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The complexity of a supply chain makes product safety or quality issues extremely difficult to track, especially for the basic agricultural food supply chains of people’s daily diets. The existing agricultural food supply chains present several major problems, such as numerous participants, inconvenient communication caused by long supply chain cycles, data distrust between participants and the centralized system. The emergence of blockchain technology effectively solves the pain-point problem existing in the traceability system of agricultural food supply chains. This paper proposes a framework based on the consortium and smart contracts to track and trace the workflow of agricultural food supply chains, implement traceability and shareability of supply chains, and break down the information islands between enterprises as much as possible to eliminate the need for the central institutions and agencies and improve the integrity of the transaction records, reliability and security. At the same time, farmers record details of the environment and crop growth data in the InterPlanetary File System (IPFS) and store file IPFS hashes in smart contracts, which not only increases data security but also alleviates the blockchain storage explosion problem. This framework has been applied in Shanwei Lvfengyuan Modern Agricultural Development Co., Ltd. Although there are still many defects, the framework has successfully realized functions such as disintermediation and tracing of agricultural product information through QR codes. Thus, the framework proposed in this paper is of great significance and reference value for enterprises to ensure product quality and safety traceability.

Background. Hepatocellular carcinoma (HCC) has become the sixth most common cancer and the third leading cause of cancer death in the world. Although the research achievements of tumor immunotherapy have made great progress, especially the combination of immune targeted therapy has achieved good curative effect in HCC, but only a few patients are suitable for it and benefit from it. Therefore, there is an urgent need to find new effective drugs to treat HCC or to enhance the sensitivity of immunotherapy. Methods. Meloxicam, a COX2 inhibitor with strong anti-HCC potential, was screened from 800 small molecules approved by FDA. The effect of meloxicam on the proliferation, invasion, and migration of HCC cell lines was evaluated by cell phenotype analysis. The Human Protein Atlas database and the TISCH database were used to analyze COX2 data in single cells, and the TISIDB database was used to analyze the correlation of COX2 with immune function. The real-time quantitative polymerase chain reaction (qRT-PCR) and western blot were used to evaluate the level of PD-L1 and CD155 in HCC cell lines treated with meloxicam and further explore its possible mechanism. In vivo experiments were applied to verify the effect of meloxicam combined with anti-PD1 therapy on HCC tumor growth in mice. Results. Meloxicam can significantly inhibit the proliferation, invasion, and migration of HCC cells. The TISIDB database indicated that the COX2 was strongly associated with immunoinhibitors and immunostimulators. Meloxicam upregulated the level of PD-L1 in HCC cell lines and animal models. In terms of mechanism, meloxicam inhibited microRNA-200, thereby upregulating PD-L1. In vitro experiments showed that both meloxicam and anti-PD1 had inhibitory effects on the growth of HCC tumors. Compared with meloxicam and anti-PD1 alone, the combination therapy showed stronger antitumor properties. Immunohistochemical analysis confirmed that meloxicam enhanced the antitumor immune activity in the tumor microenvironment. Conclusion. Our study showed meloxicam inhibited HCC progression and enhanced the sensitivity of immunotherapy via the microRNA-200/PD-L1 pathway.

Additional file 1: Fig. S1. The cell viability of HCC-LM3 (IC50=143.2 µM) and Hep-3B (IC50=141.1 µM) cell lines after the treatment of differential doses of MDZ at 24h. Fig. S2. MDZ inhibited the migration in HCC cell lines with the presence of mitomycin-C. On the basis of the original experimental methods, Mitomycin-C (1 µg/mL; GLPBIO) was present throughout the wound healing assays to avoid the interference of cell proliferation. Representative images (A) and quantification (B) of wound healing assay on HCC-LM3 and Hep-3B cell lines after the treatment of MDZ.*p

Additional file 1: Fig. S1. (A) Relative expression of the 5 candidate circRNAs in human HCC tissues and adjacent nontumor tissues of 20 patients. (B) Cell cycle was performed in the three groups. Data were shown as mean ± SEM. Fig. S2. (A) Size distribution of CS/si-circPAK1 nanocomplexes (CS/si-circPAK1 = 50/1). (B) Zeta potential of CS/si-circPAK1 nanocomplexes (CS/si-circPAK1 = 50/1). (C) Release curve of si-circPAK1. (D) IHC analysis of Ki-67 in the tumors derived from mice, scale bar, 50 μm. Fig. S3. The positive effect of circPAK1 on HCC progression was rescued by YAP silencing. (A) The silencing efficiency of si-YAP in Lv-circPAK1 Hep-3B cells was determined by qRT-PCR. (B) The colony formation assay of Hep-3B cells transfected Lv-circPAK1 and YAP siRNA. (C) EdU incorporation assay of Hep-3B cells transfected Lv-circPAK1 and YAP siRNA, scale bar, 50 μm. (D) Transwell assay assay of Hep-3B cells transfected Lv-circPAK1 and YAP siRNA, scale bar, 200 μm. (E) Wound healing assay of Hep-3B cells transfected Lv-circPAK1 and YAP siRNA, scale bar, 100 μm. (F) HUVEC tube formation, migration and invasion assay of Hep-3B cells transfected Lv-circPAK1 and YAP siRNA, scale bar, 100 μm. *p < 0.05; **p < 0.01; ***p < 0.001. Data were shown as mean ± SEM. Fig. S4. (A) RIP-qPCR was performed to determine the association between circPAK1 and AGO2. (B) liquid chromatography mass spectrometry identified the 14–3-3ζ protein. (C) The silencing efficiency of si-14-3-3ζ in sh-circPAK1 LM3 cells was determined by qRT-PCR. (D) CircPAK1 stable overexpression Hep-3B cells were subjected to IP using 14–3-3ζ antibody or control IgG, followed by IB with 14–3-3ζ, p-LATS1/2 and YAP antibody, to confirm and determine the 14–3-3ζ- p-LATS-YAP protein complex. (E) IF assay in stable circPAK1-knockdown and 14–3-3ζsiRNA LM3 cells, scale bar, 20 μm. (F) The IC50 of lenvatinib resistance cell lines and their parental cells. Table S1. ShRNA and siRNA sequence used in this study. Table S2. Full sequence information of circPAK1. Table S3. Primer sequences used in this study. Table S4. Antibodies used in this study. Table S5. Probes used in this study. Table S6. The 44 upregulated circRNAs.

1. This study investigated the impact of melatonin and LPS on goose growth and the intestinal microbiome.2. Geese were injected with a control solution (C), LPS solution (L), melatonin solution (M), and both LPS and melatonin solution (LM), respectively. Faecal samples from each group were used to analyse microbial diversity and function for geese with different treatments.3. The results showed that the M group had a little improvement in growth compared with the C group, but were much higher than the L and LM groups. A clear distinction between M and other groups was seen with regard to alpha and beta diversity in the biome. The dominant bacteria phyla were Firmicutes, Proteobacteria, and Actinobacteria spp. in all groups. Unclassified bacteria were dominant in all groups at the genus level. Significant KEGG enrichment pathways in the M group were involved in processing metabolism and genetic information, while the L group was related to processing metabolism and environmental information.4. This study provided a foundation for future studies targeting the specific effect of important bacterial populations on goose growth performance.

A high-purity Ti (HP-Ti) sheet was subjected to small strain rolling (10% reduction) with microstructural and textural characteristics examined by electron channeling contrast imaging and electron backscatter diffraction techniques. Particular attentions were paid to misorientation and textural changes aroused by twins in the rolled HP-Ti sheet. Results show that after the 10% rolling, almost all the prior equiaxed grains in the initial specimen are twinned, leading to remarkable grain refinement. The presence of two major misorientation angle peaks around 65° and 85° is ascribed to {11–22} and {10–12} twinning, respectively, and two minor peaks around 47° and 77° are due mainly to impingement of various variants of such twins. Distinct from earlier work, the small strain rolling is confirmed to be able to induce drastic textural changes in pure Ti sheets: largely reduced texture intensity and appearance of new textural components. This can essentially be attributed to enhanced twinning activity due to much lower impurity contents of the present material. Primary {11–22} twins are mainly responsible for the new textural component of c-axes aligned near the rolling direction with spread, while the component of c-axes parallel to the normal direction is due to reorientation of secondary {10–12} twins. This study clearly demonstrates the capability of small strain rolling to effectively modify both microstructures and textures of the HP-Ti sheet and may shed some light on exploring feasible processings for such materials.

Fermentation is a good way to utilize fish by-products. In this study, the effects of mixed starter cultures and exogenous L-Lys on the physiochemical and sensory properties of fermented longsnout catfish minced meat were investigated. Fish pastes were divided into three groups, including a treated group (sample A), a mixed starter culture-treated group (sample B), and a L-Lys and mixed starter culture-treated group (sample C). The pH and total volatile base nitrogen in the sample C were the lowest among the tested samples. At the final stage of fermentation, the total acidity, amino acid nitrogen content, and free amino acid content in the sample C were the highest among the tested samples. No significant differences in the histamine content or antioxidant activities were observed among the three samples (p

Electron channeling contrast imaging and electron backscatter diffraction techniques were jointly employed to characterize microstructures in a high-purity Ti sheet surface-treated by pulsed laser. Hardness variation induced by the laser surface treatment (LST) was also examined and correlated with these microstructural characteristics. After the LST, two microstructurally distinct modification zones are identified: the phase transformation zone (PTZ) is comprised of fine α plates with interior nanotwins while the heat affected zone (HAZ) is featured by the presence of multiple sub-grains with irregular-shaped boundaries. The occurrence of β → α martensitic transformation in the PTZ during the LST-induced rapid cooling results in plate structures with scattered orientations. The sub-grains in the HAZ are formed by thermal recovery of stress-induced dislocation activities. The absence of a duplex-phase domain in the high-purity Ti leads to a sharp PTZ/HAZ interface, while the HAZ/matrix interface is obscure due to inhomogeneous high angle boundary migration. Remarkable hardness increase (by 130%) is noted in the PTZ, which can be ascribed to both greatly refined grains (α plates) and nanotwins; there is only mild hardening effect in the HAZ.