Determination of 1,3-Dioleic acid-2-palmitoyl triglyceride in Infant Formula by High Performance Liquid Chromatography

A method for the quantification of 1,3-dioleyl-2-palmitoyl-glycerol (OPO) in infant formula was developed. The samples were treated with ammonia and extracted with organic solvents. The fat containing OPO was purified on a NH2 solid-phase extraction (SPE) cartridge packed with aminopropyl as the sorbent. The eluate was separated by silver ion chromatography using 0.55% acetonitrile-hexane as the mobile phase. The detection was carried out with a high performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD). This novel procedure enabled the complete separation of OPO and its isomer 1,2-dioleyl-3-palmitoyl-glycerol (OOP), thus allowing for the accurate quantification of OPO. The developed method showed the desired linearity in the concentration range of 25–500 μg/mL with a determination coefficient (R2) of 0.999 6. The limits of detection (LOD) and limits of quantification (LOQ) were 0.30 and 0.90 g/kg, respectively. At spiked concentrations from 1 to 96 g/kg, the average recoveries of OPO varied from 97.1% to 104.2% with relative standard deviations (RSD) between 1.2% and 2.9%. The precision and accuracy of this method met the relevant requirements, and it passed the inter-laboratory collaborative validation. Our investigation analyzed 39 commercial samples of OPO-fortified infant formula in China, revealing that the measured OPO content only accounted for 28.4% to 59.7% of the labelled value, which is mainly due to the inconsistency of detection methods

Efficacy and safety of PD-1/PD-L1 inhibitor-based immune combination therapy versus sorafenib in the treatment of advanced hepatocellular carcinoma: a meta-analysis

ObjectiveTo systematically evaluate the safety and efficacy of PD-1/PD-L1 inhibitor-based immunotherapy (hereafter referred to as “combination immunotherapy”) compared with that of sorafenib in the treatment of hepatocellular carcinoma (HCC).MethodsDatabases such as PubMed, Embase, and the Cochrane Library were searched from the date of their establishment to September 2023 to identify randomized controlled trials (RCTs) of combination immunotherapy versus sorafenib for the treatment of advanced HCC. Two reviewers independently evaluated the quality of the included studies, extracted the data, and cross-checked the information. The meta-analysis was performed using RevMan 5.3 software.ResultsA total of 5 RCTs were included. The results of the meta-analysis showed the following: (1) Effectiveness. Compared to sorafenib, combination immunotherapy significantly improved overall survival (OS, HR = 0.69, 95% CI: 0.58 ~ 0.82, p < 0.01) and progression-free survival (PFS, HR = 0.62, 95% CI: 0.50 ~ 0.78, p < 0.001) in patients with advanced HCC. (2) Safety. Both groups had comparatively high incidences of adverse events (AEs), but the difference in any treatment-related adverse events was not significant between the two arms (OR = 0.98, 95% CI: 0.95 ~ 1.02, p = 0.34). The difference in the incidence of grade 1–2 adverse reactions was statistically significant (OR = 0.66, 95% CI = 0.49–0.90, p = 0.001). There were no differences in grade 3/4 TRAEs or grade 5 TRAEs (OR = 1.46, 95% CI = 0.78 ~ 2.71, p = 0.24; OR = 1.08, 95% CI = 0.73 ~ 1.58, p = 0.71).ConclusionCombined immunotherapy can significantly prolong the OS and PFS of patients with advanced HCC without increasing the incidence of adverse effects in terms of safety, but the incidence of AEs in different systems is different

Comparative analysis of miRNAs and their target transcripts between a spontaneous late-ripening sweet orange mutant and its wild-type using small RNA and degradome sequencing

Fruit ripening in citrus is not well understood at the molecular level. Knowledge of the regulatory mechanism of citrus fruit ripening at the post-transcriptional level in particular is lacking. Here, we comparatively analyzed the miRNAs and their targeted genes in a spontaneous late-ripening mutant, ‘Fengwan’ sweet orange (MT) (Citrus sinensis L. Osbeck), and its wild-type counterpart ('Fengjie 72-1', WT). Using high-throughput sequencing of small RNAs and RNA degradome tags, we identified 107 known and 21 novel miRNAs, as well as 225 target genes. A total of 24 miRNAs (16 known miRNAs and 8 novel miRNAs) were shown to be differentially expressed between MT and WT. The expression pattern of several key miRNAs and their target genes during citrus fruit development and ripening stages was examined. Csi-miR156k, csi-miR159 and csi-miR166d suppressed specific transcription factors (GAMYBs, SPLs and ATHBs) that are supposed to be important regulators involved in citrus fruit development and ripening. In the present study, miRNA-mediated silencing of target genes was found under complicated and sensitive regulation in citrus fruit. The identification of miRNAs and their target genes provide new clues for future investigation of mechanisms that regulate citrus fruit ripening

Genome-wide comprehensive analysis of transcriptomes and small RNAs offers insights into the molecular mechanism of alkaline stress tolerance in a citrus rootstock

Molecular biology: Rooting out alkaline resistance mechanisms in citrus trees The ability of citrus trees to tolerate alkaline soils may hinge upon plant hormones called auxins which regulate root growth. The discovery could aid the development of more resilient rootstocks. Alkaline stress, caused by e.g. industrial run-off, is a growing problem worldwide because it reduces the growth and survival of crops – including the most widely used citrus rootstock in China, Poncirus trifoliata. To better understand the mechanisms underpinning tolerance to soil alkalinity, Hualin Yi at Huazhong Agricultural University in Wuhan, China, and colleagues used next-generation sequencing to profile the transcription products of P. trifolata seedlings and those of an alkaline-tolerant rootstock, Ziyang xiangcheng, when they were grown in three different nutrient solutions. Auxin homeostasis appears to be a key element of citrus adaption to alkaline stress, they found - probably by encouraging lateral root branching

MdSCL8 as a Negative Regulator Participates in ALA-Induced FLS1 to Promote Flavonol Accumulation in Apples

Apples (Malus domestica) are rich in flavonols, and 5-aminolevulinic acid (ALA) plays an important role in the regulation of plant flavonoid metabolism. To date, the underlying mechanism of ALA promoting flavonol accumulation is unclear. Flavonol synthase (FLS) is a key enzyme in flavonol biosynthesis. In this study, we found that ALA could enhance the promoter activity of MdFLS1 in the ‘Fuji’ apple and improve its expression. With MdFLS1 as bait, we screened a novel transcription factor MdSCL8 by the Yeast One-Hybrid (Y1H) system from the apple cDNA library which we previously constructed. Using luciferase reporter assay and transient GUS activity assay, we verified that MdSCL8 inhibits the activity of MdFLS1 promoter and hinders MdFLS1 expression, thus reducing flavonol accumulation in apple. ALA significantly inhibited MdSCL8 expression. Therefore, ALA promoted the expression of MdFLS1 and the consequent flavonol accumulation probably by down-regulating MdSCL8. We also found that ALA significantly enhanced the gene expression of MdMYB22 and MdHY5, two positive regulators of MdFLS. We further demonstrated that MdMYB22 interacts with MdHY5, but neither of them interacts with MdSCL8. Taken together, our data suggest MdSCL8 as a novel regulator of MdFLS1 and provide important insights into mechanisms of ALA-induced flavonol accumulation in apples

A Form Stable Composite Phase Change Material for Thermal Energy Storage Applications over 700 °C

Thermal energy storage (TES) is a highly effective approach for mitigating the intermittency and fluctuation of renewable energy sources and reducing industrial waste heat. We report here recent research on the use of composite phase change materials (PCM) for applications over 700 °C. For such a category of material, chemical incompatibility and low thermal conductivity are often among the main challenges. Our aims are to address these challenges through the formulation of form-stable composite PCMs and to understand their thermophysical properties. The eutectic K2CO3-Na2CO3 salt was used as a PCM with MgO as a form stabilizer. We found that such a formulation could maintain shape stability with up to 60 wt.% PCM. With a melting point of ~710.1 °C and an energy density as high as 431.2 J/g over a temperature range between 550 °C and 750 °C, the composite PCM was shown to be thermally stable up to 885 °C. An addition of 10 wt.% SiC enhanced the overall thermal conductivity from 1.94 W·m−1 K−1 to 2.28 W·m−1 K−1, giving an enhancement of 17.53%. Analyses of thermal cycling data also showed a high extent of chemical compatibility among the ingredients of the composite PCM

Comparative analysis of miniature inverted–repeat transposable elements (MITEs) and long terminal repeat (LTR) retrotransposons in six Citrus species

Abstract Background Miniature inverted-repeat transposable elements (MITEs) and long terminal repeat (LTR) retrotransposons are ubiquitous in plants genomes, and highly important in their evolution and diversity. However, their mechanisms of insertion/amplification and roles in Citrus genome’s evolution/diversity are still poorly understood. Results To address this knowledge gap, we developed different computational pipelines to analyze, annotate and classify MITEs and LTR retrotransposons in six different sequenced Citrus species. We identified 62,010 full-length MITEs from 110 distinguished families. We observed MITEs tend to insert in gene related regions and enriched in promoters. We found that DTM63 is possibly an active Mutator-like MITE family in the traceable past and may still be active in Citrus. The insertion of MITEs resulted in massive polymorphisms and played an important role in Citrus genome diversity and gene structure variations. In addition, 6630 complete LTR retrotransposons and 13,371 solo-LTRs were identified. Among them, 12 LTR lineages separated before the differentiation of mono- and dicotyledonous plants. We observed insertion and deletion of LTR retrotransposons was accomplished with a dynamic balance, and their half-life in Citrus was ~ 1.8 million years. Conclusions These findings provide insights into MITEs and LTR retrotransposons and their roles in genome diversity in different Citrus genomes

Automated Modular Synthesis of Aptamer–Drug Conjugates for Targeted Drug Delivery

Aptamer–drug conjugates (ApDCs) are promising targeted drug delivery systems for reducing toxicity while increasing the efficacy of chemotherapy. However, current ApDC technologies suffer from problems caused by the complicated preparation and low controllability of drug–aptamer conjugation. To solve such problems, we have designed and synthesized a therapeutic module for solid phase synthesis, which is a phosphoramdite containing an anticancer drug moiety and a photocleavable linker. Using this module, we have realized automated and modular synthesis of ApDCs, and multiple drugs were efficiently incorporated into ApDCs at predesigned positions. The ApDCs not only recognize target cancer cells specifically, but also release drugs in a photocontrollable manner. We demonstrated the potential of automated and modular ApDC technology for applications in targeted cancer therapy