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Background: Minimally invasive liver resection of the posterosuperior region is considered a challenging procedure due to poor exposure and difficult bleeding control. A robotic approach is supposed to be advantageous in posterosuperior segmentectomy. Its benefits over laparoscopic liver resection (LLR) remain undetermined. This study compared robotic liver resection (RLR) and LLR in the posterosuperior region performed by a single surgeon. Materials and methods: We retrospectively analyzed consecutive RLR and LLR performed by a single surgeon between December 2020 and March 2022. Patient characteristics and perioperative variables were compared. A 1:1 propensity score matched (PSM) analysis was performed between both groups. Results: The analysis included 48 RLR and 57 LLR procedures in the posterosuperior region. After PSM analysis, 41 cases of both groups were retained. In pre-PSM cohort, the operative time in the RLR group was significantly shorter than in the LLR group (160 vs. 208 min, P = 0.001), especially in radical resection of malignant tumors (176 vs. 231 min, P = 0.004). The total Pringle maneuver duration was also markedly shorter (40 vs. 51 min, P = 0.047), and the estimated blood loss in the RLR group was lower (92 vs. 150 mL, P = 0.005). The postoperative hospital stay (POHS) in the RLR group was significantly shorter (5.4 vs. 7.5 days, P = 0.048). In PSM cohort, operative time in the RLR group was also significantly shorter (163 vs. 193 min, P = 0.036), and the estimated blood loss was lower (92 vs. 144 mL, P = 0.024). However, the total Pringle maneuver duration and POHS showed no significant difference. The complications were similar between two groups in both pre-PSM and PSM cohorts. Conclusion: RLR in the posterosuperior region was as safe and feasible as LLR. RLR was associated with reduced operative time and blood loss than LLR. [ABSTRACT FROM AUTHOR]

This study aimed to increase cordycepin production by over-expressing bio-synthetic enzyme genes, including the adenylosuccinate synthase, adenylosuccinate lyase, and 5′-nucleotidase genes. Research data showed that the extracellular and intracellular cordycepin concent of 24 recombinant strains were higher than those of C. militaris WT, indicating that over-expression of key enzyme genes increased cordycepin production. Among them, the CM-adss-5 strain had highest cordycepin production, and the extracellular and intracellular cordycepin concent were 1119.75 ± 1.61 and 65.56 ± 0.97 mg/L, which were 1.26 and 2.61 times that of C. militaris WT. This study also optimized the culture conditions of CM-adss-5 strain through single factor experiments to obtain the best culture conditions. The best culture condition was 25 °C constant temperature, 180-rpm shaking culture, fermentation period 12 days, inoculate amount 5%, initial pH 6, seed age 108 h, and liquid volume 110/250 mL. Then, the extracellular and intracellular cordycepin content of CM-adss-5 strain reached 2581.96 ± 21.07 and 164.08 ± 1.44 mg/L, which were higher by 130.6% and 150.3%, respectively. Therefore, our research provides a way to efficiently produce cordycepin for the development of cordycepin and its downstream products. [ABSTRACT FROM AUTHOR]

Background: Robotic surgery is the most recent advanced minimally invasive approach for distal pancreatectomy. However, its benefits over laparoscopic distal pancreatectomy (LDP) remain undetermined. Previous studies were limited by their small sample size or variations in surgeon skills. This study aimed to compare robotic distal pancreatectomy (RDP) performed by a single surgeon with LDP performed by skilled laparoscopic surgeons in a high-volume center. Methods: We retrospectively analyzed consecutive RDP performed by a single surgeon between December 2020 and November 2021 with LDP performed by experienced surgeons during the same period in a high-volume center. Patient characteristics and perioperative variables were compared. Results: The analysis included 55 RDP and 146 LDP procedures. The operative time in the RDP group was significantly shorter than the LDP group (171 vs. 222 min, P < 0.001), both in spleen-preserved (154 vs. 212 min, P < 0.001) and spleen-removed (192 vs. 230 min, P = 0.005) procedures. The RDP group made more frequent use of the stapler technique for pancreas transection (87.3 vs. 68.5%, P = 0.007), and its estimated blood loss was lower (79 vs. 155 mL, P < 0.001) than the LDP group. The postoperative hospital stay in the RDP group was significantly shorter than the LDP group (8 vs. 12 days, P < 0.001). The groups were similar in their complication distributions. Conclusion: RDP is as safe and feasible a minimally invasive approach as LDP. The advanced manipulation and visualization capabilities of the robotic approach in distal pancreatectomy could help reduce operative time and blood loss, and is related to shorter postoperative hospital stay. [ABSTRACT FROM AUTHOR]

Simple Summary: Chromosome 8 open reading frame 76 (C8orf76), a novel gene located in the nucleus, is highly expressed in many tumor types. Here, we present novel insights into the molecular mechanism and function of C8orf76 in HCC via in vitro and in vivo assays. On the one hand, C8orf76 could play a vital role in cell proliferation and cell cycle progression. More importantly, on the other hand, C8orf76 also acts as an important regulator of ferroptosis in HCC through activating SLC7A11 transcriptionally, resulting in elevation of GSH synthesis and lipid peroxidation resistance. Our study indicated that C8orf76 could be a novel marker for HCC diagnosis and therapeutic target for HCC patients. Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide. Chromosome 8 open reading frame 76 (C8orf76), a novel gene located in the nucleus, is highly expressed in many tumor types. However, the specific mechanisms and functions of C8orf76 in HCC remain unclear. Here, we reported for the first time that C8orf76 gene expression levels were frequently upregulated in liver cancer and significantly correlated with HCC development. C8orf76 downregulation induced G1-S arrest and inhibited cell proliferation. Intriguingly, C8orf76 deficiency could accelerate erastin or sorafenib-induced ferroptosis through increasing lipid reactive oxygen species (ROS) levels. Moreover, although C8orf76 overexpression did not affect tumorigenesis under normal conditions, it increased resistance to lipid disturbance and ferroptosis triggered by erastin or sorafenib, which further facilitated HCC cell growth and tumor progression. Mechanistically, C8orf76 bound to the promoter region of the solute carrier family 7 member 11 (SLC7A11) gene and upregulated SLC7A11 transcriptionally. SLC7A11-dependent cystine import led to sufficient GSH synthesis and lipid peroxidation inhibition, thus accelerating tumor growth. Our study indicated that C8orf76 could be a novel marker for HCC diagnosis. In addition, a better comprehensive understanding of the potential role of C8orf76 in HCC helped us develop novel therapeutic strategies for this intractable cancer. [ABSTRACT FROM AUTHOR]

Lipid metabolic reprogramming plays a pivotal role in hepatocellular carcinoma (HCC) development, but the underlying mechanisms are incompletely characterized. Long chain acyl CoA synthetase 4 (ACSL4), a member of acyl-CoA synthetases (ACS) family, has been identified as a novel marker of alpha-fetoprotein-high subtype HCC and as an oncogene. Here, we identified a new function of ACSL4 in HCC lipid metabolism. ACSL4 can modulate de novo lipogenesis by accumulating intracellular triglycerides, cholesterols, and lipid droplets in HCC. Mechanistically, ACSL4 upregulates the master lipogenesis regulator sterol regulatory element binding protein 1 (SREBP1) and its downstream lipogenic enzymes in HCC cells via c-Myc. Moreover, SREBP1 is crucial for ACSL4-mediated regulation of lipogenesis as well as HCC cell proliferation and metastasis, as SREBP1 overexpression rescues lipogenic deficiency and decreased oncogenic capabilities associated with ACSL4 suppression in vitro and in vivo. Clinically, our data showed that the expression of ACSL4 was positively correlated with that of SREBP1 in HCC patients, and the combinational biomarkers showed strong predictive value for HCC. Together, our findings uncover a new mechanism by which ACSL4 modulates aberrant lipid metabolism and promotes the progression of HCC. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel palladium catalyst immobilized on hypercrosslinked polymer was prepared via a facile Scholl coupling method. • The obtained catalyst exhibited high catalytic efficiency towards Suzuki reactions in aqueous media. • Due to the Pd coordination on the polymer surface, the trace metal leaching was achieved. • This study provides a simple approach for supporting palladium on the surface of such functional polymers. Bearing the merits of convenient functionalization and versatile framework composition, hypercrosslinked polymers are employed as promising candidates in green catalysis. In this study, a new hypercrosslinked polymer supported palladium catalyst has been synthesized based on pyrrole functionalization from triphenyl benzene and pyrrole via Scholl reaction and palladium anchoring on the polymer surface. The structure of prepared Pd catalyst was confirmed by TEM, SEM, EDX, XRD, N 2 adsorption–desorption, solid state 13C NMR, TGA, FT-IR, XPS, and ICP analyses. The novel complex can be served as an effective catalyst for the preparation of biphenyl compounds with the yields up to 100 % in EtOH: H 2 O (1:1) at 60 °C by using 0.07 mol% of catalyst in air. More importantly, the catalyst also has significant advantages in terms of facile availability of raw materials, chemical and thermal stability, and cost-effective synthesis. Due to the high specific surface area, and the coordination of pyrrole groups with palladium on the surface of this polymer, this catalyst could effectively prevent palladium leaching (<1.1 %). Furthermore, the catalyst could be recovered by simple centrifugation for four consecutive times. The study provides new insight into the immobilization of palladium on such polymer surface in other heterogeneous catalysis systems. [ABSTRACT FROM AUTHOR]

Background: N6-methyladenosine (m6A) methylation, a well-known modification with new epigenetic functions, has been reported to participate in the tumorigenesis of hepatocellular carcinoma (HCC), providing novel insights into the molecular pathogenesis of this disease. However, as the key component of m6A methylation, Wilms tumor 1-associated protein (WTAP) has not been well studied in HCC. Here we investigated the biological role and underlying mechanism of WTAP in liver cancer. Methods: We determined the expression of WTAP and its correlation with clinicopathological features using tissue microarrays and the Cancer Genome Atlas (TCGA) dataset. And we clarified the effects of WTAP on HCC cells using cell proliferation assay, colony formation, Edu assay and subcutaneous xenograft experiments. We then applied RNA sequencing combined with gene expression omnibus (GEO) data to screen candidate targets of WTAP. Finally, we investigated the regulatory mechanism of WTAP in HCC by m6A dot blot assay, methylated RNA immunoprecipitation (MeRIP) assay, dual luciferase reporter assay, RNA immunoprecipitation (RIP) assay and Chromatin immunoprecipitation (ChIP) assay. Results: We demonstrated that WTAP was highly expressed in HCC which indicated the poor prognosis, and that WTAP expression served as an independent predictor of HCC survival. Functionally, WTAP promoted the proliferation capability and tumor growth of HCC cells in vitro and in vivo. Furthermore, ETS proto-oncogene 1 (ETS1) was identified as the downstream effector of WTAP. The m6A modification regulated by WTAP led to post-transcriptional suppression of ETS1, with the implication of Hu-Antigen R (HuR) as an RNA stabilizer. Then ETS1 was found to inhibit the progression of HCC and could rescue the phenotype induced by WTAP deficiency. Moreover, WTAP modulated the G2/M phase of HCC cells through a p21/p27-dependent pattern mediated by ETS1. Conclusion: We have identified that WTAP is significantly up-regulated in HCC and promotes liver cancer development. WTAP-guided m6A modification contributes to the progression of HCC via the HuR-ETS1-p21/p27 axis. Our study is the first to report that WTAP-mediated m6A methylation has a crucial role in HCC oncogenesis, and highlights WTAP as a potential therapeutic target of HCC treatment. [ABSTRACT FROM AUTHOR]