CD36-mediated accumulation of MDSCs exerts abscopal immunosuppressive responses in hepatocellular carcinoma after insufficient microwave ablation.

The immune landscape of distant unablated tumors following insufficient microwave ablation (iMWA) in hepatocellular carcinoma (HCC) remains to be clarified. The objective of this study is to define the abscopal immune landscape in distant unablated tumor before and after iMWA for HCC. Two treatment-naive patients were recruited for tumor tissue sampling, of each with two HCC lesions. Tumor samples were obtained at before and after microwave ablation in distant unablated sites for single-cell RNA sequencing (scRNA-seq). Mouse model with bilateral hepatoma tumors were developed, and distant unablated tumors were analyzed using multicolor immunofluorescence, RNA sequencing and flow cytometry. The scRNA-seq revealed that a reduced proportion of CD8+ T cells and an increased proportion of myeloid-derived suppressor cells (MDSCs) were observed in the distant unablated tumor microenvironment (TME). A notable disruption was observed in the lipid metabolism of tumor-associated immune cells, accompanied by an upregulated expression of CD36 in tumor-infiltrating immune cells in distant unablated tumor. The administration of a CD36 inhibitor has been demonstrated to ameliorate the adverse effects induced by iMWA, primarily by reinstating the anti-tumor responses of T cells in distant unablated tumor. These findings explain the recurrence and progression of tumors after iMWA and provide a new target of immunotherapy for HCC.

Identification of NOX4 as a New Biomarker in Hepatocellular Carcinoma and Its Effect on Sorafenib Therapy.

To improve the survival of patients with hepatocellular carcinoma (HCC), new biomarkers and therapeutic targets are urgently needed. In this study, the GEO and TCGA dataset were used to explore the differential co-expressed genes and their prognostic correlation between HCC and normal samples. The mRNA levels of these genes were validated by qRT-PCR in 20 paired fresh HCC samples. The results demonstrated that the eight-gene model was effective in predicting the prognosis of HCC patients in the validation cohorts. Based on qRT-PCR results, NOX4 was selected to further explore biological functions within the model and 150 cases of paraffin-embedded HCC tissues were scored for NOX4 immunohistochemical staining. We found that the NOX4 expression was significantly upregulated in HCC and was associated with poor survival. In terms of function, the knockdown of NOX4 markedly inhibited the progression of HCC in vivo and in vitro. Mechanistic studies suggested that NOX4 promotes HCC progression through the activation of the epithelial-mesenchymal transition. In addition, the sensitivity of HCC cells to sorafenib treatment was obviously decreased after NOX4 overexpression. Taken together, this study reveals NOX4 as a potential therapeutic target for HCC and a biomarker for predicting the sorafenib treatment response.

Characterization and Antioxidant Evaluation of Four Kinds of Marine Oils in vitro.

The objective of this study was to characterize the lipid class and fatty acid composition of four kinds of marine oils including Phaeodactylum tricornutum oil (PO), Laminaria japonica oil (LO), krill oil (KO) and fish oil (FO), and evaluate their antioxidant capacities in vitro. The results indicated that compared to other three oils, PO showed the highest contents of total lipids and fucoxanthin (194.70 and 7.48 mg/g dry weight, respectively), the relatively higher content of long-chain polyunsaturated fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (30.94 % in total fatty acids), and total phenolic content (675.88 mg gallic acid equivalent /100 g lipids), thereby contribute to great advantages in scavenging free radicals such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2-azino-bis (3-ethylbenzthiazoline)-6-sulfonic acid (ABTS), peroxyl radical, as well as reducing FRAP value. In conclusion, PO should be considered as a potential ingredient for dietary supplement with antioxidant capacity.

Therapeutic Effect of Darkling Beetle (Zophobas morio) Hemolymph on Skin Thermal Injury in Mice Infected by Staphylococcus haemolyticus.

Staphylococci are the most common pathogens isolated from skin infections in livestock or companion animals. Antibiotic therapy is the best treatment for infections, but local or systemic use of antimicrobials increases the risk of bacterial resistance. Insects are rich in antimicrobial peptides, which can reduce bacterial resistance and can be used to treat bacterial infections after skin burns. We propose that the use of the darkling beetle (Z. morio) hemolymph to treat skin infections in mice by Staphylococcus haemolyticus is one of the alternatives. Z. morio hemolymph alleviated the increase in wound area temperature in mice with a skin infection, reduced the bacterial load of the wound, and accelerated the wound healing speed significantly. Pathological sections showed that Z. morio hemolymph can significantly reduce inflammatory cell infiltration, and promote skin tissue repair. Real-time fluorescent quantitative polymerase chain reaction (PCR) revealed that the Z. morio hemolymph can significantly reduce the levels of pro-inflammatory cytokines, including interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and chemokine interleukin-8 (IL-8). Our findings suggest that Z. morio antibacterial hemolymph can promote wound contraction, relieve local inflammatory responses and promote wound healing in mice infected with a heat injury, which has a positive therapeutic effect and enormous potential for skin thermal injury.

Metformin Attenuates Silica-Induced Pulmonary Fibrosis by Activating Autophagy via the AMPK-mTOR Signaling Pathway.

Long-term exposure to crystalline silica particles leads to silicosis characterized by persistent inflammation and progressive fibrosis in the lung. So far, there is no specific treatment to cure the disease other than supportive care. In this study, we examined the effects of metformin, a prescribed drug for type || diabetes on silicosis and explored the possible mechanisms in an established rat silicosis model in vivo, and an in vitro co-cultured model containing human macrophages cells (THP-1) and human bronchial epithelial cells (HBEC). Our results showed that metformin significantly alleviated the inflammation and fibrosis of lung tissues of rats exposed to silica particles. Metformin significantly reduced silica particle-induced inflammatory cytokines including transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in rat lung tissue and HBEC culture supernatant. The protein levels of Vimentin and α-smooth muscle actin (α-SMA) were significantly decreased by metfomin while expression level of E-cadherin (E-Cad) increased. Besides, metformin increased the expression levels of phosphorylated adenosine 5'-monophosphate (AMP)-activated protein kinase (p-AMPK), microtubule-associated protein (MAP) light chain 3B (LC3B) and Beclin1 proteins, and reduced levels of phosphorylated mammalian target of rapamycin (p-mTOR) and p62 proteins in vivo and in vitro. These results suggest that metformin could inhibit silica-induced pulmonary fibrosis by activating autophagy through the AMPK-mTOR pathway.

Polyaspartic acid (PASP)-urea and optimised nitrogen management increase the grain nitrogen concentration of rice.

Increase in grain nitrogen concentration (GNC), which is directly affected by nitrogen (N) application, can help overcome the issues of malnutrition. Here, the effects of urea type (polyaspartic acid (PASP) urea and conventional urea) and N management method (two splits and four splits) on GNC and N concentration of head rice were investigated in field experiments conducted in Sichuan, China, in 2014 and 2015. N concentration of grain and head rice were significantly (P < 0.05) increased by N redistribution from the leaf lamina, activities of glutamine synthetase (GS), and glutamate synthase (GOGAT) at the heading stage, and N concentration and GOGAT activity in the leaf lamina at the maturity stage. Compared to conventional urea, PASP-urea significantly improved N concentration of grain and head rice by improving the activities of GS and GOGAT, thereby increasing N distribution in the leaf lamina. The four splits method, unlike the two splits method, enhanced N concentration and activities of key N metabolism enzymes of leaf lamina, leading to increased GNC and N concentration in head rice too. Overall, four splits is a feasible method for using PASP-urea and improving GNC.

Conversion of poplar into bio-oil via subcritical hydrothermal liquefaction: Structure and antioxidant capacity.

Subcritical hydrothermal liquefaction of poplar was performed at 220-280 °C, and the liquid phase produced was extracted by ethyl acetate to obtain light oil (LO), which contained LO1 (water-soluble) and LO2 (ethyl acetate-soluble). The residue was further extracted with acetone to produce heavy oil (HO) and solid residue (SR). The highest bio-oil yield of 19.88% was obtained at 260 °C. The HO produced at 260 °C had the highest content of C (69.13%) and the higher heating value was 27.97 MJ/kg. The O/C and H/C ratios of LO were higher than those of HO due to less aromatics in LO. Oxidative inhibition rates of bio-oils, measured in DPPH-ethanol solution at a concentration of 0.1 mg/mL, reached 60.76% for LO1 while 90.29% and 90.85% for LO2 and HO, respectively. The bio-oil with good antioxidant activity can be utilized as an additive in bio-diesel to improve oxidation stability.

[Mixed infections in children with Mycoplasma pneumoniae pneumonia].

OBJECTIVE: To investigate the incidence and clinical features of mixed infections in children with Mycoplasma pneumoniae (MP) pneumonia. METHOD: A total of 201 cases diagnosed as MP pneumonia were investigated for mixed infections by sputum bacterial culture, respiratory virus antigen detection and serum Chlamydia pneumoniae antibody test. For those with the indications for bronchoscopy, we also did bronchoalveolar lavage and lavage bacterial culture. RESULT: A high incidence (103/201, 51.2%) of mixed infections in children with MP pneumonia was revealed. The most frequent co-infected pathogen was Chlamydia pneumoniae (52, 25.9%), followed by viruses (29, 14.4%), and bacteria (22, 10.9%). Among viruses, respiratory syncytial virus was the most common (17, 8.5%), followed by adenovirus (6, 3.0%), parainfluenza virus type III (4, 2.0%) and influenza virus type B (2, 1.0%). Sputum bacterial culture was positive in 14/201 (7.0%) cases, Streptococcus pneumonia being most common (6, 3.0%). BALF culture yielded positive results in 11.6% (8/69), Streptococcus pneumonia was also common (5, 7.3%). Among 29 cases with MP and virus coinfection, 26 were younger than 3 years (89.7%), while for MP and Chlamydia pneumoniae coinfection, most of them were older than 3 years (40/52, 76.9%). Compared with non-mixed infections, those with mixed infections had longer fever duration (24.5% and 40.8% longer than 10 d), more frequently developed pleural effusion (11.2%, 23.3%) and large area of shadow in chest imaging (35.7%, 51.5%). White blood cell [(14.28 ± 4.99) × 10(9)/L], C-reactive protein (CRP) [69(32.5 - 99.5) mg/L] and neutrophil ratio in BALF [0.86 (0.63 - 0.91)] were much higher in children with mixed bacterial infections than that in non-mixed infections [(9.06 ± 3.47) × 10(9)/L, 3 (0 - 31.0) mg/L, 0.44 (0.03 - 0.88)]. But no significant difference was found in peripheral blood neutrophil proportion between mixed bacterial infections (0.38 ± 0.25) and non-mixed infections (0.51 ± 0.19). CONCLUSION: More than half of cases with MP pneumonia had mixed infections, most commonly caused by Chlamydia pneumonia followed by viruses. The incidence of mixed infections with bacteria was low. Mixed infections with virus were more common in young children, while mixed infection with Chlamydia pneumoniae was more common in older ones. Bacterial infections should be paid more attention, especially those caused by Streptococcus pneumoniae, for those with high peripheral white blood cell counts, high CRP levels and high proportion of neutrophils in BALF.