score and FAR are related to some clinical indicators of elderly MM patients, and have an impact on the prognosis.

[Clinical Features and Prognosis of Patients with CD5+ Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To analyze the clinical characteristics and prognosis of patients with CD5+ diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical data of 161 newly treated DLBCL patients in Gansu Provincial Hospital from January 2013 to January 2020 were retrospectively analyzed. According to CD5 expression, the patients were divided into CD5+ group and CD5- group. The clinical characteristics and prognosis of the two groups were statistically analyzed. RESULTS: The median age of patients in CD5+ group was 62 years, which was higher than 56 years in CD5- group (P =0.048). The proportion of women in CD5+ group was 62.96%, which was significantly higher than 41.79% in CD5- group (P =0.043). The proportion of patients with IPI score > 2 in CD5+ group was 62.96%, which was higher than 40.30% in CD5- group (P =0.031). Survival analysis showed that the median overall survival and progression-free survival time of patients in CD5+ group were 27(3-77) and 31(3-76) months, respectively, which were both shorter than 30(5-84) and 32.5(4-83) months in CD5- group (P =0.047, P =0.026). Univariate analysis showed that advanced age, positive CD5 expression, triple or double hit at initial diagnosis, high IPI score and no use of rituximab during chemotherapy were risk factors for the prognosis of DLBCL patients. Further Cox multivariate regression analysis showed that these factors were also independent risk factors except for advanced age. CONCLUSION: CD5+ DLBCL patients have a worse prognosis than CD5- DLBCL patients. Such patients are more common in females, with advanced age and high IPI score, which is a special subtype of DLBCL.

The electronic and optical properties of Cs2BX6 (B = Zr, Hf) perovskites with first-principle method.

The electronic structures and absorption properties of Cs2BX6 halide compounds are investigated with first principle calculation and exchange correlation functional of GGA-PBE. Pressure and halogen ion doping are employed to regulate band gap. All materials suffer transition from indirect to direct band gap semiconductors but with different phase transition pressure. Structural and band structure calculating results show that the value of phase transition pressure is mainly determined by the volume of octahedron. When the volume of vacancy octahedron is much less than B-ion octahedron, the lowest band point of B-d orbitals transforms to Γ point, then the indirect semiconductors transform into direct band gap semiconductors. Calculating results of optical absorption implied that the systems have obvious blue shift, which result in the optical properties reduced. Based on suitable band gap and higher absorption coefficient, Cs2ZrI4Br2 can be an ideal candidate for perovskites solar cells.

[Effects of Tomato Planting Years on Soil Physical and Chemical Properties and Microbial Communities].

Long-term continuous cropping of facility soils could influence soil properties; however, the differences in soil properties among different continuous cropping years are still not well understood. The objective of this study was to explore the effects of continuous cropping years of tomato on the physical and chemical properties and biological characteristics of facility soil. Conventional analysis, high-throughput sequencing, and other methods were used to examine the soil physicochemical properties, soil microbial community diversity, and enzyme activities in facility soil after continuous tomato cropping for 1-3 years, 5-7 years, and more than 10 years. As the continuous tomato cropping years increased, soil bulk density and pH decreased; soil maximal water holding capacity increased; and organic matter, total nitrogen, and total phosphorus accumulated. As continuous cropping years increased, the total salt and EC value decreased with continuous cropping for 5-7 years and increased from 5-7 years to more than 10 years continuous cropping and showed a trend of secondary soil salinization. There was a significant increase in alkaline phosphatase for 1-3 years to 5-7 years continuous tomato cropping. There were significant differences in fungal community abundance among different cropping years. The Simpson index and Shannon index of fungi showed a trend of increasing first and then decreasing with the extension of continuous cropping years and reached the maximum value at 5 years of continuous cropping. The Chao1 index decreased continuously following the cropping years. As continuous cropping years increased, Streptomyces became the dominant bacteria, and Aspergillus and Pseudaleuria became the dominant fungi. The key factors affected by continuous cropping years were available potassium and available nitrogen based on the redundancy analysis. The results of this study lay the foundation for future research on the influence of continuous cropping years on the health of facility soil.

[Microbial Diversity and Population Structure of Different Salinized Soil Types in Hebei Province].

The objective of this study was to explore the microbial diversity and community composition under saline soil and to screen the salt-tolerant microbial flora from salinization habitats. The soil from three different habitats(primary salinization, secondary salinization, and healthy soil) in Hebei Province were sampled. The convention method and high-throughput sequencing technology were used to examine the physicochemical properties and microorganism diversity. The soil chemical properties of the three habitats were significantly different. Compared with those of field soil, the soil OM, AP, AK, TS, and EC values of greenhouse soil and TS and EC values of coastal saline soil were significantly higher. However, other chemical indexes of coastal saline soil were significantly lower. The diversity index and abundance of soil bacteria in greenhouse soil were the highest, followed by those in field soil and coastal saline soil as the lowest. The diversity index and abundance of fungi in two saline habitats were significantly lower than that in field soil. The community structure of saline soil was analyzed at the phylum and genus levels. Chloroflexi and its genera and Ascomycota and its genera, such as Trichocladium and Fusarium, were the dominant microbial groups in saline soil. EC and TS were the main factors affecting microbial diversity and community composition. EC and TS were positively correlated with unclassified_A4b, unclassified_Chloroflexi, unclassified_α-Proteobacteria, Trichocladium, unclassified_Chaetomiaceae, Crassicarpon, Cephaliophora, and Sodiomyces. The results of this study lay the foundation for future research on screening microbial resources needed for saline soil remediation.