Regulation of lipid metabolism in grass carp primary hepatocytes by exosomes derived from fatty hepatocytes though GRP78.

Exosomes regulate lipid metabolism by carrying miRNAs, nucleic acids, and proteins, thereby influencing the function of receptor cells. Glucose-regulated protein 78 (GRP78) is also involved in the regulation of lipid metabolism. However, it remains unclear whether exosomes derived from fatty hepatocytes (OA-Exo) regulate lipid metabolism through the enrichment of GRP78. In this study, we observed the expression of GRP78 was significantly increased in fatty hepatocytes (incubating hepatocytes with oleic acid (OA) for 24 h) and OA-Exo (P < 0.05). In addition, OA-Exo (50 µg/mL) and GRP78 protein (1 µg/mL) significant increased the content of triacylglycerol (TG) and total cholesterol (TC), as well as up-regulated the expression of GRP78 and inositol-requiring enzyme-1alpha (IRE1α) protein (P < 0.05). We further used YUM70 (an inhibitor of GRP78) to inhibit endogenous GRP78, and compared with the YUM70 group, OA-Exo reversed the effect of YUM70 and increased the content of TG, TC, and the expression of GRP78 protein in hepatocytes (P < 0.05). Furthermore, the inhibition of the IRE1α pathway with 4µ8C resulted in a significant decrease in TG content compared to the control group (P < 0.05). However, when compared with the 4µ8C group, OA-Exo and GRP78 reversed the effect of 4µ8C and significantly increased TG content (P < 0.05). Taken together, these results indicated that OA-Exo activated IRE1α to promote lipid accumulation in hepatocytes through the enrichment of GRP78. This study provided a new perspective for further exploration of exosomal lipid metabolism in fish.

Incidence And Risk Factors Of Contrast Nephropathy After Tace In Patients With Liver Cancer And Chronic Kidney Disease.

PURPOSE: Incidence of contrast induced nephropathy (CIN) and related risk factors in patients with liver cancer and chronic kidney disease after trans-catheter arterial chemoembolization (TACE) is higher. The purpose of this study was to investigate the feasibility and safety of TACE therapy in such patients. METHODS: A retrospective analysis was performed on 103 patients with liver cancer and chronic kidney disease who underwent TACE treatments. TACE was performed according to Seldinger's technique of arterial embolization with minor modifications. Based on CIN diagnostic criteria, patients were divided into non-CIN (n=89) and CIN (n=14) groups. Multiple clinical parameters were assessed for the two groups after TACE. Serum creatinine levels were measured 48-72 h after TACE. RESULTS: Tumor size (>5 cm), TACE frequency, contrast agent dosage, solitary kidney, volume of iodized oil used in the TACE (ml) and urea levels were significantly higher in CIN group in comparison with the non-CIN group, while serum albumin and haemoglobin levels were significantly lower. Multivariate logistic regression analysis confirmed that the volume of iodized oil and TACE frequency were significantly positively correlated, and serum albumin level was negatively correlated in the CIN group. CONCLUSION: Volume of iodized oil, TACE frequency and low serum albumin levels were found to be independent risk factors for CIN after TACE. Thus, it is safe and feasible for hepatocellular carcinoma patients with chronic kidney disease to receive TACE treatment, but adverse events management after TACE needs to be addressed.

[Effect of Composite Leaching on Cadmium Removal Efficiency in Plow Layer Soil of Agricultural Land and Its Functional Regulation].

In order to explore the feasibility of soil leaching and the remediation of agricultural land polluted by medium (heavy) cadmium (Cd), the soil column was used to simulate in-situ leaching, and the citric acid (CA)+ferric chloride (FeCl3) composite leaching agent was selected. Under the optimal concentration combination and the addition amount of the composite leaching agent, the distribution characteristics of Cd in the plow-layer soil and below were investigated. The influence of the leaching process on soil health and the regulation effect of biochar were also investigated. The results showed that:① 0.1 mol·L-1 CA and 0.01 mol·L-1 FeCl3 were the best concentration combinations; under this concentration combination, when the eluent reached 9 pore volume, the content of Cd in the 20 cm soil column was lower than the risk screening value of 0.4 mg·kg-1 (GB 15618-2018) in the corresponding pH value of the tested soil after leaching. ② Under the optimal leaching conditions, the longitudinal distribution of Cd in the 60 cm soil column showed that the content of total Cd increased with the increase in soil depth after leaching, and the leachate of the soil column contained a certain amount of Cd, indicating that the leaching process promoted the downward migration of Cd. The content of available Cd in the soil after composite leaching also increased with the increase in soil depth, which was partly due to the change in exchangeable and carbonate-bound Cd in different soil layers. ③ A portion of the soil health indexes and enzyme activities decreased after CA+FeCl3 composite leaching. The addition of biochar can improve the health status of the soil after leaching; the soil health indexes and enzyme activities were restored significantly, and the risk of Cd reactivation also decreased after the addition of biochar. The results showed that part of Cd in the soil can be leached below the plow layer by CA+FeCl3 composite leaching; however, the leaching process may have a certain impact on soil health, and biochar has a significant effect on the recovery of soil after leaching.

Efficacy and Safety of Lenvatinib Combined With PD-1 Inhibitors Plus TACE for Unresectable Hepatocellular Carcinoma Patients in China Real-World.

Purpose: To evaluate the efficacy and safety of lenvatinib combined with programmed death receptor-1 signaling inhibitors plus transarterial chemoembolization (LePD1-TACE) for treatment of unresectable hepatocellular carcinoma (uHCC) in a real-world setting in China. Methods: This was a retrospective study involving consecutive patients with uHCC (n =114) receiving LePD1-TACE treatment from June 2019 to May 2021. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were calculated to evaluate the antitumor efficacy. Treatment-related adverse events (TRAEs) were analyzed to assess the safety profiles. In addition, we also evaluated prognostic factors related to survival and disease progression. Results: A total of 114 patients with a median age of 53 years were analyzed during a median follow-up duration of 10.6 months (95% confidence interval [CI]: 8.5 -12.8). The Kaplan-Meier analysis showed that the median OS was 18.0 months (95% CI: 14.1 - Not reached), the median PFS was 10.4 months (95% CI: 6.6 - 12.4). Based on modified Response Evaluation Criteria in Solid Tumors, the best ORR was 69.3% and DCR was 80.7%. Almost all patients suffered from TRAEs, the most common grade 3-4 TRAEs were hypertension (8.8%), proteinuria (3.6%), hyperbilirubinemia (1.8%), leukopenia (4.4%) and alanine aminotransferase elevation (3.6%) across all patients. The independent treatment factors associated with OS and PFS were tumor number, neutrophil-to-lymphocyte ratio (NLR) and the early tumor response. In the early tumor response (CR+PR) patients, median OS and PFS were 25.1 months (95% CI: 13.8 - Not reached) and 15.2 months (95% CI: 10.5 - 19.1). The patients with tumor number < 3 had a superior median OS and PFS (25.1, 16.4 months) compared to patients with tumor number ≥ 3 (14.1 months, P = 0.012; 6.6 months, P = 0.007). The patients with NLR ≤ 2.165 had a longer median OS and PFS (Not reached, 15.2 months) than those with NLR > 2.165 (17.7 months, P = 0.003; 7.5 months, P = 0.047). Conclusion: In this real-world study, LePD1-TACE triple therapy showed encouraging efficiency and manageable safety in patients with uHCC. The tumor number (< 3), NLR (≤ 2.165) and early tumor response (CR+PR) could be one of the prognostic markers.

Coexistence of situs inversus totalis and hepatocellular carcinoma: A series of nine cases and a literature review.

Hepatocellular carcinoma (HCC) is the most commonly diagnosed carcinoma and one of the leading causes of cancer-related deaths worldwide. Situs inversus totalis (SIT) is a congenital condition where in the internal organs of the abdomen and thorax lie in mirror images of their normal position. Thus far, there are very few reports on cases of SIT coexisting with HCC. Our case series is probably the largest series in world literature. The cohort of this retrospective study included a total of nine patients diagnosed with SIT-HCC and treated in our hospital between January 2013 and May 2018. Clinical characteristics, prognostic factors, and outcomes were summarized. Treatment strategies included surgery, transarterial chemoembolization, and microwave ablation. The diagnosis and treatment of patients with SIT are challenging because of organ reversion. The current treatment strategies for different stages of liver cancer are safe and feasible for patients with SIT-HCC.

A Correlation Between Differentiation Phenotypes of Infused T Cells and Anti-Cancer Immunotherapy.

T-cell therapy, usually with ex-vivo expansion, is very promising to treat cancer. Differentiation status of infused T cells is a crucial parameter for their persistence and antitumor immunity. Key phenotypic molecules are effective and efficient to analyze differentiation status. Differentiation status is crucial for T cell exhaustion, in-vivo lifespan, antitumor immunity, and even antitumor pharmacological interventions. Strategies including cytokines, Akt, Wnt and Notch signaling, epigenetics, and metabolites have been developed to produce less differentiated T cells. Clinical trials have shown better clinical outcomes from infusion of T cells with less differentiated phenotypes. CD27+, CCR7+ and CD62L+ have been the most clinically relevant phenotypic molecules, while Tscm and Tcm the most clinically relevant subtypes. Currently, CD27+, CD62L+ and CCR7+ are recommended in the differentiation phenotype to evaluate strategies of enhancing stemness. Future studies may discover highly clinically relevant differentiation phenotypes for specific T-cell production methods or specific subtypes of cancer patients, with the advantages of precision medicine.

Lenvatinib in combination with transarterial chemoembolization for treatment of unresectable hepatocellular carcinoma (uHCC): a retrospective controlled study.

PURPOSE: To compare the efficacy and safety of combined treatment with lenvatinib and transarterial chemoembolization (TACE) versus TACE only in patients with unresectable hepatocellular carcinoma (uHCC). METHODS: Of the 120 patients enrolled in this study, 60 patients received treatment with TACE only, and 60 patients received TACE plus lenvatinib. We retrospectively compared the clinical outcomes including overall survival (OS), progression-free survival (PFS), and tumor response between the two groups. Both PFS and tumor response were based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Adverse events were analyzed to assess the safety profiles. RESULTS: The 1-year and 2-year OS rates were significantly higher in the TACE + lenvatinib group (88.4% and 79.8%) than that in the TACE group (79.2% and 49.2%, p = 0.047). A similar PFS benefit was observed in the TACE + lenvatinib group (1-y PFS rate: 78.4% vs. 64.7%, 2-y PFS rate: 45.5% vs. 38.0%, p < 0.001). The best overall objective response rate (ORR) was also better with TACE + lenvatinib treatment (ORR: 68.3% vs. 31.7%, p < 0.001) and disease control rate (DCR) numerically increased in the TACE + lenvatinib treatment (93.3% vs. 86.7%, p = 0.224). Patients' liver function remained comparable to baseline in the TACE + lenvatinib group. The most common adverse events were decreased albumin (55.0%), hypertension (48.3%) and decreased platelet count (46.7%) in the TACE + lenvatinib group. CONCLUSIONS: Combination treatment with TACE and lenvatinib may significantly improve clinical outcomes over TACE monotherapy with a manageable safety profile for unresectable HCC. The efficacy of the combination treatment should be validated in prospective studies with a large sample size.

[Interaction and Mechanism Between Conditioning Agents and Two Elements in the Soil Enriched with Phosphorus and Cadmium].

Focusing on agricultural soil enriched in phosphorus and cadmium (total Cd=0.94 mg·kg-1 and total P=0.86g·kg-1), indoor cultivation experiments were conducted according to the length of the middle rice growth period and the following crop planting period in Hubei. The bioavailability of soil phosphorus and cadmium were examined along with their morphological changes and coupling effect under the influence of material biochar (BC), calcium magnesium phosphate fertilizer (CMP), and fly ash (FA). The results showed that:① When cultured for 140 days, the content of available phosphorus in the soil treated with the conditioning agents was significantly increased compared with the control soil, available phosphorus reached 22.47-37.81mg·kg-1, and the optimal growth requirements of rice were met without additional application of phosphate fertilizer, and adding BC had the best effect. ② The phosphorus in the test soil is mainly inorganic orthophosphate, and the content of different forms of inorganic phosphorus increased under the action of the conditioning agents. The fixed O-P and Ca10-P in the soil gradually changed to more active forms (Ca2-P, Ca8-P, Al-P and Fe-P) over time. ③ The effective Cd content of the soil treated with the conditioning agents was significantly reduced by 8.74%-17.48% relative to the control treatment, which was mainly related to the effect of the three conditioning agents on soil pH. At the same time, compared with the control, the addition of a conditioning agent significantly reduced the exchangeable Cd, and the carbonate-bound Cd and the residual Cd were increased. The abundance of active groups at the surface is related to the adsorption and chelation of Cd2+. The results showed that the three conditioners have the dual functions of phosphorus activation and cadmium passivation in phosphorus-and cadmium-enriched soil, and the effect of biomass carbon and calcium magnesium phosphate fertilizer was greatest, which persisted across the entire rice growth period to the sowing date of the next crop.

[Effects of the Immobilization of Cadmium in Soil Alone or Combined with Foliar Application of Selenium on Cadmium Accumulation in the Plants of Different Genotypes of Tsai-tai].

To explore the safe utilization of technology in mildly and moderately cadmium (Cd)-contaminated farmland and realize the safe production of agricultural products, two different cadmium-accumulating genotypes of Tsai-tai were used as test crops, using the pot experiment method. The same six treatments were set on the soil where the two test crops were planted:control (CK), addition of 3% (mass fraction) biochar (BC), addition of 0.17% calcium magnesium phosphate fertilizers (CMP), foliar application of 3 mg·L-1 Na2SeO3 aqueous solution (Se), BC+Se, and CMP+Se, to study the changes in available cadmium in soil under different treatments and the characteristics of cadmium accumulation in different parts of the plant. The results showed that:① Under the same treatment, the content of available cadmium in soil near the root of the low-cadmium-accumulating genotype of Tsai-tai of Jinqiuhong Ⅲ was significantly lower than that of the high-cadmium-accumulating genotype of Shiyuehong. BC and CMP had a significant passivating effect on cadmium in the soil near the root of Jinqiuhong Ⅲ, and the passivating effect of BC was better than that of CMP; the effect of passivating treatment was significantly better than that of foliar application of selenium. ② The root system of Tsai-tai of Jinqiuhong Ⅲ had a stronger ability to accumulate cadmium than that of Shiyuehong, and the accumulated cadmium tended to be stored in the root. There were no synergistic effects between the foliar application of selenium and the two kinds of passivants on inhibiting the transfer and enrichment of cadmium to the edible parts of Tsai-tai. ③ Under the treatments of BC and CMP, the content of cadmium in the edible part of Tsai-tai of Jinqiuhong Ⅲ was lower than the limit value of cadmium in GB 2762-2017 (0.10 mg·kg-1). This study shows that for mildly and moderately cadmium-contaminated farmland, applying green passivants such as biochar, calcium magnesium phosphate fertilizers, and planting crops with weak absorption and low accumulation can achieve the safe use of the cadmium-contaminated farmland and safe production of agricultural products.

[Effect of Biochar on Changes of the Temperature Sensitivity of Soil Respiration and Bacterial Community Structure].

To explore the effects of biochar on the temperature sensitivity of soil respiration and microbial community structure, the soil was subjected to an indoor culture test under two major treatments which were control (CK) and the addition of 3% (mass ratio) biochar (BC). Each major treatment contained four temperature conditions. We analyzed the changes in soil CO2 emission, the content of different soil organic carbon, and the characteristics of the soil bacterial community. The results showed that:①The input of biochar to soil respiration under various temperature conditions was promoted in the early stage and inhibited in the later stage, and after 14 days of cultivation, the input of biochar significantly reduced the temperature sensitivity Q10 values of soil respiration. ② For soil organic carbon fractions, the decline rate of the content of soil inert organic carbon under the CK treatment increased with increasing temperature, and was sensitive to the changes in temperature. However, the input of biochar significantly reduced the temperature sensitivity of the soil inert organic carbon, and narrowed its decline rate under each temperature condition. The decline rate did not increase with increasing temperature. ③The 16S rDNA high-throughput sequencing results showed that at the end of the cultivation, the relative abundance of Massilia in the soil of the CK treatment decreased with increasing temperature, and the input of biochar significantly increased its temperature sensitivity, making the decline rate increase. In contrast to Massilia, the relative abundance of Haliangium in soil of the CK treatment increased significantly with increasing temperature, and the input of biochar significantly reduced its temperature sensitivity, rendering the difference of relative abundance between each temperature condition not significant. This study shows that the input of biochar can significantly reduce the temperature sensitivity of soil respiration, which is related to decreased temperature sensitivity of soil inert organic carbon, and the change in the relative abundance of Massilia and Haliangium after the input of biochar.